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Sample records for congenital horner syndrome

  1. Unilateral straight hair and congenital horner syndrome.

    PubMed

    Wang, Frederick M; Wertenbaker, Christian; Cho, Hyung; Marmor, Maury A; Ahn-Lee, Sandra S; Bernard, Bruno A

    2012-06-01

    Congenital Horner syndrome is a rare disorder that accounts for less than 5% of all cases of Horner syndrome. Like Horner syndrome in general, it consists primarily of ptosis, miosis, and anhidrosis. Congenital Horner syndrome may manifest some special features such as iris heterochromia since the sympathetic nervous system is an essential component for the development and maintenance of eye color. We present 3 cases of unilateral straight hair in association with congenital Horner syndrome in which the patients had straight hair ipsilateral to the Horner syndrome, whereas on the contralateral side, it was curly, and we discuss possible mechanisms for this phenomenon.

  2. Autosomal dominant congenital Horner's syndrome in a Dutch family.

    PubMed Central

    Hageman, G; Ippel, P F; te Nijenhuis, F C

    1992-01-01

    A Dutch family is reported with congenital Horner's syndrome in five cases spanning five generations, with symptoms of varying degree but mainly ptosis and meiosis. Heterochromia iridium, anhidrosis, and enophthalmos were not present. The site of the lesion may be in the region between Gasser's ganglion and the short vertical segment of the internal carotid artery near the siphon. There are only four previous reports showing autosomal dominant inheritance of congenital Horner's syndrome. Images PMID:1548493

  3. Congenital horner syndrome with heterochromia iridis associated with ipsilateral internal carotid artery hypoplasia.

    PubMed

    Deprez, Fabrice C; Coulier, Julie; Rommel, Denis; Boschi, Antonella

    2015-04-01

    Horner syndrome (HS), also known as Claude-Bernard-Horner syndrome or oculosympathetic palsy, comprises ipsilateral ptosis, miosis, and facial anhidrosis. We report herein the case of a 67-year-old man who presented with congenital HS associated with ipsilateral hypoplasia of the internal carotid artery (ICA), as revealed by heterochromia iridis and confirmed by computed tomography (CT). CT evaluation of the skull base is essential to establish this diagnosis and distinguish aplasia from agenesis/hypoplasia (by the absence or hypoplasia of the carotid canal) or from acquired ICA obstruction as demonstrated by angiographic CT.

  4. Congenital Horner Syndrome with Heterochromia Iridis Associated with Ipsilateral Internal Carotid Artery Hypoplasia

    PubMed Central

    Coulier, Julie; Rommel, Denis; Boschi, Antonella

    2015-01-01

    Background Horner syndrome (HS), also known as Claude-Bernard-Horner syndrome or oculosympathetic palsy, comprises ipsilateral ptosis, miosis, and facial anhidrosis. Case Report We report herein the case of a 67-year-old man who presented with congenital HS associated with ipsilateral hypoplasia of the internal carotid artery (ICA), as revealed by heterochromia iridis and confirmed by computed tomography (CT). Conclusions CT evaluation of the skull base is essential to establish this diagnosis and distinguish aplasia from agenesis/hypoplasia (by the absence or hypoplasia of the carotid canal) or from acquired ICA obstruction as demonstrated by angiographic CT. PMID:25749818

  5. [An adult case of congenital Horner's syndrome with heterochromia iridis--with special reference to alteration of Horner's sign associated with development].

    PubMed

    Uyama, E; Maeda, J; Adachi, K; Yu, T C; Araki, S

    1989-10-01

    It is well known that when the Horner's syndrome is congenital, a defect in pigmentation of the iris is usual; all or part of the iris remains light brown. We reported an adult case of congenital Horner's syndrome with remission and relapse of unilateral ptosis. A 25-year-old man was admitted to our hospital for ophthalmologic surgical treatment of right ptosis. According to the patient's mother, the patient was delivered with the aid of forceps at birth, and the right ptosis was observed during the first few days of his life. At 2 to 3 years of age, his parents noted lighter color of the right eye. The right ptosis was gradually improved as he grew older. However, he developed right ptosis again with left meralgia paresthesia since eighteen age. At age 25 years, he was noted to have right ptosis, right miosis (the left pupil measured 4.5 mm in diameter and the right 3.0 mm), right heterochromia iridis with pigmented iris nevi, and left meralgia paresthesia . Laboratory data of urine, blood and CSF as well as radiological studies of chest X-ray, skull X-ray, spine X-ray, brain MRI and spinal cord MRI showed unremarkable. Sweating test was intact, pharmacologic test to Horner's syndrome with 5% cocaine and 1.25% 1-epinephrine indicated that the damage was pointed to the post ganglionic sympathetic neuron. Ten patients with congenital Horner's syndrome reported in Japan since 1953 were reviewed including our case. Ten of eleven were male and Horner's sign was recorded on the left eye in 8 cases.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Horner syndrome: clinical perspectives

    PubMed Central

    Kanagalingam, Sivashakthi; Miller, Neil R

    2015-01-01

    Horner syndrome consists of unilateral ptosis, an ipsilateral miotic but normally reactive pupil, and in some cases, ipsilateral facial anhidrosis, all resulting from damage to the ipsilateral oculosympathetic pathway. Herein, we review the clinical signs and symptoms that can aid in the diagnosis and localization of a Horner syndrome as well as the causes of the condition. We emphasize that pharmacologic testing can confirm its presence and direct further testing and management. PMID:28539793

  7. Genetics Home Reference: Horner syndrome

    MedlinePlus

    ... childhood cancer of the nerve tissues called a neuroblastoma . Horner syndrome can also be caused by problems ... roles of imaging and urine studies to detect neuroblastoma and other responsible mass lesions. Am J Ophthalmol. ...

  8. Horner Syndrome: A Clinical Review.

    PubMed

    Martin, Timothy J

    2018-02-21

    Horner syndrome results from an interruption of the oculosympathetic pathway. Patients with Horner syndrome present with a slightly droopy upper lid and a smaller pupil on the affected side; less commonly, there is a deficiency of sweating over the brow or face on the affected side. This condition does not usually cause vision problems or other significant symptoms, but is important as a warning sign that the oculosympathetic pathway has been interrupted, potentially with serious and even life-threatening processes. The oculosympathetic pathway has a long and circuitous course, beginning in the brain and traveling down the spinal cord to exit in the chest, then up the neck and into the orbit. Therefore, this syndrome with unimpressive clinical findings and insignificant symptoms may be a sign of serious pathology in the head, chest, or neck. This clinical review discusses how to identify the signs, confirm the diagnosis, and evaluate the many causes of Horner syndrome.

  9. [Iris heterochromia in acquired Horner's syndrome].

    PubMed

    Beynat, J; Soichot, P; Bidot, S; Dugas, B; Creuzot-Garcher, C; Bron, A

    2007-09-01

    Horner's syndrome (HS) is related to an interruption of the oculosympathetic nerve pathway. The classic clinical findings associated with this condition are ptosis, miosis, and enophthalmos. Heterochromia is typically described in congenital HS, but it is an uncommon finding in acquired HS. We report a case of post-traumatic HS associated with heterochromia. A literature review indicates that this type of heterochromia may be related to a reduction in the number of iris melanocytes. This mechanism may be the same in the physiological iris color modifications in adulthood.

  10. Anisocoria and Horner's Syndrome

    MedlinePlus

    ... In children, Horner’s syndrome may be caused by neuroblastoma, a tumor arising in another part of the body. Although rare, the risk of neuroblastoma is significantly greater with acquired Horner’s syndrome than ...

  11. Does Horner's syndrome in infancy require investigation?

    PubMed Central

    George, N; Gonzalez, G; Hoyt, C

    1998-01-01

    AIMS—To evaluate whether isolated Horner's syndrome presenting in the first year of life warrants investigation.
METHOD—Retrospective review of 23 children presenting with Horner's syndrome in the first year of life.
RESULTS—In 16 patients (70%) no cause was identified. Birth trauma was the most common identifiable cause (four patients). Twenty one children (91%) had urinary vanillylmandelic acid (VMA) measured and 13 patients (57%) underwent either computed tomography or magnetic resonance imaging of the chest and neck. These investigations revealed previously undisclosed pathology in only two—one ganglioneuroma of the left pulmonary apex and one cervical neuroblastoma. A further patient was known to have abdominal neuroblastoma before presenting with Horner's syndrome. There were no cases of Horner's syndrome occurring after cardiothoracic surgery. Long term follow up of the patients (mean 9.3 years) has not revealed further pathology.
CONCLUSIONS—Routine diagnostic imaging of isolated Horner's syndrome in infancy is unnecessary. Infants should be examined for cervical or abdominal masses and involvement of other cranial nerves. If the Horner's syndrome is truly isolated then urinary VMA levels and follow up in conjunction with a paediatrician should detect any cases associated with neuroblastoma. Further investigation is warranted if the Horner's syndrome is acquired or associated with other signs such as increasing heterochromia, a cervical mass, or cranial nerve palsies.

 Keywords: Horner's syndrome; neuroblastoma PMID:9536881

  12. Acquired heterochromia with horner syndrome in two adults.

    PubMed

    Diesenhouse, M C; Palay, D A; Newman, N J; To, K; Albert, D M

    1992-12-01

    Heterochromia iridis, asymmetry of iris pigmentation, has been well described with congenital Horner syndrome. Acquired heterochromia associated with lesions in the ocular sympathetic pathways in adulthood, however, is rare. Two cases are reported in which sympathectomy in adults resulted in ipsilateral Horner syndrome with heterochromia. In each case, pharmacologic testing with cocaine and hydroxyamphetamine was performed. In both cases, sympathectomy occurred at the level of the second order neuron, but hydroxyamphetamine testing suggested at least partial third order neuron involvement. Acquired heterochromia can occur in adults. The partial response to hydroxyamphetamine in the two cases presented may reflect trans-synaptic degeneration of the postganglionic neuron. A reduction in trophic influences on iris melanocytes may have contributed to the observed heterochromia.

  13. Black widow spider envenomation, a rare cause of Horner's syndrome.

    PubMed

    Strowd, Roy E; Scott, Blake; Walker, Francis O

    2012-06-01

    Horner's syndrome involves a triad of eyelid ptosis, miosis, and facial anhidrosis that results from disruption of the oculosympathetic pathway. Acquired Horner's syndrome is associated with a variety of medical conditions including Pancoast tumor and carotid dissection. We report the unique case of a 47-year-old man presenting with Horner's syndrome 4 weeks after black widow spider envenomation. Workup did not reveal any alternative explanatory etiology. We hypothesize that late sequelae of black widow spider envenomation secondary to autonomic nerve injury or retrograde axonal transport after mechanical inoculation may have led to an acquired defect in the oculosympathetic pathway resulting in a Horner's syndrome. This case introduces a rare cause of Horner's syndrome and highlights the importance of environmental exposures in the evaluation of these patients. Copyright © 2012 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

  14. Horner's Syndrome Incidental to Medullary Thyroid Carcinoma Excision: Case Report and Brief Literature Review

    PubMed Central

    Mastronikolis, Nicholas S.; Spiliopoulou, Sofia P.; Zolota, Vassiliki; Papadas, Theodoros A.

    2016-01-01

    Horner's syndrome is characterized by a combination of ipsilateral miosis, blepharoptosis, enophthalmos, facial anhidrosis, and iris heterochromia in existence of congenital lesions. The syndrome results from a disruption of the ipsilateral sympathetic innervation of the eye and ocular adnexa at different levels. Though rare, thyroid and neck surgery could be considered as possible causes of this clinical entity. We present a case of Horner's syndrome in a patient after total thyroidectomy and neck dissection for medullary thyroid cancer with neck nodal disease and attempt a brief review of the relevant literature. PMID:27200201

  15. Post-thyroidectomy iatrogenic Horner's syndrome with heterochromia.

    PubMed

    Ulusoy, Mahmut Oğuz; Kıvanç, Sertaç Argun; Atakan, Mehmet; Mayalı, Hüseyin

    2016-03-01

    To present a case of iatrogenic Horner's syndrome seen together with the heterochromia in the post-thyroidectomy period. A 23-year-old female patient was admitted to our clinic with complaints of low vision in the eye and difference in eye color that developed over the past two years. In the left eye, myosis and minimal ptosis (∼1 mm) was detected, and the color of the iris was lighter than the right eye. The pre-diagnosis of left iatrogenic Horner's syndrome was finalized after 0.5% topical apraclonidine test. Heterochromia can be observed in iatrogenic Horner's syndrome.

  16. Acquired Intermittent Pediatric Horner Syndrome due to Neuroblastoma.

    PubMed

    Cohen, Liza M; Elliott, Alexandra; Freitag, Suzanne K

    A 3-month-old male developed intermittent left upper eyelid ptosis at the age of 1 month that was gradually increasing in frequency and duration. Examination revealed anisocoria and left upper and lower eyelid ptosis, consistent with a left Horner syndrome. Imaging showed a mass in the left superior posterior mediastinum, which was resected, and pathology was consistent with neuroblastoma. Eight months thereafter, the patient underwent left upper eyelid ptosis repair. Cases of infantile acquired Horner syndrome due to neuroblastoma are rare. To the authors' knowledge, there has only been one case described that presented with intermittent symptoms. The authors report the second case of intermittent acquired Horner syndrome due to neuroblastoma. This case demonstrates the importance of recognizing that Horner syndrome may present with subtle and intermittent symptoms. In a pediatric patient, one should maintain suspicion for neuroblastoma.

  17. Horner Syndrome in Children: A Clinical Condition with Serious Underlying Disease.

    PubMed

    Barrea, Christophe; Vigouroux, Tiphaine; Karam, Joe; Milet, Ariane; Vaessen, Sandrine; Misson, Jean-Paul

    2016-08-01

    Aim Horner syndrome corresponds to the clinical triad of miosis, ptosis, and facial anhidrosis. These symptoms are related to injury of the oculosympathetic chain. In children, Horner syndrome is classified as congenital or acquired. While the diagnosis is made through clinical examination, there is some debate regarding the use of imaging modalities and the extent of anatomical coverage required. Methods Here, we describe two cases of children with acute Horner syndrome. We then review the literature about the different etiology and discuss the interest of some investigations. Results Case 1: An 8-month-old girl without personal or familial history, has presented a right acquired Horner syndrome without additional signs. Frontal chest radiography and ultrasonography of the neck and the abdomen was first achieved and returned normal. The cerebral and cervical magnetic resonance imaging (MRI) with angiographic sequences performed in a second time was also normal. Finally, an enhanced thoracic computed tomography (CT)-scan demonstrated a mass at the right pulmonary apex. Case 2: A 9-year-old boy without personal or familial history has presented an acute headache with loss of consciousness during a basketball competition. Upon waking up, the child has right hemiplegia, aphasia, and left Horner syndrome. The cerebral CT scan realized in the first line was normal. The MRI with angiographic sequences demonstrated M1 left carotid dissection with homolateral white matter infarction. Conclusion Imaging studies seem critical in delineating the nature and extent of any underlying pathology along the oculosympathetic pathway in children presenting a Horner syndrome. In these patients, a history of trauma or surgery may reduce the need for extensive systemic evaluation. Without such anamnesis, a decision to proceed with further evaluation is made with consideration of the relative incidence of tumor, especially neuroblastoma, or other treatable lesions. In this

  18. Horner syndrome in glandular fever: a case report.

    PubMed

    West, E V; Sheerin, F; Bates, J E H M

    2016-02-01

    This study aimed to present and discuss the case of a patient with known glandular fever who presented with Horner syndrome. A 35-year-old patient with known glandular fever developed acute unilateral Horner syndrome, a previously undescribed complication of this common illness. Magnetic resonance imaging and magnetic resonance angiography showed that enlarged intra-carotid sheath lymphoid tissue was likely to be the underlying cause of sympathetic nerve disruption. The case is described, the anatomy of the sympathetic chain is discussed and possible alternative pathophysiological mechanisms are reviewed. This is the first report in the worldwide literature of Horner syndrome arising as a result of compression from enlarged lymph nodes in glandular fever.

  19. Horner's syndrome: an electron microscopic study of a human iris.

    PubMed Central

    McCartney, A. C.; Riordan-Eva, P.; Howes, R. C.; Spalton, D. J.

    1992-01-01

    Electron microscopy was performed on the irides of a man with a history of a long standing Horner's syndrome which resulted in iris heterochromia. Comparison of his normal brown iris with the depigmented blue iris showed depletion of anterior border cells and absence of sympathetic nerve fibres. Stromal melanocyte numbers were also diminished but melanosome numbers within the residual cells were not significantly different. Postnatal maintenance of stromal and anterior border zone pigmentation, derived from the neural crest, would appear to be dependent on an intact sympathetic nerve supply in contrast to the iris pigment epithelium which remains normally unaffected in Horner's syndrome. Images PMID:1486079

  20. Heterochromia iridis and Horner's syndrome due to paravertebral neurilemmoma.

    PubMed

    Sayed, A K; Miller, B A; Lack, E E; Sallan, S E; Levey, R H

    1983-01-01

    A case of heterochromia iridis and Horner's syndrome is reported in a 7-year old girl with paravertebral neurilemmoma. These clinical findings can be useful in the early diagnosis of mediastinal tumors in the paravertebral axis. While typically associated with neuroblastoma, these findings can be due to tumors which are inately benign--in this case neurilemmoma. The mechanism for heterochromia is briefly discussed.

  1. Rare Complications of Cervical Spine Surgery: Horner's Syndrome.

    PubMed

    Traynelis, Vincent C; Malone, Hani R; Smith, Zachary A; Hsu, Wellington K; Kanter, Adam S; Qureshi, Sheeraz A; Cho, Samuel K; Baird, Evan O; Isaacs, Robert E; Rahman, Ra'Kerry K; Polevaya, Galina; Smith, Justin S; Shaffrey, Christopher; Tortolani, P Justin; Stroh, D Alex; Arnold, Paul M; Fehlings, Michael G; Mroz, Thomas E; Riew, K Daniel

    2017-04-01

    A multicenter retrospective case series. Horner's syndrome is a known complication of anterior cervical spinal surgery, but it is rarely encountered in clinical practice. To better understand the incidence, risks, and neurologic outcomes associated with Horner's syndrome, a multicenter study was performed to review a large collective experience with this rare complication. We conducted a retrospective multicenter case series study involving 21 high-volume surgical centers from the AOSpine North America Clinical Research Network. Medical records for 17 625 patients who received subaxial cervical spine surgery from 2005 to 2011 were reviewed to identify occurrence of 21 predefined treatment complications. Descriptive statistics were provided for baseline patient characteristics. Paired t test was used to analyze changes in clinical outcomes at follow-up compared to preoperative status. In total, 8887 patients who underwent anterior cervical spine surgery at the participating institutions were screened. Postoperative Horner's syndrome was identified in 5 (0.06%) patients. All patients experienced the complication following anterior cervical discectomy and fusion. The sympathetic trunk appeared to be more vulnerable when operating on midcervical levels (C5, C6), and most patients experienced at least a partial recovery without further treatment. This collective experience suggests that Horner's syndrome is an exceedingly rare complication following anterior cervical spine surgery. Injury to the sympathetic trunk may be limited by maintaining a midline surgical trajectory when possible, and performing careful dissection and retraction of the longus colli muscle when lateral exposure is necessary, especially at caudal cervical levels.

  2. High thoracic ossification of ligamentum flavum causing partial Horner syndrome.

    PubMed

    Kim, Dong Ha; Lee, Su Hun; Lee, Jun Seok; Song, Geun Sung; Son, Dong Wuk

    2018-02-28

    We report a case of high thoracic ossification of the ligamentum flavum (OLF) causing a partial Horner's syndrome. A 57-year-old man developed a walking disorder, as well as right-sided miosis and anhidrosis. Magnetic resonance imaging demonstrated a spinal cord compressing T2-T3 OLF. The patient improved after surgery.

  3. [Horner's syndrome and paresthesia in the trigeminal nerve territory secondary to epidural analgesia for labor].

    PubMed

    Ferreira, Céline; Macedo, Ana Luísa; Almeida, Valentina

    2018-03-01

    Currently, epidural analgesia is a common procedure for labor analgesia. Although it is considered a safe technique, it is not without complications. Horner's syndrome and paresthesia within the trigeminal nerve distribution are rare complications of epidural analgesia. We report a case of a pregnant woman who developed Horner's syndrome and paresthesia within the distribution of the trigeminal nerve following epidural analgesia for the relief of labor pain. Copyright © 2018 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  4. A Case of Horner's Syndrome following Ultrasound-Guided Infraclavicular Brachial Plexus Block.

    PubMed

    Walid, Trabelsi; Mondher, Belhaj Amor; Mohamed Anis, Lebbi; Mustapha, Ferjani

    2012-01-01

    Horner's syndrome results from paralysis of the ipsilateral sympathetic cervical chain (stellate ganglion) caused by surgery, drugs (mainly high concentrations of local anesthetics), local compression (hematoma or tumor), or inadequate perioperative positioning of the patient. It occurs in 100% of the patients with an interscalene block of the brachial plexus and can also occur in patients with other types of supraclavicular blocks.In this case report, we presented a case of Horner's syndrome after performing an ultrasound-guided infraclavicular brachial plexus block with 15 mL of bupivacaine 0.5%. It appeared 40 minutes after the block with specific triad (ptosis, miosis, and exophtalmia) and quickly disappears within 2 hours and a half without any sequelae. Horner's syndrome may be described as an unpleasant side effect because it has no clinical consequences in itself. For this reason anesthesiologists should be aware of this syndrome, and if it occurs patients should be reassured and monitored closely.

  5. Sixth nerve palsy + ipsilateral Horner's Syndrome = Parkinson's Syndrome.

    PubMed

    Ebner, Roberto N; Ayerza, Dolores Ribero; Aghetoni, Fernando

    2015-01-01

    To present five patients with VIth nerve palsy and ipsilateral Horner's Syndrome (HS), as a result of cavernous sinus alteration. Consecutive case series. Five patients presented abducens palsy with horizontal diplopia (3 in primary position and 2 in lateral gaze only) and ipsilateral HS. Apraclonidine 0.5% drops evidenced sympathetic denervation in all patients 40-60 min after instillation. All 5 cases had neuroimages (MRI in 3 cases, Computerized Tomography - CT in one case and Magnetic Resonance Angiography - MRA in one case) demonstrating cavernous sinus lesions; 2 meningiomas, 1 carotid-cavernous aneurism, 1 foreign body (bullet) and 1 squamous cell carcinoma. Lesions on the cavernous sinus need to be considered in cases of abducens nerve palsy and ipsilateral Horner's Syndrome.

  6. Horner's syndrome and contralateral abducens nerve palsy associated with zoster meningitis.

    PubMed

    Cho, Bum-Joo; Kim, Ji-Soo; Hwang, Jeong-Min

    2013-12-01

    A 55-year-old woman presented with diplopia following painful skin eruptions on the right upper extremity. On presentation, she was found to have 35 prism diopters of esotropia and an abduction limitation in the left eye. Two weeks later, she developed blepharoptosis and anisocoria with a smaller pupil in the right eye, which increased in the darkness. Cerebrospinal fluid analysis showed pleocytosis and a positive result for immunoglobulin G antibody to varicella zoster virus. She was diagnosed to have zoster meningitis with Horner's syndrome and contralateral abducens nerve palsy. After intravenous antiviral and steroid treatments, the vesicular eruptions and abducens nerve palsy improved. Horner's syndrome and diplopia resolved after six months. Here we present the first report of Horner's syndrome and contralateral abducens nerve palsy associated with zoster meningitis.

  7. Rhabdomyolysis resulting in concurrent Horner's syndrome and brachial plexopathy: a case report.

    PubMed

    Lee, Susan C; Geannette, Christian; Wolfe, Scott W; Feinberg, Joseph H; Sneag, Darryl B

    2017-08-01

    This case report describes a 29-year-old male who presented with immediate onset of Horner's syndrome and ipsilateral brachial plexopathy after sleeping with his arm dangling outside a car window for 8 h. Outside workup and imaging revealed rhabdomyolysis of the left neck musculature. Subsequent electrodiagnostic testing and high-resolution brachial plexus magnetic resonance imaging at the authors' institution attributed the Horner's syndrome and concurrent brachial plexopathy to rhabdomyolysis of the longus colli and scalene musculature, which had compressed-and consequently scar tethered-the cervical sympathetic trunk and brachial plexus. This case of co-existent Horner's syndrome and brachial plexopathy demonstrates the role of high-resolution brachial plexus MRI in diagnosing plexopathy and the importance of being familiar with plexus and paravertebral muscle anatomy.

  8. Invited Commentary: Evaluation of Horner Syndrome in the MRI Era.

    PubMed

    Kawasaki, Aki

    2018-03-01

    This Invited Commentary discusses the following article: BACKGROUND:: To identify the etiologies of adult Horner syndrome (HS) in the MRI era using a targeted evaluation approach and to assess the value and yield of targeted imaging. A retrospective chart review was performed of 200 adult outpatients with HS, confirmed with cocaine eyedrop testing. Patients were divided into subgroups based on the presence or absence of symptoms and those who did or did not receive additional testing with hydroxyamphetamine drops. Imaging was obtained based on pharmacologic localization and/or clinical evaluation. The etiology of HS and the yield of imaging were determined in all subgroups. Imaging showed causative lesions in 24 of 179 (12.84%) imaged patients with HS, and 13 (69.0%) were determined "idiopathic." Of the patients who underwent testing with hydroxyamphetamine drops (132 patients), 86 had a postganglionic localization with an imaging yield of 8.1%, and 46 had preganglionic cause with an imaging yield of 21.7%. Fifty-three patients (26.5%) never noticed ptosis/anisocoria before examination, and the imaging yield in this subgroup was 2.8%. Eighteen of the 200 patients (9.0%) had serious pathology, including carotid artery dissection, brain, or neck mass, and 6 of these (31.6%) had acute symptoms and/or pain. HS is most often idiopathic with serious pathology being relatively infrequent. When determining etiology, the absence of symptoms is not predictive of the pathology. However, acute onset of symptoms and/or pain are possible indicators for serious pathology. Localizing the lesion using hydroxyamphetamine drops whenever obtainable and available is still an efficient way to target imaging evaluation.

  9. Carotid artery dissection presenting with isolated headache and Horner syndrome after minor head injury.

    PubMed

    Creavin, Samuel Thomas; Rice, Claire M; Pollentine, Adrian; Cowburn, Philip

    2012-11-01

    A woman aged 31 years presented to the emergency department after a minor head injury. She reported mild headache and a metallic taste in her mouth. Full neurologic examination was remarkable only for left-sided Horner syndrome. Left internal carotid artery dissection was confirmed on magnetic resonance imaging. She was treated with aspirin. Symptoms and signs persisted 3 months later, but there was no additional neurologic deficit. We stress the importance of early detection of Horner syndrome to minimize the risk of disabling stroke.

  10. The Degree of Anisocoria in Pediatric Patients With Horner Syndrome When Compared to Children Without Disease.

    PubMed

    Suh, Sarah H; Suh, Donny W; Benson, Christy

    2016-05-01

    To study the magnitude of anisocoria in pediatric patients using the plusoptiX A08 (plusoptiX GmbH, Nuremberg, Germany) photoscreener as compared to a literature review of pediatric patients with known Horner syndrome to determine if anisocoria alone should raise suspicion for the diagnosis. The medical records of 592 consecutive patients, neonates to 9 years old, were collected and analyzed. All patients had complete ophthalmic examinations that included photoscreening with the plusoptiX A08. Data included age, pupil sizes, and anisocoria. A complete literature search of documented pupillary size in pediatric patients with the diagnosis of Horner syndrome was performed. This was then compared to the normative pediatric pupil data from the study. Of the 592 children without Horner syndrome, 372 had an anisocoria of 0.1 to 0.5 mm (62.84%), 167 had an anisocoria of 0.6 to 1.2 mm (28.16%), and 21 had an anisocoria of 1.3 mm or greater (3.70%). There was no correlation between increasing age and severity of anisocoria (P = .55). For pediatric patients with a diagnosis of Horner syndrome, the average level of anisocoria was 1.37 mm in room light and 2 mm in darkness. In room light, three children had anisocoria of 0.1 to 0.5 mm (9.4%), 14 had anisocoria of 0.6 to 1.2 mm (43.8%), and 15 had anisocoria of 1.3 mm or greater (46.9%). In darkness, the level of anisocoria increased in 19 patients, causing the first category, 0.1 to 0.5 mm, to include 1 patient (3.1%), the second group to include 5 patients (15.6%), and the last group to include 26 patients (81.3%). Other associated signs/symptoms included ptosis (100%), heterochromia (28.1%), anhidrosis (9.4%), straight hair on affected/curly on unaffected side (9.4%), and neck mass (6.3%). In 37.5% of cases, imaging results were negative and no specific etiology was determined. In a study of 592 children without Horner syndrome, the average pupillary size increased with age, but the degree of anisocoria remained stable with

  11. Horner Syndrome associated with a Herniated Cervical Disc: A Case Report.

    PubMed

    Ma, Hyunjin; Kim, Insoo

    2012-06-01

    Horner syndrome (HS) occurs when there is interruption of the oculosympathetic pathway. The causes of HS are various, but HS originated from herniated cervical disc is very few. HS attributable to the lesion of the first-order neuron of cervical spinal cord is extremely rare. A 41-year old male was admitted for sudden onset of left ptosis and right side numbness. Neurological examination revealed ptosis, miosis and facial anhidrosis on the left side. MRI and CT scans demonstrated large left paramedian disc herniation with cord compression at the C4-5 level. The herniated disc was removed through anterior approach and his symptoms were improved after the operation.

  12. Irreversible Horner's syndrome diagnosed by aproclonidine test due to benign thyroid nodule.

    PubMed

    M, Coskun; A, Aydogan; C, Gokce; O, Ilhan; Ov, Ozkan; H, Gokce; H, Oksuz

    2013-01-01

    We are reporting an irreversible Horner Syndrome (HS) in a patient with benign thyroid gland nodule in which thyroidectomy was performed for treatment. A 37-year-old female was admitted to our clinic with a swelling in the left lobe of the thyroid gland and ptosis at the left eyelid. The clinical diagnosis of HS was confirmed pharmacologically by aproclonidine. Histopathologic examination of thyroidectomy specimen was reported as benign nodule. To the best of our knowledge, this is a very rare report in terms of thyroid benign nodule associated with irreversible HS due to cervical sympathetic chain compression.

  13. Congenital nephrotic syndrome

    MedlinePlus

    ... may be high. There may be signs of malnutrition. A urinalysis reveals fat and large amounts of ... The disorder often leads to infection, malnutrition, and kidney failure. ... die within the first year. Congenital nephrotic syndrome ...

  14. Neuropharmacological lesion localization in idiopathic Horner's syndrome in Golden Retrievers and dogs of other breeds.

    PubMed

    Simpson, Katherine M; Williams, David L; Cherubini, Giunio B

    2015-01-01

    To investigate whether idiopathic Horner's syndrome (HS) in Golden Retrievers is an exclusively preganglionic disorder based on denervation hypersensitivity pharmacological testing with phenylephrine. Medical records of dogs presented with HS between 2000 and 2012. Dogs presented with additional ocular or systemic signs were excluded. Clinical data examined included age, sex, duration of clinical signs, ancillary diagnostic test results, and time to mydriasis on topical ocular application of 1% phenylephrine. Lesions were diagnosed as postganglionic (mydriasis within 20 min) or preganglionic (mydriasis between 20 and 45 min). Medical records of 21 dogs of nine different breeds were included. An etiopathogenesis for Horner's syndrome was determined in five dogs, none of which were Golden Retrievers. All diagnoses correlated with pharmacological lesion localization. Ten Golden Retrievers were included (eight male and two female) with a mean age of 8.5 years (range: 4-13). Lesion localization was diagnosed as postganglionic in eight (mean: 10 min [range: 6-18]) and preganglionic in two Golden Retrievers (20 and 24 min). All cases were unilateral and had completely resolved within 15 weeks (range: 11-20). Recurrence was not reported in any of the patients. Idiopathic postganglionic HS was diagnosed in eight of 10 Golden Retrievers contradicting previous reports of a purely preganglionic localization. Etiopathogenesis of canine idiopathic HS remains to be determined; nevertheless, a vascular etiology cannot be excluded. Future studies using magnetic resonance angiography may aid in clarifying the pathogenesis. © 2013 American College of Veterinary Ophthalmologists.

  15. [What would you do in front of a patient with a Horner syndrome?

    PubMed

    Camós-Carreras, A; Fontana, S; Ortiz-Pérez, S

    2018-03-01

    Horner's syndrome (HS) occurs when there is disruption to the oculosympathetic pathway. Its features include eyelid ptosis, miosis and anhidrosis. The aetiology of this syndrome is varied and includes tumours, trauma, vascular disease and iatrogenic. Different pharmacologic tests are used for diagnosis, such as cocaine, hydroxyamphetamine and apraclonidine; while neuroimaging helps elucidating the aetiology. We present a case of a 63-year-old female referred to our service with a 4-month history of right eyelid ptosis. During examination right miosis was noted. The patient reported a history of multinodular goiter. Pharmacologic tests and neuroimaging confirmed the diagnosis of HS secondary to thyroid disease. Copyright © 2016 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

  16. Horner syndrome

    MedlinePlus

    ... in vision problems related to the nervous system (neuro-ophthalmologist). ... Baloh RW, Jen JC. Neuro-ophthalmology. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 25th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 424. Thurtell ...

  17. Horner Syndrome

    MedlinePlus

    ... order neurons This neuron pathway leads from the hypothalamus at the base of the brain, passes through ... nerve damage in this region may include: Lung cancer Tumor of the myelin sheath (schwannoma) Damage to ...

  18. Brown-Séquard syndrome without vascular injury associated with Horner's syndrome after a stab injury to the neck

    PubMed Central

    Jones, Margaret; Zumsteg, Jennifer

    2016-01-01

    Case Description This case reviews the acute care and rehabilitation course of a 44-year-old right-handed woman after an assault with a pocketknife. She suffered multiple stab wounds including penetrating injury to the left side of her neck. Physical examination revealed left hemiplegia (motor score = 57), impaired pinprick sensation on the right caudal to the C5 dermatome, impaired joint position sense on the left, and left ptosis and miosis. Initially she was unable to stand without maximum assistance. MR imaging revealed transection of the left hemicord at the C5 level without cord hemorrhage. CTA of the neck was negative for vascular injury. She completed 18 days of acute inpatient rehabilitation. She used forearm crutches for ambulation at time of discharge. Prior to discharge the patient provided written permission for a case report. Discussion Stab wounds are the most common cause of traumatic Brown-Séquard syndrome. Horner's syndrome is common in spinal cord lesions occurring in the cervical or thoracic region, however the combination of Horner's and Brown-Séquard syndromes is less commonly reported. In this case report, we review recommendations regarding initial imaging following cervical stab wounds, discuss anatomy and associated neurological findings in Brown-Séquard and Horner's syndromes, and review the expected temporal course of motor recovery. Conclusions Facilitating motor recovery and optimizing function after Brown-Séquard spinal cord injury are important roles for the rehabilitation team. Imaging is necessary to rule out cord hemorrhage or vascular injury and to clinically correlate cord damage with physical examination findings and expected functional impairments. Documenting associated anisocoria and explaining this finding to the patient is an important element of spinal cord injury education. Commonly, patients with Brown-Séquard injuries demonstrate remarkable motor recovery and regain voluntary motor strength and functional

  19. [Horner syndrome and brachial plexus blockade after epidural anesthesia for obstetric labor and cesarean section].

    PubMed

    Molins Ballabriga, G; Vacas, Y; Jiménez, F; Borras, R; Mailan, J

    2011-01-01

    A 30-year-old woman (ASA II, obese) in her 40th week of a first pregnancy required epidural analgesia for labor. When the cervix had dilated to 5 cm, the epidural infusion was started with a 9-mL bolus of 0.2% ropivacaine and 50 pg of fentanyl, after a negative test dose. An infusion of 0.2% ropivacaine and 1 microg/mL of fentanyl was started at a rate of 8 mL/h. A cesarean section was required after insufficient progress was made during 8 hours of labor. Eight milliliters of 0.75% ropivacaine was administered to provide anesthesia to T4; cesarean delivery was completed without complications. Early during postoperative recovery, in addition to motor blockade of the legs, the patient experienced a right brachial plexus blockade and Horner syndrome on the same side. Both effects disappeared spontaneously (1 and 4 hours later, respectively).

  20. A rare presentation of spontaneous internal carotid artery dissection with Horner's syndrome, VIIth, Xth and XIIth nerve palsies.

    PubMed

    Majeed, Azer; Ribeiro, Nuno Pedro Lobato; Ali, Asem; Hijazi, Mohsen; Farook, Hina

    2016-10-01

    Spontaneous internal carotid artery dissection (sICAD) is an uncommon cause of isolated cranial nerve palsies. Commonly patients present with stroke, headache, facial pain and Horner's syndrome, with upto 16% having cranial nerve palsies. We present the case of a 55-year-old man who presented with hoarseness, dysphagia and tongue swelling, mimicking a tongue base tumor. He was found to have unilateral VIIth, Xth and XIIth nerve palsies with Horner's syndrome. Magnetic resonance imaging showed high signal changes and loss of signal void in right internal carotid artery, later confirmed by Angiography as a dissection with pseudo-aneurysm. He was started on anticoagulation and made a good recovery on discharge. This case presents a unique combination of cranial nerve palsies due to internal carotid artery dissection (ICAD) and to our knowledge is the first reported case in the literature. Early recognition and institution of appropriate therapy is critical to prevention of ischemic stroke.

  1. A rare presentation of spontaneous internal carotid artery dissection with Horner's syndrome, VIIth, Xth and XIIth nerve palsies

    PubMed Central

    Majeed, Azer; Ribeiro, Nuno Pedro Lobato; Ali, Asem; Hijazi, Mohsen; Farook, Hina

    2016-01-01

    Spontaneous internal carotid artery dissection (sICAD) is an uncommon cause of isolated cranial nerve palsies. Commonly patients present with stroke, headache, facial pain and Horner's syndrome, with upto 16% having cranial nerve palsies. We present the case of a 55-year-old man who presented with hoarseness, dysphagia and tongue swelling, mimicking a tongue base tumor. He was found to have unilateral VIIth, Xth and XIIth nerve palsies with Horner's syndrome. Magnetic resonance imaging showed high signal changes and loss of signal void in right internal carotid artery, later confirmed by Angiography as a dissection with pseudo-aneurysm. He was started on anticoagulation and made a good recovery on discharge. This case presents a unique combination of cranial nerve palsies due to internal carotid artery dissection (ICAD) and to our knowledge is the first reported case in the literature. Early recognition and institution of appropriate therapy is critical to prevention of ischemic stroke. PMID:27699055

  2. The friction sweat test as a new method for detecting facial anhidrosis in patients with Horner's syndrome.

    PubMed

    Rosenberg, M L

    1989-10-15

    Forty-eight patients with Horner's syndrome documented by cocaine test were examined with the friction sweat test, a method of detecting a mild sweating asymmetry using alcohol and a standard office prism bar. In all but one patient, the results of the friction test corresponded with the results predicted by the history, physical examination, and Paredrine testing, or with the results of a starch-iodine sweat test. The test is a quick, simple, and reproducible procedure that allows a more accurate determination of the location of the Horner's syndrome at the initial office visit, and therefore assists in determining what tests need to be performed in the further examination of the patient.

  3. Spontaneous cervical intradural disc herniation presenting with Brown-Séquard and Horner's syndrome: lesson learned from a very unique case.

    PubMed

    Baudracco, Irene; Grahovac, Gordan; Russo, Vittorio M

    2017-05-01

    Cervical spontaneous intradural disc herniation (IDH) is an extremely rare condition. We describe a unique case of a patient presenting with a Brown-Séquard syndrome (BSS) and Horner's syndrome (HS). This study aimed to report an unusual case of spontaneous cervical intradural disc herniation that presented with Horner's and Brown-Séquard syndrome (BSS) and discuss difficulties in preoperative diagnosis and treatment difficulties of intradural cervical disc. Notes and images review, and analysis of the relevant literature. A 45-year old female presented with acute Horner's syndrome and Brown-Séquard syndrome. The magnetic resonance imaging of cervical spine revealed C4-5 disc extrusion with cord compression. The patient underwent urgent decompression through an anterior cervical corpectomy and fusion. Patient fully recovered 6 months after disease onset. We would like to emphasize that prompt and anterior cervical decompression is the treatment of choice, as it directly address the problem and allows dura repair in spontaneous cervical disc herniation.

  4. Congenital and infantile nephrotic syndromes.

    PubMed

    Norio, R; Rapola, J

    1989-01-01

    A nephrotic syndrome which appears during the first few months of life always provides a diagnostic challenge. Congenital nephrosis of the Finnish type (CNF) is a distinct, recessively inherited entity provided that the diagnostic criteria are kept strict. Very important but often forgotten is the presence of a large placenta. Among other alterations tubular dilatations are typical histological findings, even if not pathognomonic. Greatly elevated AFP concentration in the amniotic fluid, due to intrauterine proteinuria, offers an unfailing prenatal diagnosis in CNF but is seldom useful in other types. Renal transplantation has radically changed the prognosis of this otherwise lethal disorder. The histopathological diagnosis diffuse mesangial sclerosis (DMS) was supposed to represent another etiological entity, probably also autosomal recessive. It, however, seems to be heterogenous. The Drash syndrome (nephrotic syndrome, male pseudohermaphroditism and Wilms' tumor) has interesting connections with this group. The number of cases of congenital, infantile and/or familial nephrotic syndromes other than CNF and DMS seems to be surprisingly large. Their exact classification is still not possible. Even if late, "infantile" onset rules out the diagnosis of CNF, many etiological alternatives remain for the "congenital" cases.

  5. Isolated abducens nerve paresis associated with incomplete Horner's syndrome caused by petrous apex fracture--case report and anatomical study.

    PubMed

    Ozveren, M F; Uchida, K; Erol, F S; Tiftikci, M T; Cobanoglu, B; Kawase, T

    2001-10-01

    A 17-year-old male presented with a wound on the right temporal region, oozing hemorrhagic necrotic brain tissue and cerebrospinal fluid, following a fall. Computed tomography showed temporoparietal and petrous apex fractures on the right. Neurological examination revealed abducens nerve paresis, ptosis, and myosis on the right side. The patient was treated surgically for the removal of the free bony fragments at the fracture site and to close the dural tear. The abducens nerve paresis, ptosis, and myosis persisted at the 3rd monthly postoperative follow-up examination. The anatomy of the abducens nerve at the petroclival region was studied in four cadaveric heads. Two silicone-injected heads were used for microsurgical dissections and two for histological sections. The abducens nerve has three different angulations in the petroclival region, located at the dural entrance porus, the petrous apex, and the lateral wall of the cavernous segment of the internal carotid artery. The abducens nerve had fine anastomoses with the trigeminal nerve and the periarterial sympathetic plexus. There were fibrous connections extending inside the venous space of the petroclival area. The abducens nerve seems to be vulnerable to damage in the petroclival region, either directly by trauma to its dural porus and petrous apex or indirectly by stretching of the nerve through the nervous and/or fibrous connections. Concurrent functional loss of the abducens nerve and the periarterial sympathetic plexus clinically manifested as incomplete Horner's syndrome in our patient.

  6. Netherton syndrome associated with idiopathic congenital hemihypertrophy.

    PubMed

    Yerebakan, Ozlem; Uğuz, Ayşen; Keser, Ibrahim; Lüleci, Güven; Ciftçioğlu, Mehmet Akif; Başaran, Erdal; Alpsoy, Erkan

    2002-01-01

    Netherton syndrome is a rare genodermatosis comprised of anichthyosiform dermatitis, hair shaft defects, and atopic features. Other problems associated with Netherton syndrome are delayed growth and development, immune abnormalities, recurrent infections, and intermittent aminoaciduria. We describe an 18-month-old girl with Netherton syndrome who had idiopathic congenital hemihypertrophy on her right side with contralateral benign nephromegaly in addition to the characteristic clinical signs of the syndrome. To our knowledge, this is the first case of Netherton syndrome associated with idiopathic congenital hemihypertrophy to be reported.

  7. Bilateral Congenital Lacrimal Fistula in Down Syndrome

    PubMed Central

    Singh, Manpreet; Singh, Usha

    2013-01-01

    Congenital lacrimal fistulae are rare in Down syndrome and bilateral presentation is very unusual. It can be associated with nasolacrimal duct obstruction. We report a 3-year-old female with Down syndrome who presented with watering and discharge from both eyes and bilateral fistulous openings present inferonasal to the medial canthus. Upon examination, the lacrimal sac regurgitation test was positive on both sides. Our case report documents a distinctive case of bilateral congenital lacrimal fistulae in association with Down syndrome. It was managed successfully by primary fistulectomy and nasolacrimal duct probing. PMID:24014994

  8. Molecular Pathophysiology of Congenital Long QT Syndrome

    PubMed Central

    Bohnen, M. S.; Peng, G.; Robey, S. H.; Terrenoire, C.; Iyer, V.; Sampson, K. J.; Kass, R. S.

    2016-01-01

    Ion channels represent the molecular entities that give rise to the cardiac action potential, the fundamental cellular electrical event in the heart. The concerted function of these channels leads to normal cyclical excitation and resultant contraction of cardiac muscle. Research into cardiac ion channel regulation and mutations that underlie disease pathogenesis has greatly enhanced our knowledge of the causes and clinical management of cardiac arrhythmia. Here we review the molecular determinants, pathogenesis, and pharmacology of congenital Long QT Syndrome. We examine mechanisms of dysfunction associated with three critical cardiac currents that comprise the majority of congenital Long QT Syndrome cases: 1) IKs, the slow delayed rectifier current; 2) IKr, the rapid delayed rectifier current; and 3) INa, the voltage-dependent sodium current. Less common subtypes of congenital Long QT Syndrome affect other cardiac ionic currents that contribute to the dynamic nature of cardiac electrophysiology. Through the study of mutations that cause congenital Long QT Syndrome, the scientific community has advanced understanding of ion channel structure-function relationships, physiology, and pharmacological response to clinically employed and experimental pharmacological agents. Our understanding of congenital Long QT Syndrome continues to evolve rapidly and with great benefits: genotype-driven clinical management of the disease has improved patient care as precision medicine becomes even more a reality. PMID:27807201

  9. Congenital chloride diarrhea misdiagnosed as Bartter syndrome.

    PubMed

    Eğrıtaş, Odül; Dalgiç, Buket; Wedenoja, Satu

    2011-06-01

    Congenital chloride diarrhea is the most frequent secretory-type diarrhea during the infantile period in the presence of normal intestinal mucosa. The disease has an autosomal recessive inheritance. Although approximately half of the reported cases to date are from Finland, a much higher incidence has been reported among Arabic people. The defective gene is SLC26A3, which encodes a Na-independent CL/HCO3 exchanger that is expressed primarily in the apical brush border membrane of ileal enterocytes and colonic epithelium. The disease is characterized by dehydration and hypochloremic metabolic alkalosis. Bartter syndrome, cystic fibrosis and pyloric stenosis also lead to similar electrolyte disturbances in the early neonatal period. The diagnosis of congenital chloride diarrhea can be confirmed by measuring the fecal concentration of Cl, which always exceeds 90 mmol/L in patients with normal water and electrolyte balance. Here, we report a patient with congenital chloride diarrhea misdiagnosed as Bartter syndrome until 20 months of age.

  10. Genetics Home Reference: congenital central hypoventilation syndrome

    MedlinePlus

    ... Samuels M, Stevens CA, Berry-Kravis EM, Weese-Mayer DE. PHOX2B mutation-confirmed congenital central hypoventilation syndrome: ... Citation on PubMed Axelrod FB, Chelimsky GG, Weese-Mayer DE. Pediatric autonomic disorders. Pediatrics. 2006 Jul;118( ...

  11. Congenital Zika syndrome, time to communicate experiences.

    PubMed

    Del Carpio-Orantes, Luis

    2018-04-19

    In this communication, we call on nations that have a high incidence of congenital syndrome due to Zika to start publishing their experiences to integrate better diagnosis and treatment protocols for these affected children, who alone have a high morbidity and mortality rate. quality of life, which could be improved by knowing better that they suffer.

  12. Handicapping Conditions Associated with the Congenital Rubella Syndrome.

    ERIC Educational Resources Information Center

    Vernon, McCay; And Others

    1980-01-01

    The authors discuss the incidence of impairments diagnosed among children with congenital rubella syndrome. Approximately 73 percent are hearing impaired, at least 35 percent have congenital heart disorders, and 33 percent have visual defects. (Author)

  13. Congenital constriction band syndrome with limb defects.

    PubMed

    Koskimies, Eeva; Syvänen, Johanna; Nietosvaara, Yrjänä; Mäkitie, Outi; Pakkasjärvi, Niklas

    2015-01-01

    The purpose of this study was to clarify the spectrum of congenital constriction band syndrome (CBS) and associated anomalies and mortality in Finland. Register-based data were analyzed for children with congenital constriction bands in upper and lower extremities as a part of an ongoing study on 419 upper limb defects and 171 lower limb defects occurring among 753,342 births in Finland during 1993 to 2005. A total of 71 cases with limb CBS were identified during the 13-year study period. The birth prevalence was 0.9 per 10 000 births (1:10 600). Infant mortality was 4.6% (3/65) and perinatal mortality 12.7% (9/71). In 35 cases (49%) only upper limbs were affected and in 13 cases (18%) there were constriction defects only in lower limbs. In 23 cases (32%) both upper and lower limbs were involved. None of the cases associated with a known syndrome. However, in 21 cases (30%) the child had other anomalies associated with constriction rings: pes equinovarus in 8/21, cleft palate in 5/21, congenital heart defect in 6/21, and other anomalies in 14/21. Eighteen (25%) had low birth weight, 22 (31%) were born preterm, and 8 children (11%) were small for gestational age. Children with associated anomalies showed higher mortality, shorter duration of gestation, and lower birth weight. CBS is rare and comprises approximately 12% of all congenital upper limb defects and 14% of lower limb defects. Other skeletal and nonskeletal anomalies are present in 30% of the affected children, suggesting a possible genetic etiology. More detailed characterization of the children with associated anomalies may shed light to the pathogenetic mechanisms of this syndrome. Population-based register study/II.

  14. Congenital Syndromes and Mildly Handicapped Students: Implications for Special Educators.

    ERIC Educational Resources Information Center

    Smith, Sandra M.

    1989-01-01

    Many learning disabilities or cases of mild retardation are due to medically diagnosable, congenital syndromes, such as fetal alcohol syndrome, sex chromosome abnormalities, multiple anomaly syndromes, phenylketonuria, and Tourette Syndrome. These syndromes are discussed, and suggestions are given for special education management. (Author/JDD)

  15. Congenital myasthenic syndrome: a case report.

    PubMed

    Ceylan, A; Tuncer, O; Sayin, R; Peker, E; Caksen, H; Sari, S

    2011-01-01

    Congenital myasthenic syndromes (CMS) are diseases of the neuromuscular junction. They usually belong to the disease groups that begin in the infantile or childhood period and carry genetic characteristics. The following is important in establishing the diagnosis of this disease: clinical findings, electromyography, genetic tests, determination of serum acetylcholine receptor antibodies. Acetylcholine esterase inhibitor drugs are used in treatment of CMS. A seven-month old male patient was brought to our department with the complaints of difficult breathing, falling of the eyelids and swallowing difficulty. With clinical and laboratory findings, he was diagnosed with congenital myasthenia and treatment was started. CMS should be suspected in patients with no pathological findings on the physical examination, and normal chest X-rays.

  16. Dual radiopharmaceutical imaging in congenital asplenia syndrome.

    PubMed

    Rao, B K; Shore, R M; Lieberman, L M; Polcyn, R E

    1982-12-01

    Asplenia was suspected in one patient with combined immunodeficiency syndrome and 5 with congenital cardiac anomalies who had Howell-Jolly bodies on peripheral blood smears. 99mTc-sulfur colloid scans were equivocal for absence of the spleen. When they were compared with the 99mTc-PIPIDA hepatobiliary images, a discrepancy in organ morphology between the two scans indicated that the spleen was present, whereas similarity of the two images suggested asplenia. This procedure was useful in establishing asplenia in 4 patients and confirming the presence of a rudimentary or ectopic spleen in 2 others. Unequivocal demonstration of the spleen on the sulfur colloid scans makes the hepatobiliary study unnecessary, while unequivocal demonstration of a normal-appearing liver without splenic activity may warrant a tagged red-cell study for a more complete evaluation.

  17. Dual radiopharmaceutical imaging in congenital asplenia syndrome

    SciTech Connect

    Rao, B.K.; Shore, R.M.; Lieberman, L.M.

    1982-12-01

    Asplenia was suspected in one patient with combined immunodeficiency syndrome and 5 with congenital cardiac anomalies who had Howell-Jolly bodies on peripheral blood smears. /sup 99m/Tc-sulfur colloid scans were equivocal for absence of the spleen. When they were compared with the /sup 99m/Tc-PIPIDA hepatobiliary images, a discrepancy in organ morphology between the two scans indicated that the spleen was present, whereas similarity of the two images suggested asplenia. This procedure was useful in establishing asplenia in 4 patients and confirming the presence of a rudimentary or ectopic spleen in 2 others. Unequivocal demonstration of the spleen on the sulfur colloidmore » scans makes the hepatobiliary study unnecessary, while unequivocal demonstration of a normal-appearing liver without splenic activity may warrant a tagged red-cell study for a more complete evaluation.« less

  18. Dual radiopharmaceutical imaging in congenital asplenia syndrome

    SciTech Connect

    Rao, B.K.; Shore, R.M.; Lieberman, L.M.

    1982-12-01

    Asplenia was suspected in one patient with combined immunodeficiency syndrome and 5 with congenital cardiac anomalies who had Howell-Jolly bodies on peripheral blood smears. /sup 99//sup m/Tc-sulfur colloid scans were equivocal for absence of the spleen. When they were compared with the /sup 99//sup m/Tc-PIPIDA hepatobiliary images, a discrepancy in organ morphology between the two scans indicated that the spleen was present, whereas similarity of the two images suggested asplenia. This procedure was useful in establishing asplenia in 4 patients and confirming the presence of a rudimentary or ectopic spleen in 2 others. Unequivocal demonstration of the spleen on themore » sulfur colloid scans makes the hepatobiliary study unnecessary, while unequivocal demonstration of abnormal-appearing liver without splenic activity may warrant a tagged red-cell study for a more complete evaluation.« less

  19. Congenital central hypoventilation syndrome: a case report.

    PubMed

    Crowell, Bresney A; Bissinger, Robin L; Conway-Orgel, Margaret

    2011-06-01

    Congenital central hypoventilation syndrome (CCHS) is a relatively rare, life-threatening, and lifelong multisystem disorder characterized by autonomic nervous system dysfunction, which mostly manifests as failure to maintain ventilatory homeostasis during sleep. Infants with CCHS have inadequate sensitivity to hypoxia and hypercapnia during sleep and in some cases during wakefulness, leading to persistent apnea. This article reports a case of CCHS in a 38-week-gestation infant who presented on day of life 2 with persistent apnea. Diagnosis of primary pulmonary, cardiac, metabolic, neurologic disease, or injury was excluded before the diagnosis of CCHS was made. The diagnosis was confirmed by a PHOX2B sequence analysis. A tracheotomy was performed and the infant was discharged home on a home ventilator with outpatient follow-up. The clinical presentation of CCHS, as well as diagnosis and treatment strategies, is reviewed.

  20. Congenital varicella syndrome: A systematic review.

    PubMed

    Ahn, Ki Hoon; Park, Yun-Jung; Hong, Soon-Cheol; Lee, Eun Hee; Lee, Ji-Sung; Oh, Min-Jeong; Kim, Hai-Joong

    2016-07-01

    Varicella-zoster virus (VZV) is a teratogen that can cross the placenta and cause the congenital varicella syndrome (CVS), which is characterised by multi-system anomalies. There have been 130 reported cases of CVS from 1947 to 2013. The estimated incidence of CVS was 0.59% and 0.84% for women infected with VZV during the entire pregnancy and for those infected the first 20 weeks of pregnancy, respectively. Nine cases were reported at 21-27 weeks of gestation and one case was identified at 36 weeks. Herpes zoster caused CVS in two cases. Regarding treatment, varicella zoster immunoglobulin treatment, irrespective of gestational age, should be considered in addition to antiviral drugs for women who have been exposed to or infected with virus.

  1. The congenital intrahepatic arterioportal fistula syndrome: elucidation and proposed classification.

    PubMed

    Norton, Seamus P; Jacobson, Kevan; Moroz, Stanley P; Culham, Gordon; Ng, Vicky; Turner, Justine; John, Philip

    2006-08-01

    Congenital intrahepatic arterioportal fistula is a rare but treatable cause of portal hypertension for which early recognition may lead to successful radiological management. We report an infant presenting with severe failure to thrive, melena and splenomegaly due to a congenital intrahepatic arterioportal fistula, successfully ablated after multiple trials of superselective transarterial embolization. Comprehensive review of congenital cases provides an understanding of the key clinical features defining this syndrome. A classification system is proposed, upon which treatment decisions may be based.

  2. Primary congenital glaucoma associated with Patau syndrome with long survival.

    PubMed

    Jaru-Ampornpan, Pimkwan; Kuchtey, John; Dev, V G; Kuchtey, Rachel

    2010-06-23

    Ocular abnormalities are common in Patau syndrome (trisomy 13), but only a few cases with congenital glaucoma have been reported, some of which were associated with other ocular defects. This report describes a case of primary congenital glaucoma in an 11-year-old patient with full trisomy 13. Copyright 2010, SLACK Incorporated.

  3. Congenital varicella syndrome as an unusual cause of congenital malformation: report of one case.

    PubMed

    Huang, C S; Lin, S P; Chiu, N C; Hung, H Y

    2001-01-01

    Intrauterine infections with varicella-zoster virus following maternal varicella in early pregnancy and resulting in congenital malformations are rare. Herein we report a child with congenital varicella syndrome characterized by low birth weight, cicatricial scarring, hypoplasia of both lower extremities with joint contracture, congenital hip dislocation, corneal opacity, atresia of the sigmoid colon and a rarely associated cloaca anomaly. The varicella IgG remained positive after she was seven months old. Her mother developed chickenpox at the 14th week of gestation. The purpose of this article is to raise pediatricians' index of suspicion for congenital varicella syndrome when an infant is born with multiple congenital malformations with an apparent history of maternal varicella infection.

  4. Congenital corneal staphyloma as a complication of Kabuki syndrome.

    PubMed

    Tanaka, Ryuma; Takenouchi, Toshiki; Uchida, Keiko; Sato, Takeshi; Fukushima, Hiroyuki; Yoshihashi, Hiroshi; Takahashi, Takao; Tsubota, Kazuo; Kosaki, Kenjiro

    2012-08-01

    Kabuki syndrome has long been clinically defined based mainly on its characteristic eye features. The recent discovery of MLL2 as a causative gene of Kabuki syndrome has enabled the extreme end of the phenotype to be explored. We herein report on two patients with striking visible congenital staphyloma at birth. A diagnosis of Kabuki syndrome was subsequently made in both patients based on a constellation of characteristic eye features, cardiac abnormalities and severe developmental delay, and finally by the confirmation of MLL2 mutations. In conclusion, congenital corneal staphyloma is a complication of Kabuki syndrome with MLL2 mutations. Copyright © 2012 Wiley Periodicals, Inc.

  5. Genomic imbalances in syndromic congenital heart disease.

    PubMed

    Molck, Miriam Coelho; Simioni, Milena; Paiva Vieira, Társis; Sgardioli, Ilária Cristina; Paoli Monteiro, Fabíola; Souza, Josiane; Fett-Conte, Agnes Cristina; Félix, Têmis Maria; Lopes Monlléo, Isabella; Gil-da-Silva-Lopes, Vera Lúcia

    To identify pathogenic genomic imbalances in patients presenting congenital heart disease (CHD) with extra cardiac anomalies and exclusion of 22q11.2 deletion syndrome (22q11.2 DS). 78 patients negative for the 22q11.2 deletion, previously screened by fluorescence in situ hybridization (FISH) and/or multiplex ligation probe amplification (MLPA) were tested by chromosomal microarray analysis (CMA). Clinically significant copy number variations (CNVs ≥300kb) were identified in 10% (8/78) of cases. In addition, potentially relevant CNVs were detected in two cases (993kb duplication in 15q21.1 and 706kb duplication in 2p22.3). Genes inside the CNV regions found in this study, such as IRX4, BMPR1A, SORBS2, ID2, ROCK2, E2F6, GATA4, SOX7, SEMAD6D, FBN1, and LTPB1 are known to participate in cardiac development and could be candidate genes for CHD. These data showed that patients presenting CHD with extra cardiac anomalies and exclusion of 22q11.2 DS should be investigated by CMA. The present study emphasizes the possible role of CNVs in CHD. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  6. Congenital varicella syndrome: still a problem?

    PubMed

    Auriti, Cinzia; Piersigilli, Fiammetta; De Gasperis, Marco Rossi; Seganti, Giulio

    2009-01-01

    A woman contracted chickenpox in the 12th week of gestation. Her general practitioner and later the consultant obstetrician warned her about the small risk of giving birth to a disabled child. She decided to continue the pregnancy without undergoing invasive tests to diagnose fetal intrauterine infection. Symptoms of congenital varicella syndrome (CVS) were detected by ultrasound in the 29th and 34th weeks of gestation. On admission to hospital, the baby was not considered infectious and was not isolated because polymerase chain reaction analysis to detect varicella zoster virus (VZV) DNA in the blood, cerebrospinal fluid, saliva, skin scrapings and feces gave negative results. He was also not separated from his mother. The mother was without clinical complications. Varicella during pregnancy may result in VZV transmission to the fetus or newborn. Intrauterine VZV infection in the first 28 weeks of gestation may result in CVS with limb deformities, brain abnormalities and mental retardation. Usually the newborn is not infectious, and therapy and isolation are unnecessary. When the mother catches the infection in the second trimester, the newborn may manifest shingles in the first 2 years of life. A maternal rash erupting 5 days before to 2 days after delivery is frequently associated with clinically severe varicella in the newborn, leading to high mortality if untreated. Then the newborn is infectious and must be isolated. This case report underlines the need for expert medical counseling for women who contract chickenpox at any time during pregnancy. It also underlines the importance of immunizing susceptible women of childbearing age before they become pregnant. Copyright (c) 2009 S. Karger AG, Basel.

  7. Congenital cataracts in two siblings with Wolfram syndrome.

    PubMed

    Mets, Rebecca B; Emery, Sarah B; Lesperance, Marci M; Mets, Marilyn B

    2010-12-01

    Wolfram syndrome is characterized by optic atrophy, insulin dependent diabetes mellitus, diabetes insipidus and deafness. There are several other associated conditions reported in the literature, but congenital or early childhood cataracts are not among them. Observational case series with confirmatory genetic analysis. A pair of siblings, followed over 17 years, who manifest congenital or early childhood cataracts, diabetes insipidus, diabetes mellitus, optic atrophy, and deafness. They are both compound heterozygotes for mutations (V415 deletion and A684V substitution) in the WFS1 gene. Their father has congenital sensorineural hearing loss and developed optic atrophy. He is heterozygous for A684V in WFS1. Wolfram syndrome should be in the differential diagnosis of genetic syndromes associated with congenital and early childhood cataracts. Here, we report on a mother who is a phenotypically normal carrier of an autosomal recessive Wolfram syndrome gene, and a father who has some of the findings of the syndrome and carries a single mutation that appears to be responsible for his hearing loss and optic atrophy. Their 2 children are compound heterozygotes and manifest the full Wolfram syndrome, in addition to cataracts.

  8. Congenital rubella syndrome: a matter of concern.

    PubMed

    Martínez-Quintana, Efrén; Castillo-Solórzano, Carlos; Torner, Nuria; Rodríguez-González, Fayna

    2015-03-01

    Congenital rubella syndrome (CRS), an important cause of severe birth defects, remains a public health problem in a significant number of countries. Therefore, global health experts encourage use of rubella vaccination, with the primary aim of preventing CRS. While large-scale rubella vaccination during the last decade has drastically reduced or eliminated both the virus and CRS in Europe and the Americas, many countries in Africa, South-East Asia, the Eastern Mediterranean, and the Western Pacific have not yet incorporated any type of rubella-containing vaccine into their immunization schedule. As a result, through travel and migration, rubella has been imported into countries that had successfully eliminated the virus, leading to outbreaks and the reestablishment of endemic transmission. The objective of this study was to identify the key factors required for CRS elimination (prevalence reduction, vaccination strategies, and surveillance methods) by reviewing publications in PubMed on rubella and CRS (systematic reviews, country experiences, and position papers from the World Health Organization (WHO) and other intergovernmental organizations). Based on the results of the review, to eliminate rubella and CRS in endemic areas and reduce re-emergence in previously disease-free areas, all countries should carry out two types of mass rubella vaccination campaigns: 1) one single mass national immunization campaign targeting all men and women 5-39+ years old (with the upper age limit depending on the year in which the rubella-containing vaccine was introduced and the epidemiology of rubella in the country) and 2) incorporation of an rubella-containing vaccine in routine childhood immunization programs, including regular vaccination campaigns for 12-month-olds and measles follow-up campaigns. In addition to mass rubella immunization campaigns and routine childhood vaccination programs, the following measures should be taken to help fight rubella and CRS: 1) surveillance

  9. Initial Description of the Presumed Congenital Zika Syndrome.

    PubMed

    Miranda-Filho, Demócrito de Barros; Martelli, Celina Maria Turchi; Ximenes, Ricardo Arraes de Alencar; Araújo, Thalia Velho Barreto; Rocha, Maria Angela Wanderley; Ramos, Regina Coeli Ferreira; Dhalia, Rafael; França, Rafael Freitas de Oliveira; Marques Júnior, Ernesto Torres de Azevedo; Rodrigues, Laura Cunha

    2016-04-01

    To provide an initial description of the congenital syndrome presumably associated with infection by Zika virus compared with other syndromes including congenital infections of established etiologies. We provide an overview of a published case series of 35 cases, a clinical series of 104 cases, and published and unpublished reports of clinical and laboratory findings describing cases diagnosed since the beginning of the epidemic of microcephaly in Brazil. About 60% to 70% of mothers report rash during pregnancy; mainly in the first trimester. Principal features are microcephaly, facial disproportionality, cutis girata, hypertonia/spasticity, hyperreflexia, and irritability; abnormal neuroimages include calcifications, ventriculomegaly, and lissencephaly. Hearing and visual abnormalities may be present. Preliminary data suggest that severe congenital abnormalities are linked to Zika virus infection. Cases have severe abnormalities, and although sharing many characteristics with congenital abnormalities associated with other viral infections, abnormalities presumably linked to the Zika virus may have distinguishing characteristics. These severe neurologic abnormalities may result in marked mental retardation and motor disabilities for many surviving offspring. Affected nations need to prepare to provide complex and costly multidisciplinary care that children diagnosed with this new congenital syndrome will require.

  10. Congenital varicella syndrome in a monochorionic diamniotic twin pregnancy

    PubMed Central

    Villota, Vania A; Delgado, Julián; Pachajoa, Harry

    2014-01-01

    Congenital varicella syndrome encompasses a broad spectrum of malformations present in children of mothers who developed chickenpox during the first 20 weeks of gestation. We report a case of a monochorionic diamniotic twin pregnancy, with maternal exposure to chickenpox during the thirteenth week of gestation, which produced one symptomatic and one healthy child. PMID:25097633

  11. Congenital varicella syndrome in a monochorionic diamniotic twin pregnancy.

    PubMed

    Villota, Vania A; Delgado, Julián; Pachajoa, Harry

    2014-05-01

    Congenital varicella syndrome encompasses a broad spectrum of malformations present in children of mothers who developed chickenpox during the first 20 weeks of gestation. We report a case of a monochorionic diamniotic twin pregnancy, with maternal exposure to chickenpox during the thirteenth week of gestation, which produced one symptomatic and one healthy child.

  12. Ophthalmic Manifestations of Congenital Zika Syndrome in Colombia and Venezuela.

    PubMed

    Yepez, Juan B; Murati, Felipe A; Pettito, Michele; Peñaranda, Carlos F; de Yepez, Jazmin; Maestre, Gladys; Arevalo, J Fernando

    2017-05-01

    The ocular manifestations and sequelae of Zika virus infection are not well known. Recently, the World Health Organization changed the declaration of Zika as a public health emergency and designated the viral outbreak and related microcephaly clusters as a long-term program of work. This change indicates the urgent need to evaluate and document ophthalmic manifestations in patients for timely management of this disease. In addition, confirmation whether the public health problem in Brazil extends to other regions in South America is needed. To report the ocular manifestations of congenital Zika syndrome with microcephaly in Colombia and Venezuela. This prospective case series included 43 patients from 2 ophthalmic centers in Colombia and Venezuela who underwent evaluation from October 1, 2015, through June 30, 2016, and were clinically diagnosed with congenital Zika syndrome. Twenty patients were Hispanic; 13, African; 8, white; and 2, Native American. Ophthalmic and systemic evaluations and serologic testing were performed on all infants. Patients underwent external ocular examination and dilated ophthalmoscopy. Serologic testing ruled out toxoplasmosis, rubella, cytomegalovirus, syphilis, and human immunodeficiency virus. Ophthalmic manifestations of congenital Zika syndrome. Of the 43 patients included in this series (28 female and 15 male), the mean (SD) age at examination was 2.1 (1.5) months. The mothers of all the children had no ophthalmic findings and did not report ocular symptoms during pregnancy. All patients had bilateral ophthalmic manifestations. Optic nerve findings included hypoplasia with the double-ring sign, pallor, and increased cup-disc ratio in 5 patients (11.6%). Macular abnormalities included mild to severe pigment mottling in 27 patients (63%) and lacunar maculopathy in 3 (6.9%). Chorioretinal scarring was present in 3 patients (7%). Eleven patients (26%) had a combination of lesions in the posterior pole. Five patients (12%) were

  13. Associated congenital anomalies among cases with Down syndrome.

    PubMed

    Stoll, Claude; Dott, Beatrice; Alembik, Yves; Roth, Marie-Paule

    2015-12-01

    Down syndrome (DS) is the most common congenital anomaly widely studied for at least 150 years. However, the type and the frequency of congenital anomalies associated with DS are still controversial. Despite prenatal diagnosis and elective termination of pregnancy for fetal anomalies, in Europe, from 2008 to 2012 the live birth prevalence of DS per 10,000 was 10. 2. The objectives of this study were to examine the major congenital anomalies occurring in infants and fetuses with Down syndrome. The material for this study came from 402,532 consecutive pregnancies of known outcome registered by our registry of congenital anomalies between 1979 and 2008. Four hundred sixty seven (64%) out of the 728 cases with DS registered had at least one major associated congenital anomaly. The most common associated anomalies were cardiac anomalies, 323 cases (44%), followed by digestive system anomalies, 42 cases (6%), musculoskeletal system anomalies, 35 cases (5%), urinary system anomalies, 28 cases (4%), respiratory system anomalies, 13 cases (2%), and other system anomalies, 26 cases (3.6%). Among the cases with DS with congenital heart defects, the most common cardiac anomaly was atrioventricular septal defect (30%) followed by atrial septum defect (25%), ventricular septal defect (22%), patent ductus arteriosus (5%), coarctation of aorta (5%), and tetralogy of Fallot (3%). Among the cases with DS with a digestive system anomaly recorded, duodenal atresia (67%), Hirschsprung disease (14%), and tracheo-esophageal atresia (10%) were the most common. Fourteen (2%) of the cases with DS had an obstructive anomaly of the renal pelvis, including hydronephrosis. The other most common anomalies associated with cases with DS were syndactyly, club foot, polydactyly, limb reduction, cataract, hydrocephaly, cleft palate, hypospadias and diaphragmatic hernia. Many studies to assess the anomalies associated with DS have reported various results. There is no agreement in the literature as to

  14. The phenotypic spectrum of congenital Zika syndrome.

    PubMed

    Del Campo, Miguel; Feitosa, Ian M L; Ribeiro, Erlane M; Horovitz, Dafne D G; Pessoa, André L S; França, Giovanny V A; García-Alix, Alfredo; Doriqui, Maria J R; Wanderley, Hector Y C; Sanseverino, Maria V T; Neri, João I C F; Pina-Neto, João M; Santos, Emerson S; Verçosa, Islane; Cernach, Mirlene C S P; Medeiros, Paula F V; Kerbage, Saile C; Silva, André A; van der Linden, Vanessa; Martelli, Celina M T; Cordeiro, Marli T; Dhalia, Rafael; Vianna, Fernanda S L; Victora, Cesar G; Cavalcanti, Denise P; Schuler-Faccini, Lavinia

    2017-04-01

    In October 2015, Zika virus (ZIKV) outbreak the Brazilian Ministry of Health (MoH). In response, the Brazilian Society of Medical Genetics established a task force (SBGM-ZETF) to study the phenotype of infants born with microcephaly due to ZIKV congenital infection and delineate the phenotypic spectrum of this newly recognized teratogen. This study was based on the clinical evaluation and neuroimaging of 83 infants born during the period from July, 2015 to March, 2016 and registered by the SBGM-ZETF. All 83 infants had significant findings on neuroimaging consistent with ZIKV congenital infection and 12 had confirmed ZIKV IgM in CSF. A recognizable phenotype of microcephaly, anomalies of the shape of skull and redundancy of the scalp consistent with the Fetal Brain Disruption Sequence (FBDS) was present in 70% of infants, but was most often subtle. In addition, features consistent with fetal immobility, ranging from dimples (30.1%), distal hand/finger contractures (20.5%), and feet malpositions (15.7%), to generalized arthrogryposis (9.6%), were present in these infants. Some cases had milder microcephaly or even a normal head circumference (HC), and other less distinctive findings. The detailed observation of the dysmorphic and neurologic features in these infants provides insight into the mechanisms and timings of the brain disruption and the sequence of developmental anomalies that may occur after prenatal infection by the ZIKV. © 2017 Wiley Periodicals, Inc.

  15. The Syndrome of Perisylvian Polymicrogyria with Congenital Arthrogryposis

    PubMed Central

    Poduri, Annapurna; Chitsazzadeh, Vida; D’Arrigo, Stefano; Fedrizzi, Ermellina; Pantaleoni, Chiara; Riva, Daria; Busse, Claudia; Küster, Helmut; Duplessis, Adre; Gaitanis, John; Sahin, Mustafa; Garganta, Cheryl; Topcu, Meral; Dies, Kira A.; Barry, Brenda J.; Partlow, Jennifer; Barkovich, A. James; Walsh, Christopher A.; Chang, Bernard S.

    2009-01-01

    Background Bilateral perisylvian polymicrogyria (BPP) is a well-recognized malformation of cortical development commonly associated with epilepsy, cognitive impairment, and oromotor apraxia. Reports have suggested the association of BPP with arthrogryposis multiplex congenita. We sought to investigate the clinical, electrophysiological, and neuroradiological features of this combined syndrome to determine if there are unique features that distinguish BPP with arthrogryposis from BPP alone. Methods Cases of BPP with congenital arthrogryposis were identified from a large research database of individuals with polymicrogyria. Clinical features (including oromotor function, seizures, and joint contractures), MR brain imaging, and results of neuromuscular testing were reviewed. Results Ten cases of BPP with congenital arthrogryposis were identified. Most cases had some degree of oromotor apraxia. Only a few had seizures, but a majority of cases were still young children. Electrophysiological studies provided evidence for lower motor neuron or peripheral nervous system involvement. On brain imaging, bilateral polymicrogyria (PMG) centered along the Sylvian fissures was seen, with variable extension frontally or parietally; no other cortical malformations were present. We did not identify obvious neuroimaging features that distinguish this syndrome from that of BPP without arthrogryposis. Conclusions The clinical and neuroimaging features of the syndrome of BPP with congenital arthrogryposis appear similar to those seen in cases of isolated BPP without joint contractures, but electrophysiological studies often demonstrate coexistent lower motor neuron or peripheral nervous system pathology. These findings suggest that BPP with arthrogryposis may have a genetic etiology with effects at two levels of the neuraxis. PMID:19751967

  16. Congenital high airway obstruction syndrome (CHAOS) associated with cervical myelomeningocele.

    PubMed

    Adin, Mehmet Emin

    2017-10-01

    Congenital high airway obstruction syndrome (CHAOS) is a rare and potentially fatal entity resulting from complete or near complete developmental airway obstruction. Although most reported cases of CHAOS are sporadic, the condition may also be associated with certain syndromes and a variety of cervical masses. Meningocele and myelomeningocele have not yet been reported in association with CHAOS. We describe the typical constellation of sonographic findings in a case of early diagnosis of CHAOS associated with cervical myelomeningocele. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:507-510, 2017. © 2016 Wiley Periodicals, Inc.

  17. Genetics Home Reference: congenital nephrotic syndrome

    MedlinePlus

    ... Group. Nephrotic syndrome in the first year of life: two thirds of cases are caused by mutations in 4 genes (NPHS1, NPHS2, WT1, and LAMB2). Pediatrics. 2007 Apr;119(4):e907-19. Epub 2007 Mar 19. Citation on PubMed Machuca E, Benoit G, ...

  18. [Pulmonary hypertension associated with congenital heart disease and Eisenmenger syndrome].

    PubMed

    Calderón-Colmenero, Juan; Sandoval Zárate, Julio; Beltrán Gámez, Miguel

    2015-01-01

    Pulmonary arterial hypertension is a common complication of congenital heart disease (CHD). Congenital cardiopathies are the most frequent congenital malformations. The prevalence in our country remains unknown, based on birthrate, it is calculated that 12,000 to 16,000 infants in our country have some cardiac malformation. In patients with an uncorrected left-to-right shunt, increased pulmonary pressure leads to vascular remodeling and endothelial dysfunction secondary to an imbalance in vasoactive mediators which promotes vasoconstriction, inflammation, thrombosis, cell proliferation, impaired apotosis and fibrosis. The progressive rise in pulmonary vascular resistance and increased pressures in the right heart provocated reversal of the shunt may arise with the development of Eisenmenger' syndrome the most advanced form de Pulmonary arterial hypertension associated with congenital heart disease. The prevalence of Pulmonary arterial hypertension associated with CHD has fallen in developed countries in recent years that is not yet achieved in developing countries therefore diagnosed late as lack of hospital infrastructure and human resources for the care of patients with CHD. With the development of targeted medical treatments for pulmonary arterial hypertension, the concept of a combined medical and interventional/surgical approach for patients with Pulmonary arterial hypertension associated with CHD is a reality. We need to know the pathophysiological factors involved as well as a careful evaluation to determine the best therapeutic strategy. Copyright © 2014 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

  19. Congenital stridor with feeding difficulty as a presenting symptom of Dok7 congenital myasthenic syndrome.

    PubMed

    Jephson, Chris G; Mills, Nikki A; Pitt, Matthew C; Beeson, David; Aloysius, Annie; Muntoni, Francesco; Robb, Stephanie A; Bailey, C Martin

    2010-09-01

    The congenital myasthenic syndromes (CMS) are a group of genetic disorders of neuromuscular transmission causing fatigable weakness. Symptoms may be present from birth, but diagnosis is often delayed for several years, notably in post-synaptic CMS due to mutations in the DOK7 gene. Recently, we noted a subgroup of children with CMS in whom congenital stridor and bilateral vocal cord palsy predated other symptoms. All had mutations in the DOK7 gene. The purpose of this study was to review our population of DOK7 CMS patients with congenital stridor and assess whether there were other phenotypic features which might raise suspicion of a diagnosis of CMS in the neonatal period, in the absence of limb weakness and ptosis and prompt earlier referral for neurophysiological investigation, genetic diagnosis and appropriate treatment. A retrospective case review of 11 DOK7 CMS patients at a tertiary referral centre. Six patients were identified with DOK7 mutations and congenital stridor, four requiring intubation soon after birth. Four patients had a diagnosis of bilateral vocal cord palsy and three required tracheostomy, successfully decannulated in one after 3 years. All six patients had difficulty with feeding, with weak suck and swallow necessitating nasogastric feeding in five, two of whom required gastrostomy. Despite all six children having had neonatal symptoms, the mean age at CMS diagnosis was 5 years and 9 months. CMS, particularly caused by mutations in the DOK7 gene, is a rare but treatable cause of congenital stridor in the neonate. A combination of congenital stridor, especially with an apparently idiopathic bilateral vocal cord palsy and weak suck and swallow should alert the clinician to the possibility of CMS and prompt early referral for neurophysiology and genetic investigations. Confirmation of a CMS diagnosis enables treatment to be initiated, informed management of the VCP and anticipation of myasthenic symptoms, particularly life

  20. Clinical profile of congenital rubella syndrome in Yogyakarta, Indonesia.

    PubMed

    Herini, Elisabeth S; Gunadi; Triono, Agung; Wirastuti, Fita; Iskandar, Kristy; Mardin, Niprida; Soenarto, Yati

    2018-02-01

    Congenital rubella syndrome (CRS) has many severe neurological manifestations and other systemic consequences. Although various studies have been done in Indonesia, there are no conclusive results on CRS incidence. The aim of this study was therefore to investigate the incidence, clinical manifestations and outcomes of CRS in Yogyakarta, Indonesia. A descriptive study involving a review of congenital anomalies associated with CRS was carried out at Dr Sardjito Hospital, Yogyakarta, Indonesia, from July 2008 to June 2013. CRS was categorized according to the World Health Organization (WHO) classification. This study involved children aged <1 year old, and was conducted at the outpatient clinic, pediatric and neonatology wards. A total of 201 children met the criteria for suspected CRS during the 5 year study. Of those patients, 6% were classified as having laboratory-confirmed CRS, 21.4% as having clinically compatible CRS, and 72.6% as having discarded CRS (i.e. a suspected case that does not meet the criteria for CRS). The estimated incidence of laboratory-confirmed CRS and laboratory-confirmed and clinically compatible CRS in Yogyakarta, Indonesia during the study period was 0.05:1,000 and 0.25:1,000 live births, respectively. Of the laboratory-confirmed CRS patients, 83.3% of children had congenital heart disease (CHD), 75% had hearing impairment, 66.7% had congenital cataract and 50% had microcephaly. Furthermore, none of the mothers was vaccinated against rubella. The incidence of CRS in infants in Yogyakarta Indonesia is considered high, with most clinical manifestations being CHD, hearing impairment and congenital cataract. This emphasizes the necessity for epidemiological study of CRS in other hospitals and the importance of establishing a national rubella vaccination program in Indonesia. © 2017 Japan Pediatric Society.

  1. Type V Pouch Colon, Prune Belly Syndrome, and Congenital Anterior Urethrocutaneous Fistula

    PubMed Central

    Raj, Prince; Birua, Hirendra

    2017-01-01

    Congenital pouch colon (CPC) or short colon syndrome is a rare type of anorectal malformation(ARM). Type V is the rarest form of CPC. We present a 1-day-old male child with type V CPC with prune belly syndrome and congenital anterior urethrocutaneous fistula (CAUF). PMID:28770135

  2. Type V Pouch Colon, Prune Belly Syndrome, and Congenital Anterior Urethrocutaneous Fistula.

    PubMed

    Raj, Prince; Birua, Hirendra

    2017-01-01

    Congenital pouch colon (CPC) or short colon syndrome is a rare type of anorectal malformation(ARM). Type V is the rarest form of CPC. We present a 1-day-old male child with type V CPC with prune belly syndrome and congenital anterior urethrocutaneous fistula (CAUF).

  3. Prevalence of the Congenital Long QT Syndrome

    PubMed Central

    Schwartz, Peter J; Stramba-Badiale, Marco; Crotti, Lia; Pedrazzini, Matteo; Besana, Alessandra; Bosi, Giuliano; Gabbarini, Fulvio; Goulene, Karine; Insolia, Roberto; Mannarino, Savina; Mosca, Fabio; Nespoli, Luigi; Rimini, Alessandro; Rosati, Enrico; Salice, Patrizia; Spazzolini, Carla

    2009-01-01

    Background: The prevalence of genetic arrhythmogenic diseases is unknown. For the long QT syndrome (LQTS), figures ranging from 1:20,000 to 1:5,000 were published but none was based on actual data. Our objective was to define the prevalence of LQTS. Methods and Results: In 18 maternity hospitals an ECG was performed in 44,596 infants 15-25 days old (43,080 Caucasians). In infants with a QTc >450 ms the ECG was repeated within 1-2 weeks. Genetic analysis, by screening 7 LQTS genes, was performed in 28/31 (90%) and in 14/28 (50%) of infants with, respectively, a QTc >470 ms or between 461 and 470 ms. A QTc of 451-460, of 461-470, and >470 ms was observed in 184 (0.41%), in 28 (0.06%), and in 31 (0.07%) infants. Among genotyped infants, disease-causing mutations were found in 12/28 (43%) with a QTc >470 ms and in 4/14 (29%) with a QTc of 461-470 ms. One genotype-negative infant (QTc 482 ms) was diagnosed affected by LQTS on clinical grounds. Among family members of genotype-positive infants, 51% were found to carry disease-causing mutations. In total, 17/43,080 Caucasian infants were affected by LQTS demonstrating a prevalence of at least 1:2,534 apparently healthy live-births (95% C.I. 1:1,583- 1:4,350). Conclusions: This study provides the first data-based estimate of the prevalence of LQTS among Caucasians. Based on the non-genotyped infants with QTc between 451 and 470 ms we advance the hypothesis that this prevalence might be close to 1:2,000. ECG-guided molecular screening can identify most infants affected by LQTS and unmask affected relatives, thus allowing effective preventive measures. PMID:19841298

  4. Congenital Short-Bowel Syndrome in an Adult Dog.

    PubMed

    Clancy, Chad S; Jensen, Khrista A; Van Wettere, Arnaud J

    2018-05-01

    A 3.5-year-old, neutered male pit bull dog was euthanized following an approximately 1-year history of intractable diarrhea and weight loss of undetermined cause. At necropsy, the dog was emaciated. The ratio of total intestinal length (duodenum to rectum) to crown-to-rump length was 2.5, in contrast to an average of 5.3 (range, 3.7-6.1) in 10 control dogs examined at necropsy. There was diffuse dilation of the intestinal lumen, consistent with congenital intestinal hypoplasia resulting in short-bowel syndrome. Histologically, the intestinal mucosal was hyperplastic, further supporting the diagnosis of short-bowel syndrome. To the authors' knowledge, this is the first case of this condition in the veterinary literature.

  5. Prenatal exposures and congenital heart defects in Down syndrome infants.

    PubMed

    Fixler, D E; Threlkeld, N

    1998-07-01

    The purpose of this study was to determine whether there are important differences in maternal and environmental prenatal risk factors between liveborn Down syndrome infants with congenital heart defects and Down syndrome infants without heart defects. Using a case control study design, we evaluated the risk associated with maternal illness, drug ingestion, substance usage, and chemical exposures in the home or workplace. The period of risk selected was 3 months before and 3 months after the last menstrual period, because cardiac development occurs early, before the mother may become aware of her pregnancy. Because fetal survival in Down syndrome may be more vulnerable to various exposures, controls were selected who also had trisomy 21. Of 171 infants studied, 89 were cases with congenital heart disease, and 82 were controls without heart disease. All interviews were performed by one nurse practitioner using a structured standardized questionnaire. Cases and controls had similar maternal ages, family incomes, parental education levels, and contraceptive practices before pregnancy. No differences were found between case and control mothers for maternal illness, medication use, or consumption of caffeinated beverages, cigarettes, or alcohol. Reporting of recreational drug usage was infrequent, may reflect underreporting, and did not differ between cases and controls. Maternal exposures were commonly reported for pesticides (50%), hair dyes (22%), craft paints (8%), varnishes (7%), and solvents (3.5%). However, in none of the categories was maternal exposure significantly more prevalent among case mothers than among control mothers. The failure of this study to identify risk factors for cardiac malformations may be attributable to the small differences in reported frequencies reducing statistical power or to the possibility that cardiac malformation in Down syndrome is a direct result of chromosomal duplication.

  6. Sleep EEG patterns in infants with congenital Zika virus syndrome.

    PubMed

    Carvalho, Maria Durce Costa Gomes; Miranda-Filho, Demócrito de Barros; van der Linden, Vanessa; Sobral, Paula Fabiana; Ramos, Regina Coeli Ferreira; Rocha, Maria Ângela Wanderley; Cordeiro, Marli Tenório; de Alencar, Sarah Pinheiro; Nunes, Magda Lahorgue

    2017-01-01

    To describe sleep EEG patterns of neonates, and infants with microcephaly due to congenital Zika virus (ZikV) syndrome. A descriptive case series of EEGs performed in a cohort of neonates with microcephaly monitored from October 2015 to February 2016 at a University Hospital in Northeast Brazil. Infants were investigated following an established protocol that includes EEG, neuroimaging studies, PCR and specific antibodies for ZikV detection. EEGs (n=37) from 37 infants were reviewed. Age at investigation varied from 1 to 5months (mean=2.6). Diffuse low voltage (n=7), background asymmetry (n=6) and modified hypsarrhythmia with or without burst-suppression (n=11), were the main background abnormalities identified. Interictal EEG abnormalities were identified in 23 recordings (62%) and localized as focal frontal (n=8) or occipital (n=2) spikes/sharp, multifocal spikes/sharp waves (n=13). Electrographic seizures without clinical manifestation were identified in 4 recordings and characterized as focal pseudo rhythmic pattern. Further findings were focal high amplitude slow waves that were registered in the frontal (n=3) or occipital (n=1) regions. Different types of EEG abnormalities were encountered with a predominance of interictal epileptogenic activity and hypsarrhythmia. Sleep EEGs in congenital Zika virus syndrome are consistently abnormal even in infants who have not yet developed epilepsy. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  7. The congenital long QT syndrome Type 3: An update.

    PubMed

    Pérez-Riera, Andrés Ricardo; Barbosa-Barros, Raimundo; Daminello Raimundo, Rodrigo; da Costa de Rezende Barbosa, Marianne Penachini; Esposito Sorpreso, Isabel Cristina; de Abreu, Luiz Carlos

    Congenital long QT syndrome type 3 (LQT3) is the third in frequency compared to the 15 forms known currently of congenital long QT syndrome (LQTS). Cardiac events are less frequent in LQT3 when compared with LQT1 and LQT2, but more likely to be lethal; the likelihood of dying during a cardiac event is 20% in families with an LQT3 mutation and 4% with either an LQT1 or an LQT2 mutation. LQT3 is consequence of mutation of gene SCN5A which codes for the Nav1.5 Na + channel α-subunit and electrocardiographically characterized by a tendency to bradycardia related to age, prolonged QT/QTc interval (mean QTc value 478 ± 52 ms), accentuated QT dispersion consequence of prolonged ST segment, late onset of T wave and frequent prominent U wave because of longer repolarization of the M cell across left ventricular wall. Copyright © 2017 Indian Heart Rhythm Society. Production and hosting by Elsevier B.V. All rights reserved.

  8. Congenital myasthenic syndrome: presentation, electrodiagnosis, and muscle biopsy.

    PubMed

    Gurnett, Christina A; Bodnar, Judy A; Neil, Jeffrey; Connolly, Anne M

    2004-03-01

    We report 10 children with congenital myasthenic syndromes diagnosed by clinical features, electrodiagnostic studies, and response to acetylcholinesterase inhibitors. Age at diagnosis (mean = 4.4 years; range 0.2-10 years) correlated with age fatigue was recognized. Symptoms at presentation included mild gross motor development delay (7/10), speech articulation difficulty (5/10), and respiratory and feeding difficulties resulting in poor growth in 7 of 10 children. None of the five children with possible presynaptic abnormalities had decremental compound muscle action potential responses to 2 Hz repetitive nerve stimulation. Instead, electrodiagnostic studies showed a more than 100% increment of compound muscle action potential amplitude during 50 Hz repetitive nerve stimulation in two children and sustained compound muscle action potential decrement to 2 Hz repetitive nerve stimulation after depletion (10 Hz stimulation for 10 min) in four children. Muscle biopsies (n = 7) showed mild to severe variation in fiber size. Our experience suggests that many children with congenital myasthenic syndromes might be undiagnosed because of atypical presentation and because additional electrophysiologic studies are required.

  9. Association between Michelin tire baby syndrome and congenital panhyopituitarism in an Iranian girl.

    PubMed

    Haghshenas, Zahra; Tajziehchi, Leila; Ghavami, Fakhredin

    2014-08-01

    Michelin tire baby syndrome is a rare syndrome, diagnosed clinically by multiple circumferential skin folds. Multiple noncutaneous anomalies have been described with this syndrome. We report a case of Michelin tire baby syndrome with congenital panhypopituitarism. To date, there is no report of association between these two disorders.

  10. Hospital-based surveillance of congenital rubella syndrome in Indonesia.

    PubMed

    Herini, Elisabeth Siti; Gunadi; Triono, Agung; Mulyadi, Asal Wahyuni Erlin; Mardin, Niprida; Rusipah; Soenarto, Yati; Reef, Susan E

    2017-03-01

    Congenital rubella syndrome (CRS) has serious consequences, such as miscarriage, stillbirth, and severe birth defects in infants, resulting from rubella virus infection during pregnancy. However, rubella vaccine has not yet been implemented in Indonesia. This study aimed (1) to estimate the incidence of CRS in Indonesia, (2) describe the clinical features of CRS at our referral hospital, and (3) pilot a CRS surveillance system to be extended to other hospitals. We conducted a 4-month prospective surveillance study of infants aged <1 year with suspected CRS in 2013 at an Indonesian hospital. Infants with suspected CRS were examined for rubella-specific IgM antibody or rubella IgG antibody levels. Of 47 suspected cases of CRS, 11/47 (23.4%), 9/47 (19.1%), and 27/47 (57.5%) were diagnosed as laboratory-confirmed, clinically compatible, and discarded CRS, respectively. The most common defects among laboratory-confirmed CRS cases were hearing impairment (100%), congenital cataracts (72.7%), microcephaly (72.7%), and congenital heart defects (45.5%). The number of laboratory-confirmed CRS cases among Indonesian infants is high. Furthermore, hearing impairment is the most common clinical feature of CRS in infants. Our findings indicate the importance of implementation of rubella vaccine in Indonesia. Conducting hospital-based surveillance of CRS in other hospitals in Indonesia may be appropriate. What is Known: •Congenital rubella syndrome (CRS) has serious consequences in infants resulting from rubella virus infection during pregnancy. •The incidence of CRS in most developed countries has greatly decreased since implementation of rubella vaccination. •Rubella vaccine has not yet been implemented in many developing countries. What is New: •The number of laboratory-confirmed CRS cases among Indonesian infants was high. •Implementation of rubella vaccine into immunization programs in Indonesia is important because of the high number of CRS cases. •Our study

  11. Congenital Zika syndrome with arthrogryposis: retrospective case series study.

    PubMed

    van der Linden, Vanessa; Filho, Epitacio Leite Rolim; Lins, Otavio Gomes; van der Linden, Ana; Aragão, Maria de Fátima Viana Vasco; Brainer-Lima, Alessandra Mertens; Cruz, Danielle Di Cavalcanti Sousa; Rocha, Maria Angela Wanderley; Sobral da Silva, Paula Fabiana; Carvalho, Maria Durce Costa Gomes; do Amaral, Fernando José; Gomes, Joelma Arruda; Ribeiro de Medeiros, Igor Colaço; Ventura, Camila V; Ramos, Regina Coeli

    2016-08-09

    To describe the clinical, radiological, and electromyographic features in a series of children with joint contractures (arthrogryposis) associated with congenital infection presumably caused by Zika virus. Retrospective case series study. Association for Assistance of Disabled Children, Pernambuco state, Brazil. Seven children with arthrogryposis and a diagnosis of congenital infection presumably caused by Zika virus during the Brazilian microcephaly epidemic. Main clinical, radiological, and electromyographic findings, and likely correlation between clinical and primary neurological abnormalities. The brain images of all seven children were characteristic of congenital infection and arthrogryposis. Two children tested positive for IgM to Zika virus in the cerebrospinal fluid. Arthrogryposis was present in the arms and legs of six children (86%) and the legs of one child (14%). Hip radiographs showed bilateral dislocation in seven children, subluxation of the knee associated with genu valgus in three children (43%), which was bilateral in two (29%). All the children underwent high definition ultrasonography of the joints, and there was no evidence of abnormalities. Moderate signs of remodeling of the motor units and a reduced recruitment pattern were found on needle electromyography (monopolar). Five of the children underwent brain computed tomography (CT) and magnetic resonance imaging (MRI) and the remaining two CT only. All presented malformations of cortical development, calcifications predominantly in the cortex and subcortical white matter (especially in the junction between the cortex and white matter), reduction in brain volume, ventriculomegaly, and hypoplasia of the brainstem and cerebellum. MRI of the spine in four children showed apparent thinning of the cord and reduced ventral roots. Congenital Zika syndrome should be added to the differential diagnosis of congenital infections and arthrogryposis. The arthrogryposis was unrelated to the abnormalities

  12. Congenital Zika syndrome with arthrogryposis: retrospective case series study

    PubMed Central

    Filho, Epitacio Leite Rolim; Lins, Otavio Gomes; Aragão, Maria de Fátima Viana Vasco; Brainer-Lima, Alessandra Mertens; Cruz, Danielle Di Cavalcanti Sousa; Rocha, Maria Angela Wanderley; Sobral da Silva, Paula Fabiana; Carvalho, Maria Durce Costa Gomes; do Amaral, Fernando José; Gomes, Joelma Arruda; Ribeiro de Medeiros, Igor Colaço; Ventura, Camila V; Ramos, Regina Coeli

    2016-01-01

    Objective To describe the clinical, radiological, and electromyographic features in a series of children with joint contractures (arthrogryposis) associated with congenital infection presumably caused by Zika virus. Design Retrospective case series study. Setting Association for Assistance of Disabled Children, Pernambuco state, Brazil. Participants Seven children with arthrogryposis and a diagnosis of congenital infection presumably caused by Zika virus during the Brazilian microcephaly epidemic. Main outcome measures Main clinical, radiological, and electromyographic findings, and likely correlation between clinical and primary neurological abnormalities. Results The brain images of all seven children were characteristic of congenital infection and arthrogryposis. Two children tested positive for IgM to Zika virus in the cerebrospinal fluid. Arthrogryposis was present in the arms and legs of six children (86%) and the legs of one child (14%). Hip radiographs showed bilateral dislocation in seven children, subluxation of the knee associated with genu valgus in three children (43%), which was bilateral in two (29%). All the children underwent high definition ultrasonography of the joints, and there was no evidence of abnormalities. Moderate signs of remodeling of the motor units and a reduced recruitment pattern were found on needle electromyography (monopolar). Five of the children underwent brain computed tomography (CT) and magnetic resonance imaging (MRI) and the remaining two CT only. All presented malformations of cortical development, calcifications predominantly in the cortex and subcortical white matter (especially in the junction between the cortex and white matter), reduction in brain volume, ventriculomegaly, and hypoplasia of the brainstem and cerebellum. MRI of the spine in four children showed apparent thinning of the cord and reduced ventral roots. Conclusions Congenital Zika syndrome should be added to the differential diagnosis of congenital

  13. Congenital heart defects in molecularly proven Kabuki syndrome patients.

    PubMed

    Digilio, Maria Cristina; Gnazzo, Maria; Lepri, Francesca; Dentici, Maria Lisa; Pisaneschi, Elisa; Baban, Anwar; Passarelli, Chiara; Capolino, Rossella; Angioni, Adriano; Novelli, Antonio; Marino, Bruno; Dallapiccola, Bruno

    2017-11-01

    The prevalence of congenital heart defects (CHD) in Kabuki syndrome ranges from 28% to 80%. Between January 2012 and December 2015, 28 patients had a molecularly proven diagnosis of Kabuki syndrome. Pathogenic variants in KMT2D (MLL2) were detected in 27 patients, and in KDM6A gene in one. CHD was diagnosed in 19/27 (70%) patients with KMT2D (MLL2) variant, while the single patient with KDM6A change had a normal heart. The anatomic types among patients with CHD included aortic coarctation (4/19 = 21%) alone or associated with an additional CHD, bicuspid aortic valve (4/19 = 21%) alone or associated with an additional CHD, perimembranous subaortic ventricular septal defect (3/19 = 16%), atrial septal defect ostium secundum type (3/19 = 16%), conotruncal heart defects (3/19 = 16%). Additional CHDs diagnosed in single patients included aortic dilatation with mitral anomaly and hypoplastic left heart syndrome. We also reviewed CHDs in patients with a molecular diagnosis of Kabuki syndrome reported in the literature. In conclusion, a CHD is detected in 70% of patients with KMT2D (MLL2) pathogenic variants, most commonly left-sided obstructive lesions, including multiple left-sided obstructions similar to those observed in the spectrum of the Shone complex, and septal defects. Clinical management of Kabuki syndrome should include echocardiogram at the time of diagnosis, with particular attention to left-sided obstructive lesions and mitral anomalies, and annual monitoring for aortic arch dilatation. © 2017 Wiley Periodicals, Inc.

  14. Congenital Auricular Malformations: Description of Anomalies and Syndromes.

    PubMed

    Bartel-Friedrich, Sylva

    2015-12-01

    Half of the malformations in the ear, nose, and throat region affect the ear. Malformations of the external ear (pinna or auricle with external auditory canal [EAC]) are collectively termed microtia. Microtia is a congenital anomaly that ranges in severity from mild structural abnormalities to complete absence of the external ear (anotia). Microtia occurs more frequently in males (∼2 or 3:1), is predominantly unilateral (∼70-90%), and more often involves the right ear (∼60%). The reported prevalence varies geographically from 0.83 to 17.4 per 10,000 births. Microtia may be genetic (with family history, spontaneous mutations) or acquired. Malformations of the external ear can also involve the middle ear and/or inner ear. Microtia may be an isolated birth defect, but associated anomalies or syndromes are described in 20 to 60% of cases, depending on study design. These generally fit within the oculo-auriculo-vertebral spectrum; defects are located most frequently in the facial skeleton, facial soft tissues, heart, and vertebral column, or comprise a syndrome (e.g., Treacher Collins syndrome). Diagnostic investigation of microtia includes clinical examination, audiologic testing, genetic analysis and, especially in higher grade malformations with EAC deformities, computed tomography (CT) or cone-beam CT for the planning of surgery and rehabilitation procedures, including implantation of hearing aids. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  15. Severe congenital thrombocytopaenia – first clinical manifestation of Noonan syndrome

    PubMed Central

    Nunes, Paula; Aguilar, Sara; Prado, Sara Noéme; Palaré, Maria João; Ferrão, Anabela; Morais, Anabela

    2012-01-01

    This report focuses on a male infant, the first born of non-consanguineous parents diagnosed with polyhydramnios at 26 weeks of gestation. The newborn was admitted during the neonatal period with bleeding diathesis associated with a low platelet count at birth (5×109/l).The authors registered a persistent low platelet count (9000–129 000/l) during the infants 1st year of life. Physical examination revealed a petechial rash, a dysmorphic face and bilateral cryptorchidism, in the absence of organomegaly. Additionally, cardiologic evaluation revealed an aortic valve dysplasia and an atrial septal defect, while bone marrow biopsy and aspiration were found normal. Throughout the investigation, the authors excluded congenital infection, alloimmune and familiar thrombocytopaenia, Fanconi anaemia and thrombocytopaenia absent radius syndrome. The cytogenetic analysis revealed a mutation in the PTPN11 gene associated with Noonan syndrome. Here the author highlights that severe neonatal thrombocytopaenia is a manifestation that should be considered in the diagnosis and clinical management of Noonan’s syndrome. PMID:22605701

  16. Cortical thickness in a case of congenital unilateral perisylvian syndrome.

    PubMed

    Kotini, A; Camposano, S; Hara, K; Salat, D; Cole, A; Stufflebeam, S; Halgren, E

    2004-11-30

    In congenital perisylvian syndrome, there is polymicrogyric cortex distributed in variable extensions around the sylvian fissure. Unilateral cases usually present with congenital hemiparesis, while bilateral cases have pseudobulbar paralysis of the oropharingoglossal region. Both unilateral and bilateral cases have a high rate of epilepsy. Polymicrogyric cortex is characterized by too many small convolutions. Often there are no intervening sulci, and almost no white matter can be seen under them. On MRI they appear to have increased thickness. Bilateral and symmetric polimycrogiria can be hard to recognize on standard MRIs. Accurate and automated methods for measuring the thickness of cerebral cortex are available. They have mainly been used to study a variety of disorders with diminished cortical thickness. We studied a case of right perisylvian polymicrogyria, who presented in adult life with epilepsy and had a normal neurological exam. Fischl and Dale's automated cortical thickness analysis rendered a very clear picture of increased cortical thickness with values up to 9 mm in the affected areas (normal cortical thickness varies between 1 and 4.5 mm). The thickest areas were seen over grossly abnormal gyri on the reconstructed cerebral cortex. On MEG he presented a prominent and monotonous 9 Hz activity that was located within the limits of a thick gyrus. There was a significant difference of thickness between homologous hemispheric areas. To our surprise some areas of the left hemisphere also appeared to have increased thickness, raising the question of a bilateral asymmetric case.

  17. Congenital varicella syndrome in a very low birthweight preterm infant.

    PubMed

    Neubauer, Vera; Griesmaier, Elke; Trawoger, Rudolf; Kiechl-Kohlendorfer, Ursula

    2011-07-01

    Congenital varicella syndrome (CVS) is a rare but deleterious consequence of primary varicella zoster virus (VZV) infection during pregnancy. Typical CVS stigmata are cerebral abnormalities, eye diseases and segmentally distributed, cicatricial skin lesions. In this paper the authors report on a male preterm infant, born at 30 weeks of gestation, who developed pustular skin lesions at the age of 4 weeks. The mother had suffered from chickenpox at 14 weeks of gestation. Apart from skin manifestations, critical bronchopulmonary dysplasia made the infant conspicuous. The VZV genome was detected in blood, respiratory secretions and skin lesions. At age 10 weeks he presented with extensive intestinal wall perforation, considered to be related to CVS, which finally led to death. This case shows for the first time the clinical course of CVS in a preterm infant. It illustrates the need for discussion of comprehensive VZV vaccination for seronegative women of childbearing age.

  18. Diclazuril Protects against Maternal Gastrointestinal Syndrome and Congenital Toxoplasmosis.

    PubMed

    Oz, Helieh S; Tobin, Thomas

    2014-01-01

    Toxoplasmosis is a common cause of foodborne, gastrointestinal and congenital syndrome with particularly severe or unknown health consequences. There is no safe and effective preventive or therapeutic modality against congenital toxoplasmosis or to eliminate the persistent chronic infection. Diclazuril to be safe in pregnancy and effective against gastrointestinal toxoplasmosis. CD1 programmed pregnant mice were divided into groups and administered a diet containing diclazuril, or sham control. Treatments were initiated on Day 5 of pregnancy and continued until Day 16 when dams were euthanatized. On Day 8 of pregnancy dams were infected intraperitoneally with escalating doses of tachyzoites (0, 100, 300, 600) from Type II strain. Dams were monitored daily for distress, pain, and abortion and samples collected at the end of the experiments. Infected dams developed moderate to severe Toxoplasma related complications in tachyzoites dose dependent manner. Animals became anemic and showed hydrothorax, and ascities. Diclazuril effectively protected dams from ascities and anemia (p < 0.05). Infected dams showed splenomegaly, with massive infiltration of epithelioid cells compared with the protective effect of diclazuril in treated animals. Infected dams exhibited severe hepatitis (score 0 to 4 scale = 3.5 ± 0.01) with influx of inflammatory and plasma cells, dysplastic hepatocytes, multinucleated giant cell transformation and hepatic cells necrosis. Diclazuril treatment significantly protected dams from hepatitis, also in tachyzoites dose (100, 300, 600) dependent manner (respectively infected-treated versus infected controls, p < 0.001, p < 0.01 and p < 0.05). Colonic tissues were significantly shortened in length, with infiltration of lymphocytes, and macrophages and microabscess formations in the cryptic structures, with significant improvement in diclazuril treated animals. Additionally, the number of fetuses, fetal length and fetal weight were preserved in

  19. Diclazuril Protects against Maternal Gastrointestinal Syndrome and Congenital Toxoplasmosis

    PubMed Central

    Oz, Helieh S.; Tobin, Thomas

    2014-01-01

    Background Toxoplasmosis is a common cause of foodborne, gastrointestinal and congenital syndrome with particularly severe or unknown health consequences. There is no safe and effective preventive or therapeutic modality against congenital toxoplasmosis or to eliminate the persistent chronic infection. Hypothesis Diclazuril to be safe in pregnancy and effective against gastrointestinal toxoplasmosis. Methods CD1 programmed pregnant mice were divided into groups and administered a diet containing diclazuril, or sham control. Treatments were initiated on Day 5 of pregnancy and continued until Day 16 when dams were euthanatized. On Day 8 of pregnancy dams were infected intraperitoneally with escalating doses of tachyzoites (0, 100, 300, 600) from Type II strain. Dams were monitored daily for distress, pain, and abortion and samples collected at the end of the experiments. Results Infected dams developed moderate to severe Toxoplasma related complications in tachyzoites dose dependent manner. Animals became anemic and showed hydrothorax, and ascities. Diclazuril effectively protected dams from ascities and anemia (p < 0.05). Infected dams showed splenomegaly, with massive infiltration of epithelioid cells compared with the protective effect of diclazuril in treated animals. Infected dams exhibited severe hepatitis (score 0 to 4 scale = 3.5 ± 0.01) with influx of inflammatory and plasma cells, dysplastic hepatocytes, multinucleated giant cell transformation and hepatic cells necrosis. Diclazuril treatment significantly protected dams from hepatitis, also in tachyzoites dose (100, 300, 600) dependent manner (respectively infected-treated versus infected controls, p < 0.001, p < 0.01 and p < 0.05). Colonic tissues were significantly shortened in length, with infiltration of lymphocytes, and macrophages and microabscess formations in the cryptic structures, with significant improvement in diclazuril treated animals. Additionally, the number of fetuses, fetal length and

  20. Type IV neonatal Bartter syndrome complicated with congenital chloride diarrhea.

    PubMed

    Sakallı, Hale; Bucak, Hakan İbrahim

    2012-01-01

    Pseudo-Bartter syndrome encompasses a heterogenous group of disorders similar to Bartter syndrome. Sometimes a few status may be nested, as in our case presented here. An 8-month-old boy was referred to our hospital with of intractable diarrhea, polyuria, persistent hypokalemia, abdominal distension and failure to thrive. He was born in the 34 6/7 gestational week (GW) to consanguineous parents. In the 30(th) GW polyhydramnios was verified by ultrasonography. The laboratory results showed hypokalemic-hypochloremic metabolic alkalosis, hyponatremia, and increased urinary loss of chloride, potassium and calcium. An audiogram test revealed complete sensorineural deafness. Ultrasonography revealed medullary nephrocalcinosis in both kidneys. Elevated plasma renin activity and aldosterone were found and a provisional diagnosis of type-IV neonatal Bartter syndrome was made. Treatment with indomethacin, spironolactone and additional intake of NaCl/KCl was initiated. Despite these therapies, the child's diarrhea persisted but serum potassium concentration normalized, and hypercalciuria and urine output reduced. After determining the high fecal chloride concentration, there was an immediate decompensation of the disease on indomethacin withdrawal, thus a diagnosis of type IV neonatal Bartter syndrome complicated with congenital chloride diarrhea was considered. Indomethacin, spironolactone and supplementary therapies with NaCl/KCl were continued, which resulted in the normalization of serum electrolytes as well as his physical development, but high contents of chloride in urine and faeces and nephrocalcinosis remains unchanged during 1-year follow-up. Because of the clinical and laboratory simulations between the various diseases that lead to hypokalemic-hypochloremic metabolic alkalosis, patients must be evaluated carefully.

  1. Congenital Deafness with Cardiac Arrhythmias: The Jervell and Lange-Nielsen Syndrome.

    ERIC Educational Resources Information Center

    Wahl, Richard A.; Macdonald, Dick, II

    1980-01-01

    The Jervell and Lange-Nielsen syndrome, affecting 0.3 percent of congenitally deaf persons, consists of severe cardiac arrhythmias and sensorineural hearing loss. The authors recommend that every congenitally deaf child with suspicious symptoms receive an electrocardiogram and that professionals who work with deaf children not only inform…

  2. Congenital optic tract syndrome: magnetic resonance imaging and scanning laser ophthalmoscopy findings.

    PubMed

    Murphy, M A; Grosof, D H; Hart, W M

    1997-12-01

    Lesions of the optic tract produce a distinctive pattern of optic atrophy and visual field loss and may be due to either congenital or acquired causes. We report a case of a congenital optic tract syndrome and correlate the magnetic resonance imaging findings with the appearance of nerve fiber layer defects found by confocal scanning laser ophthalmoscopy.

  3. [Congenital syndromes of oculomotor disturbances--diagnosis and results of surgical treatment].

    PubMed

    Kubatko-Zielińska, A; Krzystkowa, K M

    1995-05-01

    During the period of 30 years (1964-1994), 363 children with different congenital syndromes of oculomotor disturbances were treated: 300 with Duane's retraction syndrome, 29 with Moebius syndrome, 34 with the superior oblique tendon sheath syndrome of Brown. Symptoms of these syndromes are presented. The choice of appropriate therapy of oculomotor disturbances are described. For aesthetic indications surgical treatment was carried out in 142 (47.3%) patients with retraction syndrome, in 20 (68.7%) with Moebius syndrome and in 23 (67.75%) with Brown's syndrome. Marked reduction of deviation in primary position and reduction of anomalous head posture were obtained.

  4. Overview of Usher's Syndrome: Congenital Deafness and Progressive Loss of Vision

    ERIC Educational Resources Information Center

    Vernon, McCay

    1974-01-01

    Usher's syndrome, a genetic condition causing congenital profound hearing loss and a progressive blindness due to retinitis pigmentosa, affects an estimated three to six percent of children in educational and rehabilitative programs for the hearing impaired. (Author)

  5. Congenital chloride diarrhea misdiagnosed as pseudo-Bartter syndrome.

    PubMed

    Saneian, Hossein; Bahraminia, Emad

    2013-09-01

    Congenital chloride diarrhea (CCD) is a rare autosomal recessive disease which is characterized by intractable diarrhea of infancy, failure to thrive, high fecal chloride, hypochloremia, hypokalemia, hyponatremia and metabolic alkalosis. In this case report, we present the first female and the second official case of CCD in Iran. A 15-month-old girl referred to our hospital due to failure to thrive and poor feeding. She had normal kidneys, liver and spleen. Treating her with Shohl's solution, thiazide and zinc sulfate did not result in weight gain. Consequently, pseudo-Bartter syndrome was suspected, she was treated with intravenous (IV) therapy to which she responded dramatically. In addition, hypokalemia resolved quickly. Since this does not usually happen in patients with the pseudo-Bartter syndrome, stool tests were performed. Abnormal level of chloride in stool suggested CCD and she was thus treated with IV fluid replacement, Total parentral nutrition and high dose of oral omeprazole (3 mg/kg/day). She gained 1 kg of weight and is doing fine until present. CCD is a rare hereditary cause of intractable diarrhea of infancy. It should be considered in infants with unknown severe electrolyte disturbances.

  6. [Clinical and neuropsychological characteristics in congenital central hypoventilation syndrome].

    PubMed

    Seijas-Gomez, R; Esteso-Orduna, B; Melero-Llorente, J; Fournier-Del Castillo, M C

    2018-05-01

    Congenital central hypoventilation syndrome (CCHS) syndrome is a rare disease caused by mutations in the PHOX2B gene. Patients show a reduced response to hypercapnia and hypoxia accompanied by diffuse disturbances of the autonomic nervous system and occasionaly also disturbances in neuroimaging. A specific neuropsychological profile has not been described in children and adolescents with CCHS. We describe three cases (aged between 4 and 19 years) with different profiles of affectation in cognitive and functionality. These profiles are compared with the features described in the literature about neuropsychology in CCHS. The profile of functional impairment in the CCHS is variable: in case 1, a severe global developmental delay with autistic features and marked functional involvement is described. In case 2, bilateral atrophy of the hippocampus is associated with involvement in social cognition and in executive functions with moderate functional repercussion. Case 3 shows difficulties in some cognitive executive functions (planning and non-verbal fluency), but without functional repercussion. Neuropsychological assessment can help in the clinical management of these patients by determining and guiding the need for rehabilitation treatments.

  7. Congenital central hypoventilation syndrome: not just another rare disorder.

    PubMed

    Chen, Maida Lynn; Keens, Thomas G

    2004-09-01

    Congenital central hypoventilation syndrome (CCHS) is a rare syndrome, present from birth, and is defined as the failure of automatic control of breathing. Patients have absent or negligible ventilatory sensitivity to hypercapnia and hypoxaemia during sleep and wakefulness. Therefore, especially while asleep, children with CCHS experience progressive hypercapnia and hypoxaemia. They lack arousal responses and sensations of dyspnoea to the endogenous challenges of isolated hypercapnia and hypoxaemia and to the combined stimulus of hypercapnia and hypoxaemia. Patients with CCHS do not exhibit signs of respiratory distress when challenged with hypercarbia or hypoxia. The diagnosis is one of exclusion, ruling out any primary pulmonary, cardiac, metabolic or neurologic cause for central hypoventilation. CCHS is associated with other manifestations of autonomic nervous system dysfunction, including Hirschsprung's disease. All patients with CCHS require lifelong ventilatory support during sleep but some will be able to maintain adequate ventilation without assistance while awake once past infancy. However, some CCHS patients require ventilatory support for 24h/day. Modalities of home mechanical-assisted ventilation include positive pressure ventilation via tracheostomy, non-invasive positive pressure ventilation (bi-level ventilation), negative pressure ventilation and diaphragmatic pacers. Supplemental oxygen alone is inadequate treatment. With early diagnosis and adequate ventilatory support, these children can have good outcomes and lead productive lives.

  8. Adams-Oliver syndrome associated with cutis marmorata telangiectatica congenita and congenital cataract: a case report.

    PubMed

    Fayol, Laurence; Garcia, Patricia; Denis, Danièle; Philip, Nicole; Simeoni, Umberto

    2006-04-01

    A female infant presented with Adams-Oliver syndrome (AOS), intrauterine growth retardation, severe cutis marmorata telangiectatica congenita, bilateral congenital cataract, and periventricular lesions. The here-reported association of bilateral congenital cataract with AOS is original. Adams-Oliver syndrome is a genetic defect that causes a vasculopathy and leads to a variety of phenotypes. This observation further supports the current understanding of the physiopathology of AOS.

  9. Congenital Zika syndrome and neuroimaging findings: what do we know so far?

    PubMed

    Ribeiro, Bruno Niemeyer de Freitas; Muniz, Bernardo Carvalho; Gasparetto, Emerson Leandro; Ventura, Nina; Marchiori, Edson

    2017-01-01

    Although infection with the Zika virus was first recognized in 1942, it received little attention until 2007, when a true pandemic spread throughout Africa, Asia, and the Americas. Since then, numerous forms of central nervous system involvement have been described, mainly malformations related to congenital infection. Although the neuroimaging findings in congenital Zika syndrome are not pathognomonic, many are quite suggestive of the diagnosis, and radiologists should be prepared to interpret such findings accordingly. The objective of this article is to review the computed tomography and magnetic resonance imaging findings in congenital Zika syndrome.

  10. Left-sided congenital heart lesions in mosaic Turner syndrome.

    PubMed

    Bouayed Abdelmoula, Nouha; Abdelmoula, Balkiss; Smaoui, Walid; Trabelsi, Imen; Louati, Rim; Aloulou, Samir; Aloulou, Wafa; Abid, Fatma; Kammoun, Senda; Trigui, Khaled; Bedoui, Olfa; Denguir, Hichem; Mallek, Souad; Ben Aziza, Mustapha; Dammak, Jamila; Kaabi, Oldez; Abdellaoui, Nawel; Turki, Fatma; Kaabi, Asma; Kamoun, Wafa; Jabeur, Jihen; Ltaif, Wided; Chaker, Kays; Fourati, Haytham; M'rabet, Samir; Ben Ameur, Hedi; Gouia, Naourez; Mhiri, Mohamed Nabil; Rebai, Tarek

    2018-04-01

    In the era of the diseasomes and interactome networks, linking genetics with phenotypic traits in Turner syndrome should be studied thoroughly. As a part of this stratagem, mosaicism of both X and Y chromosome which is a common finding in TS and an evaluation of congenital heart diseases in the different situations of mosaic TS types, can be helpful in the identification of disturbed sex chromosomes, genes and signaling pathway actors. Here we report the case of a mosaic TS associated to four left-sided CHD, including BAV, COA, aortic aneurysms and dissections at an early age. The mosaicism included two cell lines, well-defined at the cytogenetic and molecular levels: a cell line which is monosomic for Xp and Xq genes (45,X) and another which is trisomic for pseudoautosomal genes that are present on the X and Y chromosomes and escape X inactivation: 45,X[8]/46,X,idic(Y)(pter→q11.2::q11.2→pter)[42]. This case generates two hypotheses about the contribution of genes linked to the sex chromosomes and the signaling pathways involving these genes, in left-sided heart diseases. The first hypothesis suggests the interaction between X chromosome and autosomal genes or loci of aortic development, possibly dose-dependent, and which could be in the framework of TGF-β-SMAD signaling pathways. The second implies that left-sided congenital heart lesions involve sex chromosomes loci. The reduced dosage of X chromosome gene(s), escaping X inactivation during development, contributes to this type of CHD. Regarding our case, these X chromosome genes may have homologues at the Y chromosome, but the process of inactivation of the centromeres of the isodicentric Y spreads to the concerned Y chromosome genes. Therefore, this case emerges as an invitation to consider the mosaics of Turner syndrome and to study their phenotypes in correlation with their genotypes to discover the underlying developmental and genetic mechanisms, especially the ones related to sex chromosomes.

  11. Growth curves in Down syndrome with congenital heart disease.

    PubMed

    Sica, Caroline D'Azevedo; Cesa, Claudia Ciceri; Pellanda, Lucia Campos

    2016-01-01

    To assess dietary habits, nutritional status and food frequency in children and adolescents with Down syndrome (DS) and congenital heart disease (CHD). Additionally, we attempted to compare body mass index (BMI) classifications according to the World Health Organization (WHO) curves and curves developed for individuals with DS. Cross-sectional study including individuals with DS and CHD treated at a referral center for cardiology, aged 2 to 18 years. Weight, height, BMI, total energy and food frequency were measured. Nutritional status was assessed using BMI for age and gender, using curves for evaluation of patients with DS and those set by the WHO. 68 subjects with DS and CHD were evaluated. Atrioventricular septal defect (AVSD) was the most common heart disease (52.9%). There were differences in BMI classification between the curves proposed for patients with DS and those proposed by the WHO. There was an association between consumption of vitamin E and polyunsaturated fatty acids. Results showed that individuals with DS are mostly considered normal weight for age, when evaluated using specific curves for DS. Reviews on specific curves for DS would be the recommended practice for health professionals so as to avoid precipitated diagnosis of overweight and/or obesity in this population.

  12. Congenital Hypogonadotropic Hypogonadism and Kallmann Syndrome: Past, Present, and Future

    PubMed Central

    2015-01-01

    The proper development and coordination of the hypothalamic-pituitary-gonadal (HPG) axis are essential for normal reproductive competence. The key factor that regulates the function of the HPG axis is gonadotrophin-releasing hormone (GnRH). Timely release of GnRH is critical for the onset of puberty and subsequent sexual maturation. Misregulation in this system can result in delayed or absent puberty and infertility. Congenital hypogonadotropic hypogonadism (CHH) and Kallmann syndrome (KS) are genetic disorders that are rooted in a GnRH deficiency but often accompanied by a variety of non-reproductive phenotypes such as the loss of the sense of smell and defects of the skeleton, eye, ear, kidney, and heart. Recent progress in DNA sequencing technology has produced a wealth of information regarding the genetic makeup of CHH and KS patients and revealed the resilient yet complex nature of the human reproductive neuroendocrine system. Further research on the molecular basis of the disease and the diverse signal pathways involved will aid in improving the diagnosis, treatment, and management of CHH and KS patients as well as in developing more precise genetic screening and counseling regime. PMID:26790381

  13. Recurrent Congenital Diaphragmatic Hernia in Ehlers-Danlos Syndrome

    SciTech Connect

    Lin, I.C.; Ko, S.F.; Shieh, C.S.

    2006-10-15

    Ehlers-Danlos syndrome (EDS) includes a group of connective tissue disorders with abnormal collagen metabolism and a diverse clinical spectrum. We report two siblings with EDS who both presented with congenital diaphragmatic hernia (CDH). The elder sister suffered from recurrent diaphragmatic hernia twice and EDS was overlooked initially. Echocardiography as well as contrast-enhanced magnetic resonance angiography (MRA) showed dilatation of the pulmonary artery, and marked elongation and tortuosity of the aorta and its branches. A diagnosis of EDS was eventually established when these findings were coupled with the clinical features of hyperelastic skin. Her younger brother also had similar features. Thismore » report emphasizes that EDS may present as CDH in a small child which could easily be overlooked. Without appropriate surgery, diaphragmatic hernia might occur. Echocardiographic screening is recommended in patients with CDH. Contrast-enhanced MRA can be helpful in delineation of abnormally tortuous aortic great vessels that are an important clue to the early diagnosis of EDS.« less

  14. Mammillary Body and Fornix Injury in Congenital Central Hypoventilation Syndrome

    PubMed Central

    Kumar, Rajesh; Lee, Kwanoo; Macey, Paul M.; Woo, Mary A.; Harper, Ronald M.

    2011-01-01

    Congenital central hypoventilation syndrome (CCHS) is accompanied by reduced ventilatory sensitivity to CO2 and O2, respiratory drive failure during sleep, impaired autonomic, fluid, and food absorption regulation, and affective and cognitive deficits, including memory deficiencies. The deficits likely derive from neural injury, reflected as structural damage and impaired functional brain responses to ventilatory and autonomic challenges. Brain structures playing essential memory roles, including the hippocampus and anterior thalamus, are damaged in CCHS. Other memory formation circuitry, the fornix and mammillary bodies, have not been evaluated. We collected two high-resolution T1-weighted image series from 14 CCHS and 31 control subjects, using a 3.0 Tesla magnetic resonance imaging scanner. Image series were averaged and reoriented a standard template; areas containing the mammillary bodies and fornices were over sampled, and body volumes and fornix cross-sectional areas were calculated and compared between groups. Both left and right mammillary body volumes and fornix cross-sectional areas were significantly reduced in CCHS over control subjects, controlling for age, gender, and intracranial volume. Damage to these structures may contribute to memory deficiencies found in CCHS. Hypoxic processes, together with diminished neuroprotection from micronutrient deficiencies secondary to fluid and dietary absorption issues, may contribute to the injury. PMID:19581831

  15. Mammillary body and fornix injury in congenital central hypoventilation syndrome.

    PubMed

    Kumar, Rajesh; Lee, Kwanoo; Macey, Paul M; Woo, Mary A; Harper, Ronald M

    2009-10-01

    Congenital central hypoventilation syndrome (CCHS) is accompanied by reduced ventilatory sensitivity to CO2 and O2, respiratory drive failure during sleep, impaired autonomic, fluid, and food absorption regulation, and affective and cognitive deficits, including memory deficiencies. The deficits likely derive from neural injury, reflected as structural damage and impaired functional brain responses to ventilatory and autonomic challenges. Brain structures playing essential memory roles, including the hippocampus and anterior thalamus, are damaged in CCHS. Other memory formation circuitry, the fornix and mammillary bodies, have not been evaluated. We collected two high-resolution T1-weighted image series from 14 CCHS and 31 control subjects, using a 3.0-Tesla magnetic resonance imaging scanner. Image series were averaged and reoriented to a standard template; areas containing the mammillary bodies and fornices were over sampled, and body volumes and fornix cross-sectional areas were calculated and compared between groups. Both left and right mammillary body volumes and fornix cross-sectional areas were significantly reduced in CCHS over control subjects, controlling for age, gender, and intracranial volume. Damage to these structures may contribute to memory deficiencies found in CCHS. Hypoxic processes, together with diminished neuroprotection from micronutrient deficiencies secondary to fluid and dietary absorption issues, may contribute to the injury.

  16. Visual impairment in children with congenital Zika syndrome.

    PubMed

    Ventura, Liana O; Ventura, Camila V; Lawrence, Linda; van der Linden, Vanessa; van der Linden, Ana; Gois, Adriana L; Cavalcanti, Milena M; Barros, Eveline A; Dias, Natalia C; Berrocal, Audina M; Miller, Marilyn T

    2017-08-01

    To describe the visual impairment associated with ocular and neurological abnormalities in a cohort of children with congenital Zika syndrome (CZS). This cross-sectional study included infants with microcephaly born in Pernambuco, Brazil, from May to December 2015. Immunoglobulin M antibody capture enzyme-linked immunosorbent assay for the Zika virus on the cerebrospinal fluid samples was positive for all infants. Clinical evaluation consisted of comprehensive ophthalmologic examination including visual acuity, visual function assessment, visual developmental milestone, neurologic examination, and neuroimaging. A total of 32 infants (18 males [56%]) were included. Mean age at examination was 5.7 ± 0.9 months (range, 4-7 months). Visual function and visual developmental milestone could not be tested in 1 child (3%). Visual impairment was detected in 32 infants (100%). Retinal and/or optic nerve findings were observed in 14 patients (44%). There was no statistical difference between the patients with ocular findings and those without (P = 0.180). All patients (100%) demonstrated neurological and neuroimaging abnormalities; 3 (9%) presented with late-onset of microcephaly. Children with CZS demonstrated visual impairment regardless of retina and/or optic nerve abnormalities. This finding suggests that cortical/cerebral visual impairment may be the most common cause of blindness identified in children with CZS. Copyright © 2017 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

  17. Muscle magnetic resonance imaging in congenital myasthenic syndromes

    PubMed Central

    Morrow, Jasper M.; Rodriguez Cruz, Pedro M.; Sinclair, Christopher D.J.; Fischmann, Arne; Thornton, John S.; Knight, Steve; Norbury, Ray; White, Mel; Al‐hajjar, Michal; Carboni, Nicola; Jayawant, Sandeep; Robb, Stephanie A.; Yousry, Tarek A.; Beeson, David; Palace, Jacqueline

    2016-01-01

    ABSTRACT Introduction In this study we investigated muscle magnetic resonance imaging in congenital myasthenic syndromes (CMS). Methods Twenty‐six patients with 9 CMS subtypes and 10 controls were imaged. T1‐weighted (T1w) and short‐tau inversion recovery (STIR) 3‐Tesla MRI images obtained at thigh and calf levels were scored for severity. Results Overall mean the T1w score was increased in GFPT1 and DPAGT1 CMS. T1w scans of the AChR‐deficiency, COLQ, and CHAT subjects were indistinguishable from controls. STIR images from CMS patients did not differ significantly from those of controls. Mean T1w score correlated with age in the CMS cohort. Conclusions MRI appearances ranged from normal to marked abnormality. T1w images seem to be especially abnormal in some CMS caused by mutations of proteins involved in the glycosylation pathway. A non‐selective pattern of fat infiltration or a normal‐appearing scan in the setting of significant clinical weakness should suggest CMS as a potential diagnosis. Muscle MRI could play a role in differentiating CMS subtypes. Muscle Nerve 54: 211–219, 2016 PMID:26789134

  18. Cornelia de Lange syndrome: Congenital heart disease in 149 patients.

    PubMed

    Ayerza Casas, Ariadna; Puisac Uriol, Beatriz; Teresa Rodrigo, María Esperanza; Hernández Marcos, María; Ramos Fuentes, Feliciano J; Pie Juste, Juan

    2017-10-11

    Cornelia de Lange syndrome (CdLS) is produced by mutations in genes that encode regulatory or structural proteins of the cohesin complex. Congenital heart disease (CHD) is not a major criterion of the disease, but it affects many individuals. The objective of this study was to study the incidence and type of CHD in patients with CdLS. Cardiological findings were evaluated in 149 patients with CdLS and their possible relationship with clinical and genetic variables. A percentage of 34.9 had CHD (septal defects 50%, pulmonary stenosis 27%, aortic coarctation 9.6%). The presence of CHD was related with neonatal hospitalisation (P=.04), hearing loss (P=.002), mortality (P=.09) and lower hyperactivity (P=.02), it being more frequent in HDAC8+ patients (60%), followed by NIPBL+ (33%) and SMC1A+ (28.5%). While septal defects predominate in NIPBL+, pulmonary stenosis is more common in HDAC8+. Patients with CdLS have a high incidence of CHD, which varies according to the affected gene, the most frequent findings being septal defects and pulmonary stenosis. Perform a cardiologic study in all these patients is suggested. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  19. Mutations in GMPPB cause congenital myasthenic syndrome and bridge myasthenic disorders with dystroglycanopathies

    PubMed Central

    Belaya, Katsiaryna; Rodríguez Cruz, Pedro M.; Liu, Wei Wei; Maxwell, Susan; McGowan, Simon; Farrugia, Maria E.; Petty, Richard; Walls, Timothy J.; Sedghi, Maryam; Basiri, Keivan; Yue, Wyatt W.; Sarkozy, Anna; Bertoli, Marta; Pitt, Matthew; Kennett, Robin; Schaefer, Andrew; Bushby, Kate; Parton, Matt; Lochmüller, Hanns; Palace, Jacqueline; Muntoni, Francesco

    2015-01-01

    Congenital myasthenic syndromes are inherited disorders that arise from impaired signal transmission at the neuromuscular junction. Mutations in at least 20 genes are known to lead to the onset of these conditions. Four of these, ALG2, ALG14, DPAGT1 and GFPT1, are involved in glycosylation. Here we identify a fifth glycosylation gene, GMPPB, where mutations cause congenital myasthenic syndrome. First, we identified recessive mutations in seven cases from five kinships defined as congenital myasthenic syndrome using decrement of compound muscle action potentials on repetitive nerve stimulation on electromyography. The mutations were present through the length of the GMPPB, and segregation, in silico analysis, exon trapping, cell transfection followed by western blots and immunostaining were used to determine pathogenicity. GMPPB congenital myasthenic syndrome cases show clinical features characteristic of congenital myasthenic syndrome subtypes that are due to defective glycosylation, with variable weakness of proximal limb muscle groups while facial and eye muscles are largely spared. However, patients with GMPPB congenital myasthenic syndrome had more prominent myopathic features that were detectable on muscle biopsies, electromyography, muscle magnetic resonance imaging, and through elevated serum creatine kinase levels. Mutations in GMPPB have recently been reported to lead to the onset of muscular dystrophy dystroglycanopathy. Analysis of four additional GMPPB-associated muscular dystrophy dystroglycanopathy cases by electromyography found that a defective neuromuscular junction component is not always present. Thus, we find mutations in GMPPB can lead to a wide spectrum of clinical features where deficit in neuromuscular transmission is the major component in a subset of cases. Clinical recognition of GMPPB-associated congenital myasthenic syndrome may be complicated by the presence of myopathic features, but correct diagnosis is important because affected

  20. Congenital diaphragmatic hernia in a case of patau syndrome: a rare association.

    PubMed

    A, Jain; P, Kumar; A, Jindal; Yk, Sarin

    2015-01-01

    Congenital diaphragmatic hernia (CDH) occurs in 5-10% associated with chromosomal abnormalities like, Pallister Killian syndrome, Trisomy 18, and certain deletions.. Association of CDH with trisomy 13 (Patau syndromes) is very rare. Here, we report such an unusual association, where surgical repair was done, but eventually the case succumbed as a result of multiple fatal co-morbidities.

  1. Congenital Diaphragmatic Hernia in a Case of Patau Syndrome: A Rare Association

    PubMed Central

    A, Jain; P, Kumar; A, Jindal; Yk, Sarin

    2015-01-01

    Congenital diaphragmatic hernia (CDH) occurs in 5-10% associated with chromosomal abnormalities like, Pallister Killian syndrome, Trisomy 18, and certain deletions.. Association of CDH with trisomy 13 (Patau syndromes) is very rare. Here, we report such an unusual association, where surgical repair was done, but eventually the case succumbed as a result of multiple fatal co-morbidities. PMID:26034714

  2. Congenital Zika Syndrome: Characterizing the Pattern of Anomalies for Pediatric Healthcare Providers

    PubMed Central

    Moore, Cynthia A.; Staples, J. Erin; Dobyns, William B.; Pessoa, André; Ventura, Camila V.; da Fonseca, Eduardo Borges; Ribeiro, Erlane Marques; Ventura, Liana O.; Neto, Norberto Nogueira; Arena, J. Fernando; Rasmussen, Sonja A.

    2017-01-01

    Importance Zika virus infection can be passed prenatally from a pregnant woman to her fetus. There is sufficient evidence to conclude that intrauterine Zika virus infection is a cause of microcephaly and serious brain anomalies, but the full spectrum of anomalies has not been delineated. To inform pediatric healthcare providers who may be called upon to evaluate and manage affected infants and children, we review the most recent evidence to better characterize congenital Zika syndrome. Observations We reviewed published reports of congenital anomalies occurring in fetuses or infants with presumed or laboratory-confirmed intrauterine Zika virus infection. Congenital anomalies were considered in the context of the presumed pathogenetic mechanism related to the neurotropic properties of the virus. We conclude that congenital Zika syndrome is a recognizable pattern of structural anomalies and functional disabilities secondary to central and perhaps peripheral nervous system damage. Although many of the components of this syndrome such as cognitive, sensory and motor disabilities are shared by other congenital infections, there are five features that are rarely seen with other congenital infections or are unique to congenital Zika virus infection: severe microcephaly with partially collapsed skull; thin cerebral cortices with subcortical calcifications; macular scarring and focal pigmentary retinal mottling; congenital contractures; and marked early hypertonia and symptoms of extrapyramidal involvement. Conclusions and Relevance Although the full spectrum of adverse reproductive outcomes caused by Zika virus infection is not yet determined, a distinctive phenotype, the congenital Zika syndrome, has emerged. Recognition of this phenotype by healthcare providers for infants and children can help ensure appropriate etiologic evaluation as well as comprehensive clinical investigation to define the range of anomalies in an affected infant and determine essential follow

  3. Congenital stapes malformation: Rare conductive hearing loss in a patient with Waardenburg syndrome.

    PubMed

    Melzer, Jonathan M; Eliason, Michael; Conley, George S

    2016-04-01

    Waardenburg syndrome is a known autosomal dominant cause of congenital hearing loss. It is characterized by a distinctive phenotypic appearance and often involves sensorineural hearing loss. Temporal bone abnormalities and inner ear dysmorphisms have been described in association with the disease. However, middle ear abnormalities as causes of conductive hearing loss are not typically seen in Waardenburg syndrome. We discuss a case of an 8-year-old female who meets diagnostic criteria for Waardenburg syndrome type 3 and who presented with a bilateral conductive hearing loss associated with congenital stapes fixation. We discuss management strategy in this previously unreported phenotype. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  4. Active surveillance for congenital rubella syndrome in Yangon, Myanmar.

    PubMed Central

    Thant, Kyaw-Zin; Oo, Win-Mar; Myint, Thein-Thein; Shwe, Than-Nu; Han, Aye-Maung; Aye, Khin-Mar; Aye, Kay-Thi; Moe, Kyaw; Thein, Soe; Robertson, Susan E.

    2006-01-01

    OBJECTIVE: Rubella vaccine is not included in the immunization schedule in Myanmar. Although surveillance for outbreaks of measles and rubella is conducted nationwide, there is no routine surveillance for congenital rubella syndrome (CRS). Therefore, we organized a study to assess the burden of CRS. METHODS: From 1 December 2000 to 31 December 2002 active surveillance for CRS was conducted among children aged 0-17 months at 13 hospitals and 2 private clinics in Yangon, the capital city. Children with suspected CRS had a standard examination and a blood sample was obtained. All serum samples were tested for rubella-specific IgM; selected samples were tested for rubella-specific IgG and for rubella RNA by reverse transcriptase-polymerase chain reaction (RT-PCR). FINDINGS: A total of 81 children aged 0-17 months were suspected of having CRS. Of these, 18 children had laboratory-confirmed CRS (7 were IgM positive; 7 were RT-PCR positive; and 10 were IgG positive at > 6 months of age). One additional child who tested positive by RT-PCR and whose mother had had rubella during pregnancy but who had a normal clinical examination was classified as having congenital rubella infection. During 2001-02 no rubella outbreaks were detected in Yangon Division. In the 31 urban townships of Yangon Division, the annual incidence was 0.1 laboratory-confirmed cases of CRS per 1000 live births. CONCLUSION: This is the first population-based study of CRS incidence from a developing country during a rubella-endemic period; the incidence of CRS is similar to endemic rates found in industrialized countries during the pre-vaccine era. Rubella-specific IgG tests proved practical for diagnosing CRS in children aged > 6 months. This is one of the first studies to report on the use of rubella-specific RT-PCR directly on serum samples; further studies are warranted to confirm the utility of this method as an additional means of diagnosing CRS. PMID:16501710

  5. [Congenital hypogonadotropic hypogonadism and Kallmann syndrome in males].

    PubMed

    Ghervan, Cristina; Young, Jacques

    2014-02-01

    Congenital hypogonadotropic hypogonadism (CHH) and Kallmann syndrome (KS) are a group of rare disorders responsible for complete or partial pubertal failure due to lack or insufficient secretion of the pituitary gonadotropins LH and FSH. The underlying neuroendocrine abnormalities are classically divided into two main groups: molecular defects of the gonadotrope cascade leading to isolated normosmic CHH (nCHH), and developmental abnormalities affecting the hypothalamic location of GnRH neurons, but also olfactory bulbs and tracts morphogenesis and responsible for KS. Identification of genetic abnormalities related to CHH/KS has provided major insights into the pathways critical for the development, maturation and function of the gonadotrope axis. In patients affected by nCHH, particularly in familial cases, genetic alterations affecting GnRH secretion (mutations in GNRH1, GPR54/KISS1R and TAC3 and TACR3) or the GnRH sensitivity of gonadotropic cells (GNRHR) have been found. Mutations in KAL1, FGFR1/FGF8/FGF17, PROK2/PROKR2, NELF, CHD7, HS6ST1, WDR11, SEMA3A, SOX10, IL17RD2, DUSP6, SPRY4, and FLRT3 have been associated with KS but sometimes also with its milder hyposmic/normosmic CHH clinical variant. A number of observations, particularly in sporadic cases, suggest that CHH/KS is not always a monogenic mendelian disease as previously thought but rather a digenic or potentially oligogenic condition. Before the age of 18 years, the main differential diagnosis of isolated nCHH is the relatively frequent constitutional delay of growth and puberty (CDGP). However, in male patients with pubertal delay and low gonadotropin levels, the presence of micropenis and/or cryptorchidism argues strongly in favor of CHH and against CDGP. CHH/KS are not always congenital life-long disorders as initially thought, because in nearly 10 % of patients the disease seems not permanent, as evidenced by partial recovery of the pulsatile activity of the hypothalamic-pituitary-gonadal axis

  6. Pulmonary Hypertension in Congenital Heart Disease: Beyond Eisenmenger Syndrome.

    PubMed

    Krieger, Eric V; Leary, Peter J; Opotowsky, Alexander R

    2015-11-01

    Patients with adult congenital heart disease have an increased risk of developing pulmonary hypertension. There are several mechanisms of pulmonary hypertension in patients with adult congenital heart disease, and understanding them requires a systematic approach to define the patient's hemodynamics and physiology. This article reviews the updated classification of pulmonary hypertension in patients with adult congenital heart disease with a focus on pathophysiology, diagnostics, and the evaluation of pulmonary hypertension in special adult congenital heart disease populations. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Congenital marked hypertrichosis and Laband syndrome in a child: overlap between the gingival fibromatosis-hypertrichosis and Laband syndromes.

    PubMed

    Lacombe, D; Bioulac-Sage, P; Sibout, M; Daussac, E; Lesure, F; Manchart, J P; Battin, J

    1994-01-01

    Gingival fibromatosis may be reported as an isolated finding or associated with a number of distinct and frequently inherited group of disorders. The characteristics of the Laband syndrome include gingival hyperplasia, dysplasia of the terminal phalanges and nails of extremities, hepatosplenomegaly and facial dysmorphism. Another well-known syndrome with gingival fibromatosis associates generalized hypertrichosis and inconstant mental retardation and epilepsy. We report a case with features of Laband syndrome and congenital marked hypertrichosis, suggesting overlap between these two genetic disorders.

  8. Management of laryngomalacia in children with congenital syndrome: the role of supraglottoplasty.

    PubMed

    Escher, Anette; Probst, Rudolf; Gysin, Claudine

    2015-04-01

    Supraglottoplasty is the surgical procedure of choice for severe laryngomalacia and has shown to be successful in most cases; however, patients with medical comorbidities present a higher rate of failure. To date, the best management of laryngomalacia in children with congenital syndrome remains unclear. To study the outcome of supraglottoplasty in children with severe laryngomalacia, and to analyze the management and outcome in infants with a congenital syndrome. Retrospective medical records review from January 2003 to October 2012 of all patients who underwent laser supraglottoplasty for severe laryngomalacia at the University Children's Hospital Zurich, Switzerland. Thirty-one patients were included; median age at time of surgery was 3.5 months. Three patients (10%) had a genetically proven congenital syndrome with associated neurologic anomalies. Overall success rate was 87%. Failures were observed in four (13%) of 31 cases; including all three patients presenting a congenital syndrome. Supraglottoplasty is an effective and safe treatment for laryngomalacia in otherwise healthy children. Signs of a possible underlying predominant neurologic origin and discrepancy between the clinical presentation and the endoscopic findings have to be taken into account, as in children with congenital syndrome with neurologic anomalies the risk of failure is higher. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Identification of mutations in the MYO9A gene in patients with congenital myasthenic syndrome

    PubMed Central

    O’Connor, Emily; Töpf, Ana; Müller, Juliane S.; Cox, Daniel; Evangelista, Teresinha; Colomer, Jaume; Abicht, Angela; Senderek, Jan; Hasselmann, Oswald; Yaramis, Ahmet; Laval, Steven H.

    2016-01-01

    Abstract Congenital myasthenic syndromes are a group of rare and genetically heterogenous disorders resulting from defects in the structure and function of the neuromuscular junction. Patients with congenital myasthenic syndrome exhibit fatigable muscle weakness with a variety of accompanying phenotypes depending on the protein affected. A cohort of patients with a clinical diagnosis of congenital myasthenic syndrome that lacked a genetic diagnosis underwent whole exome sequencing in order to identify genetic causation. Missense biallelic mutations in the MYO9A gene, encoding an unconventional myosin, were identified in two unrelated families. Depletion of MYO9A in NSC-34 cells revealed a direct effect of MYO9A on neuronal branching and axon guidance. Morpholino-mediated knockdown of the two MYO9A orthologues in zebrafish, myo9aa/ab, demonstrated a requirement for MYO9A in the formation of the neuromuscular junction during development. The morphants displayed shortened and abnormally branched motor axons, lack of movement within the chorion and abnormal swimming in response to tactile stimulation. We therefore conclude that MYO9A deficiency may affect the presynaptic motor axon, manifesting in congenital myasthenic syndrome. These results highlight the involvement of unconventional myosins in motor axon functionality, as well as the need to look outside traditional neuromuscular junction-specific proteins for further congenital myasthenic syndrome candidate genes. PMID:27259756

  10. [Good's syndrome and congenital toxoplasmosis due to maternal reactivation during pregnancy].

    PubMed

    Tahiri, J; Fouyssac, F; Morel, O; Maatouk, A

    2017-05-01

    Good syndrome is a rare condition in which thymoma is associated with hypogammaglobulinemia. It is characterized by an increased susceptibility to infections. We report a woman with Good's syndrome diagnosed after severe congenital toxoplasmosis in her daughter, even though she was immunized against this infection during pregnancy. This presentation is very unusual by its early diagnosis and to our knowledge is the first report of parasitic infection in this syndrome. Copyright © 2016. Published by Elsevier SAS.

  11. Eisenmenger syndrome and long-term survival in patients with Down syndrome and congenital heart disease.

    PubMed

    Körten, Marc-André; Helm, Paul C; Abdul-Khaliq, Hashim; Baumgartner, Helmut; Kececioglu, Deniz; Schlensak, Christian; Bauer, Ulrike M M; Diller, Gerhard-Paul

    2016-10-01

    To characterise patients with trisomy 21 (Down syndrome, DS) based on the data of the German National Register for Congenital Heart Defects, to identify changes in the availability of surgical therapy over time and to analyse the impact of these changes on developing Eisenmenger syndrome (ES) as well as survival. Out of 1549 patients with DS with congenital heart disease in the National Register for Congenital Heart Defects, 894 patients (55% female, mean age 17.5 years) had a post-tricuspid shunt lesion (atrioventricular septal defect 69.5%, ventricular septal defect 27.7%, patent arterial duct 2.6%) and were included in the current study. The likelihood of being treated interventionally or surgically before the age of 1 year increased significantly over time. In parallel, the likelihood of developing ES decreased over time (53% birth cohort during 1950s/1960s vs 0.5% birth cohort during 2000-2009, p<0.0001). Overall survival after 1, 10, 20 and 40 years was 96.8%, 94.1%, 92.6% and 75.5%, respectively. Patients with ES had a significantly worse survival compared with those without ES (HR 18.1; 95% CI 7.2 to 45.4; p<0.0001). The availability of surgical correction was associated with a decrease in the likelihood of developing ES. Patients with DS still have reduced survival prospects compared with the general population, but this effect is largely driven by patients developing ES who still have a very poor prognosis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  12. [Respiratory infections, Down's syndrome and congenital heart disease: the CIVIC 21 study].

    PubMed

    Medrano López, C; García-Guereta Silva, L; Lirio Casero, J; García Pérez, J

    2009-07-01

    We compare hospitalisation rates for acute respiratory tract infection in children younger than 24 months with significant congenital heart disease without Down's syndrome with those with Down's syndrome with or without congenital heart disease. This was an epidemiological, multicentre (53 Spanish hospitals), observational and prospective study, from October 2006 to April 2007. A total of 1085 patients were followed-up, of which 806 did not have Down's syndrome and 279 with Down's syndrome: 135 with significant, 38 with non significant and 105 without congenital heart disease. A total of 147 patients (13.1%; 95% CI, 11.2-15.2%) required hospitalisation due to respiratory infection. Rates in patients without and with Down's syndrome were 11% vs 19.1%. In the Down's group, 26.3% had no significant, a 23% had significant and 11.4% had no congenital heart disease. The main diagnosis was bronchiolitis (59.4%). An infectious agent was found in 36.2% cases. The specific admission rate due to respiratory syncytial virus was 4.4%, with differences in children without vs with Down's syndrome (3.2% vs 7.8%). In the Down's patients we found rates of 15.8%, 9.3% and 3% in the non-significant, significant and no congenital heart disease. Immunoprophylaxis against respiratory syncytial virus rates were 83.4% vs 39.9% in no Down's versus Down's syndrome patients. No differences were found in hospital stay or the severity. Hospital admission rates due to respiratory infection, and specifically respiratory syncytial virus, were higher in the Down's patients, particularly in the group with no significant congenital heart disease and low immunoprophylaxis against respiratory syncytial virus.

  13. Sleep findings in Brazilian children with congenital Zika syndrome.

    PubMed

    Pinato, Luciana; Ribeiro, Erlane M; Leite, Rebeka F P; Lopes, Thayse F; Pessoa, André L S; Guissoni Campos, Leila M; Piffer, Giovanna E; Souza, Ana L D M; Giacheti, Célia M

    2018-03-01

    Zika virus infection during pregnancy may result in congenital Zika syndrome (CZS), whose characteristics are being described. The present study aimed to investigate the sleep characteristics of 136 infants/toddlers (88 with CZS and 48 with typical development (TD), age and gender matched, 60% girls and 40% boys in both groups) using the Brief Infant Sleep Questionnaire. The ages of children in both groups ranged from 5 to 24 months (CZS 15.9 ± 0.4 vs. TD 15.8 ± 1.0 months, P= 0.90). The results show that 34.1% of CZS and 2% of TD children were defined as poor sleepers, 15% of CZS and 2% of TD children remained awake at night for a period longer than 1 hour, and 24% of CZS and 2% of TD children slept less than 9 hours. The CZS group showed shorter total sleep time (CZS 11.24 ± 2.6 vs. TD 12.02 ± 1.9 hours, P= 0.03) and shorter nocturnal sleep duration than the TD group (CZS 8.2 ± 0.2 vs. TD 9.4 ± 0.2 hours, P= 0.0002). In contrast to the control group (P= 0.02, r= -0.34), in the CZS group, no correlation was found between age and nocturnal wakefulness. Future studies should explore these data in relation to the development and maturation of the central nervous system of these children. Considering the well-known consequences of poor sleep quality on health in several populations, the presence of sleep disorders should be considered in CZS using multidisciplinary treatments.

  14. Visual impairment evaluation in 119 children with congenital Zika syndrome.

    PubMed

    Ventura, Liana O; Ventura, Camila V; Dias, Natália de C; Vilar, Isabelle G; Gois, Adriana L; Arantes, Tiago E; Fernandes, Luciene C; Chiang, Michael F; Miller, Marilyn T; Lawrence, Linda

    2018-04-11

    To assess visual impairment in a large sample of infants with congenital Zika syndrome (CZS) and to compare with a control group using the same assessment protocol. The study group was composed of infants with confirmed diagnosis of CZS. Controls were healthy infants matched for age, sex, and socioeconomic status. All infants underwent comprehensive ophthalmologic evaluation including visual acuity, visual function assessment, and visual developmental milestones. The CZS group included 119 infants; the control group, 85 infants. At examination, the mean age of the CZS group was 8.5 ± 1.2 months (range, 6-13 months); of the controls, 8.4 ± 1.8 months (range, 5-12 months; P = 0.598). Binocular Teller Acuity Card (TAC) testing was abnormal in 107 CZS infants and in 4 controls (89.9% vs 5% [P < 0.001]). In the study group, abnormal monocular TAC results were more frequent in eyes with funduscopic alterations (P = 0.008); however, 104 of 123 structurally normal eyes (84.6%) also presented abnormal TAC results. Binocular contrast sensitivity was reduced in 87 of 107 CZS infants and in 8 of 80 controls (81.3% vs 10% [P < 0.001]). The visual development milestones were less achieved by infants with CZS compared to controls (P < 0.001). Infants with CZS present with severe visual impairment. A protocol for assessment of the ocular findings, visual acuity, and visual developmental milestones tested against age-matched controls is suggested. Copyright © 2018. Published by Elsevier Inc.

  15. CENTRAL AUTONOMIC REGULATION IN CONGENITAL CENTRAL HYPOVENTILATION SYNDROME

    PubMed Central

    Ogren, Jennifer A.; Macey, Paul M.; Kumar, Rajesh; Woo, Mary A.; Harper, Ronald M.

    2010-01-01

    Congenital central hypoventilation syndrome (CCHS) patients show significant autonomic dysfunction in addition to the well-described loss of breathing drive during sleep. Some characteristics, e.g., syncope, may stem from delayed sympathetic outflow to the vasculature; other symptoms, including profuse sweating, may derive from overall enhanced sympathetic output. The dysregulation suggests significant alterations to autonomic regulatory brain areas. Murine models of the genetic mutations present in the human CCHS condition indicate brainstem autonomic nuclei are targeted; however, the broad range of symptoms suggests more widespread alterations. We used functional magnetic resonance imaging (fMRI) to assess neural response patterns to the Valsalva maneuver, an autonomic challenge eliciting a sequence of sympathetic and parasympathetic actions, in nine CCHS and 25 control subjects. CCHS patients showed diminished and time-lagged heart rate responses to the Valsalva maneuver, and muted fMRI signal responses across multiple brain areas. During the positive pressure phase of the Valsalva maneuver, CCHS responses were muted, but were less so in recovery phases. In rostral structures, including the amygdala and hippocampus, the normal declining patterns were replaced by increasing trends or more modest declines. Earlier onset responses appeared in the hypothalamus, midbrain, raphé pallidus, and left rostral ventrolateral medulla. Phase-lagged responses appeared in cerebellar pyramis and anterior cingulate cortex. The time-distorted and muted central responses to autonomic challenges likely underlie the exaggerated sympathetic action and autonomic dyscontrol in CCHS, impairing cerebral autoregulation, possibly exacerbating neural injury, and enhancing the potential for cardiac arrhythmia. PMID:20211704

  16. Congenital central hypoventilation syndrome (CCHS): Circadian temperature variation.

    PubMed

    Saiyed, Rehan; Rand, Casey M; Carroll, Michael S; Koliboski, Cynthia M; Stewart, Tracey M; Brogadir, Cindy D; Kenny, Anna S; Petersen, Emily K E; Carley, David W; Weese-Mayer, Debra E

    2016-03-01

    Congenital central hypoventilation syndrome (CCHS) is a rare neurocristopathy, which includes a control of breathing deficit and features of autonomic nervous system (ANS) dysregulation. In recognition of the fundamental role of the ANS in temperature regulation and rhythm and the lack of any prior characterization of circadian temperature rhythms in CCHS, we sought to explore peripheral and core temperatures and circadian patterning. We hypothesized that CCHS patients would exhibit lower peripheral skin temperatures (PST), variability, and circadian rhythmicity (vs. controls), as well as a disrupted relationship between core body temperature (CBT) and PST. PST was sampled every 3 min over four 24-hr periods in CCHS cases and similarly aged controls. CBT was sampled in a subset of these recordings. PST was recorded from 25 CCHS cases (110,664 measures/230 days) and 39 controls (78,772 measures/164 days). Simultaneous CBT measurements were made from 23 CCHS patients. In CCHS, mean PST was lower overall (P = 0.03) and at night (P = 0.02), and PST variability (interquartile range) was higher at night (P = 0.05) (vs. controls). PST circadian rhythm remained intact but the phase relationship of PST to CBT rhythm was extremely variable in CCHS. PST alterations in CCHS likely reflect altered autonomic control of peripheral vascular tone. These alterations represent a previously unreported manifestation of CCHS and may provide an opportunity for therapeutic intervention. The relationship between temperature dysregulation and CCHS may also offer insight into basic mechanisms underlying thermoregulation. © 2015 Wiley Periodicals, Inc.

  17. Congenital mydriasis and prune belly syndrome in a child with an ACTA2 mutation.

    PubMed

    Brodsky, Michael C; Turan, Kadriye Erkan; Khanna, Cheryl L; Patton, Alice; Kirmani, Salman

    2014-08-01

    We report the association of congenital mydriasis with prune belly syndrome and cerebrovascular anomalies in a 9-year-old boy who was found to have an ACTA2 mutation. This case illustrates the spectrum of systemic malformations that are attributable to mutations in ACTA2 and expands the spectrum of cerebrovascular anomalies that are now known to accompany congenital mydriasis. Copyright © 2014 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

  18. Phenotype-genotype discordance in congenital malformations with communication disorders resembling trisomy 18 (Edwards syndrome).

    PubMed

    Pruszewicz, Antoni; Wiskirska-Woźnica, Bożena; Wojnowski, Waldemar; Czerniejewska, Hanna; Jackowska, Joanna; Jarmuż, Małgorzata; Szyfter, Krzysztof; Leszczyńska, Małgorzata

    2014-01-01

    Female, 6 FINAL DIAGNOSIS: Phenotype-genotype discordance in congenital malformations with communication disorders resembling trisomy 18 (Edwards syndrome) Symptoms: - - Clinical Procedure: - Specialty: Otolaryngology. Congenital defects. Communication process disorders are very frequent in rare cases of chromosomal aberrations (deletions, insertions, and trisomies) such as Down syndrome (trisomy 21), Turner syndrome, Edwards syndrome (trisomy 18), or Patau syndrome (trisomy 13). Sometimes phenotype may delusively correspond to the characteristic features of a given syndrome, but genotype tests do not confirm its presence. We present the case of a 6-year-old girl admitted to the Clinic of Phoniatrics and Audiology for the assessment of communication in the course of congenital malformations with phenotype characteristic for trisomy 18 (Edwards syndrome). Immediately upon birth, dysmorphic changes suggesting trisomy 18 (Edwards syndrome) were observed, but trisomy 18 was excluded after karyotype test results were normal (46, XX). DISTURBED ARTICULATION WAS DIAGNOSED: deformed linguo-dental and palatal sounds, interdental realization with flat tongue of the /s/, /z/, /c/, /dz/, /ś/, /ź/, /ć/, /dz/ sounds (sigmatismus interdentalis). Hearing loss was confirmed.

  19. Phenotype-genotype discordance in congenital malformations with communication disorders resembling trisomy 18 (Edwards syndrome)

    PubMed Central

    Pruszewicz, Antoni; Wiskirska-Woźnica, Bożena; Wojnowski, Waldemar; Czerniejewska, Hanna; Jackowska, Joanna; Jarmuż, Małgorzata; Szyfter, Krzysztof; Leszczyńska, Małgorzata

    2014-01-01

    Patient: Female, 6 Final Diagnosis: Phenotype-genotype discordance in congenital malformations with communication disorders resembling trisomy 18 (Edwards syndrome) Symptoms: — Medication: — Clinical Procedure: — Specialty: Otolaryngology Objective: Congenital defects Background: Communication process disorders are very frequent in rare cases of chromosomal aberrations (deletions, insertions, and trisomies) such as Down syndrome (trisomy 21), Turner syndrome, Edwards syndrome (trisomy 18), or Patau syndrome (trisomy 13). Sometimes phenotype may delusively correspond to the characteristic features of a given syndrome, but genotype tests do not confirm its presence. Case Report: We present the case of a 6-year-old girl admitted to the Clinic of Phoniatrics and Audiology for the assessment of communication in the course of congenital malformations with phenotype characteristic for trisomy 18 (Edwards syndrome). Immediately upon birth, dysmorphic changes suggesting trisomy 18 (Edwards syndrome) were observed, but trisomy 18 was excluded after karyotype test results were normal (46, XX). Conclusions: Disturbed articulation was diagnosed: deformed linguo-dental and palatal sounds, interdental realization with flat tongue of the /s/, /z/, /c/, /dz/, /ś/, /ź/, /ć/, /dz/ sounds (sigmatismus interdentalis). Hearing loss was confirmed. PMID:24478819

  20. Dynamics in prevalence of Down syndrome in children with congenital heart disease.

    PubMed

    Pfitzer, Constanze; Helm, Paul C; Rosenthal, Lisa-Maria; Berger, Felix; Bauer, Ulrike M M; Schmitt, Katharina Rl

    2018-01-01

    We assessed the dynamics in the prevalence of children with congenital heart disease (CHD) and Down syndrome in Germany with regard to phenotype, severity, and gender. Data from patients with CHD and Down syndrome born between 1980 and 2014 were analyzed, who are registered with the German National Register for Congenital Heart Defects. One thousand six hundred eighteen CHD patients with Down syndrome were identified. The prevalence of children born with both Down syndrome and CHD was constant from 2005 to 2009 but increased from 2010 to 2014. Regarding CHD groups, complex and simple lesions have become more equal since 2005. The number of simple lesions with shunt has a peak prevalence in the period of 2010-2014. Atrioventricular septal defect was the most common CHD phenotype, but temporal changes were found within the group of CHD phenotypes over the observation period. Our findings suggest a growing number of CHD and Down syndrome, which may be the result of improved medical management and progress in educational, social, and financial support. This development is noteworthy as it adds new aspects to present discussions in the media and political settings. What is known: • Congenital heart disease is regarded to be the most important clinical phenomenon in children with Down syndrome, due to its significant impact on morbidity and mortality. • New developments in prenatal diagnostic and therapy management of congenital heart disease continue to influence the number of patients diagnosed with congenital heart disease and Down syndrome. What is New: • This study provides essential data giving the first overview of the dynamics in the prevalence of congenital heart disease and Down syndrome over an extended length of time up to 2015 in a large patient cohort, taking recent developments into account. • Our data suggest a growing prevalence of congenital heart disease and Down syndrome, which may be the result of improved medical management for Down syndrome

  1. Infantile spasms: an early epileptic manifestation in some patients with the congenital bilateral perisylvian syndrome.

    PubMed

    Kuzniecky, R; Andermann, F; Guerrini, R

    1994-10-01

    We report four patients with infantile spasms and the congenital bilateral perisylvian syndrome. Onset of spasms occurred during the first 6 months of life. Response to corticotropin treatment was prompt and resulted in resolution of seizures in all patients. Epilepsy developed in the four children after an interval of 2 to 12 years. Developmental outcome was variable; three were severely restricted and one was married and lived independently. Imaging studies revealed bilateral perisylvian lesions characteristic of polymicrogyria. Infantile spasms may be the presenting seizure type in some patients with the congenital bilateral perisylvian syndrome.

  2. Parenting Styles and the Depressive Syndrome in Congenitally Blind Individuals.

    ERIC Educational Resources Information Center

    Lambert, Robert; West, Malcolm

    1980-01-01

    The article discusses the effect on congenitally blind children of three types of parents: those who are overprotective, those who push the child toward independence too soon, and those who are "good enough." (Author)

  3. Change in prevalence of congenital defects in children with Prader-Willi syndrome.

    PubMed

    Torrado, M; Foncuberta, M E; Perez, M F de Castro; Gravina, L P; Araoz, H V; Baialardo, E; Chertkoff, L P

    2013-02-01

    The aim of this study was to assess the prevalence of congenital defects observed in patients with Prader-Willi syndrome (PWS) and to compare this prevalence with that described in the general population. In addition, these findings were correlated with the different etiologic subtypes. A total of 180 children with PWS followed for 13 years were included in this study. Diagnosis was confirmed by the methylation test, and genetic subtypes were established by using fluorescence in situ hybridization or multiplex ligation-dependent probe amplification and microsatellite analyses. The prevalence of congenital defects was compared with national and international registries of congenital defects in the general population (Estudio Colaborativo Latinoamericano de Malformaciones Congénitas, European Surveillance of Congenital Anomalies, and the New York Registry). Twenty-two percent of the patients presented congenital defects with a risk of 5.4 to 18.7 times higher than that of the general population. The most frequent congenital defects were heart defects, renoureteral malformations, vertebral anomalies, hip dysplasia, clubfoot, and agenesis/hypoplasia of the corpus callosum. Each of these congenital defects was significantly more frequent in the children with PWS than in the general population. The congenital heart defects were more frequent in girls than in boys with PWS. No significant differences were found when the defects were correlated with the different etiologic subtypes. An increased prevalence of congenital defects was found in our PWS patients. This finding suggests the need for further studies in PWS children that allow physicians to detect the congenital defects found in this series and, thus, to anticipate complications, with the ultimate aim of enhancing the management of PWS patients.

  4. Multiple verruciform xanthomas in the setting of congenital hemidysplasia with ichthyosiform erythroderma and limb defects syndrome.

    PubMed

    Xu, Xiu-Lian; Huang, Li-Ming; Wang, Qiang; Sun, Jian-Fang

    2015-01-01

    Congenital hemidysplasia with ichthyosiform erythroderma and limb defects (CHILD) syndrome is a rare X-linked dominant disease characterized by peculiar cutaneous presentations and skeletal abnormalities. Verruciform xanthoma (VX)-like histologic changes occasionally occur in CHILD syndrome, but typical VX-like lesions coexisting with CHILD syndrome are rare. In this study we report a rare case of multiple, coexisting VXs on the vulva and left lower limb of an 11-year-old Chinese girl who also exhibited the typical clinical presentations and limb defects of CHILD syndrome. Histologic and immunohistochemical analyses showed that the lesions were typical VXs. © 2013 Wiley Periodicals, Inc.

  5. Pulmonary Hypertension in a Patient With Congenital Heart Defects and Heterotaxy Syndrome.

    PubMed

    Yousuf, Tariq; Kramer, Jason; Jones, Brody; Keshmiri, Hesam; Dia, Muhyaldeen

    2016-01-01

    Heterotaxy syndrome, also called isomerism, is a condition in which abdominal and thoracic organs are located in abnormal body positions. Pulmonary hypertension (PHTN) is an uncommon clinical feature of heterotaxy syndrome. We describe the case of a 26-year-old male who developed PHTN as a rare manifestation of heterotaxy syndrome. To our knowledge, PHTN has never been reported as a prominent clinical feature in a patient with heterotaxy syndome and congenital cardiac abnormalities. It is important for the clinician to be aware of potentially serious consequences of PHTN in the setting of heterotaxy syndrome.

  6. Multiple congenital anomalies/mental retardation syndrome with multiple circumferential skin creases: a new syndrome?

    PubMed

    Tinsa, Faten; Aissa, Khaoula; Meddeb, Mounira; Bousnina, Dorra; Boussetta, Khadija; Bousnina, Souad

    2009-02-01

    We describe a combination of multiple congenital anomalies, a severe psychomotor retardation and seizures in a 9-year-old Tunisian boy with circumferential ringed skin creases. He had symmetrical circumferential skin creases on arms, legs, and penis. Craniofacial anomalies included: an elongated face, tight forehead, hypertelorism, bilateral epicanthic folds, upslanting palpebral fissures, microphthalmia, convergent strabismus, wide nasal bridge, aberrant teeth, dental caries, and low-set posteriorly rotated ears with overfolded thick helices. He had also ureterocele, hypospadias, and others anomalies. The magnetic resonance imaging of the brain showed hypoplastic vermis, hypoplastic corpus callosum, and dilatation of ventricles. Chromosomal analysis revealed a normal male karyotype with 46,XY. Skin biopsy was normal. To the best of our knowledge, this combination of anomalies has not been reported and this case may be a unique syndrome.

  7. Congenital glaucoma as an ophthalmic manifestation of Frank-Ter Haar syndrome.

    PubMed

    Aktas, Zeynep; Karaca, Emine Esra; Dogan, Nurcan; Çakmak, Tugba; Unlu, Metin; Tok, Levent; Hasanreisoglu, Murat

    2014-04-01

    We report on a patient with Frank-Ter Haar syndrome that is associated with high intraocular pressures. A 21-day-old male patient was referred to our clinic for surgical treatment of congenital glaucoma. On ophthalmic examination, he had buphthalmos, mild corneal edema and high IOP readings in both eyes. The patient underwent uneventful trabeculotomy surgery, bilaterally. Marked bilateral anterior iris insertion was noted during the surgery. Childhood glaucoma may be associated with Frank-Ter Haar syndrome.

  8. Effect of Congenital Heart Defects on Language Development in Toddlers with Down Syndrome

    ERIC Educational Resources Information Center

    Visootsak, J.; Hess, B.; Bakeman, R.; Adamson, L. B.

    2013-01-01

    Background: Down syndrome (DS, OMIM #190685) is the most commonly identified genetic form of intellectual disability with congenital heart defect (CHD) occurring in 50% of cases. With advances in surgical techniques and an increasing lifespan, this has necessitated a greater understanding of the neurodevelopmental consequences of CHDs. Herein, we…

  9. Parkes-Weber syndrome associated with a congenital short femur of the affected limb.

    PubMed

    Fernandez-Pineda, I; Lopez-Gutierrez, J C

    2009-03-01

    The association of capillary malformation, high-flow arteriovenous fistulas, and limb hypertrophy corresponds to Parkes-Weber syndrome. Most of cases are sporadic, although a first familial case has been recently reported. We report the first observation of a Parkes-Weber vascular anomaly with an underlying congenital short femur.

  10. Congenital hypertrichosis, cardiomegaly, and osteochondrodysplasia (Cantú syndrome): a new case with unusual radiological findings.

    PubMed

    Concolino, D; Formicola, S; Camera, G; Strisciuglio, P

    2000-05-29

    We report on a new case of a syndrome first described by Cantú et al. [1982: Hum Genet 60:36-41] comprising congenital hypertrichosis, "coarse" facial appearance, and mild osteochondrodysplasia. Our case has some unusual radiological findings, namely proximal and distal megaepiphyses of long bones and advanced bone age.

  11. Thyroxine-Based Screening for Congenital Hypothyroidism in Neonates with Down Syndrome.

    PubMed

    Erlichman, Ira; Mimouni, Francis B; Erlichman, Matityahu; Schimmel, Michael S

    2016-06-01

    To ascertain whether thyroxine (T4)-based screening programs for congenital hypothyroidism (initial measurement of total T4 [tT4] followed by thyroid stimulating hormone [TSH] measurement in patients with tT4 <10th percentile) identifies congenital hypothyroidism in all neonates with Down syndrome. Retrospective cohort study of 159 neonates with Down syndrome, born during the period 1998-2007 were included. Screening test results were compared with those of the general population. All primary care physicians of these infants were contacted and infants' thyroid status verified. tT4 concentrations in children with Down syndrome were significantly lower, and TSH higher than those in the general population; tT4 concentrations did not correlate with screening TSH concentrations. Twenty children with Down syndrome were treated with L-thyroxin within the first month of life although only 10 babies had been identified by the routine screening test. T4-based screening does not identify many cases of congenital hypothyroidism in neonates with Down syndrome. We recommend that neonates with Down syndrome be screened by simultaneous measurements of both tT4 and TSH. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Current Surgical Outcomes of Congenital Heart Surgery for Patients With Down Syndrome in Japan.

    PubMed

    Hoashi, Takaya; Hirahara, Norimichi; Murakami, Arata; Hirata, Yasutaka; Ichikawa, Hajime; Kobayashi, Junjiro; Takamoto, Shinichi

    2018-01-25

    Current surgical outcomes of congenital heart surgery for patients with Down syndrome are unclear.Methods and Results:Of 29,087 operations between 2008 and 2012 registered in the Japan Congenital Cardiovascular Surgery Database (JCCVSD), 2,651 were carried out for patients with Down syndrome (9%). Of those, 5 major biventricular repair procedures [ventricular septal defect repair (n=752), atrioventricular septal defect repair (n=452), patent ductus arteriosus closure (n=184), atrial septal defect repair (n=167), tetralogy of Fallot (TOF) repair (n=108)], as well as 2 major single ventricular palliations [bidirectional Glenn (n=21) and Fontan operation (n=25)] were selected and their outcomes were compared. The 90-day and in-hospital mortality rates for all 5 major biventricular repair procedures and bidirectional Glenn were similarly low in patients with Down syndrome compared with patients without Down syndrome. On the other hand, mortality after Fontan operation in patients with Down syndrome was significantly higher than in patients without Down syndrome (42/1,558=2.7% vs. 3/25=12.0%, P=0.005). Although intensive management of pulmonary hypertension is essential, analysis of the JCCVSD revealed favorable early prognostic outcomes after 5 major biventricular procedures and bidirectional Glenn in patients with Down syndrome. Indication of the Fontan operation for patients with Down syndrome should be carefully decided.

  13. Life and Death of a Child with Down Syndrome and a Congenital Heart Condition: Experiences of Six Couples

    ERIC Educational Resources Information Center

    Reilly, Deirdre; Huws, Jaci; Hastings, Richard; Vaughan, Frances

    2010-01-01

    Individuals with Down syndrome are at increased risk of congenital heart conditions (CHCs), and mortality is higher in people with Down syndrome and a CHC than those without (J. C. Vis et al., 2009). As a consequence, parents of children with Down syndrome and a CHC are more likely to outlive their child. In this research, semistructured…

  14. Dominant ER Stress-Inducing WFS1 Mutations Underlie a Genetic Syndrome of Neonatal/Infancy-Onset Diabetes, Congenital Sensorineural Deafness, and Congenital Cataracts.

    PubMed

    De Franco, Elisa; Flanagan, Sarah E; Yagi, Takuya; Abreu, Damien; Mahadevan, Jana; Johnson, Matthew B; Jones, Garan; Acosta, Fernanda; Mulaudzi, Mphele; Lek, Ngee; Oh, Vera; Petz, Oliver; Caswell, Richard; Ellard, Sian; Urano, Fumihiko; Hattersley, Andrew T

    2017-07-01

    Neonatal diabetes is frequently part of a complex syndrome with extrapancreatic features: 18 genes causing syndromic neonatal diabetes have been identified to date. There are still patients with neonatal diabetes who have novel genetic syndromes. We performed exome sequencing in a patient and his unrelated, unaffected parents to identify the genetic etiology of a syndrome characterized by neonatal diabetes, sensorineural deafness, and congenital cataracts. Further testing was performed in 311 patients with diabetes diagnosed before 1 year of age in whom all known genetic causes had been excluded. We identified 5 patients, including the initial case, with three heterozygous missense mutations in WFS1 (4/5 confirmed de novo). They had diabetes diagnosed before 12 months (2 before 6 months) (5/5), sensorineural deafness diagnosed soon after birth (5/5), congenital cataracts (4/5), and hypotonia (4/5). In vitro studies showed that these WFS1 mutations are functionally different from the known recessive Wolfram syndrome-causing mutations, as they tend to aggregate and induce robust endoplasmic reticulum stress. Our results establish specific dominant WFS1 mutations as a cause of a novel syndrome including neonatal/infancy-onset diabetes, congenital cataracts, and sensorineural deafness. This syndrome has a discrete pathophysiology and differs genetically and clinically from recessive Wolfram syndrome. © 2017 by the American Diabetes Association.

  15. [Change in our approach in the surgical management of congenital heart defects in patients with Down syndrome, 1974-2016].

    PubMed

    Hartyánszky, István; Bogáts, Gábor

    2016-10-01

    Congenital heart defects are frequently present in patients with Down syndrome. The authors analyzed the impact of changing approach in surgical management of congenital heart defect on the life expectancy of patients with Down syndrome. Between 1974 and 1997 the data of 359 children with Down syndrome were collected. Among them 255 patients had no surgery and the mortality in this group was 25.9%, whereas the mortality in the group of 104 patients who underwent palliative surgery was 8.6%. Surgical management of congenital heart defects provides the same life expectancy for these patients as compared to Down patients without cardiac defects. Primary reconstruction is the preferable surgical procedure in infancy that provides good results. Nowadays the number of the operated grown-up congenital heart disease patients with Down syndrome is increasing. During the last three years 82 grown-up congenital heart disease patients, including 4 patients with Down syndrome (aged between 24 and 60 years) were reconstructed successfully. Due to the successful surgery in infancy the population of grown-up congenital heart disease patients with Down syndrome is increasing. The cardiac surgeons are ready to do everything for the optimal life expectancy of these patients. However, management of special problems (indication and necessity of reoperation, optimal age) in patients with Down syndrome poses a great challenge for cardiologists and cardiac surgeons. Orv. Hetil., 2016, 157(40), 1601-1603.

  16. Congenital rubella syndrome surveillance as a platform for surveillance of other congenital infections, Peru, 2004-2007.

    PubMed

    Whittembury, Alvaro; Galdos, Jorge; Lugo, María; Suárez-Ognio, Luis; Ortiz, Ana; Cabezudo, Edwin; Martínez, Mario; Castillo-Solórzano, Carlos; Andrus, Jon Kim

    2011-09-01

    Rubella during pregnancy can cause serious fetal abnormalities and death. Peru has had integrated measles/rubella surveillance since 2000 but did not implement congenital rubella syndrome (CRS) surveillance until 2004, in accordance with the Pan American Health Organization recommendations for rubella elimination. The article describes the experience from the CRS sentinel surveillance system in Peru. Peru has maintained a national sentinel surveillance system for reporting confirmed and suspected CRS cases since 2004. A surveillance protocol was implemented with standardized case definitions and instruments in the selected sentinel sites. Each sentinel site completes their case investigations and report forms and sends the reports to the Health Region Epidemiology Department, which forwards the data to the national Epidemiology Department. CRS surveillance data were analyzed for the period 2004-2007. During the period 2004-2007, 16 health facilities, which are located in 9 of the 33 health regions, representing the 3 main geographical areas (coast, mountain, and jungle), were included as sentinel sites for the CRS surveillance. A total of 2061 suspected CRS cases were reported to the system. Of these, 11 were classified as CRS and 23 as congenital rubella infection. Factors significantly associated with rubella vertical transmission were: (1) in the mother, maternal history of rash during pregnancy (odds ratio [OR], 12.0; 95% confidence interval [CI], 3.8-37.8); (2) and in the infant, pigmentary retinopathy (OR, 18.4; 95% CI, 3.2-104.6), purpura (OR, 14.7; 95% CI, 2.8-78.3), and developmental delay (OR, 4.4; 95% CI, 1.75-11.1). The surveillance system has been able to identify rubella vertical transmission, reinforcing the evidence that rubella was a public health problem in Peru. This system may serve as a platform to implement surveillance for other congenital infections in Peru.

  17. Pseudo-Bartter syndrome in an infant with congenital chloride diarrhoea.

    PubMed

    Igrutinović, Zoran; Peco-Antić, Amira; Radlović, Nedeljko; Vuletić, Biljana; Marković, Slavica; Vujić, Ana; Rasković, Zorica

    2011-01-01

    Pseudo-Bartter syndrome encompasses a heterogenous group of disorders similar to Bartter syndrome. We are presenting an infant with pseudo-Bartter syndrome caused by congenital chloride diarrhoea. A male newborn born in the 37th gestational week (GW) to young healthy and non-consanguineous parents. In the 35th GW a polyhydramnios with bowel dilatation was verified by ultrasonography. After birth he manifested several episodes of hyponatremic dehydration with hypochloraemia, hypokalaemia and metabolic alkalosis, so as Bartter syndrome was suspected treatment with indomethacin, spironolactone and additional intake of NaCl was initiated. However, this therapy gave no results, so that at age six months he was rehospitalized under the features of persistent watery diarrhoea, vomiting, dehydration and acute renal failure (serum creatinine 123 micromol/L). The laboratory results showed hyponatraemia (123 mmol/L), hypokalaemia (3.1 mmol/L), severe hypochloraemia (43 mmol/L), alcalosis (blood pH 7.64, bicarbonate 50.6 mmol/L), high plasma renin (20.6 ng/ml) and aldosterone (232.9 ng/ml), but a low urinary chloride concentration (2.1 mmol/L). Based on these findings, as well as the stool chloride concentration of 110 mmol/L, the patient was diagnosed congenital chloride diarrhoea. In further course, the patient was treated by intensive fluid, sodium and potassium supplementation which resulted in the normalization of serum electrolytes, renal function, as well as his mental and physical development during 10 months of follow-up. Persistent watery diarrhoea with a high concentration of chloride in stool is the key finding in the differentiation of congenital chloride diarrhoea from Bartter syndrome. The treatment of congenital chloride diarrhoea consists primarily of adequate water and electrolytes replacement.

  18. Clinical presentation and management of congenital ptosis

    PubMed Central

    Marenco, Marco; Macchi, Ilaria; Macchi, Iacopo; Galassi, Emilio; Massaro-Giordano, Mina; Lambiase, Alessandro

    2017-01-01

    Congenital ptosis is a rare condition characterized by lower positioning of the upper eyelid that is present at birth and is a clinical condition that is persistent if not treated. It may be unilateral or bilateral and may be associated with other ocular disorders or systemic conditions, including Marcus Gunn, Horner, and Duane syndromes. It is a benign condition but causes functional, cosmetic, and psychological problems in children. However, not all patients need to undergo surgery, and usually only patients at risk of amblyopia need a prompt surgical correction, while in other cases, surgery can be postponed. The grade of ptosis, the eyelid function, and the amblyopic risk are the parameters that affect the ophthalmologist’s decision on timing of surgery and the surgical technique to be used. In fact, there are several types of surgical techniques to correct a congenital ptosis, although very often more than one is needed to obtain an acceptable result. This paper reviews the causes of congenital ptosis and associated diseases. Particular emphasis is given to surgical management and different procedures available to correct the upper eyelid anomaly and avoid permanent damage to visual function. PMID:28280295

  19. Distal 4p microdeletion in a case of Wolf-Hirschhorn syndrome with congenital diaphragmatic hernia.

    PubMed

    Casaccia, Germana; Mobili, Luisa; Braguglia, Annabella; Santoro, Francesco; Bagolan, Pietro

    2006-03-01

    Wolf-Hirschhorn syndrome (WHS) is a well-known genetic condition characterized by typical facial anomalies, midline defects, skeletal anomalies, prenatal and postnatal growth retardation, hypotonia, mental retardation, and seizures. Affected patients with a microdeletion on distal 4p present a milder phenotype that lacks congenital malformations. WHS is rarely associated with congenital diaphragmatic hernia (CDH), and only 8 cases are reported in the literature. In almost all cases of CDH and WHS a large deletion of the short arm of chromosome 4 is present. A microdeletion of 2.6 Mb on distal 4p associated with CDH and multiple congenital malformations (i.e., cleft palate) is reported for the first time. Such a microdeletion should prompt a molecular study for WHS when in a fetus/newborn with CDH the association with cleft lip/palate and typical facial appearance (flat facial profile, hypertelorism) is found. Copyright 2006 Wiley-Liss, Inc.

  20. Niikawa-Kuroki (Kabuki) syndrome with congenital sensorineural deafness: evidence for a wide spectrum of inner ear abnormalities.

    PubMed

    Tekin, Mustafa; Fitoz, Suat; Arici, Serap; Cetinkaya, Ergun; Incesulu, Armagan

    2006-05-01

    Hearing loss, mainly due to recurrent otitis media, has been reported in approximately 40% of individuals with Niikawa-Kuroki (Kabuki) syndrome (NKS). Sensorineural hearing loss leading to congenital or prelingual deafness has been described rarely. We have identified two unrelated individuals with Niikawa-Kuroki syndrome among 535 probands who have severe to profound sensorineural deafness. Bilateral absence of the cochlea with dilated dysplastic vestibule and unilateral enlarged vestibule were demonstrated in these two individuals. In conclusion, Niikawa-Kuroki syndrome should be kept in mind when evaluating an individual with congenital deafness and a wide spectrum of inner ear abnormalities occurs in this syndrome.

  1. Two Infants with Presumed Congenital Zika Syndrome, Brownsville, Texas, USA, 2016-2017.

    PubMed

    Howard, Ashley; Visintine, John; Fergie, Jaime; Deleon, Miguel

    2018-04-01

    Since 2007, Zika virus has spread through the Pacific Islands and the Americas. Beginning in 2016, women in Brownsville, Texas, USA, were identified as possibly being exposed to Zika virus during pregnancy. We identified 18 pregnant women during 2016-2017 who had supportive serologic or molecular test results indicating Zika virus or flavivirus infection. Two infants were evaluated for congenital Zika syndrome after identification of prenatal microcephaly. Despite standard of care testing of mothers and neonates, comparative results were unreliable for mothers and infants, which highlights the need for clinical and epidemiologic evidence for an accurate diagnosis. A high index of suspicion for congenital Zika syndrome for at-risk populations is useful because of current limitations of testing.

  2. Mutations in DPAGT1 Cause a Limb-Girdle Congenital Myasthenic Syndrome with Tubular Aggregates

    PubMed Central

    Belaya, Katsiaryna; Finlayson, Sarah; Slater, Clarke R.; Cossins, Judith; Liu, Wei Wei; Maxwell, Susan; McGowan, Simon J.; Maslau, Siarhei; Twigg, Stephen R.F.; Walls, Timothy J.; Pascual Pascual, Samuel I.; Palace, Jacqueline; Beeson, David

    2012-01-01

    Congenital myasthenic syndromes are a heterogeneous group of inherited disorders that arise from impaired signal transmission at the neuromuscular synapse. They are characterized by fatigable muscle weakness. We performed whole-exome sequencing to determine the underlying defect in a group of individuals with an inherited limb-girdle pattern of myasthenic weakness. We identify DPAGT1 as a gene in which mutations cause a congenital myasthenic syndrome. We describe seven different mutations found in five individuals with DPAGT1 mutations. The affected individuals share a number of common clinical features, including involvement of proximal limb muscles, response to treatment with cholinesterase inhibitors and 3,4-diaminopyridine, and the presence of tubular aggregates in muscle biopsies. Analyses of motor endplates from two of the individuals demonstrate a severe reduction of endplate acetylcholine receptors. DPAGT1 is an essential enzyme catalyzing the first committed step of N-linked protein glycosylation. Our findings underscore the importance of N-linked protein glycosylation for proper functioning of the neuromuscular junction. Using the DPAGT1-specific inhibitor tunicamycin, we show that DPAGT1 is required for efficient glycosylation of acetylcholine-receptor subunits and for efficient export of acetylcholine receptors to the cell surface. We suggest that the primary pathogenic mechanism of DPAGT1 mutations is reduced levels of acetylcholine receptors at the endplate region. These individuals share clinical features similar to those of congenital myasthenic syndrome due to GFPT1 mutations, and their disorder might be part of a larger subgroup comprising the congenital myasthenic syndromes that result from defects in the N-linked glycosylation pathway and that manifest through impaired neuromuscular transmission. PMID:22742743

  3. Congenital rhabdomyosarcoma, central precocious puberty, hemihypertrophy and hypophosphatemic rickets associated with epidermal nevus syndrome.

    PubMed

    Shahgholi, Elham; Mollaian, Mansour; Haghshenas, Zahra; Honarmand, Malektaj

    2011-01-01

    We describe a newborn girl with right-sided extended epidermal nevus, congenital rhabdomyosarcoma of the inguinal area at birth who had developed central precocious puberty, hemihypertrophy and vitamin D3-responsive hypophosphatemic rickets at the age of 14 months. Our patient demonstrates a much broader and polymorphic spectrum of organ systems involvement in epidermal nevus syndrome at a very early age of her life.

  4. Congenital hypertrichosis, osteochondrodysplasia, and cardiomegaly: Cantú syndrome.

    PubMed

    Robertson, S P; Kirk, E; Bernier, F; Brereton, J; Turner, A; Bankier, A

    1999-08-06

    Cantú syndrome (hypertrichosis, osteochondrodysplasia, cardiomegaly) is a rare condition, previously reported in 13 patients. We report on two additional patients with this disorder. One of the patients had pulmonary hypertension of unknown cause which was responsive to steroid therapy. She also had unusual, deep plantar creases, not reported previously in Cantú syndrome. Autosomal recessive inheritance has been suggested previously on the basis of sib recurrence in one family and consanguinity in another. We have performed a segregation analysis based on all reported families to date; the data indicate autosomal recessive inheritance is unlikely. A new dominant mutation or microdeletion syndrome are more likely possibilities, sib recurrence possibly representing gonadal mosaicism. Copyright 1999 Wiley-Liss, Inc.

  5. Three Novel Mutations in theNPHS1Gene in Vietnamese Patients with Congenital Nephrotic Syndrome.

    PubMed

    Nguyen, Thi Kim Lien; Pham, Van Dem; Nguyen, Thu Huong; Pham, Trung Kien; Nguyen, Thi Quynh Huong; Nguyen, Huy Hoang

    2017-01-01

    Congenital nephrotic syndrome, a rare and severe disease, is inherited as an autosomal recessive trait. The disease manifests shortly after birth and occurs predominantly in families of Finnish origin but has now been observed in all countries and races. Mutations in the NPHS1 gene, which encodes nephrin, are the main causes of congenital nephrotic syndrome in patients. In this study, we report the first mutational analysis of the NPHS1 gene in three unrelated children from three different Vietnamese families. These patients were examined and determined to be suffering from congenital nephrotic syndrome in the Department of Pediatrics, Vietnam National Hospital of Pediatrics. All 29 exons and exon-intron boundaries of NPHS1 were analyzed by PCR and DNA sequencing. Genetic analysis of the NPHS1 gene revealed one compound heterozygous variant p.Glu117Lys, one heterozygous missense mutation p.Asp310Asn, and one heterozygous frame-shifting mutation (c.3250_3251insG causing p.Val1084Glyfs⁎12) in patient 1. In patient 2, one heterozygous variant p.Glu117Lys and one novel heterozygous missense mutation p.Ser324Ala were identified. Finally, a novel missense mutation p.Arg802Leu and a novel nonsense mutation (c.2442C>G causing p.K792⁎) were identified in patient 3.

  6. Use of next-generation sequencing as a diagnostic tool for congenital myasthenic syndrome.

    PubMed

    Das, Alvin S; Agamanolis, Dimitri P; Cohen, Bruce H

    2014-11-01

    The clinical presentation of congenital myasthenic syndromes is similar to many other neuromuscular disorders of infancy, and with 12 known discrete genetic forms of congenital myasthenic syndromes, both the diagnosis and treatment decisions present clinical challenges. We report a 20-month-old boy with rapsyn deficiency. At birth, he presented with a weak cry, hypotonia, joint contractures, and facial deformity. Because of respiratory difficulty associated with muscle fatigue, he spent a total of 71 days in the neonatal intensive care unit and 47 days in the pediatric intensive care unit. Imaging study results were normal, along with a battery of metabolic tests and electrodiagnostic studies. A limited genetic evaluation for reversible cytochrome c oxidase deficiency was negative, as was the oligonucleotide microarray. A muscle biopsy demonstrated myofiber atrophy in a pattern consistent with early denervation. Based on nonspecific and nondiagnostic results, whole-exome (next generation) sequencing was performed. This study identified two confirmed pathogenic mutations in the RAPSN gene that are associated with congenital myasthenic syndrome (OMIM 608931). The patient was treated with pyridostigmine at 16 months of age, which resulted in a dramatic improvement in muscle tone and strength and a steady resolution of joint contractures. Four months after treatment was initiated, he was beginning to bear weight and was able to sit unsupported and vocalize full words. This patient serves to highlight next-generation sequencing as an important diagnostic tool that can result in life-saving treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Wildervanck’s syndrome and mirror movements: a congenital disorder of axon migration?

    PubMed Central

    Högen, Tobias; Chan, Wai-Man; Riedel, Eva; Brüning, Roland; Chang, Hannah H.; Engle, Elizabeth C.

    2012-01-01

    Cell outgrowth and migration in the developing nervous system result from guidance cues, whose molecular bases and clinical correlates are only partly known. We describe a patient with brain stem malformation, paroxysmal left sided lacrimation when eating (“crocodile tears”) and mirror movements in addition to Wildervanck’s cervico-oculo-acusticus (COA) syndrome, which encompasses Klippel–Feil anomaly, congenital hearing loss and Duane’s syndrome. The unique symptom constellation has not been reported in that combination before and can be discussed in the context of congenital disordered axonal migration based on dysfunction of signalling pathways. However, mutations in some recently discovered genes, associated with single findings also present in our patient, were not found. Therefore, we suppose that the disturbance of an as yet unknown regulatory factor may explain the congenital malformation syndrome of our patient. In general, only a few human disorders have yet been found to result from defects in axon guidance. Nevertheless, disorders of axon guidance can certainly be regarded as a new category of neurodevelopmental disorders. PMID:21947222

  8. Congenital vascular anomalies in amniotic band syndrome of the limbs.

    PubMed

    Daya, Mahendra; Makakole, Manti

    2011-03-01

    Bone abnormalities and nerve compression are sparsely reported features of amniotic band syndrome. No studies of the vascular architecture of limbs affected by this syndrome have been published. Patients with amniotic band syndrome affecting the limbs were evaluated in the period between 1997 and 2007. The arterial blood supply was studied using magnetic resonance angiography or computed tomographic angiography. The subjects comprised 8 patients with bilateral and 2 with unilateral limb involvement. The patients' ages ranged from 2 months to 8 years. The male-to-female ratio was 4:6. A total of 20 limbs was investigated, comprising 18 lower limbs and 2 upper limbs. The amniotic bands were divided into superficial or deep. The patients were divided into 4 groups: group 1, thigh bands; group 2, below-knee amputations; group 3, leg bands; and group 4, upper limb bands. A single patient in group 1 with a deep band had a persistent sciatic artery. In group 2, three limbs demonstrated attenuated segments in the superficial femoral artery and/or abnormalities arising at the popliteal artery division. In group 3 (14 legs), 7 with deep bands showed some anomaly either in the popliteal artery division or its branches or both. In the other 7, and in group 4, all with superficial bands, no vascular abnormalities were seen except in one. Our findings show that amniotic band syndrome is definitely associated with vascular abnormalities and the depth of the band is an important contributory factor. Copyright © 2011. Published by Elsevier Inc.

  9. Maternal phenylketonuria syndrome: congenital heart defects, microcephaly, and developmental outcomes.

    PubMed

    Rouse, B; Matalon, R; Koch, R; Azen, C; Levy, H; Hanley, W; Trefz, F; de la Cruz, F

    2000-01-01

    A cohort of women with phenylketonuria (PKU) were selected to explore the impact of phenylalanine (Phe) levels and other factors on congenital heart defects (CHDs), microcephaly, and development of their offspring. Three hundred fifty-four women with PKU were followed up weekly with diet records, blood Phe levels, and sonograms obtained at 18 to 20 and 32 weeks' gestation. At birth, 413 offspring were examined and followed up at 6 months and annually by means of Bayley Mental Developmental Index and Psychomotor Developmental Index tests at 1 and 2 years. The women had Wechsler Adult Intelligence Scales and DNA testing. Thirty-one offspring had CHDs; of these, 17 also had microcephaly. Mean Phe levels at 4 to 8 weeks' gestation predicted CHDs (P <.0001). An infant with a CHD had a 3-fold risk of having microcephaly when the mother had higher Phe levels (P =.02). The Bayley Mental Developmental Index and Psychomotor Developmental Index scores correlated with both CHDs (P =.037 and.0015, respectively) and microcephaly (P =.0001 for both). No direct relationship to the PKU mutation was found. None of the women whose offspring had CHDs had blood Phe levels in control during the first 8 weeks of gestation. Women with PKU need to be well controlled on a low-phenylalanine diet before conception and throughout pregnancy.

  10. A recessive Nav1.4 mutation underlies congenital myasthenic syndrome with periodic paralysis

    PubMed Central

    Habbout, Karima; Poulin, Hugo; Rivier, François; Giuliano, Serena; Sternberg, Damien; Fontaine, Bertrand; Eymard, Bruno; Morales, Raul Juntas; Echenne, Bernard; King, Louise; Hanna, Michael G.; Männikkö, Roope; Chahine, Mohamed; Nicole, Sophie

    2016-01-01

    Objective: To determine the molecular basis of a complex phenotype of congenital muscle weakness observed in an isolated but consanguineous patient. Methods: The proband was evaluated clinically and neurophysiologically over a period of 15 years. Genetic testing of candidate genes was performed. Functional characterization of the candidate mutation was done in mammalian cell background using whole cell patch clamp technique. Results: The proband had fatigable muscle weakness characteristic of congenital myasthenic syndrome with acute and reversible attacks of most severe muscle weakness as observed in periodic paralysis. We identified a novel homozygous SCN4A mutation (p.R1454W) linked to this recessively inherited phenotype. The p.R1454W substitution induced an important enhancement of fast and slow inactivation, a slower recovery for these inactivated states, and a frequency-dependent regulation of Nav1.4 channels in the heterologous expression system. Conclusion: We identified a novel loss-of-function mutation of Nav1.4 that leads to a recessive phenotype combining clinical symptoms and signs of congenital myasthenic syndrome and periodic paralysis, probably by decreasing channel availability for muscle action potential genesis at the neuromuscular junction and propagation along the sarcolemma. PMID:26659129

  11. Microform holoprosencephaly with bilateral congenital elbow dislocation; increasing the phenotypic spectrum of Steinfeld syndrome.

    PubMed

    Jones, Gabriela E; Robertson, Lisa; Maniyar, Amit; Shammas, Christos; Phelan, Marie M; Vasudevan, Pradeep C; Tanteles, George A

    2016-03-01

    Steinfeld syndrome (MIM #184705) was first reported in 1982. It is characterised by holoprosencephaly and limb defects, however other anomalies may also be present. Following the initial description, three further cases have been reported in the literature. We report on a 23-year-old girl, with features of microform holoprosencephaly and bilateral congenital elbow dislocation in association with hypoplastic radial heads. She was identified to have a variant in the CDON gene inherited from her father who had ocular hypotelorism, but no other clinical features. We discuss the clinical features of Steinfeld syndrome, and broaden the phenotypic spectrum of this condition. Structural analysis suggests that this variant could lead to destabilisation of binding of CDON with hedgehog proteins. Further work needs to be done to confirm whether mutations in the CDON gene are the cause of Steinfeld syndrome. © 2016 Wiley Periodicals, Inc.

  12. Congenital Syphilis Presenting with Only Nephrotic Syndrome: Reemergence of a Forgotten Disease.

    PubMed

    Kim, Yun Hee; Song, Ji Ho; Kim, Chan Jong; Yang, Eun Mi

    2017-08-01

    Syphilis infection has re-emerged after years of declining incidence. The prevalence of congenital syphilis (CS) has increased in Korea and other countries during the last few decades. Untreated infants develop symptoms such as rhinorrhea, anemia, jaundice, cutaneous lesions, hepatosplenomegaly, and pseudoparalysis within weeks or months. Significant renal disease is uncommon in CS, and clinical renal involvement varies from mild transient proteinuria to frank nephrosis. We report a 2-month-old infant with CS who presented with only nephrotic syndrome (NS). The previously healthy infant presented with NS and showed no other syphilitic manifestations. Remission of the NS was achieved with adequate penicillin treatment. No recurrence of proteinuria was observed during the 1 year of follow-up. Although rare, this long forgotten disease continues to affect pregnant women, resulting in prenatal or postnatal mortality. We still consider the possibility of syphilitic nephropathy and therefore serologic testing for congenital NS. © 2017 The Korean Academy of Medical Sciences.

  13. Fragile X syndrome in two siblings with major congenital malformations

    SciTech Connect

    Giampietro, P.F.; Haas, B.R.; Lipper, E.

    1996-05-17

    We report on 2 brothers with both fragile X and VACTERL-H syndrome. The first sibling, age 5, had bilateral cleft lip and palate, ventricular septal defect, and a hypoplastic thumb. The second sibling, age 2{1/2}, had a trachesophageal fistula, esophageal atresia, and vertebral abnormality. High-resolution chromosome analysis showed a 46,XY chromosome constitution in both siblings. By PCR and Southern blot analysis, the siblings were found to have large triplet repeat expansions in the fragile X gene (FMR 1) and both had methylation mosaicism. Enzyme kinetic studies of iduronate sulfatase demonstrated a two-fold increase in activity in the first sib asmore » compared to the second. Possible mechanisms through which the fragile X mutation can cause down-regulation of adjacent loci are discussed. 24 refs., 4 figs.« less

  14. Cardiac conduction abnormalities and congenital immunodeficiency in a child with Kabuki syndrome: Case report

    PubMed Central

    Shah, Maulik; Bogucki, Brian; Mavers, Melissa; deMello, Daphne E; Knutsen, Alan

    2005-01-01

    Background Since it's recognition in 1981, a more complete phenotype of Kabuki syndrome is becoming evident as additional cases are identified. Congenital heart defects and a number of visceral abnormalities have been added to the typical dysmorphic features originally described. Case Report In this report we describe the clinical course of a child diagnosed with Kabuki syndrome based on characteristic clinical, radiological and morphologic features who died of a cardiac arrhythmia at 11-months of age. This infant, however, had abnormal pulmonary architecture and alterations in his cardiac conduction system resulting in episodes of bradycardia and asystole. This child also had an immunological phenotype consistent with common variable immunodeficiency. His clinical course consisted of numerous hospitalizations for recurrent bacterial infections and congenital hypogammaglobulinemia characterized by low serum IgG and IgA but normal IgM levels, and decreased antibody levels to immunizations. T-, B- and NK lymphocyte subpopulations and T-cell function studies were normal. Conclusion This child may represent a more severe phenotype of Kabuki syndrome. Recurrent infections in a child should prompt a thorough immunological evaluation. Additionally, electrophysiology testing may be indicated if cardiopulmonary events occur which are not explained by anatomic defects. PMID:16042804

  15. Ballantyne syndrome and congenital anaemia associated with Parvovirus B19 infection: case report and review.

    PubMed

    Schoberer, M; Rink, A; Rath, W; Orlikowsky, T

    2013-10-01

    Acute maternal Parvovirus B19 infection affects about 1% of all pregnancies worldwide. Diaplacental transmission of Parvovirus B19 during the second trimester can cause complications like foetal hydrops, premature delivery or foetal loss in about 20-30% of these pregnancies, whereas the majority of maternal infections remain clinically silent. In individual cases, foetoplacental hydrops (of various origins) can trigger a rare form of Preeclampsia in the pregnant woman. The developing maternal oedema in this situation apparently "mirrors" the hydropic state of the foetus. The symptom triad of foetal hydrops, foetoplacental oedema and maternal anasarca defines Ballantyne syndrome. We report a case of Parvovirus-induced Ballantyne syndrome including a 10-year follow-up of mother and child. While the mother recovered rapidly after (preterm) delivery, the infection complicated the first months of life of the neonate. Congenital transfusion-dependent red cell aplasia and cholestatic hepathopathy took a chronic course but resolved under IVIG treatment. Follow-up now finds both the former neonate and the mother entirely recovered. Current knowledge on Ballantyne syndrome as well as perigestational Parvovirus infections including congenital anaemia is briefly reported and pathophysiological hypotheses are discussed. © Georg Thieme Verlag KG Stuttgart · New York.

  16. Vestibular dehiscence syndrome caused by a labyrinthine congenital cholesteatoma.

    PubMed

    Fiorino, Francesco; Pizzini, Francesca B; Mattellini, Barbara; Barbieri, Franco

    2015-02-01

    A 40-year-old man presented with conductive hearing loss and pressure- and sound-related vestibular symptoms. Computed tomography and diffusion-weighted magnetic resonance imaging revealed the presence of a cholesteatoma involving the vestibular labyrinth. The patient underwent a canal-wall-up tympanoplasty, which revealed evidence of a disruption of the vestibular labyrinth and a wide dehiscence of the vestibule, which was immediately resurfaced. At the 2-month follow-up, the patient's pressure- and sound-related vestibular symptoms had disappeared. Pure-tone audiometry showed a reduction in the air-bone gap with a slight deterioration of bone conduction and an improvement in the air-conduction threshold. Fistulization of the otic capsule produces a "third window," which can lead to a dehiscence syndrome. One possible cause is a cholesteatoma of the middle ear or petrous bone. When the vestibule is invaded by a cholesteatoma, hearing is almost invariably lost, either pre- or postoperatively. However, in our case, wide opening of the vestibule resulted in hearing preservation.

  17. Follow-up brain imaging of 37 children with congenital Zika syndrome: case series study.

    PubMed

    Petribu, Natacha Calheiros de Lima; Aragao, Maria de Fatima Vasco; van der Linden, Vanessa; Parizel, Paul; Jungmann, Patricia; Araújo, Luziany; Abath, Marília; Fernandes, Andrezza; Brainer-Lima, Alessandra; Holanda, Arthur; Mello, Roberto; Sarteschi, Camila; Duarte, Maria do Carmo Menezes Bezerra

    2017-10-13

    Objective  To compare initial brain computed tomography (CT) scans with follow-up CT scans at one year in children with congenital Zika syndrome, focusing on cerebral calcifications. Design  Case series study. Setting  Barão de Lucena Hospital, Pernambuco state, Brazil. Participants  37 children with probable or confirmed congenital Zika syndrome during the microcephaly outbreak in 2015 who underwent brain CT shortly after birth and at one year follow-up. Main outcome measure  Differences in cerebral calcification patterns between initial and follow-up scans. Results  37 children were evaluated. All presented cerebral calcifications on the initial scan, predominantly at cortical-white matter junction. At follow-up the calcifications had diminished in number, size, or density, or a combination in 34 of the children (92%, 95% confidence interval 79% to 97%), were no longer visible in one child, and remained unchanged in two children. No child showed an increase in calcifications. The calcifications at the cortical-white matter junction which were no longer visible at follow-up occurred predominately in the parietal and occipital lobes. These imaging changes were not associated with any clear clinical improvements. Conclusion  The detection of cerebral calcifications should not be considered a major criterion for late diagnosis of congenital Zika syndrome, nor should the absence of calcifications be used to exclude the diagnosis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  18. Structural and functional differences in PHOX2B frameshift mutations underlie isolated or syndromic congenital central hypoventilation syndrome

    PubMed Central

    Benfante, Roberta; Di Zanni, Eleonora; Cardani, Silvia; Adamo, Annalisa; Fornasari, Diego; Ceccherini, Isabella

    2017-01-01

    Abstract Heterozygous mutations in the PHOX2B gene are causative of congenital central hypoventilation syndrome (CCHS), a neurocristopathy characterized by defective autonomic control of breathing due to the impaired differentiation of neural crest cells. Among PHOX2B mutations, polyalanine (polyAla) expansions are almost exclusively associated with isolated CCHS, whereas frameshift variants, although less frequent, are often more severe than polyAla expansions and identified in syndromic CCHS. This article provides a complete review of all the frameshift mutations identified in cases of isolated and syndromic CCHS reported in the literature as well as those identified by us and not yet published. These were considered in terms of both their structure, whether the underlying indels induced frameshifts of either 1 or 2 steps (“frame 2” and “frame 3” mutations respectively), and clinical associations. Furthermore, we evaluated the structural and functional effects of one “frame 3” mutation identified in a patient with isolated CCHS, and one “frame 2” mutation identified in a patient with syndromic CCHS, also affected with Hirschsprung's disease and neuroblastoma. The data thus obtained confirm that the type of translational frame affects the severity of the transcriptional dysfunction and the predisposition to isolated or syndromic CCHS. PMID:29098737

  19. [Case report of Ito-syndrome associated with congenital hemihypertrophy from the orthopaedic point of view].

    PubMed

    Gärtner, C M; Sabo, D

    2005-01-01

    We report on the orthopaedic treatment of a patient with the very rare Ito syndrome and congenital hemihypertrophy. The leading symptom is the lamellar depigmentation of the skin for which it is synonymously called incontinantia pigmenti acromians. Further anomalies are found in the central nervous system, as well as the ocular and the musculoskeletal systems. The treatment of the hemihypertrophy and the coexistent dysplasia of the hip with a combination of intertrochanteric shortening osteotomy and a triple osteotomy are specified and further methods are discussed.

  20. Congenital gluteus maximus contracture syndrome - a case report with review of imaging findings

    PubMed Central

    Kotha, Vamshi Krishna; Reddy, Rajasekhar; Reddy, M. Venkateshwar; Moorthy, Rangubatla Sathyanrayana; Kishan, Tatikonda Venkat

    2014-01-01

    Although the clinical features of gluteus maximus contracture syndrome have been frequently described, imaging features have been seldom described. Most commonly reported cases are those following intramuscular injection in the gluteal region although congenital contracture is an uncommon but important occurrence. This condition has most often been reported in children of school going age. These patients often present with difficulty in squatting, limitation of hip motion or specific deformities and often require surgical correction. We describe the plain radiography, ultrasonography (USG) and magnetic resonance imaging (MRI) features of this condition in a patient with no previous known history of intramuscular injections. PMID:24967033

  1. Is Congenital Amusia a Disconnection Syndrome? A Study Combining Tract- and Network-Based Analysis.

    PubMed

    Wang, Jieqiong; Zhang, Caicai; Wan, Shibiao; Peng, Gang

    2017-01-01

    Previous studies on congenital amusia mainly focused on the impaired fronto-temporal pathway. It is possible that neural pathways of amusia patients on a larger scale are affected. In this study, we investigated changes in structural connections by applying both tract-based and network-based analysis to DTI data of 12 subjects with congenital amusia and 20 demographic-matched normal controls. TBSS (tract-based spatial statistics) was used to detect microstructural changes. The results showed that amusics had higher diffusivity indices in the corpus callosum, the right inferior/superior longitudinal fasciculus, and the right inferior frontal-occipital fasciculus (IFOF). The axial diffusivity values of the right IFOF were negatively correlated with musical scores in the amusia group. Network-based analysis showed that the efficiency of the brain network was reduced in amusics. The impairments of WM tracts were also found to be correlated with reduced network efficiency in amusics. This suggests that impaired WM tracts may lead to the reduced network efficiency seen in amusics. Our findings suggest that congenital amusia is a disconnection syndrome.

  2. Is Congenital Amusia a Disconnection Syndrome? A Study Combining Tract- and Network-Based Analysis

    PubMed Central

    Wang, Jieqiong; Zhang, Caicai; Wan, Shibiao; Peng, Gang

    2017-01-01

    Previous studies on congenital amusia mainly focused on the impaired fronto-temporal pathway. It is possible that neural pathways of amusia patients on a larger scale are affected. In this study, we investigated changes in structural connections by applying both tract-based and network-based analysis to DTI data of 12 subjects with congenital amusia and 20 demographic-matched normal controls. TBSS (tract-based spatial statistics) was used to detect microstructural changes. The results showed that amusics had higher diffusivity indices in the corpus callosum, the right inferior/superior longitudinal fasciculus, and the right inferior frontal-occipital fasciculus (IFOF). The axial diffusivity values of the right IFOF were negatively correlated with musical scores in the amusia group. Network-based analysis showed that the efficiency of the brain network was reduced in amusics. The impairments of WM tracts were also found to be correlated with reduced network efficiency in amusics. This suggests that impaired WM tracts may lead to the reduced network efficiency seen in amusics. Our findings suggest that congenital amusia is a disconnection syndrome. PMID:29033806

  3. Prolonged Tp-e Interval in Down Syndrome Patients with Congenitally Normal Hearts.

    PubMed

    Kucuk, Mehmet; Karadeniz, Cem; Ozdemir, Rahmi; Meşe, Timur

    2018-03-25

    Heterogeneity of ventricular repolarization has been assessed by using the QT dispersion in Down syndrome (DS) patients with congenitally normal hearts. However, novel repolarization indexes, the Tp-e interval and Tp-e/QT ratio, have not previously been evaluated in these patients. The aim of this study was to evaluate the Tp-e interval and Tp-e/QT ratio in DS patients without congenital heart defects. Twelve-lead surface electrocardiograms of 160 DS patients and 110 age- and sex-matched healthy controls were used to evaluate and compare the Tp-e interval, Tp-e dispersion, and Tp-e/QT ratio. Heart rate, Tp-e interval, Tp-e dispersion, Tp-e/QT and Tp-e/QTc ratios were significantly higher in DS group than in the controls. Myocardial repolarization indexes in DS patients with congenitally normal hearts were found to be prolonged compared to those in normal controls. Further evaluation is warranted to reveal a relationship between prolonged repolarization indexes and arrhythmic events in these patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  4. Congenital nephrotic syndrome of the Finnish type maps to the long arm of chromosome 19

    SciTech Connect

    Kestilae, M.; Maennikkoe, M.; Tryggvason, K.

    1994-05-01

    Congenital nephrotic syndrome of the Finnish (CNF) is an autosomal recessive disease that is characterized by massive proteinuria and nephrotic syndrome at birth. CNF represents a unique, apparently specific dysfunction of the renal basement membranes, and the estimated incidence of CNF in the isolated population of Finland is 1 in 8,000 newborns. The basic defect is unknown, and no specific biochemical defect or chromosomal aberrations have been described. Here the authors report the assignment of the CNF locus to 19[sub q]12-q13.1 on the basis of linkage analysis in 17 Finnish families. Multipoint analyses and observed recombination events place the CNFmore » locus between multiallelic markers D19S416 and D19S224, and the significant linkage disequilibrium observed suggests that the CNF gene lies in the immediate vicinity of the markers D19S224 and D19S220. 16 refs., 4 figs., 4 tabs.« less

  5. [Congenital myasthenic syndromes: difficulties in the diagnosis, course and prognosis, and therapy--The French National Congenital Myasthenic Syndrome Network experience].

    PubMed

    Eymard, B; Stojkovic, T; Sternberg, D; Richard, P; Nicole, S; Fournier, E; Béhin, A; Laforêt, P; Servais, L; Romero, N; Fardeau, M; Hantaï, D

    2013-02-01

    Congenital myasthenic syndromes (CMS) are a heterogeneous group of disorders caused by genetic defects affecting neuromuscular transmission and leading to muscle weakness accentuated by exertion. Three different aspects have been investigated by members of the national French CMS Network: the difficulties in making a proper diagnosis; the course and long-term prognosis; and the response to therapy, especially for CMS that do not respond to cholinesterase inhibitors. CMS diagnosis is late in most cases because of confusion with other entities such as: congenital myopathies, due to the frequent presentation in patients of myopathies such as permanent muscle weakness, atrophy and scoliosis, and the abnormalities of internal structure, diameter and distribution of fibers (type I predominance, type II atrophy) seen on biopsy; seronegative autoimmune myasthenia gravis, when CMS is of late onset; and metabolic myopathy, with the presence of lipidosis in muscle. The long-term prognosis of CMS was studied in a series of 79 patients recruited with the following gene mutations: CHRNA; CHRNE; DOK7; COLQ; RAPSN; AGRN; and MUSK. Disease-course patterns (progressive worsening, exacerbation, stability, improvement) could be variable throughout life in a given patient. DOK7 patients had the most severe disease course with progressive worsening: of the eight wheelchair-bound and ventilated patients, six had mutations of this gene. Pregnancy was a frequent cause of exacerbation. Anticholinesterase agents are the first-line therapy for CMS patients, except for cases of slow-channel CMS, COLQ and DOK7. In our experience, 3,4-DAP was a useful complement for several patients harboring CMS with AChR loss or RAPSN gene mutations. Ephedrine was given to 18 patients (eight DOK7, five COLQ, four AGRN and one RAPSN). Tolerability was good. Therapeutic responses were encouraging even in the most severely affected patients, particularly with DOK7 and COLQ. Salbutamol was a good alternative in

  6. Are there any association between polycistic ovary syndrome and congenital abnormalities of Müllerian ducts.

    PubMed

    Tubić-Pavlović, Aleksandra; Radović-Janosević, Dragana; Petrić, Aleksandra; Stefanović, Milan

    2014-06-01

    There are many specificities of merital infertility and sometimes surprising connections between some thinks with no connections at first sight. Examinations of these patients imply diagnostic actions such as the blood basal hormone sample, doing hysterosalpingography, ultrahysterosonography, ultrasound examinations, and sometimes laparoscopy and hysteroscopy if there are necessary. The aim of the study was to determine the characteristics of the connection between policystic ovary (PCO) syndrome (Sy) and congenital Müllerian ducts abnormalities. This study included 356 patients treated in the period from January 1, to December 31, 2009, in the Department of Infertility of the Clinic for Obstetrics and Gynecology in Nis, Serbia. Exclusion criteria were no myoma, ovary cysts, tubal and male factors of infertility. A total of 180 patients were divided into 3 groups: the group I with PCO sy, the group II with uterine congenital malformation and the group III with a combination of these disorders. The middle age of patients was 29.6 +/- 4.8, body mass index (BMI) was 26.1 +/- 4,8 kg/m2 the middle thicknes of endometrium was 5.2 + 2.7 mm, and there were no significant differences between the examined groups. There were no significant among in a number of miscarriages in the examined groups. We found that PCO Sy and congenital abnormalities of Müllerian ducts were conjoint in 30% of examined patients. Conjoined PCO Sy and congenital abnormalities of Müllerian ducts do not result in a higher number of miscarriages than only either PCO Sy or abnormalities of Müllerian ducts. It is important to check BMI, basal level of follicle stimulating hormone and number of antral follicles because the induction protocol and concentracion of inductors depends on these characteristics, thus, the succsessful cycles and pregnancy.

  7. Congenital malformations and other comorbidities in 125 women with Mayer-Rokitansky-Küster-Hauser syndrome.

    PubMed

    Kapczuk, Karina; Iwaniec, Kinga; Friebe, Zbigniew; Kędzia, Witold

    2016-12-01

    To describe congenital malformations and coexisting disorders occurring in 125 Polish women with Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS). The syndrome is defined as uterovaginal aplasia in female with normal 46,XX karyotype. A retrospective analysis of the clinical data of MRKHS patients diagnosed or treated at the Gynecology and Obstetrics Clinical Hospital of Poznan University of Medical Sciences between 2010 and 2015. Sixty-eight patients (54,4%) were found to have one or more coexisting anomalies. Thirty-eight patients (55,9% of cases with concomitant malformations, 30,4% of the entire study group) had coexisting anomalies of at least two organ systems. The most frequent extragenital malformations were skeletal anomalies found in 40 patients (32%) and renal anomalies found in 36 patients (28,8%). Fifty-seven patients (45,6%) were diagnosed with typical form (type 1) and 16 (12,8%) with the atypical form (type 2) of MRKHS. In the other 52 patients (41,6%) we diagnosed MURCS association. Five of our patients (4%) had karyotype abnormalities. Our study confirms complexity and clinical heterogeneity of MRKHS. Concomitant congenital malformations are present in about half of MRKHS women. A significant proportion of patients have coexisting anomalies of at least two organ systems. The most common coexisting findings are musculoskeletal and renal abnormalities. Chromosomal aberrations may be present in patients with either typical or atypical form of MRKHS. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Velocardiofacial syndrome in Mexican patients: Unusually high prevalence of congenital heart disease.

    PubMed

    Márquez-Ávila, Candy Sue; Vizcaíno-Alarcón, Alfredo; García-Delgado, Constanza; Núñez-Martínez, Paulina María; Flores-Ramírez, Francisco; Reyes-de la Rosa, Alejandra del Pilar; Mendelsberg-Fishbein, Paola; Ibarra-Grajeda, Diana; Medina-Bravo, Patricia; Balderrábano-Saucedo, Norma; Esteva-Solsona, Salvador; Márquez-Quiróz, Luz del Carmen; Flores-Cuevas, Arturo; Sánchez-Urbina, Rocío; Morales-Jiménez, Ariadna Berenice; Garibay-Nieto, Nayely; Del Bosque-Garza, Jesús; Pietropaolo-Cienfuegos, Dino; Gutiérrez-Camacho, Claudia; García-Morales, Leticia; Morán-Barroso, Verónica Fabiola

    2015-11-01

    Velocardiofacial syndrome (VCFS) is the most common microdeletion syndrome with an incidence of 1:4000 live births. Its phenotype is highly variable with facial, velopharyngeal, cardiac, endocrine, immunologic and psychiatric abnormalities. It is caused by a microdeletion in chromosome 22q11.2. We present 7 years of experience evaluating patients with VCFS regarding their main clinical characteristics. The patients included were multidisciplinary evaluated and had a positive FISH analysis for del22q11.2. A total of 62 patients were assessed, a 34 female/28 male ratio was observed with ages ranging from 9 days to 16 years, all but one patient had typical facial features. A diagnosis of congenital heart disease was established in 97% of the patients; other clinical characteristics were identified with different percentages such as cleft palate, and hypocalcaemia. Three cases had a familial presentation. While the clinical findings of this study were in general terms in keeping with the literature, it is interesting the unexpectedly high percentage of congenital heart disease identified in Mexican children with VCFS that also was the main cause for clinical referral. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. Ocular abnormalities in congenital Zika syndrome: are the ophthalmoscopic findings "the top of the iceberg"?

    PubMed

    de Oliveira Dias, João Rafael; Ventura, Camila V; de Paula Freitas, Bruno; Prazeres, Juliana; Ventura, Liana O; Bravo-Filho, Vasco; Aleman, Tomas; Ko, Albert Icksang; Zin, Andréa; Belfort, Rubens; Maia, Mauricio

    2018-04-23

    Zika virus (ZIKV) is an arbovirus mainly transmitted to humans by mosquitoes from Aedes genus. Other ways of transmission include the perinatal and sexual routes, blood transfusion, and laboratory exposure. Although the first human cases were registered in 1952 in African countries, outbreaks were only reported since 2007, when entire Pacific islands were affected. In March 2015, the first cases of ZIKV acute infection were notified in Brazil and, to date, 48 countries and territories in the Americas have confirmed local mosquito-borne transmission of ZIKV. Until 2015, ZIKV infection was thought to only cause asymptomatic or mild exanthematous febrile infections. However, after explosive ZIKV outbreaks in Polynesia and Latin American countries, it was confirmed that ZIKV could also lead to Guillain-Barré syndrome and congenital birth abnormalities. These abnormalities, which can include neurologic, ophthalmologic, audiologic, and skeletal findings, are now considered congenital Zika syndrome (CZS). Brain abnormalities in CZS include cerebral calcifications, malformations of cortical development, ventriculomegaly, lissencephaly, hypoplasia of the cerebellum and brainstem. The ocular findings, which are present in up to 70% of infants with CZS, include iris coloboma, lens subluxation, cataract, congenital glaucoma, and especially posterior segment findings. Loss of retinal pigment epithelium, the presence of a thin choroid, a perivascular choroidal inflammatory infiltrate, and atrophic changes within the optic nerve were seen in histologic analyses of eyes from deceased fetuses. To date, there is no ZIKV licensed vaccines or antiviral therapies are available for treatment. Preventive measures include individual protection from mosquito bites, control of mosquito populations and the use of barriers measures such as condoms during sexual intercourse or sexual abstinence for couples either at risk or after confirmed infection. A literature review based on studies that

  10. Evaluating CHARGE syndrome in congenital hypogonadotropic hypogonadism patients harboring CHD7 variants.

    PubMed

    Xu, Cheng; Cassatella, Daniele; van der Sloot, Almer M; Quinton, Richard; Hauschild, Michael; De Geyter, Christian; Flück, Christa; Feller, Katrin; Bartholdi, Deborah; Nemeth, Attila; Halperin, Irene; Pekic Djurdjevic, Sandra; Maeder, Philippe; Papadakis, Georgios; Dwyer, Andrew A; Marino, Laura; Favre, Lucie; Pignatelli, Duarte; Niederländer, Nicolas J; Acierno, James; Pitteloud, Nelly

    2017-11-16

    PurposeCongenital hypogonadotropic hypogonadism (CHH), a rare genetic disease caused by gonadotropin-releasing hormone deficiency, can also be part of complex syndromes (e.g., CHARGE syndrome). CHD7 mutations were reported in 60% of patients with CHARGE syndrome, and in 6% of CHH patients. However, the definition of CHD7 mutations was variable, and the associated CHARGE signs in CHH were not systematically examined.MethodsRare sequencing variants (RSVs) in CHD7 were identified through exome sequencing in 116 CHH probands, and were interpreted according to American College of Medical Genetics and Genomics guidelines. Detailed phenotyping was performed in CHH probands who were positive for CHD7 RSVs, and genotype-phenotype correlations were evaluated.ResultsOf the CHH probands, 16% (18/116) were found to harbor heterozygous CHD7 RSVs, and detailed phenotyping was performed in 17 of them. Of CHH patients with pathogenic or likely pathogenic CHD7 variants, 80% (4/5) were found to exhibit multiple CHARGE features, and 3 of these patients were reclassified as having CHARGE syndrome. In contrast, only 8% (1/12) of CHH patients with nonpathogenic CHD7 variants exhibited multiple CHARGE features (P = 0.01).ConclusionPathogenic or likely pathogenic CHD7 variants rarely cause isolated CHH. Therefore a detailed clinical investigation is indicated to clarify the diagnosis (CHH versus CHARGE) and to optimize clinical management.Genetics in Medicine advance online publication, 16 November 2017; doi:10.1038/gim.2017.197.

  11. Genetic diseases: congenital central hypoventilation, Rett, and Prader-Willi syndromes.

    PubMed

    Gallego, Jorge

    2012-07-01

    The present review summarizes current knowledge on three rare genetic disorders of respiratory control, congenital central hypoventilation syndrome (CCHS), Rett syndrome (RTT), and Prader-Willi syndrome (PWS). CCHS is characterized by lack of ventilatory chemosensitivity caused by PHOX2B gene abnormalities consisting mainly of alanine expansions. RTT is associated with episodes of tachypneic and irregular breathing intermixed with breathholds and apneas and is caused by mutations in the X-linked MECP2 gene encoding methyl-CpG-binding protein. PWS manifests as sleep-disordered breathing with apneas and episodes of hypoventilation and is caused by the loss of a group of paternally inherited genes on chromosome 15. CCHS is the most specific disorder of respiratory control, whereas the breathing disorders in RTT and PWS are components of a more general developmental disorder. The main clinical features of these three disorders are reviewed with special emphasis on the associated brain abnormalities. In all three syndromes, disease-causing genetic defects have been identified, allowing the development of genetically engineered mouse models. New directions for future therapies based on these models or, in some cases, on clinical experience are delineated. Studies of CCHS, RTT, and PWS extend our knowledge of the molecular and cellular aspects of respiratory rhythm generation and suggest possible pharmacological approaches to respiratory control disorders. This knowledge is relevant for the clinical management of many respiratory disorders that are far more prevalent than the rare diseases discussed here. 2012 American Physiological Society. Compr Physiol 2:2037-2061, 2012.

  12. Congenital ocular motor apraxia with wheel-rolling ocular torsion-a neurodiagnostic phenotype of Joubert syndrome.

    PubMed

    Papanagnu, Eleni; Klaehn, Lindsay D; Bang, Genie M; Ghadban, Rafif; Mohney, Brian G; Brodsky, Michael C

    2014-08-01

    Joubert syndrome is a multisystem disorder that is associated with a constellation of cyclic ocular motor disturbances. We describe 2 children with congenital ocular motor apraxia who displayed wheel-rolling torsional eye movements and tonic alternating cyclodeviations of the eyes on retinal examination as a neurodiagnostic phenotype of Joubert syndrome. Copyright © 2014 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

  13. Genetic Syndromes Associated with Congenital Cardiac Defects and Ophthalmologic Changes - Systematization for Diagnosis in the Clinical Practice

    PubMed Central

    Oliveira, Priscila H. A.; Souza, Beatriz S.; Pacheco, Eimi N.; Menegazzo, Michele S.; Corrêa, Ivan S.; Zen, Paulo R. G.; Rosa, Rafael F. M.; Cesa, Claudia C.; Pellanda, Lucia C.; Vilela, Manuel A. P.

    2018-01-01

    Background Numerous genetic syndromes associated with heart disease and ocular manifestations have been described. However, a compilation and a summarization of these syndromes for better consultation and comparison have not been performed yet. Objective The objective of this work is to systematize available evidence in the literature on different syndromes that may cause congenital heart diseases associated with ocular changes, focusing on the types of anatomical and functional changes. Method A systematic search was performed on Medline electronic databases (PubMed, Embase, Cochrane, Lilacs) of articles published until January 2016. Eligibility criteria were case reports or review articles that evaluated the association of ophthalmic and cardiac abnormalities in genetic syndrome patients younger than 18 years. Results The most frequent genetic syndromes were: Down Syndrome, Velo-cardio-facial / DiGeorge Syndrome, Charge Syndrome and Noonan Syndrome. The most associated cardiac malformations with ocular findings were interatrial communication (77.4%), interventricular communication (51.6%), patent ductus arteriosus (35.4%), pulmonary artery stenosis (25.8%) and tetralogy of Fallot (22.5%). Conclusion Due to their clinical variability, congenital cardiac malformations may progress asymptomatically to heart defects associated with high morbidity and mortality. For this reason, the identification of extra-cardiac characteristics that may somehow contribute to the diagnosis of the disease or reveal its severity is of great relevance. PMID:29538527

  14. CONGENITAL ABNORMALITIES OF CRANIAL NERVE DEVELOPMENT: OVERVIEW, MOLECULAR MECHANISMS, AND FURTHER EVIDENCE OF HETEROGENEITY AND COMPLEXITY OF SYNDROMES WITH CONGENITAL LIMITATION OF EYE MOVEMENTS

    PubMed Central

    Traboulsi, Elias I

    2004-01-01

    ABSTRACT Purpose The clinical and molecular genetic classification of syndromes with congenital limitation of eye movements and evidence of cranial nerve dysgenesis continues to evolve. This monograph details clinical and molecular genetic data on a number of families and isolated patients with congenital fibrosis of the extraocular muscles (CFEOM) and related disorders, and presents an overview of the mechanisms of abnormal patterns of motor and sensory cranial nerve development in these rare syndromes. Methods Clinical examination of one patient with CFEOM1, one family with clinical features of CFEOM2, one family with recessive CFEOM3, one family with horizontal gaze palsy and progressive scoliosis (HGPPS), and four patients with various combinations of congenital cranial nerve abnormalities. Genotyping of families with CFEOM and HGPPS for polymorphic markers in the regions of the three known CFEOM loci and in the HGPPS region, and mutation analysis of the ARIX and KIF21A genes in patients with CFEOM were performed according to standard published protocols. Results The patient with CFEOM1 had the second most common mutation in KIF21A, a 2861 G>A mutation that resulted in an R954Q substitution. The family with CFEOM2 phenotype did not map to the CFEOM2 locus. The family with recessive CFEOM3 did not map to any of the known loci. The HGPPS family mapped to 11q23–q25. One patient had optic nerve hypoplasia and fifth nerve dysfunction. Two patients had the rare combination of Möbius syndrome and CFEOM. One patient had Möbius syndrome and fifth nerve dysfunction. Conclusions There is genetic heterogeneity in CFEOM2 and CFEOM3. Abnormalities in sensory nerves can also accompany abnormalities of motor nerves, further substantiating the effect of individual mutations on developing motor as well as sensory cranial nerve nuclei. PMID:15747768

  15. Urofacial syndrome: a genetic and congenital disease of aberrant urinary bladder innervation.

    PubMed

    Woolf, Adrian S; Stuart, Helen M; Roberts, Neil A; McKenzie, Edward A; Hilton, Emma N; Newman, William G

    2014-04-01

    The urofacial, or Ochoa, syndrome is characterised by congenital urinary bladder dysfunction together with an abnormal grimace upon smiling, laughing and crying. It can present as fetal megacystis. Postnatal features include urinary incontinence and incomplete bladder emptying due to simultaneous detrusor muscle and bladder outlet contractions. Vesicoureteric reflux is often present, and the condition can be complicated by urosepsis and end-stage renal disease. The syndrome has long been postulated to have neural basis, and it can be familial when it is inherited in an autosomal recessive manner. Most individuals with urofacial syndrome genetically studied to date carry biallelic, postulated functionally null mutations of HPSE2 or, less commonly, of LRIG2. Little is known about the biology of the respective encoded proteins, heparanase 2 and leucine-rich repeats and immunoglobulin-like domains 2. Nevertheless, the observations that heparanase 2 can bind heparan sulphate proteolgycans and inhibit heparanase 1 enzymatic activity and that LRIG2 can modulate receptor tyrosine kinase growth factor signalling each point to biological roles relevant to tissue differentiation. Moreover, both heparanase 2 and LRIG2 proteins are detected in autonomic nerves growing into fetal bladders. The collective evidence is consistent with the hypothesis that urofacial syndrome genes code for proteins which work in a common pathway to facilitate neural growth into, and/or function within, the bladder. This molecular pathway may also have relevance to our understanding of the pathogenesis of other lower tract diseases, including Hinman-Allen syndrome, or non-neurogenic neurogenic bladder, and of the subset of individuals who have primary vesicoureteric reflux accompanied by bladder dysfunction.

  16. A mother and three daughters with congenital dislocation of the hip and a characteristic facial appearance: a new syndrome?

    PubMed

    Collins, A L; Dennis, N R; Clarke, N; Pope, F M

    1995-10-01

    We describe a mother and her three daughters who all have bilateral congenital dislocation of the hip. The mother has had no other medical problems and is on the 90th centile for height. Her three daughters resemble each other strongly with facial characteristics which include hypertelorism, epicanthic folds, puffiness around the eyes, a flat mid-face and a carp-shaped mouth. All three daughters are on the 3rd centile for height, with their head circumference on a higher centile and all had an ASD. Other features include congenital dislocation of one knee (one), congenital inguinal hernia (one) and vesico-ureteric reflux (one). They also have clinodactyly and hyperextensible finger joints, both features also seen in their father, whose height is on the 3rd centile and who had bilateral congenital inguinal herniae. Collagen studies of skin and ligament were normal. This family does not appear to fit with any of the recognized congenital dislocation syndromes and we suggest that they may represent a previously undescribed syndrome.

  17. 14q12 microdeletions excluding FOXG1 give rise to a congenital variant Rett syndrome-like phenotype

    PubMed Central

    Ellaway, Carolyn J; Ho, Gladys; Bettella, Elisa; Knapman, Alisa; Collins, Felicity; Hackett, Anna; McKenzie, Fiona; Darmanian, Artur; Peters, Gregory B; Fagan, Kerry; Christodoulou, John

    2013-01-01

    Rett syndrome is a clinically defined neurodevelopmental disorder almost exclusively affecting females. Usually sporadic, Rett syndrome is caused by mutations in the X-linked MECP2 gene in ∼90–95% of classic cases and 40–60% of individuals with atypical Rett syndrome. Mutations in the CDKL5 gene have been associated with the early-onset seizure variant of Rett syndrome and mutations in FOXG1 have been associated with the congenital Rett syndrome variant. We report the clinical features and array CGH findings of three atypical Rett syndrome patients who had severe intellectual impairment, early-onset developmental delay, postnatal microcephaly and hypotonia. In addition, the females had a seizure disorder, agenesis of the corpus callosum and subtle dysmorphism. All three were found to have an interstitial deletion of 14q12. The deleted region in common included the PRKD1 gene but not the FOXG1 gene. Gene expression analysis suggested a decrease in FOXG1 levels in two of the patients. Screening of 32 atypical Rett syndrome patients did not identify any pathogenic mutations in the PRKD1 gene, although a previously reported frameshift mutation affecting FOXG1 (c.256dupC, p.Gln86ProfsX35) was identified in a patient with the congenital Rett syndrome variant. There is phenotypic overlap between congenital Rett syndrome variants with FOXG1 mutations and the clinical presentation of our three patients with this 14q12 microdeletion, not encompassing the FOXG1 gene. We propose that the primary defect in these patients is misregulation of the FOXG1 gene rather than a primary abnormality of PRKD1. PMID:22968132

  18. Multiple congenital malformations of Wolf-Hirschhorn syndrome are recapitulated in Fgfrl1 null mice.

    PubMed

    Catela, Catarina; Bilbao-Cortes, Daniel; Slonimsky, Esfir; Kratsios, Paschalis; Rosenthal, Nadia; Te Welscher, Pascal

    2009-01-01

    Wolf-Hirschhorn syndrome (WHS) is caused by deletions in the short arm of chromosome 4 (4p) and occurs in about one per 20,000 births. Patients with WHS display a set of highly variable characteristics including craniofacial dysgenesis, mental retardation, speech problems, congenital heart defects, short stature and a variety of skeletal anomalies. Analysis of patients with 4p deletions has identified two WHS critical regions (WHSCRs); however, deletions targeting mouse WHSCRs do not recapitulate the classical WHS defects, and the genes contributing to WHS have not been conclusively established. Recently, the human FGFRL1 gene, encoding a putative fibroblast growth factor (FGF) decoy receptor, has been implicated in the craniofacial phenotype of a WHS patient. Here, we report that targeted deletion of the mouse Fgfrl1 gene recapitulates a broad array of WHS phenotypes, including abnormal craniofacial development, axial and appendicular skeletal anomalies, and congenital heart defects. Fgfrl1 null mutants also display a transient foetal anaemia and a fully penetrant diaphragm defect, causing prenatal and perinatal lethality. Together, these data support a wider role for Fgfrl1 in development, implicate FGFRL1 insufficiency in WHS, and provide a novel animal model to dissect the complex aetiology of this human disease.

  19. Trauma due to Self-aggression in Patient with Waardenburg Syndrome associated with Congenital Anomalies.

    PubMed

    Marta, Sara Nader; Kawakami, Roberto Yoshio; Sgavioli, Claudia Almeida Prado Piccino; Correa, Ana Eliza; D'Árk de Oliveira El Kadre, Guaniara; Carvalho, Ricardo Sandri

    2016-08-01

    Waardenburg syndrome (WS) is an inherited autosomal dominant genetic disorder presenting variable penetrance and expressivity, with an estimated prevalence of 1:42,000. Clinical characteristics of WS include lateral displacement of the internal eye canthus, hyperplasia of the medial portion of the eyebrows, prominent and broad nasal base, congenital deafness, pigmentation of the iris and skin, and white forelock. A 24-year-old male patient, previously diagnosed with WS, was referred to the Special Needs Dental Clinic of Sacred Heart University, Bauru, Brazil. Parents reported that the patient was experiencing self-mutilation, particularly in the oral region. He presented multiple congenital anomalies, including anophthalmia, mental retardation, low-set ears, and leg deformities. Clinical oral examination revealed hypodontia, abnormalities in dental morphology, extensive dental caries, periodontal disease, and fistulae. Extensive scars on the tongue, lips, and hands caused by self-mutilation were also observed. In accordance with his family and neurologist, full-mouth extraction under general anesthesia was performed, especially considering his severe self-aggressive behavior and the necessity to be fed with soft-food diet due to his inability to chew. After the surgical procedure, a significant reduction in the patient's irritability and gain of weight were reported in the follow-ups of 30, 60, and 180 days.

  20. Immunolocalization and Distribution of Rubella Antigen in Fatal Congenital Rubella Syndrome

    PubMed Central

    Lazar, Mihaela; Perelygina, Ludmila; Martines, Roosecelis; Greer, Patricia; Paddock, Christopher D.; Peltecu, Gheorghe; Lupulescu, Emilia; Icenogle, Joseph; Zaki, Sherif R.

    2015-01-01

    Background An estimated 100,000 cases of congenital rubella syndrome (CRS) occur worldwide each year. The reported mortality rate for infants with CRS is up to 33%. The cellular mechanisms responsible for the multiple congenital defects in CRS are presently unknown. Here we identify cell types positive for rubella virus (RV) in CRS infants. Methods Cells and organs involved in RV replication were identified in paraffin-embedded autopsy tissues from three fatal case-patients by histopathologic examination and immunohistochemical (IHC) staining using a rabbit polyclonal RV antibody. Normal rabbit antisera and RV antisera preabsorbed with highly purified RV served as negative controls. Results RV antigen was found in interstitial fibroblasts in the heart, adventitial fibroblasts of large blood vessels, alveolar macrophages, progenitor cells of the outer granular layer of the brain, and in capillary endothelium and basal plate in the placenta. The antibody specificity was verified by IHC staining of multiple tissue sections from other infectious disease cases. RV infection of each cell type is consistent with abnormalities which have been identified in patients with CRS, in the heart, large blood vessels, and brain. Antigen distribution was consistent with inflammatory response to vascular injury and systemic spread of RV. Conclusions The identification of RV positive cell types in CRS is important to better understand the pathology and pathogenesis of CRS. PMID:26870820

  1. Progress in Rubella and Congenital Rubella Syndrome Control and Elimination - Worldwide, 2000-2016.

    PubMed

    Grant, Gavin B; Reef, Susan E; Patel, Minal; Knapp, Jennifer K; Dabbagh, Alya

    2017-11-17

    Although rubella virus infection usually causes a mild fever and rash illness in children and adults, infection during pregnancy, especially during the first trimester, can result in miscarriage, fetal death, stillbirth, or infants with a constellation of congenital malformations known as congenital rubella syndrome (CRS) (1). Rubella is a leading vaccine-preventable cause of birth defects. Preventing these adverse pregnancy outcomes is the focus of rubella vaccination programs. In 2011, the World Health Organization (WHO) updated guidance on the preferred strategy for introduction of rubella-containing vaccine (RCV) into national immunization schedules and recommended an initial vaccination campaign, usually targeting children aged 9 months-14 years (1). The Global Vaccine Action Plan 2011-2020 (GVAP), endorsed by the World Health Assembly in 2012, includes goals to eliminate rubella in at least five of the six WHO regions by 2020 (2). This report updates a previous report (3) and summarizes global progress toward rubella and CRS control and elimination from 2000 to 2016. As of December 2016, 152 (78%) of 194 countries had introduced RCV into the national immunization schedule, representing an increase of 53 countries since 2000, including 20 countries that introduced RCV after 2012.

  2. Congenital Myasthenic Syndromes or Inherited Disorders of Neuromuscular Transmission: Recent Discoveries and Open Questions

    PubMed Central

    Nicole, Sophie; Azuma, Yoshiteru; Bauché, Stéphanie; Eymard, Bruno; Lochmüller, Hanns; Slater, Clarke

    2017-01-01

    Congenital myasthenic syndromes (CMS) form a heterogeneous group of rare diseases characterized by fatigable muscle weakness. They are genetically-inherited and caused by defective synaptic transmission at the cholinergic neuromuscular junction (NMJ). The number of genes known to cause CMS when mutated is currently 30, and the relationship between fatigable muscle weakness and defective functions is quite well-understood for many of them. However, some of the most recent discoveries in individuals with CMS challenge our knowledge of the NMJ, where the basis of the pathology has mostly been investigated in animal models. Frontier forms between CMS and congenital myopathy, which have been genetically and clinically identified, underline the poorly understood interplay between the synaptic and extrasynaptic molecules in the neuromuscular system. In addition, precise electrophysiological and histopathological investigations of individuals with CMS suggest an important role of NMJ plasticity in the response to CMS pathogenesis. While efficient drug-based treatments are already available to improve neuromuscular transmission for most forms of CMS, others, as well as neurological and muscular comorbidities, remain resistant. Taken together, the available pathological data point to physiological issues which remain to be understood in order to achieve precision medicine with efficient therapeutics for all individuals suffering from CMS. PMID:29125502

  3. Congenital short QT syndrome and implantable cardioverter defibrillator treatment: inherent risk for inappropriate shock delivery.

    PubMed

    Schimpf, Rainer; Wolpert, Christian; Bianchi, Francesca; Giustetto, Carla; Gaita, Florenzo; Bauersfeld, Urs; Borggrefe, Martin

    2003-12-01

    A congenital short QT interval constitutes a new primary electrical abnormality associated with syncope and/or sudden cardiac death. We report on the initial use of implantable cardioverter defibrillator (ICD) therapy in patients with inherited short QT interval and discuss sensing abnormalities and detection issues. In five consecutive patients from two unrelated European families who had structurally normal hearts, excessively shortened QT intervals, and a strong positive family history of sudden cardiac death, ICDs were placed for primary and secondary prevention. Mean QT intervals were 252 +/- 13 ms (QTc 287 +/- 13 ms). Despite normal sensing behavior during intraoperative and postoperative device testing, 3 of 5 patients experienced inappropriate shock therapies for T wave oversensing 30 +/- 26 days after implantation. Programming lower sensitivities and decay delays prevented further inappropriate discharges. The congenital short QT syndrome constitutes a new clinical entity with an increased risk for sudden cardiac death. Currently, ICD treatment is the only therapeutic option. In patients with short QT interval and implanted ICD, increased risk for inappropriate therapy is inherent due to the detection of short-coupled and prominent T waves. Careful testing of ICD function and adaptation of sensing levels and decay delays without sacrificing correct arrhythmia detection are essential.

  4. Rubella and Congenital Rubella Syndrome in the Philippines: A Systematic Review

    PubMed Central

    Fabay, Xenia Cathrine J.; Vinarao, Ariel B.; Manalastas, Ricardo

    2016-01-01

    Background. As part of regional elimination efforts, rubella-containing vaccines (RCV) have recently been introduced in the Philippines, yet the true burden of rubella and congenital rubella syndrome (CRS) in the country is largely unknown. Objective. To provide baseline information on rubella and CRS prior to routine vaccine introduction in the Philippines. Methods. We conducted a systematic literature review on rubella and CRS in the Philippines, including a cross-sectional study conducted in 2002 among 383 pregnant women attending the obstetric outpatient clinic of the Philippine General Hospital to assess rubella susceptibility of women of childbearing age. Results. 15 locally published and unpublished studies were reviewed. Susceptibility to rubella among women of childbearing age was higher in rural communities. Retrospective reviews revealed congenital heart diseases, cataracts, and hearing impairments to be most common presentations in children of CRS. In the cross-sectional study, 59 (15.4%) of the 383 pregnant women enrolled were seronegative for rubella IgG. Conclusion. Similar to other countries introducing RCV, it was only recently that surveillance for rubella has been established. Previous studies show substantial disabilities due to CRS and a substantial proportion of susceptible women who are at risk for having babies affected with CRS. Establishment of CRS surveillance and enhanced awareness on rubella case detection should be prioritized. PMID:28115948

  5. A new case of holoprosencephaly-polydactyly syndrome with alobar holoprosencephaly, preaxial polydactyly and congenital glaucoma.

    PubMed

    Sandal, G; Tok, L; Ormeci, A R

    2014-01-01

    We report a case of a female baby born at 34 weeks of gestation. Birth weight was 1760 g (10th-25th centile), length 41cm (10th-25th centile) and head circumference 27cm (< 10th centile). Clinical examination revealed microcephaly, hypotelorism, micrognathia, a flat rudimentary nose, high palate, thick dysplastic low-set ears, a short neck, preaxial polydactyly of the right hand, and overriding toes. Investigations showed bilateral congenital glaucoma, alobar holoprosencephaly, severe ventriculomegaly and absence midline structures of the brain, a large atrial septal defect. The karyotype was 46,XX. The case was also diagnosed as having holoprosencephaly-polydactyly syndrome (pseudotrisomy 13) because she had alobar holoprosencephaly, preaxial polydactyly, facial dysmorfism (hypotelorism, micrognathia, a flat rudimentary nose, high palate, thick dysplastic low-set ears) and normal karyotype.

  6. A new device for the care of Congenital Central Hypoventilation Syndrome patients during sleep.

    PubMed

    Cavalleri, M; Carcano, A; Morandi, F; Piazza, C; Maggioni, E; Reni, G

    2013-01-01

    Congenital Central Hypoventilation Syndrome (CCHS) is a genetic disease that causes an autonomous nervous system dysregulation. Patients are unable to have a correct ventilation, especially during sleep, facing risk of death. Therefore, most of them are mechanically ventilated during night and their blood oxygenation is monitored, while a supervisor keeps watch over them. If low oxygen levels are detected by the pulse-oximeter, an alarm fires; the supervisor deals with the situation and, if there is neither a technical problem nor a false alarm, wakes the subject, as CCHS patients usually recover from hypoxia when roused from sleep. During a single night multiple alarms may occur, causing fractioned sleep for the subject and a lasting state of anxiety for supervisors.

  7. Congenital myasthenic syndrome due to novel CHAT mutations in an ethnic kadazandusun family.

    PubMed

    Tan, Joo-San; Ambang, Tomica; Ahmad-Annuar, Azlina; Rajahram, Giri Shan; Wong, Kum Thong; Goh, Khean Jin

    2016-05-01

    Choline acetyltransferase (CHAT) gene mutations cause a rare presynaptic congenital myasthenic syndrome due to impaired acetylcholine resynthesis. We report 2 Kadazandusun brothers with novel heterozygous CHAT mutations. The siblings were from a family of 7 children of nonconsanguineous parents, 3 who died from apneic crises. Both presented in infancy with ptosis and exertional limb weakness, but only 1 apnea episode was reported in the older sibling. The elder brother had a positive edrophonium test, and both were negative for acetylcholine receptor antibodies but improved with pyridostigmine treatment. A subsequent repetitive nerve stimulation test showed marked decremental response in the abductor digiti minimi only after prolonged ulnar nerve stimulation. Two novel CHAT gene mutations, p.Val306Leu and p.Ser704del were detected; the parents carried 1 mutation each. Differences in survival demonstrate phenotypic variability within the same family and a relatively good long-term outcome of the surviving siblings. © 2016 Wiley Periodicals, Inc.

  8. Autosomal dominant inheritance in Cantú syndrome (congenital hypertrichosis, osteochondrodysplasia, and cardiomegaly).

    PubMed

    Lazalde, B; Sánchez-Urbina, R; Nuño-Arana, I; Bitar, W E; de Lourdes Ramírez-Dueñas, M

    2000-10-23

    Cantú syndrome (CS) is characterized by congenital hypertrichosis, osteochondrodysplasia, cardiomegaly, and coarse facial appearance; autosomal recessive inheritance has been postulated. We report on a Mexican family with CS; the affected members are the 44-year-old father and his two children (a male and female), aged 14 and 4 years, respectively; each shows the classic characteristics, but the father and the brother also have a previously unreported feature, namely, a thick calvarium. This is the first reported instance of male-to-male transmission of CS. With the paternal age effect found in the reported sporadic cases and the segregation analysis [Robertson et al., 1999], autosomal dominant inheritance is more likely than autosomal recessive inheritance. The cases of affected sibs reported by Cantú et al. [1982] could be explained by parental gonadal mosaicism. Copyright 2000 Wiley-Liss, Inc.

  9. Fetal and neonatal abnormalities due to congenital rubella syndrome: a review of literature.

    PubMed

    Yazigi, Alexandre; De Pecoulas, Aurelia Eldin; Vauloup-Fellous, Christelle; Grangeot-Keros, Liliane; Ayoubi, Jean-Marc; Picone, Olivier

    2017-02-01

    Rubella virus infection during the first trimester of pregnancy can cause congenital rubella syndrome (CRS). We aimed to describe the abnormalities in order to define the ultrasound features to look for when performing prenatal scans. The goal of this review is to focus specifically on the signs of CRS accessible to prenatal diagnosis. We analyzed every case of CRS described before and/or after birth that we identified in the Pubmed database and classified them as accessible or not to prenatal diagnosis. The most frequently reported malformations accessible to prenatal diagnosis were: cardiac septal defects, pulmonary artery stenosis, microcephaly, cataract, microphtalmia, and hepatosplenomegaly. This extensive literature review shows that the ultrasound features of CRS are not well known, even though rubella was the first teratogenic virus described. This review will help clinicians in the management of rubella during pregnancy by clarifying the findings to be sought.

  10. Expanding the phenotype of congenital central hypoventilation syndrome impacts management decisions.

    PubMed

    Byers, Heather M; Chen, Maida; Gelfand, Andrew S; Ong, Bruce; Jendras, Marisa; Glass, Ian A

    2018-04-25

    Congenital central hypoventilation syndrome (CCHS) is a neurocristopathy caused by pathogenic heterozygous variants in the gene paired-like homeobox 2b (PHOX2B). It is characterized by severe infantile alveolar hypoventilation. Individuals may also have diffuse autonomic nervous system dysfunction, Hirschsprung disease and neural crest tumors. We report three individuals with CCHS due to an 8-base pair duplication in PHOX2B; c.691_698dupGGCCCGGG (p.Gly234Alafs*78) with a predominant enteral and neural crest phenotype and a relatively mild respiratory phenotype. The attenuated respiratory phenotype reported here and elsewhere suggests an emergent genotype:phenotype correlation which challenges the current paradigm of invoking mechanical ventilation for all infants diagnosed with CCHS. Best treatment requires careful clinical judgment and ideally the assistance of a care team with expertise in CCHS. © 2018 Wiley Periodicals, Inc.

  11. Genotype- and Phenotype-Guided Management of Congenital Long QT Syndrome

    PubMed Central

    Giudicessi, John R.; Ackerman, Michael J.

    2014-01-01

    Congenital Long QT syndrome (LQTS) is a genetically heterogeneous collection of heritable disorders of myocardial repolarization linked by their shared clinical phenotype of QT prolongation on electrocardiogram and an increased risk of potentially life-threatening cardiac arrhythmias. At the molecular level, mutations in 15 distinct LQTS-susceptibility genes that encode ion channel pore-forming α-subunits and accessory/auxiliary subunits central to the electromechanical function of the heart have been implicated in its pathogenesis. Over the past two decades, our evolving understanding of the electrophysiological mechanisms by which specific genetic substrates perturb the cardiac action potential has translated into vastly improved approaches to the diagnosis, risk stratification, and treatment of patients with LQTS. In this Review, we detail how our understanding of the molecular underpinnings of LQTS has yielded numerous clinically meaningful genotype-phenotype correlations and how these insights have translated into genotype- and phenotype-guided approaches to the clinical management of LQTS. PMID:24093767

  12. WAGR syndrome and congenital hypothyroidism in a child with a Mosaic 11p13 deletion.

    PubMed

    Huynh, Minh Tuan; Boudry-Labis, Elise; Duban, Bénédicte; Andrieux, Joris; Tran, Cong Toai; Tampere, Heidi; Ceraso, Delphine; Manouvrier, Sylvie; Tachdjian, Gérard; Roche-Lestienne, Catherine; Vincent-Delorme, Catherine

    2017-06-01

    Wilm's tumor, aniridia, genitourinary anomalies, and mental retardation (WAGR) syndrome, a rare genetic disorder, is caused by the loss of 11p13 region including PAX6 and WT1. We report novel findings in a 28-month-old boy with aniridia, Wilm's tumor, congenital hypothyroidism, and sublingual thyroid ectopia. He was found to have a mosaic 5.28 Mb interstitial deletion of chromosome 11p13 deleting PAX6 and WT1. In order to clarify the mechanism underlying his thyroid dysgenesis, sequence analysis of candidate thyroid developmental genes was performed. We identified a FOXE1: c.532_537delGCCGCC p.(Ala178_Ala179del) variant that predisposes to thyroid ectopia. Taken together, this is the first report of mosaic 11p13 deletion in association with thyroid dysgenesis. We also propose a model of complex interactions of different genetic variants for this particular phenotype in the present patient. © 2017 Wiley Periodicals, Inc.

  13. Syndromic congenital diarrhoea: new SPINT2 mutation identified in the UAE.

    PubMed

    Bou Chaaya, Solange; Eason, Julian D; Ofoegbu, Bibian N

    2017-07-16

    We are reporting a new mutation in the SPINT2 gene (c.443G>A (p. Arg148His)) that explains the association of choanal atresia with congenital sodium diarrhoea (CSD) in an Emirati family in the Middle East. To our knowledge, this mutation is neither listed in a mutation database nor described in the literature. Similar to other patients with CSD associated with SPINT2, this child remains dependent on parenteral nutrition for fluids and nutritional support resulting in failure to thrive. The determination of the molecular basis of syndromic CSD will facilitate prenatal and postnatal diagnosis of patients and will contribute to counselling of affected families, especially in areas like the UAE where consanguineous marriages are not uncommon. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  14. Bilateral congenital lacrimal fistulas in an adult as part of ectrodactyly-ectodermal dysplasia-clefting syndrome: A rare anomaly.

    PubMed

    Ghosh, Debangshu; Saha, Somnath; Basu, Sumit Kumar

    2015-10-01

    Ectrodactyly-ectodermal dysplasia and clefting syndrome or "Lobster claw" deformity is a rare congenital anomaly that affects tissues of ectodermal and mesodermal origin. Nasolacrimal duct (NLD) obstruction with or without atresia of lacrimal passage is a common finding of such a syndrome. The authors report here even a rarer presentation of the syndrome which manifested as bilateral NLD obstruction and lacrimal fistula along with cleft lip and palate, syndactyly affecting all four limbs, mild mental retardation, otitis media, and sinusitis. Lacrimal duct obstruction and fistula were managed successfully with endoscopic dacryocystorhinostomy (DCR) which is a good alternative to lacrimal probing or open DCR in such a case.

  15. SCALP syndrome: sebaceous nevus syndrome, CNS malformations, aplasia cutis congenita, limbal dermoid, and pigmented nevus (giant congenital melanocytic nevus) with neurocutaneous melanosis: a distinct syndromic entity.

    PubMed

    Lam, Joseph; Dohil, Magdalene A; Eichenfield, Lawrence F; Cunningham, Bari B

    2008-05-01

    Nevus sebaceus syndrome (SNS) is a constellation of nevus sebaceus with extracutaneous findings, including the ophthalmologic nervous, and musculoskeletal systems. Didymosis aplasticosebacea is a recently described entity consisting of aplasia cutis congenita and nevus sebaceus, implying twin spotting (didymosis). We describe a neonate with a nevus sebaceus on the scalp and a limbal dermoid on her left eye. Contiguous with the nevus sebaceus was a giant congenital melanocytic nevus and numerous areas of membranous aplasia cutis congenita. We propose the acronym SCALP (nevus sebaceus, central nervous system malformations, aplasia cutis congenita, limbal dermoid, pigmented nevus) to summarize the unique features of this case and review the two similar cases in the literature.

  16. Ephedrine treatment in congenital myasthenic syndrome due to mutations in DOK7(LOE Classification)

    PubMed Central

    Lashley, D.; Palace, J.; Jayawant, S.; Robb, S.; Beeson, D.

    2010-01-01

    Background: Mutations in the postsynaptic adaptor protein Dok-7 underlie congenital myasthenic syndrome (CMS) with a characteristic limb girdle pattern of muscle weakness. Patients usually do not respond to or worsen with the standard CMS treatments: cholinesterase inhibitors and 3,4-diaminopyridine. However, anecdotal reports suggest they may improve with ephedrine. Methods: This was an open prospective follow-up study to determine muscle strength in response to ephedrine in Dok-7 CMS. Patients were first evaluated as inpatients for suitability for a trial of treatment with ephedrine. The response was assessed at 2 and 6 to 8 months follow-up clinic visits using a quantitative myasthenia gravis (severity) score (QMG) and mobility measures. Results: Ten out of 12 of the cohort with DOK7 mutations tolerated ephedrine. We noted a progressive response to treatment over the 6 to 8 months assessment period with a significant improvement at the final QMG score (p = 0.009). Mobility scores also improved (p = 0.0006). Improvements in the subcomponents of the QMG score that measured proximal muscle function (those muscle groups most severely affected) were most marked, and in some cases were dramatic. All patients reported enhanced activities of daily living at 6–8 months. Conclusion: Ephedrine appears to be an effective treatment for Dok-7 CMS. It is well-tolerated by most patients and improvement in strength can be profound. Determining the long-term response and the most effective dosing regimen will require further research. Classification of evidence: This study provides Class IV evidence that ephedrine given at doses between 15 and 90 mg/day improves muscle strength in patients with documented mutations in DOK7. GLOSSARY 3,4-DAP = 3,4-diaminopyridine; CMS = congenital myasthenic syndrome; EOM = external ocular muscles; FVC = forced vital capacity; MuSK = muscle-specific tyrosine kinase; NMJ = neuromuscular junction; QMG = quantitative myasthenia gravis (severity

  17. Mapping of the locus for congenital nephrotic syndrome of the Finnish type (CNF) on chromosome 19

    SciTech Connect

    Kestilae, M.; Maennikkoe, M.; Tryggvason, K.

    1994-09-01

    Congenital nephrotic syndrome of the Finnish type (CNF) is an autosomal recessive disease which forms a distinct entity among congenital nephrotic syndromes. It is characterized by massive proteinuria starting already in utero, large placenta and manifestation of nephrosis soon after birth. The incidence in Finland is about 1 in 8000 newborns, and the disease has been reported occasionally in other countries, particularly in Minnesota, USA. The gene defect in CNF is unknown, but the gene product is likely to be important for kidney development of glomerular filtration. We have used a random mapping approach in 17 Finnish CNF families resultingmore » in the localization of the gene to chromosome 19q12-q13.1. Based on observed recombination events, the CNF locus is flanked by markers D19S191 and D19S224 corresponding to a region under 1 Mb in physical length. Cosmid contigs have been isolated from this region and at least two new polymorphic CA-repeat markers (MKMM1, MKMM2) have been identified from those clones. Statistically highly significant linkage disequilibrium can be observed with markers MKMM1, D19S224 and D19S220, the allelic association being about 65%. The most common haplotype, which was combined from these markers, is found in 60% of chromosomes carrying the CNF mutation. This work has enabled DNA-based diagnosis of CNF, and recently linkage and linkage disequilibrium analyses were used in prenatal diagnostics in a family with one affected child and two healthy siblings. DNA isolated from chorion villus biopsy was analyzed using markers D19S191, MKMM1, D19S224 and D19S220, and the fetus was shown to have the same genotype as the affected child.« less

  18. Pediatric patient with systemic lupus erythematosus & congenital acquired immunodeficiency syndrome: An unusual case and a review of the literature

    PubMed Central

    Chalom, Elizabeth C; Rezaee, Fariba; Mendelson, Joel

    2008-01-01

    The coexistence of systemic lupus erythematosus (SLE) in patients with congenital human immunodeficiency virus (HIV) infection is rare. This is a case report of a child diagnosed with SLE at nine years of age. She initially did well on non-steroidal anti-inflammatory agents, hydroxychloroquine, and steroids. She then discontinued her anti-lupus medications and was lost to follow-up. At 13 years of age, her lupus symptoms had resolved and she presented with intermittent fevers, cachexia, myalgias, arthralgias, and respiratory symptoms. Through subsequent investigations, the patient was ultimately diagnosed with congenitally acquired immunodeficiency syndrome (AIDS). PMID:18452619

  19. Pediatric patient with systemic lupus erythematosus & congenital acquired immunodeficiency syndrome: An unusual case and a review of the literature.

    PubMed

    Chalom, Elizabeth C; Rezaee, Fariba; Mendelson, Joel

    2008-05-01

    The coexistence of systemic lupus erythematosus (SLE) in patients with congenital human immunodeficiency virus (HIV) infection is rare. This is a case report of a child diagnosed with SLE at nine years of age. She initially did well on non-steroidal anti-inflammatory agents, hydroxychloroquine, and steroids. She then discontinued her anti-lupus medications and was lost to follow-up. At 13 years of age, her lupus symptoms had resolved and she presented with intermittent fevers, cachexia, myalgias, arthralgias, and respiratory symptoms. Through subsequent investigations, the patient was ultimately diagnosed with congenitally acquired immunodeficiency syndrome (AIDS).

  20. Recurrent progressive anterior segment fibrosis syndrome following a descemet-stripping endothelial keratoplasty in an infant with congenital aniridia

    PubMed Central

    Kothari, Mihir; Rao, Kavita; Moolani, Samita

    2014-01-01

    Progressive anterior segment fibrosis syndrome (ASFS), after intraocular surgery in older children (≥9 years) and adults with congenital aniridia, is described in the literature. In this report, we describe an unique case of ASFS in an infant with congenital aniridia following a combined trabeculotomy-ectomy and its recurrence after a descemet stripping endothelial keratoplasty. The ophthalmologists should be well aware of this entity and warn the parents about its possibilities. Use of immunomodulators or prolonged anti-inflammatory therapy may be considered to prevent its occurrence. PMID:24618492

  1. Phakomatosis Pigmentovascularis Associated With Sturge–Weber Syndrome, Ota Nevus, and Congenital Glaucoma

    PubMed Central

    Yang, Yangfan; Guo, Xiujuan; Xu, Jiangang; Ye, Yiming; Liu, Xiaoan; Yu, Minbin

    2015-01-01

    Abstract Phakomatosis pigmentovascularis (PPV) is a rare congenital malformation syndrome that is characterized by a combination of capillary abnormalities and dermal melanocytosis. We describe 3 cases of PPV combined with bilateral Sturge–Weber syndrome (SWS), Ota nevus, and congenital glaucoma. Case 1 was a 2-year-old boy. Facial port-wine stains distributed along the 3 branches of his trigeminal nerves, which suggested the existence of SWS. Gray-blue patches were spread over the frontal and temporal areas of bilateral face, waist, buttocks, and thigh. Bilateral triangular alopecia was found on the temporal scalp. The diagnosis of Ota nevus was made by the bilateral scleral malanocystosis. Increased intraocular pressure, enlarged cornea, and pathologic optic disc cupping supported the diagnoses of infantile bilateral glaucoma. Case 2 was a 4-year-old boy. Port-wine stains were found on the face along the 3 branches of the trigeminal nerve and distributed along the trunk, arms, and legs. Mongolian spots spread over his frontal and temporal areas of the bilateral face, waist, buttocks, thigh, abdomen, and back. Infantile glaucoma was found in both eyes. Ota nevus were found in the both eyes. Optic coherent tomography (OCT) scans revealed increased thickness of choroid. Case 3 was a 5-year-old boy. Besides Ota nevus and infantile glaucoma in both eyes, color Doppler ultrasonography showed choroidal hemagioma. OCT scan showed increased choroidal thickness. The bilateral triangular alopecia on the child's temporal scalp was similar to that of Case 1. Cases 1 and 2 presented with port-wine stain patches that were consistent with the characteristic manifestation of PPV type IIb. However, the CMTC of Case 3 met the diagnostic criteria for PPV type Vb. Case 1 was treated with trabeculotomies in both eyes. For Cases 2 and 3, surgical interventions were not considered due to the high risks of antiglaucomatous operation complications. We prescribed them antiglaucoma

  2. Non-syndromic congenital hypogonadotropic hypogonadism: clinical presentation and genotype-phenotype relationships.

    PubMed

    Brioude, Frédéric; Bouligand, Jérôme; Trabado, Séverine; Francou, Bruno; Salenave, Sylvie; Kamenicky, Peter; Brailly-Tabard, Sylvie; Chanson, Philippe; Guiochon-Mantel, Anne; Young, Jacques

    2010-05-01

    Congenital hypogonadotropic hypogonadism (CHH) results from abnormal gonadotropin secretion, and it is characterized by impaired pubertal development. CHH is caused by defective GNRH release, or by a gonadotrope cell dysfunction in the pituitary. Identification of genetic abnormalities related to CHH has provided major insights into the pathways critical for the development, maturation, and function of the reproductive axis. Mutations in five genes have been found specifically in Kallmann's syndrome, a disorder in which CHH is related to abnormal GNRH neuron ontogenesis and is associated with anosmia or hyposmia. In combined pituitary hormone deficiency or in complex syndromic CHH in which gonadotropin deficiency is either incidental or only one aspect of a more complex endocrine disorder or a non-endocrine disorder, other mutations affecting GNRH and/or gonadotropin secretion have been reported. Often, the CHH phenotype is tightly linked to an isolated deficiency of gonadotropin secretion. These patients, who have no associated signs or hormone deficiencies independent of the deficiency in gonadotropin and sex steroids, have isolated CHH. In some familial cases, they are due to genetic alterations affecting GNRH secretion (mutations in GNRH1, GPR54/KISS1R and TAC3 and TACR3) or the GNRH sensitivity of the gonadotropic cells (GNRHR). A minority of patients with Kallmann's syndrome or a syndromic form of CHH may also appear to have isolated CHH, but close clinical, familial, and genetic studies can reorient the diagnosis, which is important for genetic counseling in the context of assisted reproductive medicine. This review focuses on published cases of isolated CHH, its clinical and endocrine features, genetic causes, and genotype-phenotype relationships.

  3. Mutations in SPINT2 cause a syndromic form of congenital sodium diarrhea.

    PubMed

    Heinz-Erian, Peter; Müller, Thomas; Krabichler, Birgit; Schranz, Melanie; Becker, Christian; Rüschendorf, Franz; Nürnberg, Peter; Rossier, Bernard; Vujic, Mihailo; Booth, Ian W; Holmberg, Christer; Wijmenga, Cisca; Grigelioniene, Giedre; Kneepkens, C M Frank; Rosipal, Stefan; Mistrik, Martin; Kappler, Matthias; Michaud, Laurent; Dóczy, Ludwig-Christoph; Siu, Victoria Mok; Krantz, Marie; Zoller, Heinz; Utermann, Gerd; Janecke, Andreas R

    2009-02-01

    Autosomal-recessive congenital sodium diarrhea (CSD) is characterized by perinatal onset of a persistent watery diarrhea with nonproportionally high fecal sodium excretion. Defective jejunal brush-border Na(+)/H(+) exchange has been reported in three sporadic patients, but the molecular basis of the disease has not been elucidated. We reviewed data from a large cohort of CSD patients (n = 24) and distinguished CSD associated with choanal or anal atresia, hypertelorism, and corneal erosions--i.e., a syndromic form of CSD--occurring in ten families from an isolated form--i.e., classic CSD--presenting in seven families. Patients from both groups have a high risk of mortality due to immediate electrolyte imbalances and complications from long-term parenteral nutrition in the first years of life, but survivors can eventually adapt to partial or complete enteral nutrition. A genome-wide SNP scan was applied and identified a homozygous c.593-1G-->A splicing mutation in SPINT2, encoding a Kunitz-type serine-protease inhibitor, in one extended kindred with syndromic CSD. The same mutation and four distinct, homozygous or compound heterozygous mutations (p.Y163C, c.1A-->T, c.337+2T-->C, c.553+2T-->A) were identified in all syndromic patients. No SPINT2 mutations were found in classic-CSD patients. SPINT2 mutations were associated with loss of protein synthesis or failure to inhibit the serine protease trypsin in vitro. We delineate syndromic CSD as a distinct disease entity caused by SPINT2 loss-of-function mutations. SPINT2 mutations might lead to an excess of yet unknown serine protease activity in affected tissues.

  4. Mutations in SPINT2 Cause a Syndromic Form of Congenital Sodium Diarrhea

    PubMed Central

    Heinz-Erian, Peter; Müller, Thomas; Krabichler, Birgit; Schranz, Melanie; Becker, Christian; Rüschendorf, Franz; Nürnberg, Peter; Rossier, Bernard; Vujic, Mihailo; Booth, Ian W.; Holmberg, Christer; Wijmenga, Cisca; Grigelioniene, Giedre; Kneepkens, C. M. Frank; Rosipal, Stefan; Mistrik, Martin; Kappler, Matthias; Michaud, Laurent; Dóczy, Ludwig-Christoph; Siu, Victoria Mok; Krantz, Marie; Zoller, Heinz; Utermann, Gerd; Janecke, Andreas R.

    2009-01-01

    Autosomal-recessive congenital sodium diarrhea (CSD) is characterized by perinatal onset of a persistent watery diarrhea with nonproportionally high fecal sodium excretion. Defective jejunal brush-border Na+/H+ exchange has been reported in three sporadic patients, but the molecular basis of the disease has not been elucidated. We reviewed data from a large cohort of CSD patients (n = 24) and distinguished CSD associated with choanal or anal atresia, hypertelorism, and corneal erosions—i.e., a syndromic form of CSD—occurring in ten families from an isolated form—i.e., classic CSD—presenting in seven families. Patients from both groups have a high risk of mortality due to immediate electrolyte imbalances and complications from long-term parenteral nutrition in the first years of life, but survivors can eventually adapt to partial or complete enteral nutrition. A genome-wide SNP scan was applied and identified a homozygous c.593−1G→A splicing mutation in SPINT2, encoding a Kunitz-type serine-protease inhibitor, in one extended kindred with syndromic CSD. The same mutation and four distinct, homozygous or compound heterozygous mutations (p.Y163C, c.1A→T, c.337+2T→C, c.553+2T→A) were identified in all syndromic patients. No SPINT2 mutations were found in classic-CSD patients. SPINT2 mutations were associated with loss of protein synthesis or failure to inhibit the serine protease trypsin in vitro. We delineate syndromic CSD as a distinct disease entity caused by SPINT2 loss-of-function mutations. SPINT2 mutations might lead to an excess of yet unknown serine protease activity in affected tissues. PMID:19185281

  5. Prevalence and profile of congenital heart disease and pulmonary hypertension in Down syndrome in a pediatric cardiology service

    PubMed Central

    Mourato, Felipe Alves; Villachan, Lúcia Roberta R.; Mattos, Sandra da Silva

    2014-01-01

    OBJECTIVE: To determine the frequence and profile of congenital heart defects in Down syndrome patients referred to a pediatric cardiologic center, considering the age of referral, gender, type of heart disease diagnosed by transthoracic echocardiography and its association with pulmonary hypertension at the initial diagnosis. METHODS: Cross-sectional study with retrospective data collection of 138 patients with Down syndrome from a total of 17,873 records. Descriptive analysis of the data was performed, using Epi-Info version 7. RESULTS: Among the 138 patients with Down syndrome, females prevailed (56.1%) and 112 (81.2%) were diagnosed with congenital heart disease. The most common lesion was ostium secundum atrial septal defect, present in 51.8%, followed by atrioventricular septal defect, in 46.4%. Ventricular septal defects were present in 27.7%, while tetralogy of Fallot represented 6.3% of the cases. Other cardiac malformations corresponded to 12.5%. Pulmonary hypertension was associated with 37.5% of the heart diseases. Only 35.5% of the patients were referred before six months of age. CONCLUSIONS: The low percentage of referral until six months of age highlights the need for a better tracking of patients with Down syndrome in the context of congenital heart disease, due to the high frequency and progression of pulmonary hypertension. PMID:25119745

  6. Surgical and visual outcomes of the type I Boston Keratoprosthesis for the management of aniridic fibrosis syndrome in congenital aniridia.

    PubMed

    Bakhtiari, Pejman; Chan, Clara; Welder, Jeffrey D; de la Cruz, Jose; Holland, Edward J; Djalilian, Ali R

    2012-05-01

    To report the clinical features and surgical management of aniridic fibrosis syndrome using the type I Boston Keratoprosthesis (KPro). Interventional case series. Retrospective chart review of 9 eyes in 9 patients with congenital aniridia that developed aniridic fibrosis syndrome. All patients had clinical diagnosis of congenital aniridia. Previously, all patients had undergone cataract surgery with posterior chamber intraocular lens (IOL) implantation and 7 patients had existing tube shunts. In all cases, fibrosis presented as progressive retrocorneal and retrolenticular membrane formation causing displacement of the IOL and secondary corneal decompensation. Two eyes had tractional folds in the retina with posterior extension of the membrane. The management included IOL explantation in 7 of 9 cases, removal of fibrosis with pars plana vitrectomy in all 9 patients, and implantation of a type I Boston KPro in all eyes. At a mean final follow-up of 26.1 months (range 6 to 48 months), vision remained improved in all patients. No patient had recurrence of the fibrotic membrane after KPro implantation. This study represents another case series describing aniridic fibrosis syndrome and the largest study to report utilization of the type I Boston KPro in such patients. As the fibrosis can cause IOL dislocation, corneal decompensation, hypotony, and retinal detachment, monitoring for aniridic fibrosis syndrome in congenital aniridia with early surgical intervention is recommended. Type I Boston KPro may be considered in the surgical treatment of this condition. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Aberrant neural responses to cold pressor challenges in congenital central hypoventilation syndrome.

    PubMed

    Macey, Paul M; Macey, Katherine E; Woo, Mary A; Keens, Thomas G; Harper, Ronald M

    2005-04-01

    Patients with congenital central hypoventilation syndrome (CCHS), a condition characterized by impaired ventilatory responses to chemoreceptor stimulation, do not show the normal increase in respiratory rate and respiratory-related heart rate variation to cold forehead stimulation, a challenge that bypasses central chemoreceptors. We hypothesized that a forehead cold pressor challenge would reveal abnormal neural response patterns, as assessed by functional magnetic resonance imaging, in brain regions that are responsible for the integration of cold afferent stimulation with respiratory and cardiovascular output in patients with CCHS. Primary sensory thalamic and cortical areas for the forehead showed diminished responses in 13 patients with CCHS (ventilator dependent during sleep but not waking, no Hirschsprung's disease) compared with 14 control subjects, despite initial signal changes in the cortex being similar in both groups. Cerebellar cortex and deep nuclei; basal ganglia; and middle to posterior cingulate, insular, frontal, and temporal cortices showed reduced signal rises in patients with CCHS. Areas within the frontal and anterior cingulate cortices exhibited marked signal declines in control subjects but little change in patients with CCHS. No response occurred in either group in the dorsal medulla, but medial and ventral medullary areas showed enhanced signals in patients with CCHS. The cold pressor stimulation did not recruit dorsal medullary sites that would be affected by PHOX2B (a mutation of which is associated with the syndrome) expression in either group but demonstrated deficient cerebellar and medial medullary influences that, by action on rostral sites, may underlie the loss of respiratory responses.

  8. A case of craniofacial dysmorphism, congenital heart defects, coccygeal skin folds, generalized skeletal alterations, and hemihypertrophy with linear skin hypopigmentation: a new syndrome?

    PubMed

    Nishimura, G; Nagai, T

    1998-01-01

    The case of a Japanese girl with a unique combination of congenital malformations is reported. The malformations include craniofacial dysmorphism, congenital heart defects, coccygeal skin folds, generalized skeletal alterations, and hemihypertrophy with linear skin hypopigmentation that indicated somatic mosaicism of a mutated gene or a submicroscopic chromosomal aberration. The phenotype in our patient overlapped significantly with, but was not completely consistent with, that of ter Haar syndrome, a recently elucidated malformation syndrome with an autosomal recessive trait. The present patient may have represented a previously undescribed malformation syndrome, or an atypical manifestation of ter Haar syndrome due to somatic mosaicism.

  9. Genotype Positive Long QT Syndrome in Patients With Coexisting Congenital Heart Disease.

    PubMed

    Ebrahim, Mohammed A; Williams, Matthew R; Shepard, Suzanne; Perry, James C

    2017-07-15

    Congenital long QT syndrome (LQTS) is characterized by QT prolongation with predisposition to life-threatening arrhythmia. There have been sporadic reports of LQTS coexisting with more common forms of congenital heart disease (CHD). However, the diagnosis of LQTS when CHD is present may be confounded by several common variables including postoperative electromechanical factors predisposing to ventricular arrhythmia, intrinsic, and postoperative QRS abnormalities. This report documents a single-center experience with patients who have both genetically confirmed LQTS and CHD to examine their modes of presentation and factors associated with making the diagnosis of LQTS in this patient population, as well as potential confounding variables that may mask or delay both LQTS diagnosis and initiation of therapy. A retrospective review was performed of subjects with confirmed LQTS and associated CHD from 1999 to January 2017. Genetic analysis was performed predominantly using commercially available panel testing. A chart review included detailed analysis of electrocardiograms, 24-hour 3-lead rhythm monitors and exercise stress test tracings as well as the genetic test reports. QT intervals were measured using Bazett's formula. Eleven patients were identified. Four patients had LQTS type 1, 6 had LQTS type 2, and 1 had a disease-associated mutation in KCNQ1 and a variant of unknown significance in KCNH2 gene. Two patients had positive cascade screening. Arrhythmia presentations of the LQTS were at both extremes of the cohort age range (in-utero and midchildhood age). There was a seeming overrepresentation of conotruncal anomalies and/or arch anomalies, with 7 of the 11 patients. In conclusion, the diagnosis of LQTS may be challenging in the setting of CHD (a prolonged ST segment may be helpful), and high index of suspicion is required. The overall incidence of LQTS in CHD appears extremely rare, but the diagnosis and true incidence may be masked by confounding

  10. Prenatal diagnosis of 17q12 duplication and deletion syndrome in two fetuses with congenital anomalies.

    PubMed

    Li, Ru; Fu, Fang; Zhang, Yong-Ling; Li, Dong-Zhi; Liao, Can

    2014-12-01

    The objective of this study was to characterize the genetic abnormalities in two fetuses with congenital anomalies in prenatal screening. The mother of Fetus 1 was 26 years old and had a second trimester serum screening that indicated the fetus was at low risk. The prenatal ultrasound and magnetic resonance imaging (MRI) at 28 weeks of gestation showed mild ventriculomegaly, microcephaly, and agenesis of the corpus callosum. The mother of Fetus 2 was 25 years old and also had a second trimester serum screening that indicated the fetus was at low risk. The prenatal ultrasound at 32 weeks of gestation showed the presence of hyperechogenic and enlarged kidneys with multicystic renal dysplasia bilaterally and a persistent left superior vena cava (PLSVC). Both pregnant women underwent cord blood samplings because of the abnormal imaging results. Karyotype analysis revealed normal results in the two fetuses. Chromosome microarray analysis (CMA) was then performed to provide genetic analysis of the cord blood and parental blood samples. Ultimately, the pregnancies were both terminated. CMA detected a 1.56-Mb duplication at 17q12 in Fetus 1 and a 1.93-Mb deletion of 17q12 in Fetus 2. Both the duplicated and deleted regions included the HNF1B and LHX1 genes. Neither the duplication nor deletion was inherited from the parents. This study is the first to report the prenatal diagnosis of a 17q12 duplication syndrome. Our results further confirmed that genes in this region, including HNF1B and LHX1, are essential for normal brain and kidney development, and also indicated some genes that may be associated with the cardiovascular abnormality. Combined with imaging examination, the use of CMA will improve the diagnosis of submicroscopic chromosomal aberrations in fetuses with congenital anomalies. Copyright © 2014. Published by Elsevier B.V.

  11. Down syndrome: molecular mapping of the congenital heart disease and duodenal stenosis.

    PubMed Central

    Korenberg, J R; Bradley, C; Disteche, C M

    1992-01-01

    Down syndrome (DS) is a major cause of congenital heart and gut disease and mental retardation. DS individuals also have characteristic facies, hands, and dermatoglyphics, in addition to abnormalities of the immune system, an increased risk of leukemia, and an Alzheimer-like dementia. Although their molecular basis is unknown, recent work on patients with DS and partial duplications of chromosome 21 has suggested small chromosomal regions located in band q22 that are likely to contain the genes for some of these features. We now extend these analyses to define molecular markers for the congenital heart disease, the duodenal stenosis, and an "overlap" region for the facial and some of the skeletal features. We report the clinical, cytogenetic, and molecular analysis of two patients. The first is DUP21JS, who carries both a partial duplication of chromosome 21, including the region 21q21.1-q22.13, or proximal q22.2, and DS features including duodenal stenosis. Using quantitative Southern blot dosage analysis and 15 DNA sequences unique to chromosome 21, we have defined the molecular extent of the duplication. This includes the region defined by DNA sequences for APP (amyloid precursor protein), SOD1 (CuZn superoxide dismutase), D21S47, SF57, D21S17, D21S55, D21S3, and D21S15 and excludes the regions defined by DNA sequences for D21S16, D21S46, D21S1, D21S19, BCE I (breast cancer estrogen-inducible gene), D21S39, and D21S44. Using similar techniques, we have also defined the region duplicated in the second case occurring in a family carrying a translocation associated with DS and congenital heart disease. This region includes DNA sequences for D21S55 and D21S3 and excludes DNA sequences for D21S47 and D21S17.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 1 Figure 2 Figure 4 PMID:1531166

  12. "Fear of Success" Revisited: A Replication of Matina Horner's Study 30 Years Later.

    ERIC Educational Resources Information Center

    Engle, Jennifer

    This study updated and extended the classic "fear of success" study conducted by Matina Horner more than 30 years ago. Horner (1970) asked college students to respond to a scenario in which "Anne" or "John" is at the top of her/his medical school class. Based on the negative responses of students to "Anne,"…

  13. A Phenomenological Reinterpretation of Horner's Fear of Success in Terms of Social Class

    ERIC Educational Resources Information Center

    Ivers, Jo-Hanna; Downes, P.

    2012-01-01

    The current study developed the concept of fear of success that was originally examined by Martina Horner (1970; "Journal of Social Issues", 28(2), 157-175, 1972). The key dimension in Horner's (1970; "Journal of Social Issues", 28(2), 157-175, 1972) studies was gender. The key dimension in the current study was social class. It was hypothesised…

  14. Spectrum of Steroid-Resistant and Congenital Nephrotic Syndrome in Children: The PodoNet Registry Cohort

    PubMed Central

    Trautmann, Agnes; Bodria, Monica; Ozaltin, Fatih; Gheisari, Alaleh; Melk, Anette; Azocar, Marta; Anarat, Ali; Caliskan, Salim; Emma, Francesco; Gellermann, Jutta; Oh, Jun; Baskin, Esra; Ksiazek, Joanna; Remuzzi, Giuseppe; Erdogan, Ozlem; Akman, Sema; Dusek, Jiri; Davitaia, Tinatin; Özkaya, Ozan; Papachristou, Fotios; Firszt-Adamczyk, Agnieszka; Urasinski, Tomasz; Testa, Sara; Krmar, Rafael T.; Hyla-Klekot, Lidia; Pasini, Andrea; Özcakar, Z. Birsin; Sallay, Peter; Cakar, Nilgun; Galanti, Monica; Terzic, Joelle; Aoun, Bilal; Caldas Afonso, Alberto; Szymanik-Grzelak, Hanna; Lipska, Beata S.; Schnaidt, Sven

    2015-01-01

    Background and objectives Steroid-resistant nephrotic syndrome is a rare kidney disease involving either immune-mediated or genetic alterations of podocyte structure and function. The rare nature, heterogeneity, and slow evolution of the disorder are major obstacles to systematic genotype-phenotype, intervention, and outcome studies, hampering the development of evidence-based diagnostic and therapeutic concepts. To overcome these limitations, the PodoNet Consortium has created an international registry for congenital nephrotic syndrome and childhood-onset steroid-resistant nephrotic syndrome. Design, setting, participants, & measurements Since August of 2009, clinical, biochemical, genetic, and histopathologic information was collected both retrospectively and prospectively from 1655 patients with childhood-onset steroid-resistant nephrotic syndrome, congenital nephrotic syndrome, or persistent subnephrotic proteinuria of likely genetic origin at 67 centers in 21 countries through an online portal. Results Steroid-resistant nephrotic syndrome manifested in the first 5 years of life in 64% of the patients. Congenital nephrotic syndrome accounted for 6% of all patients. Extrarenal abnormalities were reported in 17% of patients. The most common histopathologic diagnoses were FSGS (56%), minimal change nephropathy (21%), and mesangioproliferative GN (12%). Mutation screening was performed in 1174 patients, and a genetic disease cause was identified in 23.6% of the screened patients. Among 14 genes with reported mutations, abnormalities in NPHS2 (n=138), WT1 (n=48), and NPHS1 (n=41) were most commonly identified. The proportion of patients with a genetic disease cause decreased with increasing manifestation age: from 66% in congenital nephrotic syndrome to 15%–16% in schoolchildren and adolescents. Among various intensified immunosuppressive therapy protocols, calcineurin inhibitors and rituximab yielded consistently high response rates, with 40%–45% of patients

  15. Spectrum of steroid-resistant and congenital nephrotic syndrome in children: the PodoNet registry cohort.

    PubMed

    Trautmann, Agnes; Bodria, Monica; Ozaltin, Fatih; Gheisari, Alaleh; Melk, Anette; Azocar, Marta; Anarat, Ali; Caliskan, Salim; Emma, Francesco; Gellermann, Jutta; Oh, Jun; Baskin, Esra; Ksiazek, Joanna; Remuzzi, Giuseppe; Erdogan, Ozlem; Akman, Sema; Dusek, Jiri; Davitaia, Tinatin; Özkaya, Ozan; Papachristou, Fotios; Firszt-Adamczyk, Agnieszka; Urasinski, Tomasz; Testa, Sara; Krmar, Rafael T; Hyla-Klekot, Lidia; Pasini, Andrea; Özcakar, Z Birsin; Sallay, Peter; Cakar, Nilgun; Galanti, Monica; Terzic, Joelle; Aoun, Bilal; Caldas Afonso, Alberto; Szymanik-Grzelak, Hanna; Lipska, Beata S; Schnaidt, Sven; Schaefer, Franz

    2015-04-07

    Steroid-resistant nephrotic syndrome is a rare kidney disease involving either immune-mediated or genetic alterations of podocyte structure and function. The rare nature, heterogeneity, and slow evolution of the disorder are major obstacles to systematic genotype-phenotype, intervention, and outcome studies, hampering the development of evidence-based diagnostic and therapeutic concepts. To overcome these limitations, the PodoNet Consortium has created an international registry for congenital nephrotic syndrome and childhood-onset steroid-resistant nephrotic syndrome. Since August of 2009, clinical, biochemical, genetic, and histopathologic information was collected both retrospectively and prospectively from 1655 patients with childhood-onset steroid-resistant nephrotic syndrome, congenital nephrotic syndrome, or persistent subnephrotic proteinuria of likely genetic origin at 67 centers in 21 countries through an online portal. Steroid-resistant nephrotic syndrome manifested in the first 5 years of life in 64% of the patients. Congenital nephrotic syndrome accounted for 6% of all patients. Extrarenal abnormalities were reported in 17% of patients. The most common histopathologic diagnoses were FSGS (56%), minimal change nephropathy (21%), and mesangioproliferative GN (12%). Mutation screening was performed in 1174 patients, and a genetic disease cause was identified in 23.6% of the screened patients. Among 14 genes with reported mutations, abnormalities in NPHS2 (n=138), WT1 (n=48), and NPHS1 (n=41) were most commonly identified. The proportion of patients with a genetic disease cause decreased with increasing manifestation age: from 66% in congenital nephrotic syndrome to 15%-16% in schoolchildren and adolescents. Among various intensified immunosuppressive therapy protocols, calcineurin inhibitors and rituximab yielded consistently high response rates, with 40%-45% of patients achieving complete remission. Confirmation of a genetic diagnosis but not the

  16. Congenital nonprogressive myopathy with Möbius and Robin sequence--the Carey-Fineman-Ziter syndrome: a confirmatory report.

    PubMed

    Schimke, R N; Collins, D L; Hiebert, J M

    1993-07-01

    Recently, we evaluated a 27-month-old boy with congenital generalized nonspecific myopathy, Möbius sequence, Robin sequence, and failure to thrive. We think the child has the same entity described by Carey, Fineman, and Ziter in 1982 [J Pediatr 101:353-364] and as such represents only the third example of this unusual syndrome. Review of the large number of conditions in which the Robin sequence occurs supports heterogeneity. Our case strengthens the Möbius-Robin association and further defines the Carey-Fineman-Ziter syndrome as a viable entity. It is most likely inherited as an autosomal recessive trait.

  17. haploinsufficiency leads to syndromic congenital anomalies of the kidney and urinary tract (CAKUT) in humans.

    PubMed

    Le Tanno, Pauline; Breton, Julie; Bidart, Marie; Satre, Véronique; Harbuz, Radu; Ray, Pierre F; Bosson, Caroline; Dieterich, Klaus; Jaillard, Sylvie; Odent, Sylvie; Poke, Gemma; Beddow, Rachel; Digilio, Maria Christina; Novelli, Antonio; Bernardini, Laura; Pisanti, Maria Antonietta; Mackenroth, Luisa; Hackmann, Karl; Vogel, Ida; Christensen, Rikke; Fokstuen, Siv; Béna, Frédérique; Amblard, Florence; Devillard, Francoise; Vieville, Gaelle; Apostolou, Alexia; Jouk, Pierre-Simon; Guebre-Egziabher, Fitsum; Sartelet, Hervé; Coutton, Charles

    2017-07-01

    Congenital anomalies of the kidney and urinary tract (CAKUT) represent a significant healthcare burden since it is the primary cause of chronic kidney in children. CNVs represent a recurrent molecular cause of CAKUT but the culprit gene remains often elusive. Our study aimed to define the gene responsible for CAKUT in patients with an 1q23.3q24.1 microdeletion. We describe eight patients presenting with CAKUT carrying an 1q23.3q24.1 microdeletion as identified by chromosomal microarray analysis (CMA). Clinical features were collected, especially the renal and urinary tract phenotype, and extrarenal features. We characterised PBX1 expression and localisation in fetal and adult kidneys using quantitative RT-PCR and immunohistochemistry. We defined a 276-kb minimal common region (MCR) that only overlaps with the PBX1 gene. All eight patients presented with syndromic CAKUT. CAKUT were mostly bilateral renal hypoplasia (75%). The most frequent extrarenal symptoms were developmental delay and ear malformations. We demonstrate that PBX1 is strongly expressed in fetal kidneys and brain and expression levels decreased in adult samples. In control fetal kidneys, PBX1 was localised in nuclei of medullary, interstitial and mesenchymal cells, whereas it was present in endothelial cells in adult kidneys. Our results indicate that PBX1 haploinsufficiency leads to syndromic CAKUT as supported by the Pbx1 -null mice model. Correct PBX1 dosage appears to be critical for normal nephrogenesis and seems important for brain development in humans. CMA should be recommended in cases of fetal renal anomalies to improve genetic counselling and pregnancy management. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  18. Congenital central hypoventilation syndrome associated with Hirschsprung's Disease: case report and literature review.

    PubMed

    Sandoval, Renata Lazari; Zaconeta, Carlos Moreno; Margotto, Paulo Roberto; Cardoso, Maria Teresinha de Oliveira; França, Evely Mirella Santos; Medina, Cristina Touguinha Neves; Canó, Talyta Matos; Faria, Aline Saliba de

    2016-09-01

    To report the case of a newborn with recurrent episodes of apnea, diagnosed with Congenital Central hypoventilation syndrome (CCHS) associated with Hirschsprung's disease (HD), configuring Haddad syndrome. Third child born at full-term to a non-consanguineous couple through normal delivery without complications, with appropriate weight and length for gestational age. Soon after birth he started to show bradypnea, bradycardia and cyanosis, being submitted to tracheal intubation and started empiric antibiotic therapy for suspected early neonatal sepsis. During hospitalization in the NICU, he showed difficulty to undergo extubation due to episodes of desaturation during sleep and wakefulness. He had recurrent episodes of hypoglycemia, hyperglycemia, metabolic acidosis, abdominal distension, leukocytosis, increase in C-reactive protein levels, with negative blood cultures and suspected inborn error of metabolism. At 2 months of age he was diagnosed with long-segment Hirschsprung's disease and was submitted to segment resection and colostomy through Hartmann's procedure. A genetic research was performed by polymerase chain reaction for CCHS screening, which showed the mutated allele of PHOX2B gene, confirming the diagnosis. This is a rare genetic, autosomal dominant disease, caused by mutation in PHOX2B gene, located in chromosome band 4p12, which results in autonomic nervous system dysfunction. CCHS can also occur with Hirschsprung's disease and tumors derived from the neural crest. There is a correlation between phenotype and genotype, as well as high intrafamilial phenotypic variability. In the neonatal period it can simulate cases of sepsis and inborn errors of metabolism. Copyright © 2015 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

  19. Congenital hypothyroidism due to ectopic sublingual thyroid gland in Prader-Willi Syndrome: a case report.

    PubMed

    Bocchini, Sarah; Fintini, Danilo; Grugni, Graziano; Boiani, Arianna; Convertino, Alessio; Crinò, Antonino

    2017-09-22

    Thyroid gland disorders are variably associated with Prader-Willi syndrome (PWS). Many of the clinical features in newborns with PWS are similar to those found in congenital hypothyroidism (CH). We report a case of a girl with CH and PWS. At the age of 9 months CH caused by an ectopic sublingual thyroid was diagnosed, and hormone replacement therapy was started. In spite of this treatment a decrease in growth velocity, weight excess and delayed development were observed. At the age of 9 years PWS was suspected on the basis of phenotype and genetic tests confirmed a maternal uniparental disomy of chromosome 15. This is the second reported case of hypothyroidism due to an ectopic sublingual thyroid gland in PWS suggesting that, although rare, an association between CH and PWS may exist. In our case diagnosis of PWS was delayed because mental retardation, hypotonia, obesity and short stature were initially attributed to hypothyroidism. In this context PWS should be considered in obese children with CH who do not improve adequately with l-thyroxine therapy. Also, thyroid function in all PWS children should be assessed regularly in order to avoid delayed diagnosis of hypothyroidism.

  20. Cellular and molecular characterisation of the hyper immunoglobulin M syndrome associated with congenital rubella infection.

    PubMed

    Ameratunga, Rohan; Woon, See-Tarn; Koopmans, Wikke; French, John

    2009-01-01

    The hyper-immunoglobulin M syndrome (HIM) is a rare group of immune deficiency disorders characterised by normal or increased serum IgM with normal or reduced IgG, IgA and IgE. We have undertaken detailed cellular and molecular studies in a 53-year-old man with HIM as a result of congenital rubella. No mutations were detected in the CD40 ligand, activation-induced cytidine deaminase and uracil DNA glycosylase. His T-cell responses to lectins and antigens were normal. Flow cytometry confirmed the presence of CD40 ligand on activated T cells. Most CD40-dependent functions that were tested, including B-cell proliferation, isotype switching and production of memory B cells, were normal. CD40/IL4 dependent rescue from anti-IgM-induced apoptosis was impaired. The detection of cell-surface IgG but lack of serum IgG indicated that he may have an antibody secretion defect.

  1. Screening key genes associated with congenital heart defects in Down syndrome based on differential expression network.

    PubMed

    Yu, Shan; Yi, Huani; Wang, Zhimin; Dong, Juan

    2015-01-01

    Down syndrome (DS) is the most common viable chromosomal disorder with intellectual impairment and several other developmental abnormalities. Forty to fifty percent of newborns with DS have some form of congenital heart defects (CHD). The genome of CHD in DS has already been obtained, but the underlying genomic or gene expression variation that contributes to the manifestation of a CHD in DS is still unknown. This study was aimed to analyze key genes of patients with CHD in DS. Differential expression network (DEN) approach was employed to analyze the dyeregulated genes and pathways in this study. First, the differentially expressed genes (DEGs) between CHD in DS and normal subjects were screened based on the microarray expression data. Next, the differential interactions were identified using spearman correlation coefficients of edges in different conditions. The DEN was then constructed combining both DEGs and differential interactions, and HUB genes were gained by degree centrality analysis of DEN. Meanwhile, disease genes included in the DEN were also ascertained. When analyzing gene expression values in different conditions, no DEGs were identified. While, a total of 984 gene pairs with significant differential expression were identified. Finally, the DEN was constructed only using differential edges in our study. In this network, eight HUB genes were identified, and thereinto four genes (UBC, APP, HUWE1 and SRC) were both HUB genes and disease genes. DEN approach should be taken as a useful complement to traditional differential genes methods. We provide several potential underlying biomarkers for CHD in DS.

  2. Cognitive Impairment and Brain Imaging Characteristics of Patients with Congenital Cataracts, Facial Dysmorphism, Neuropathy Syndrome.

    PubMed

    Chamova, Teodora; Zlatareva, Dora; Raycheva, Margarita; Bichev, Stoyan; Kalaydjieva, Luba; Tournev, Ivailo

    2015-01-01

    Congenital cataracts, facial dysmorphism, neuropathy (CCFDN) syndrome is a complex autosomal recessive multisystem disorder. The aim of the current study is to evaluate the degree of cognitive impairment in a cohort of 22 CCFDN patients and its correlation with patients' age, motor disability, ataxia, and neuroimaging changes. Twenty-two patients with genetically confirmed diagnosis of CCFDN underwent a detailed neurological examination. Verbal and nonverbal intelligence, memory, executive functions, and verbal fluency wеre assessed in all the patients aged 4 to 47 years. Brain magnetic resonance imaging was performed in 20 affected patients. Eighteen affected were classified as having mild intellectual deficit, whereas 4 had borderline intelligence. In all psychometric tests, evaluating different cognitive domains, CCFDN patients had statistically significant lower scores when compared to the healthy control group. All cognitive domains seemed equally affected. The main abnormalities on brain MRI found in 19/20 patients included diffuse cerebral atrophy, enlargement of the lateral ventricles, and focal lesions in the subcortical white matter, different in number and size, consistent with demyelination more pronounced in the older CCFDN patients. The correlation analysis of the structural brain changes and the cognitive impairment found a statistically significant correlation only between the impairment of short-term verbal memory and the MRI changes.

  3. Drosophila studies support a role for a presynaptic synaptotagmin mutation in a human congenital myasthenic syndrome

    PubMed Central

    Shields, Mallory C.; Bowers, Matthew R.; Fulcer, McKenzie M.; Bollig, Madelyn K.; Rock, Patrick J.; Sutton, Bryan R.; Vrailas-Mortimer, Alysia D.; Lochmüller, Hanns; Whittaker, Roger G.; Horvath, Rita

    2017-01-01

    During chemical transmission, the function of synaptic proteins must be coordinated to efficiently release neurotransmitter. Synaptotagmin 2, the Ca2+ sensor for fast, synchronized neurotransmitter release at the human neuromuscular junction, has recently been implicated in a dominantly inherited congenital myasthenic syndrome associated with a non-progressive motor neuropathy. In one family, a proline residue within the C2B Ca2+-binding pocket of synaptotagmin is replaced by a leucine. The functional significance of this residue has not been investigated previously. Here we show that in silico modeling predicts disruption of the C2B Ca2+-binding pocket, and we examine the in vivo effects of the homologous mutation in Drosophila. When expressed in the absence of native synaptotagmin, this mutation is lethal, demonstrating for the first time that this residue plays a critical role in synaptotagmin function. To achieve expression similar to human patients, the mutation is expressed in flies carrying one copy of the wild type synaptotagmin gene. We now show that Drosophila carrying this mutation developed neurological and behavioral manifestations similar to those of human patients and provide insight into the mechanisms underlying these deficits. Our Drosophila studies support a role for this synaptotagmin point mutation in disease etiology. PMID:28953919

  4. An assistive device for congenital central hypoventilation syndrome outpatients during sleep.

    PubMed

    Biffi, Emilia; Piazza, Caterina; Cavalleri, Matteo; Taddeo, Peter; Carcano, Alessandro; Morandi, Francesco; Reni, Gianluigi

    2014-10-01

    Congenital Central Hypoventilation Syndrome is a genetic disease characterized by alveolar hypoventilation and autonomic dysregulation. Patients have hypoventilations, especially during sleep, conditioning hypercapnia which can lead to neurological damage and death. They therefore need mechanical ventilators, that provide sufficient gas exchange, and pulse-oximeters that monitor oxy-hemoglobin blood concentration. Due to the restrictions regarding domiciliary assistive devices, the presence of a caregiver is required all night long. Currently, the only alarm systems available are the ones integrated in the ventilators and monitoring systems. During the night, multiple false alarms may occur, interrupting the sleep and causing anxiety. In this work we describe an assistive device that acquires real-time data from a pulse-oximeter, provides a multisensory stimulation if oxygen saturation falls under a certain threshold, and wakes up the patient if the hypoxia is severe. Tests on healthy subjects have shown that the device guarantees rapid awakenings, with a stimulator-dependent efficacy, and that it does not affect sleep efficiency. The purpose of the device is to determine a gentle awakening if mild hypoxia conditions persist, and to assure rapid awakening when a severe hypoxia occurs, reducing false alarms, improving the quality of sleep and increasing the self-sufficiency of the patients.

  5. Association between congenital heart defects and severe infections in children with Down syndrome.

    PubMed

    Faria, Paula Foresti; Nicolau, Juliana Augusta Zeglin; Melek, Marina Zaponi; de Oliveira, Nanci de Santa Palmieri; Bermudez, Beatriz Elizabeth Bagatin Veleda; Nisihara, Renato Mitsunori

    2014-01-01

    There is a high prevalence of congenital heart disease (CHD) in Down syndrome (DS) patients. Children with DS and CHD also present greater susceptibility to pulmonary infections than those without CHD. To investigate the prevalence and types of CHD and their association with severe infections in children with DS in southern Brazil seen in a reference outpatient clinic. Children aged between six and 48 months with a diagnosis of DS were included consecutively in the period May 2001 to May 2012, and the presence of CHD and severe infections (pneumonia and sepsis) was investigated, classified and analyzed. A total of 127 patients were included, of whom 89 (70.1%) had some type of CHD, 33 (37.7%) of them requiring surgical correction. Severe infections (pneumonia and sepsis) were seen in 23.6% and 5.5%, respectively. Of the cases of pneumonia, 70% had associated CHD (p=0.001) and of those with sepsis, 85% presented CHD (p=0.001). Our study showed a high prevalence of CHD and its association with severe infections in children with DS seen in southern Brazil. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  6. Identification of a Kir3.4 Mutation in Congenital Long QT Syndrome

    PubMed Central

    Yang, Yanzong; Yang, Yiqing; Liang, Bo; Liu, Jinqiu; Li, Jun; Grunnet, Morten; Olesen, Søren-Peter; Rasmussen, Hanne B.; Ellinor, Patrick T.; Gao, Lianjun; Lin, Xiaoping; Li, Li; Wang, Lei; Xiao, Junjie; Liu, Yi; Liu, Ying; Zhang, Shulong; Liang, Dandan; Peng, Luying; Jespersen, Thomas; Chen, Yi-Han

    2010-01-01

    Congenital long QT syndrome (LQTS) is a hereditary disorder that leads to sudden cardiac death secondary to fatal cardiac arrhythmias. Although many genes for LQTS have been described, the etiology remains unknown in 30%–40% of cases. In the present study, a large Chinese family (four generations, 49 individuals) with autosomal-dominant LQTS was clinically evaluated. Genome-wide linkage analysis was performed by using polymorphic microsatellite markers to map the genetic locus, and positional candidate genes were screened by sequencing for mutations. The expression pattern and functional characteristics of the mutated protein were investigated by western blotting and patch-clamp electrophysiology. The genetic locus of the LQTS-associated gene was mapped to chromosome 11q23.3-24.3. A heterozygous mutation (Kir3.4-Gly387Arg) was identified in the G protein-coupled, inwardly rectifying potassium channel subunit Kir3.4, encoded by the KCNJ5 gene. The Kir3.4-Gly387Arg mutation was present in all nine affected family members and absent in 528 ethnically matched controls. Western blotting of human cardiac tissue demonstrated significant Kir3.4 expression levels in the cardiac ventricles. Heterologous expression studies with Kir3.4-Gly387Arg revealed a loss-of-function electrophysiological phenotype resulting from reduced plasma membrane expression. Our findings suggest a role for Kir3.4 in the etiology of LQTS. PMID:20560207

  7. Congenital Rubella Syndrome: A Case Report on Changes in Viral Load and Rubella Antibody Titers.

    PubMed

    Nagasawa, Koo; Ishiwada, Naruhiko; Ogura, Atsushi; Ogawa, Tomoko; Takeuchi, Noriko; Hishiki, Haruka; Shimojo, Naoki

    2016-05-01

    To our knowledge, this is the first report of the use of real-time reverse transcription-polymerase chain reaction to assess changes in viral load in a patient with congenital rubella syndrome (CRS). Rubella-specific antibody titers were also determined. The patient was a male neonate born to a primipara with rubella infection at 10 weeks of gestation. He had no symptoms at birth, but rubella virus was detected in his pharynx, blood, and urine. His mental and physical development was normal for 1 year; however, he was diagnosed with deafness at 13 months of age. Thus, the patient was diagnosed with CRS. Rubella infection in the pharynx was almost constant until 5 months of age; however, it increased dramatically at 6 months of age. No infection was detected at 13 months. Rubella-specific immunoglobulin M titer was consistently low until 9 months of age and then decreased gradually until it became negative at 20 months of age. Rubella-specific immunoglobulin G titer was high at birth. However, it decreased at 3 months and increased again at 4 months. This titer peaked at ∼9 months and then decreased again at 13 months. This case shows that the period after the decline in maternal antibody titers, not the neonatal period, may be the most contagious period in patients with CRS. Copyright © 2016 by the American Academy of Pediatrics.

  8. Genetic predisposition to fetal alcohol syndrome: association with congenital disorders of N-glycosylation.

    PubMed

    de la Morena-Barrio, María E; Ballesta-Martínez, María J; López-Gálvez, Raquel; Antón, Ana I; López-González, Vanessa; Martínez-Ribot, Laia; Padilla, José; Miñano, Antonia; García-Algar, Oscar; Del Campo, Miguel; Corral, Javier; Guillén-Navarro, Encarna; Vicente, Vicente

    2018-01-01

    BackgroundFetal alcohol syndrome (FAS) is caused by maternal alcohol consumption during pregnancy; although additional factors might be involved, as development and severity are not directly related to alcohol intake. The abnormal glycosylation caused by alcohol might play a role in FAS according to the clinical similarities shared with congenital disorders of glycosylation (CDG). Thus, mutations underlying CDG, affecting genes involved in glycosylation, could also be involved in FAS.MethodsA panel of 74 genes involved in N-glycosylation was sequenced in 25 FAS patients and 20 controls with prenatal alcohol exposure. Transferrin glycoforms were evaluated by HPLC.ResultsRare (minor allele frequency<0.009) missense/splice site variants were more frequent in FAS than controls (84% vs. 50%; P=0.034, odds ratio: 5.25, 95% confidence interval: 1.3-20.9). Remarkably, three patients, but no controls, carried variants with functional effects identified in CDG patients. Moreover, the patient with the most severe clinical phenotype was the only one carrying two variants with functional effects. Family studies support that the combination of a genetic defect and alcohol consumption during pregnancy might have a role in FAS development.ConclusionsOur study supports that the rare variants of genes involved in N-glycosylation could play a role in the development and severity of FAS under prenatal alcohol exposure.

  9. Lethal congenital contracture syndrome (LCCS) and other lethal arthrogryposes in Finland--an epidemiological study.

    PubMed

    Pakkasjärvi, Niklas; Ritvanen, Annukka; Herva, Riitta; Peltonen, Leena; Kestilä, Marjo; Ignatius, Jaakko

    2006-09-01

    Arthrogryposis multiplex congenita is a heterogeneous group of disorders characterized by multiple contractures with an estimated frequency of 1 in 3,000 births. With improving diagnostic methods, increasing numbers of fetuses with arthrogryposis are found. The pathogenetic mechanisms are relatively well known but the epidemiology and genetics of the prenatally lethal forms of arthrogryposis are less well known. In this study we collected all cases of a multiple contractures diagnosed in Finland during 1987-2002 including live born infants, stillbirths, and terminated pregnancies. Ninety-two cases of 214 suffered intrauterine demise (68 selective pregnancy terminations and 24 stillbirths) and 58 died in infancy. In 141 out of these cases the diagnosis could be included within lethal arthrogryposes, with a prevalence of 1 in 6,985 (1.43/10,000) births. Of these, 59 had spinal cord pathology at autopsy and thus were of neurogenic origin. Thirty-nine cases had lethal congenital contracture syndrome (LCCS) clinically characterized by total immobility of the fetus at all ultrasound examinations (12 weeks or later), multiple joint contractures in both upper and lower limbs, hydrops, and fetal death before the 32nd week of pregnancy. LCCS is noted as a unique Finnish disorder with a prevalence of 1 in 25,250 (0.40/10,000) births and is a major cause of lethal arthrogryposis in Finland.

  10. Early use of Nasal-BiPAP in two infants with Congenital Central Hypoventilation syndrome.

    PubMed

    Migliori, C; Cavazza, A; Motta, M; Bottino, R; Chirico, G

    2003-07-01

    To reduce the problems caused by prolonged artificial ventilation in babies with Congenital Central Hypoventilation syndrome (CCHS). Two term infants with CCHS, weighing 4030 g and 3100 g, respectively, at the beginning of treatment and aged 53 and 31 d, respectively, were successfully ventilated with a Nasal Bilevel Positive Airway Pressure (N-BiPAP) device. In the first patient the tcPO2 recordings (mean +/- SD) during sleep were 46 +/- 12 mmHg before using N-BiPAP and 58 +/- 13 mmHg after using the device, while those for tcPCO2 were 75 +/- 9 mmHg and 49 +/- 11 mmHg, respectively. In the second patient tcPO2 during sleep was 42 +/- 3 mmHg before, and 55 +/- 5 after N-BiPAP, and for tcPCO2 the recordings were 119 +/- 24 mmHg and 55 +/- 6 mmHg, respectively, showing a significant improvement. One infant had persistent gastro-oesophageal reflux, and frontal skin abrasion caused by the face mask. Nevertheless, these complications did not necessitate the discontinuation of N-BiPAP ventilation, thus precluding prolonged use of intubation and tracheotomy. In infants with CCHS, early use of non-invasive, positive-pressure ventilation with N-BiPAP, in association with careful monitoring, can decrease problems caused by prolonged intubation and tracheotomy.

  11. Congenital bilateral perisylvian syndrome with partial epilepsy. Case report with long-term follow-up.

    PubMed

    Margari, Lucia; Lucia, Margari; Presicci, Anna; Anna, Presicci; Ventura, Patrizia; Patrizia, Ventura; Buttiglione, Maura; Maura, Buttiglione; Andreula, Cosma; Cosma, Andreula; Perniola, Tommaso; Tommaso, Perniola

    2005-01-01

    Congenital bilateral perisylvian syndrome (CBPS) is a rare neurological disorder characterised by pseudobulbar palsy, cognitive deficits and epilepsy associated with bilateral perisylvian cortical dysplasia on neuroimaging studies. We report a long-term follow-up of a 18-years girl diagnosed with CBPS according to the typical clinical and magnetic resonance imaging (MRI) features. The patient showed faciopharyngoglossomasticatory diplegia, severe dysarthria, ataxia, spastic quadriparesis and severe mental retardation. Brain MRI evidenced bilateral perisylvian cortical dysplasia. Since early life she suffered from complex febrile seizures and epilepsy consisting of complex partial attacks with affective manifestations associated with centro-temporal EEG abnormalities. During 18 years of follow-up she was treated with phenobarbital, carbamazepine, lamotrigine, gabapentin but did not show any significant clinical improvement. Subsequently, monotherapy with phenytoin (PHT) was followed by a significant clinical improvement. At age 17, because of adverse effects, PHT was gradually substituted by topiramate (TPM). Full control of seizures was obtained at the age of 17 years with TPM. EEG abnormalities throughout the years have been reduced according to the clinical course. These findings emphasised the importance of long-term follow-up, suggesting that the prognosis for epilepsy may not be predicted based on the early response to treatment or on the presence of structural encephalic abnormalities, as reported in the literature.

  12. Seizures as a Complication of Congenital Zika Syndrome in Early Infancy.

    PubMed

    Oliveira-Filho, Jamary; Felzemburgh, Ridalva; Costa, Federico; Nery, Nivison; Mattos, Adriana; Henriques, Daniele F; Ko, Albert I; For The Salvador Zika Response Team

    2018-04-23

    Zika virus transmission in Brazil was linked to a large outbreak of microcephaly but less is known about longer term anthropometric and neurological outcomes. We studied a cohort of infants born between October 31, 2015, and January 9, 2016, in a state maternity hospital, followed up for 101 ± 28 days by home visits. Microcephaly (< 2 standard deviations, Intergrowth standard) occurred in 62 of 412 (15%) births. Congenital Zika syndrome (CZS) was diagnosed in 29 patients. Among CZS patients, we observed a significant gain in anthropometric measures ( P < 0.001) but no significant gain in percentile for these measures. The main neurological outcome was epilepsy, occurring in 48% of infants at a rate of 15.6 cases per 100 patient-months, frequently requiring multiple anti-seizure medications. The cumulative fatality rate was 7.4% (95% confidence interval: 2.1-23.4%). Health-care professionals should be alerted on the high risk of epilepsy and death associated with CZS in early infancy and the need to actively screen for seizures and initiate timely treatment.

  13. Congenital Heart Disease in Cornelia de Lange Syndrome: Phenotype and Genotype Analysis

    PubMed Central

    Chatfield, Kathryn C.; Schrier, Samantha A.; Li, Jennifer; Clark, Dinah; Kaur, Maninder; Kline, Antonie D.; Deardorff, Matthew A.; Jackson, Laird S.; Goldmuntz, Elizabeth; Krantz, Ian D.

    2013-01-01

    Congenital heart disease (CHD) has been reported to occur in 14–70% of individuals with Cornelia de Lange syndrome (CdLS, OMIM 122470) and accounts for significant morbidity and mortality when present. Charts from a cohort of 479 patients with CdLS were reviewed for cardiac evaluations, gene testing and information to determine phenotypic severity. Two hundred fifty-nine individuals had either documented structural defects or minor cardiac findings. The presence of CHD was then quantified as a function of mutation status and severity of CdLS: mild, moderate, or severe. Different types of CHD were also evaluated by mutation status to assess for any genotype –phenotype correlation. NIPBL, SMC1A, and SMC3 mutation-positive patients were equally likely to have CHD, although the number of SMC1A and SMC3 mutation-positive patients were small in comparison. Structural CHDs were more likely to be present in individuals with moderate and severe CdLS than in the mild phenotype. This study evaluates the trends of CHD seen in the CdLS population and correlates these findings with genotype. PMID:22965847

  14. Congenital Myasthenic Syndrome due to DOK7 mutations in a family from Chile

    PubMed Central

    Bevilacqua, Jorge A.; Lara, Marian; Díaz, Jorge; Campero, Mario; Vázquez, Jessica; Maselli, Ricardo A.

    2017-01-01

    Congenital myasthenic syndromes (CMS) are neuromuscular transmission disorders caused by mutations in genes encoding neuromuscular junction proteins. A 61-year-old female and her older sister showed bilateral ptosis, facial and proximal limb weakness, and scoliosis since childhood. Another female sibling had milder signs, while other family members were asymptomatic. Facial nerve repetitive stimulation in the proband showed decrement of muscle responses. Single fiber EMG revealed increased jitter and blocking. Muscle biopsy showed type 2-fiber atrophy, without tubular aggregates. Mutational analysis in the three affected siblings revealed two compound heterozygous mutations in DOK7: c.1457delC, that predicts p.Pro486Argfs*13 and truncates the protein C-terminal domain, and c.473G>A, that predicts p.Arg158Gln and disruption of the dok7-MuSK interaction in the phosphotyrosine binding (PTB) domain. Unaffected family members carried only one or neither mutation. Discussion. Two of the affected sisters showed marked improvement with salbutamol treatment, which illustrates the benefits of a correct diagnosis and treatment of DOK7-CMS. PMID:29118959

  15. Congenital cervical dermal sinus tract caused tethered cord syndrome in an adult: a case report

    PubMed Central

    Karatas, Y; Ustun, ME

    2015-01-01

    The objective of this study was to report on a 34-year-old woman who presented with tethered cord syndrome due to dermal sinüs tract. A 34-year-old woman had got dermal sınüs tract admitted to our hospital with swelling on the neck, pain and numbness on the left upper limb. She was treated by surgical removal of dermal sinuses and untethering the spinal cord which is stretched by the dermal sinus. Congenital dermal sinus tracts are uncommon types of cranial and spinal dysraphisms. They can occur in the midline of the craniospinal axis from the occiput to the sacral region. For dermal sinuses, cervical region is very rare location that is reported in the literature. They are diagnosed usually in childhood with skin signs, neurological deficits, local infections and meningitis. We present a rare case of dermal sinus tract located in cervical region. Early diagnosis and treatment of cervical dermal sinus tract are important to prevent neurological deficits. PMID:28053723

  16. Congenital cervical dermal sinus tract caused tethered cord syndrome in an adult: a case report.

    PubMed

    Karatas, Y; Ustun, M E

    2015-01-01

    The objective of this study was to report on a 34-year-old woman who presented with tethered cord syndrome due to dermal sinüs tract. A 34-year-old woman had got dermal sınüs tract admitted to our hospital with swelling on the neck, pain and numbness on the left upper limb. She was treated by surgical removal of dermal sinuses and untethering the spinal cord which is stretched by the dermal sinus. Congenital dermal sinus tracts are uncommon types of cranial and spinal dysraphisms. They can occur in the midline of the craniospinal axis from the occiput to the sacral region. For dermal sinuses, cervical region is very rare location that is reported in the literature. They are diagnosed usually in childhood with skin signs, neurological deficits, local infections and meningitis. We present a rare case of dermal sinus tract located in cervical region. Early diagnosis and treatment of cervical dermal sinus tract are important to prevent neurological deficits.

  17. Bioenergetic Impairment in Congenital Muscular Dystrophy Type 1A and Leigh Syndrome Muscle Cells

    PubMed Central

    Fontes-Oliveira, Cibely C.; Steinz, Maarten; Schneiderat, Peter; Mulder, Hindrik; Durbeej, Madeleine

    2017-01-01

    Skeletal muscle has high energy requirement and alterations in metabolism are associated with pathological conditions causing muscle wasting and impaired regeneration. Congenital muscular dystrophy type 1A (MDC1A) is a severe muscle disorder caused by mutations in the LAMA2 gene. Leigh syndrome (LS) is a neurometabolic disease caused by mutations in genes related to mitochondrial function. Skeletal muscle is severely affected in both diseases and a common feature is muscle weakness that leads to hypotonia and respiratory problems. Here, we have investigated the bioenergetic profile in myogenic cells from MDC1A and LS patients. We found dysregulated expression of genes related to energy production, apoptosis and proteasome in myoblasts and myotubes. Moreover, impaired mitochondrial function and a compensatory upregulation of glycolysis were observed when monitored in real-time. Also, alterations in cell cycle populations in myoblasts and enhanced caspase-3 activity in myotubes were observed. Thus, we have for the first time demonstrated an impairment of the bioenergetic status in human MDC1A and LS muscle cells, which could contribute to cell cycle disturbance and increased apoptosis. Our findings suggest that skeletal muscle metabolism might be a promising pharmacological target in order to improve muscle function, energy efficiency and tissue maintenance of MDC1A and LS patients. PMID:28367954

  18. Joubert syndrome: congenital cerebellar ataxia with the “molar tooth”

    PubMed Central

    Romani, Marta; Micalizzi, Alessia; Valente, Enza Maria

    2013-01-01

    Joubert syndrome (JS) is a congenital cerebellar ataxia with autosomal recessive or X-linked inheritance, which diagnostic hallmark is a unique cerebellar and brainstem malformation recognizable on brain imaging, the “molar tooth sign”. Neurological signs are present from neonatal age and include hypotonia evolving into ataxia, global developmental delay, ocular motor apraxia and breathing dysregulation. These are variably associated with multiorgan involvement, mainly of the retina, kidneys, skeleton and liver. To date, 21 causative genes have been identified, all encoding for proteins of the primary cilium or its apparatus. This is a subcellular organelle that plays key roles in development and in many cellular functions, making JS part of the expanding family of ciliopathies. There is marked clinical and genetic overlap among distinct ciliopathies, which may co-occur even within families. Such variability is likely explained by an oligogenic model of inheritance, in which mutations, rare variants and polymorphisms at distinct loci interplay to modulate the expressivity of the ciliary phenotype. PMID:23870701

  19. Rubella in the Russian Federation: epidemiological features and control measures to prevent the congenital rubella syndrome.

    PubMed Central

    Semerikov, V. V.; Lavrentyeva, I. N.; Popov, V. F.; Fletcher, M. A.; Kolotov, M. E.

    2000-01-01

    A review of the epidemiology of clinical rubella in the Perm region of the Russian Federation from 1979-97 showed that the incidence was about 220 cases per 100,000 population. Congenital rubella syndrome (CRS) accounted for 15% of birth defects and for about 3.5 cases of CRS per 1000 live births per year. Surveys of the seroepidemiology of rubella infection revealed that the susceptibility rate among pregnant women (i.e. rubella virus antibody haemagglutination-inhibition (HAI) assay titres < 10) was 16.5%. As serum rubella antibody HAI titres > or = 10 both prevented infection in pregnant women and protected their foetuses, serological testing has been introduced into the routine antenatal services. Pre-existing rubella antibodies were found not to interfere with the immune response to vaccination, so selective immunization was provided to girls approaching puberty and to women of childbearing age. A programme of epidemiological surveillance is being developed to define tactics for the widescale introduction of rubella vaccination. PMID:11117959

  20. Biphasic response of subscapular skinfold thickness to hGH or IGF-1 administration to patients with congenital IGHD, congenital MPHD and Laron syndrome.

    PubMed

    Bisker-Kassif, Orly; Kauli, Rivka; Lilos, Pearl; Laron, Zvi

    2014-01-01

    To evaluate changes in adiposity in congenital GH/IGF-1 deficient children during hGH or IGF-1 treatment. 27 children with congenital isolated growth hormone deficiency (cIGHD) treated with hGH for 2.5-€“15.2 years (mean 10.0 ± 3.4), 18 children with congenital multiple pituitary hormone deficiency (cMPHD), treated with hGH for 2.3-€“17.9 years (mean 6.1 ± 4.3), and 14 children with Laron syndrome (LS) treated with IGF-1 for 1.2-12 years (mean 5.5 ± 3.7) were studied. Changes in the degree of adiposity were evaluated by subscapular skinfold thickness (SSFT), before, during and up to 2 years after treatment. All the children had various degrees of obesity. During the pretreatment period, cIGHD patients showed little changes in SSFT (P = 0.45), cMPHD and LS patients showed an increase in SSFT (P = 0.01, P = 0.06 respectively). During the initial 0.6-1.1 years of hGH/IGF-1 treatment, the SSFT decreased in all 3 groups (P < 0.001), while during subsequent years a significant increase in SSFT (P < 0.001) was observed, in all types of patients, notably in females. Only the cIGHD patients demonstrated a significant correlation between the degree of SSFT decrease and height SDS gain (R = -ˆ’0.56, P = 0.002) in the first period of treatment. Short term replacement therapy of 0.6-€“1.1 years with either hGH or IGF-1, induced a reduction in subscapular subcutaneous fat whereas prolongation of therapy led to an increase in the subcutaneous fat. © 2014 Asian Oceanian Association for the Study of Obesity . Published by Elsevier Ltd. All rights reserved.

  1. Hirschsprung disease and congenital anomalies of the kidney and urinary tract (CAKUT): a novel syndromic association.

    PubMed

    Pini Prato, Alessio; Musso, Marco; Ceccherini, Isabella; Mattioli, Girolamo; Giunta, Camilla; Ghiggeri, Gian Marco; Jasonni, Vincenzo

    2009-03-01

    Congenital anomalies of the kidney and urinary tract (CAKUT) can be associated with Hirschsprung disease (HSCR). Based on the common genetic background of enteric nervous system and kidney development, the reported association of CAKUT and HSCR seems underestimated. Therefore, we designed a prospective study aimed at determining the prevalence of CAKUT in HSCR patients and at identifying RET, glial cell line-derived neurotrophic factor (GDNF), and GDNF family receptor alpha1 (GFRalpha1) mutations or haplotypes associated with this subset of HSCR patients. Eighty-four HSCR patients consecutively admitted to our department between July 2006 and July 2007 underwent interviews, notes review, ultrasound screening (further investigation according to detected anomaly), urinalysis, and DNA extraction for molecular genetics study. Another 27 patients with isolated CAKUT were included as a control group for the molecular genetics study. Twenty-one patients (25%) with HSCR had associated CAKUT, with hydronephrosis and hypoplasia being the most frequent diagnoses. Nine of 21 CAKUT were symptomatic. Six additional patients had other non-CAKUT anomalies (for example, stones, Barter syndrome) that were excluded from association and molecular genetics analysis to avoid bias of inclusion criteria. RET mutations were found in 5 patients (4 HSCR, 1 HSCR + CAKUT, 0 CAKUT) and GDNF mutations in 3 (2 HSCR, 1 CAKUT, 0 HSCR + CAKUT). No GFRalpha1 mutations were found. Finally, the HSCR-predisposing T haplotype of RET proto-oncogene was found in 64% of HSCR, 50% of HSCR + CAKUT, and in 24% of CAKUT patients. The incidence of CAKUT in HSCR patients is 4- to 6-fold higher than expected. Therefore, a patient with HSCR has a 3- to 18-fold higher risk of developing a CAKUT, particularly hydronephrosis or hypoplasia. If we consider that the proportion of predisposing haplotype in HSCR + CAKUT patients resembles that of other syndromic HSCR, we can conclude that HSCR + CAKUT has to be considered

  2. Congenital Abnormalities and Acute Leukemia among Children with Down Syndrome: A Children’s Oncology Group Study

    PubMed Central

    Linabery, Amy M.; Blair, Cindy K.; Gamis, Alan S.; Olshan, Andrew F.; Heerema, Nyla A.; Ross, Julie A.

    2008-01-01

    Children with Down syndrome, due to their heightened risk of leukemia and increased prevalence of congenital abnormalities, comprise a valuable population in which to study etiology. A Children’s Oncology Group study investigated the causes of childhood leukemia in children with Down syndrome diagnosed at ages 0 to 19 years during the period 1997–2002. Telephone interviews were completed with mothers of 158 cases [n = 97 acute lymphoblastic leukemia (ALL) and n = 61 acute myeloid leukemia (AML)] and 173 controls. Odds ratios (OR) and 95% confidence intervals (95% CI) were computed via unconditional logistic regression to evaluate the association between congenital abnormalities and acute leukemia overall, and ALL and AML analyzed separately. The results do not provide evidence for an association among the index children (ORCombined, 0.74; 95% CI, 0.45–1.23; ORALL, 0.67; 95% CI, 0.38–1.20; ORAML,1.03; 95% CI, 0.49–2.16) or their siblings (ORCombined, 1.23; 95% CI, 0.71–2.13; ORALL, 1.12; 95% CI, 0.60–2.09; ORAML, 1.60; 95% CI, 0.66–3.86), suggesting congenital malformations do not confer additional risk of leukemia beyond the risk attributable to trisomy 21 in this population. PMID:18829445

  3. The combination of vestibular impairment and congenital sensorineural hearing loss predisposes patients to ocular anomalies, including Usher syndrome.

    PubMed

    Kletke, S; Batmanabane, V; Dai, T; Vincent, A; Li, S; Gordon, K A; Papsin, B C; Cushing, S L; Héon, E

    2017-07-01

    The co-occurrence of hearing impairment and visual dysfunction is devastating. Most deaf-blind etiologies are genetically determined, the commonest being Usher syndrome (USH). While studies of the congenitally deaf population reveal a variable degree of visual problems, there are no effective ophthalmic screening guidelines. We hypothesized that children with congenital sensorineural hearing loss (SNHL) and vestibular impairment were at an increased risk of having USH. A retrospective chart review of 33 cochlear implants recipients for severe to profound SNHL and measured vestibular dysfunction was performed to determine the ocular phenotype. All the cases had undergone ocular examination and electroretinogram (ERG). Patients with an abnormal ERG underwent genetic testing for USH. We found an underlying ocular abnormality in 81.81% (27/33) of cases; of which 75% had refractive errors, and 50% of those patients showed visual improvement with refractive correction. A total of 14 cases (42.42%; 14/33) had generalized rod-cone dysfunction on ERG suggestive of Usher syndrome type 1, confirmed by mutational analysis. This work shows that adding vestibular impairment as a criterion for requesting an eye exam and adding the ERG to detect USH increases the chances of detecting ocular anomalies, when compared with previous literature focusing only on congenital SNHL. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Findings From aCGH in Patients With Congenital Diaphragmatic Hernia (CDH): A Possible Locus for Fryns Syndrome

    PubMed Central

    Prada, C.; Russell, M.; Byrne, J.; Haug, L. Wilkins; Jennings, R.; Manning, S.; Boyd, T.K.; Fryns, J.P.; Holmes, L.B.; Donahoe, P.K.

    2010-01-01

    Congenital diaphragmatic hernia (CDH) is a common and often devastating birth defect that can occur in isolation or as part of a malformation complex. Considerable progress is being made in the identification of genetic causes of CDH. We applied array-based comparative genomic hybridization (aCGH) of ∼1Mb resolution to 29 CDH patients with prior normal karyotypes who had been recruited into our multi-site study. One patient, clinically diagnosed with Fryns syndrome, demonstrated a de novo 5Mb deletion at chromosome region 1q41–q42.12 that was confirmed by FISH. Given prior reports of CDH in association with cytogenetic abnormalities in this region, we propose that this represents a locus for Fryns syndrome, a Fryns syndrome phenocopy, or CDH. PMID:16333846

  5. Congenital Cytomegalovirus.

    PubMed

    Mestas, Erin

    2016-02-01

    Congenital cytomegalovirus (CMV) is the leading viral intrauterine infection in the United States. It causes more developmental delays and long-term sequelae than Down syndrome (trisomy 21), neural tube defects, or fetal alcohol syndrome combined. Yet, this virus, a member of the herpes virus family, is not well known to the public and its prevention is typically not discussed in obstetric offices. Although many infants with congenital CMV are asymptomatic at birth, a significant proportion still may develop sequelae. Symptomatic infants face potentially devastating consequences. Pharmacologic treatment is reserved for those with severe organ or central nervous system involvement. Treatment of infants with congenital CMV can be complex and requires extensive outpatient follow-up. To educate nurses and nurse practitioners regarding the risks, signs, treatment, and care related to congenital CMV. PubMed was searched to obtain English language publications from 2005 to 2015 for studies examining the current knowledge base of congenital cytomegalovirus, sequelae, and subsequent treatment using key terms "cytomegalovirus" combined with "congenital." A total of 18 articles were retained for analysis. Overall, the greatest risk reduction strategy for CMV transmission is education of pregnant women. In the neonate at risk for congenital CMV, early identification, antiviral treatment, and care coordination are pivotal to maximizing outcomes. Increasing understanding of congenital CMV, modes of transmission, signs of infection, and intervention strategies as well as its impact on development are essential to maximizing outcomes. The need for research exists in the area of valganciclovir's impact on sensorineural hearing loss as well as potential vaccines to protect against CMV transmission. Research is also being conducted in the area of passive immunity via administration of CMV-specific hyperimmune globulin therapy to pregnant women diagnosed with a primary CMV infection.

  6. Congenital Goitrous Hypothyroidism, Deafness and Iodide Organification Defect in Four Siblings: Pendred or Pseudo−Pendred Syndrome?

    PubMed Central

    Kılıç, Mehtap; Uçaktürk, Ahmet; Aydın, Murat

    2010-01-01

    Pendred syndrome (PDS) is an autosomal recessive disorder characterized by congenital deafness, goiter and iodide organification defect. Presence of inner ear malformations is essential for the clinical diagnosis. Most individuals with PDS are clinically and biochemically euthyroid. Mutations in the PDS gene encoding pendrin protein have been shown to be associated with PDS. It has been recently demonstrated that some families with features of PDS do not have the inner ear malformations and mutations in the PDS gene. This condition has been named as “pseudo−Pendred syndrome” (pseudo−PDS), and has been hypothesized to be of autoimmune origin. Here we report four siblings who have goiter, severe hypothyroidism, a positive perchlorate discharge test and sensorineural deafness, but not the inner ear abnormality which is diagnostic for PDS. We suggest that thyroid peroxidase (TPO) gene should be analyzed in pseudo−PDS patients with congenital goitrous hypothyroidism and deafness. Conflict of interest:None declared. PMID:21274344

  7. Adrenomegaly and septic adrenal hemorrhage (Waterhouse-Friderichsen syndrome) in the setting of congenital adrenal hyperplasia

    PubMed Central

    Ford, Kenneth L.; dePrisco, Gregory; Smerud, Michael J.

    2013-01-01

    Congenital adrenal hyperplasia refers to a spectrum of autosomal recessive inherited disorders of steroidogenesis most commonly identified on newborn screenings. We describe a young woman who presented with abdominal pain and on subsequent imaging was found to have features of congenital adrenal hyperplasia. Imaging findings, treatment, and potential complications are discussed. PMID:23814386

  8. Ephedrine treatment in congenital myasthenic syndrome due to mutations in DOK7.

    PubMed

    Lashley, D; Palace, J; Jayawant, S; Robb, S; Beeson, D

    2010-05-11

    Mutations in the postsynaptic adaptor protein Dok-7 underlie congenital myasthenic syndrome (CMS) with a characteristic limb girdle pattern of muscle weakness. Patients usually do not respond to or worsen with the standard CMS treatments: cholinesterase inhibitors and 3,4-diaminopyridine. However, anecdotal reports suggest they may improve with ephedrine. This was an open prospective follow-up study to determine muscle strength in response to ephedrine in Dok-7 CMS. Patients were first evaluated as inpatients for suitability for a trial of treatment with ephedrine. The response was assessed at 2 and 6 to 8 months follow-up clinic visits using a quantitative myasthenia gravis (severity) score (QMG) and mobility measures. Ten out of 12 of the cohort with DOK7 mutations tolerated ephedrine. We noted a progressive response to treatment over the 6 to 8 months assessment period with a significant improvement at the final QMG score (p = 0.009). Mobility scores also improved (p = 0.0006). Improvements in the subcomponents of the QMG score that measured proximal muscle function (those muscle groups most severely affected) were most marked, and in some cases were dramatic. All patients reported enhanced activities of daily living at 6-8 months. Ephedrine appears to be an effective treatment for Dok-7 CMS. It is well-tolerated by most patients and improvement in strength can be profound. Determining the long-term response and the most effective dosing regimen will require further research. This study provides Class IV evidence that ephedrine given at doses between 15 and 90 mg/day improves muscle strength in patients with documented mutations in DOK7.

  9. Response to correction of refractive errors and hypoaccommodation in children with congenital Zika syndrome.

    PubMed

    Ventura, Liana O; Lawrence, Linda; Ventura, Camila V; Dutton, Gordon N; Marinho, Polyana; Ferro, Priscila F; Gois, Adriana L; Dias, Natalia C; Ventura, Larissa; Moore, Cynthia A; Hyvärinen, Lea

    2017-12-01

    To describe the immediate response to correction of refractive errors and hypoaccommodation in children with congenital Zika syndrome (CZS). Children born between May and December 2015 with a confirmed diagnosis of CZS and enrolled in a multidisciplinary early intervention program were included in this study. All children received a comprehensive ophthalmic examination, including dynamic retinoscopy and cycloplegic refraction. Children were prescribed their full correction if they met the criteria for refractive error, and additional plus 3.00 overcorrection for strabismus, accommodative dysfunction, and/or low vision. Monocular and binocular visual responses to Lea Grating Test at 30 cm, with and without eyeglasses, were measured on day 1 of glasses wear. A total of 60 children were evaluated (mean age at evaluation, 11.5 ± 1.1 months; range, 9.0-16.0 months). Lea Grating Test responses were abnormal in all children prior to spectacle correction. Hypoaccommodation was present in 17 of 21 children (81%). Overcorrection was prescribed for all children. Visual responses were subnormal even with glasses use; however, immediate improvement in binocular vision was found in 37 children (62%) and in 74 of 119 eyes (62.2%). For the monocular visual improvement, 27 of 115 eyes (23.5%) had structural abnormalities, and 44 of 115 eyes (38.3%) were structurally normal. There was a statistical difference between the cycloplegic refraction of the children in August and in November, including emmetropia (P = 0.001), hyperopia (P = 0.000), myopia (P = 0.007), and astigmatism (P = 0.004). Eyeglasses can improve visual acuity in children with CZS. Significant changes in their refractive status over time requires periodic updates. Copyright © 2017 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

  10. Does Congenital Heart Disease Affect Neurodevelopmental Outcomes in Children with Down Syndrome?

    PubMed

    Alsaied, Tarek; Marino, Bradley S; Esbensen, Anna J; Anixt, Julia S; Epstein, Jeffery N; Cnota, James F

    2016-01-01

    The impact that congenital heart disease (CHD) has on the neurodevelopment of children with Down syndrome (DS) is unknown and potentially has implications for targeted early intervention. This study assessed the relationship between CHD that required surgery in the first year of life and neurodevelopmental, behavioral and emotional functioning outcomes in children with DS. A retrospective chart review of 1092 children (0-18 years) with DS who visited a single institution from 8/08-8/13 was performed. Children who underwent at least one of nine neurodevelopmental (cognitive, language, developmental) or academic tests were included in the analysis (N = 178). Cohort was age-divided into infants/toddlers (0-2 years), preschoolers (3-5 years), and school age/adolescent (6-18 years). Test scores of children with DS who underwent cardiac surgery in the first year of life were compared to children with DS without CHD. T test, chi-square and Mann Whitney U tests were used where appropriate. Infants/toddlers with cardiac surgery had lower scores for receptive (P = .01), expressive (P = .021) and composite language (P < .001) compared to those with no CHD. Preschoolers with cardiac surgery had lower language scores and lower visual motor scores, although not statistically significant. In school age children with cardiac surgery there were no differences in IQ scores, language scores, or academic achievement scores compared to those without CHD. Also at school-age there was no difference in the incidence of ADHD, executive function or on internalizing and externalizing behavior scores. Children with DS undergoing cardiac surgery during the first year demonstrated poorer neurodevelopmental outcomes as infants/toddler but had no difference at school age compared to children with DS without CHD. These results will guide early interventions to optimize neurodevelopmental outcomes in children with DS and will help with family counseling after CHD repair. © 2016

  11. Neurogenic bladder findings in patients with Congenital Zika Syndrome: A novel condition

    PubMed Central

    Cruz, Glaura Nisya de Oliveira; Fontes, Juliana Marin; Saad Salles, Tania Regina Dias; Boechat, Marcia Cristina Bastos; Monteiro, Ana Carolina; Moreira, Maria Elizabeth Lopes

    2018-01-01

    Introduction Congenital Zika Syndrome (CZS) has been associated with microcephaly and other central nervous system abnormalities including areas that have been implicated in the control of the lower urinary tract. As such, this descriptive case series has aimed to investigate whether CZS is linked with neurogenic bladder. Identifying such an association is paramount in the effort to recognize CZS complications that have putative treatment options that could mitigate the impact of CZS in infected children. Methods Following IRB approval, urological assessment was performed in all patients referred to our clinic between June 2016 and May 2017 who presented with confirmed CZS-associated microcephaly. The research protocol consisted of obtaining clinical history, laboratory tests, lower and upper urinary tract ultrasounds, as well as a diagnostic urodynamic evaluation. ZIKA virus infection was previously confirmed by maternal history and positive PCR in babies and mothers. Microcephaly and other central nervous system abnormalities were established based on neurological assessment and associated imaging of the central nervous system (CT head and/or Brain MRI). Results Twenty-two consecutive CZS patients were tested and confirmed to have neurogenic bladder. Of the 22 patients assessed, 21 presented with an overactive bladder combined with reduced bladder capacity and elevated detrusor filling pressures. Clinically significant increases in postvoid residual (PVR) were confirmed in 40% of cases while a urinary tract infection (UTI) was identified in 23% of cases. Conclusion Neurogenic bladder, a known treatable health condition, was confirmed in 100% of patients tested in this study, most presenting with high-risk urodynamic patterns known to lead to renal damage when left untreated. Follow up studies are necessary to provide further insight onto long-term disease progression and to investigate the response to standard therapies for neurogenic bladder. Nonetheless, we

  12. Normal sleep on mechanical ventilation in adult patients with congenital central alveolar hypoventilation (Ondine's curse syndrome).

    PubMed

    Attali, Valérie; Straus, Christian; Pottier, Michel; Buzare, Marie-Annick; Morélot-Panzini, Capucine; Arnulf, Isabelle; Similowski, Thomas

    2017-01-23

    The purpose of this study was to describe the sleep structure (especially slow wave sleep) in adults with congenital central hypoventilation syndrome (CCHS), a rare genetic disease due to mutations in the PHOX2B gene. Fourteen patients aged 23 (19.0; 24.8) years old (median [1 rst -3rd quartiles]) with CCHS underwent a sleep interview and night-time attended polysomnography with their ventilatory support. Their sleep variables were compared to those collected in 15 healthy control subjects matched for age, sex and body mass index. The latency to N3 sleep was shorter in patients (26.3 min [24.0; 30.1]) than in controls (49.5 min [34.3; 66.9]; P = 0.005), and sleep onset latency tended to be shorter in patients (14.0 min [7.0; 20.5]) than in controls (33.0 min [18.0; 49.0]; P = 0.052). Total sleep time, sleep stage percentages, sleep fragmentation as well as respiratory and movement index were within normal ranges and not different between groups. Normal sleep in adult patients with CCHS and adequate ventilator support indicates that the PHOX2 gene mutations do not affect brain sleep networks. Consequently, any complaint of disrupted sleep should prompt clinicians to look for the usual causes of sleep disorders, primarily inadequate mechanical ventilation. Shorter N3 latency may indicate a higher need for slow wave sleep, to compensate for the abnormal respiratory-related cortical activity during awake quiet breathing observed in patients with CCH.

  13. Congenital Tracheobronchomegaly (Mounier-Kuhn Syndrome) in a Woman with Human Immunodeficiency Virus: A Case Report.

    PubMed

    Fletcher, Amanda; Stowell, Justin; Jamoulis, Socrates

    2017-04-04

    Congenital tracheobronchomegaly (Mounier-Kuhn Syndrome, MKS) is a rare idiopathic disorder characterized by dilation of the central airways, including the trachea and first through fourth order bronchi. MKS disproportionately affects men and results in chronic respiratory tract infections. The diagnosis is made through the synthesis of clinical and radiological data. Here we report a unique case of MKS in a patient with human immunodeficiency virus (HIV) infection. A 45-year-old African American woman with a past medical history of HIV, tobacco and recreational drug abuse, chronic obstructive pulmonary disease, sleep apnea, and a 15-year history of recurrent respiratory infections presented with dyspnea, wheezing, a productive cough, increased yellow-green sputum production, and subjective fevers. Computerized tomography (CT) of the chest revealed striking dilation of the trachea and central bronchi. Fiberoptic bronchoscopy demonstrated a dilated trachea and bronchial tree with complete collapse of the trachea and bilateral mainstem bronchi during expiration. Serial imaging over 14 years allowed the radiologist to confidently diagnose her underlying disorder and recommend appropriate clinical management, which included mucolytics, chest physiotherapy, prophylactic vaccinations, and antibiotics during infectious exacerbations. To the best of our knowledge, there is only one reported case of MKS in the setting of HIV in the English literature. We report the second such case and outline the clinical presentation, diagnostic criteria, and management of MKS with the hope that increased awareness will prevent delayed or misdiagnosis for patients with MKS. This case highlights the common diagnostic delay for MKS and the need to include MKS in the differential diagnosis of recurrent respiratory tract infections.

  14. Choline acetyltransferase mutations causing congenital myasthenic syndrome: molecular findings and genotype-phenotype correlations

    PubMed Central

    Arredondo, Juan; Lara, Marian; Gospe, Sídney M.; Mazia, Claudio G.; Vaccarezza, Maria; Garcia-Erro, Marcela; Bowe, Constance; Chang, Celia; Mezei, Michelle; Maselli, Ricardo A.

    2015-01-01

    Choline acetyltransferase catalyzes the synthesis of acetylcholine at cholinergic nerves. Mutations in human CHAT cause a congenital myasthenic syndrome (CMS) due to impaired synthesis of ACh; this severe variant of the disease is frequently associated with unexpected episodes of potentially fatal apnea. The severity of this condition varies remarkably, and the molecular factors determining this variability are poorly understood. Furthermore, genotype–phenotype correlations have been difficult to establish in patients with biallelic mutations. We analyzed the protein expression of seven ChAT mutations, p.Val136Met, p.Arg207His, p.Arg186Trp, p.Val194Leu, p.Pro211Ala, p.Arg566Cys and p.Ser694Cys, in HEK-293 cells to phosphorylated ChAT, determined their enzyme kinetics and thermal instability, and examined their structural changes. Three mutations, p.Arg207His, p.Arg186Trp and p.Arg566Cys, are novel, and p.Val136Met and p.Arg207His are homozygous in three families and associated with severe disease. The characterization of mutants showed a decrease in the overall catalytic efficiency of ChAT; in particular, those located near the active-site tunnel produced the most seriously disruptive phenotypic effects. On the other hand, p.Val136Met is located far from both active and substrate-binding sites produced the most drastic reduction of ChAT expression. Overall, CHAT mutations producing low enzyme expression and severe kinetic effects are associated with the most severe phenotypes. PMID:26080897

  15. Loss of smell but not taste in adult women with Turner's syndrome and other congenital hypogonadisms.

    PubMed

    Ros, Cristina; Alobid, Isam; Centellas, Silvia; Balasch, Juan; Mullol, Joaquim; Castelo-Branco, Camil

    2012-11-01

    To assess the impact of Turner's syndrome (TS) and other congenital hypogonadisms (OCH) on the sense of smell and taste. An analytical study of three independent cohorts was designed: patients affected by TS, OCH, and a control group of healthy women taking contraception. Gynaecological Endocrinology Unit and Smell Clinic in Rhinology Unit of Hospital Clinic of Barcelona. Thirty TS patients between 20 and 50 years of age receiving hormone replacement treatment (HT) were included as the exposed cohort; fourteen age-matched women with OCH taking HT were recruited; forty-three age-matched healthy controls receiving hormone contraception treatment were selected as the control group. This group was matched with an historical cohort of forty healthy women without contraception, used to validate BAST-24 in Hospital Clinic of Barcelona. Clinical history, presence of nasal symptoms, general physical examination, nasal endoscopy, and Barcelona Smell Test-24 (BAST-24) and gustometry were carried out on all patients. TS physical dysmorphology features, intensity of nasal symptoms and signs of nasal obstruction were collected. BAST-24 test included 24 odours to assess both sensory (detection, memory and forced choice) and sensitivity (intensity, irritability, freshness and pleasantness) odour characteristics, as well as 4 tastes to evaluate taste domains (detection and forced choice). Healthy women taking hormone contraception felt odours with more intensity (p=0.002) and less irritability (p<0.001) than the historical cohort. TS patients showed a significant impairment in smell memory (p<0.005) and forced-choice (p<0.001) compared with controls taking contraception, whereas no differences were found in odour sensitivity. Detection of taste was successful in 100% of patients. When considering only individual tastes, none of them showed statistically significant differences between groups. Patients with TS show the impairment of smell but not of taste, compared to OCH and

  16. Upshaw-Schulman syndrome revisited: a concept of congenital thrombotic thrombocytopenic purpura.

    PubMed

    Kinoshita, S; Yoshioka, A; Park, Y D; Ishizashi, H; Konno, M; Funato, M; Matsui, T; Titani, K; Yagi, H; Matsumoto, M; Fujimura, Y

    2001-07-01

    Upshaw-Schulman syndrome (USS) is a congenital bleeding disorder characterized by repeated episodes of thrombocytopenia and microangiopathic hemolytic anemia that respond to infusions of fresh frozen plasma. Inheritance of USS has been thought to be autosomal recessive, because 2 siblings in the same family are often affected but their parents are asymptomatic. Recently, chronic relapsing thrombotic thrombocytopenic purpura (CR-TTP), reported almost exclusively in adults, was shown to be caused by inherited or acquired deficiency in the activity of a plasma von Willebrand factor-cleaving protease (vWF-CPase). The pathogenesis of USS is unknown, and a relationship between CR-YEP and USS has not been reported. We studied 3 unrelated USS patients (ST, SY, and KI) who presented with severe indirect neonatal hyperbilirubinemia. All 3 patients had undetectable vWF-CPase activity, and the inhibitors to vWF-CPase were all negative. In their parents with no clinical symptoms, vWF-CPase activities as a percentage of control samples (mother/father) were 17/20 for ST, 60/45 for SY, and 36/5.6 for KI. Thus, USS and vWF-CPase activity appear to be coinherited as autosomal recessive traits. Transfusion of fresh frozen plasma in 2 patients (ST and SY) resulted in the expected maximal increment of approximately 7% to 8% in vWF-CPase activity at 1 to 4 hours, but the levels became less than 3% within 2 days. After this decrease, platelet counts increased, plateaued in the normal range at 10 to 12 days, and declined thereafter. Thus, the 2 to 3 weeks of therapeutic benefit from plasma infusions will be discussed in relation to the intravascular lifetime of vWF-CPase.

  17. The promises and challenges of exome sequencing in familial, non-syndromic congenital heart disease.

    PubMed

    Blue, Gillian M; Humphreys, David; Szot, Justin; Major, Joelene; Chapman, Gavin; Bosman, Alexis; Kirk, Edwin P; Sholler, Gary F; Harvey, Richard P; Dunwoodie, Sally L; Winlaw, David S

    2017-03-01

    Exome sequencing is an established strategy to identify causal variants in families with two or more members affected by congenital heart disease (CHD). This unbiased approach, in which both rare and common variants are identified, makes it suitable to research complex, heterogeneous diseases such as CHD. Exome sequencing was performed on two affected members of a three generation family with atrial septal defects (ASD), suggesting a dominant inheritance pattern. Variants were filtered using two bioinformatics pipelines and prioritised according to in silico prediction programs. Segregation studies and functional analyses were used to assess co-segregation with disease and effects on protein function, respectively. Following the data and in silico analyses, ten candidate variants were prioritised. Of these, SRPK2 (c.2044C>T[p.Arg682Trp]) and NOTCH1 (c.3835C>T[p.Arg1279Cys]), co-segregated with disease in the family; however, previous functional analyses on SRPK2 make this an unlikely candidate. Functional analyses in the variant (c.3835C>T[p.Arg1279Cys]) of the known CHD gene NOTCH1 demonstrated a non-significant decrease in signalling activity. This study demonstrates both the potential, as well as the challenges, of applying exome sequencing to complex diseases such as CHD. While in silico evidence and segregation analyses in the NOTCH1 p.Arg1279Cys variant are highly suggestive of pathogenicity, the minimal change in signalling capacity suggests that other variants may be required for CHD development. This study highlights the difficulties of applying exome sequencing in familial, non-syndromic CHD in the clinical environment and a cautionary note in the interpretation of apparently causal abnormalities in silico without supportive functional data. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Congenital central hypoventilation syndrome: Broader cognitive deficits revealed by parent controls.

    PubMed

    Zelko, Frank A; Stewart, Tracey M; Brogadir, Cindy D; Rand, Casey M; Weese-Mayer, Debra E

    2018-04-01

    To investigate neurocognitive deficits in children with Congenital Central Hypoventilation Syndrome (CCHS) by comparing them to their parents, since parents comprise a particularly suitable control group matched on disease-extrinsic factors that can influence neurocognitive functioning. We compared CCHS patients to their parents and to population norms, hypothesizing that they would obtain lower intelligence test scores than both groups. We also compared patient-parent differences against patient-normative differences, to determine whether the two analytic approaches would yield different results. We administered an intelligence screening, the Shipley-2, to 21 school-aged patients (age 14.2 ± 5.5 years) with PHOX2B mutation-confirmed CCHS and their parents. Patients also received detailed clinical intellectual assessments using the Wechsler scales. CCHS patients scored significantly below parents on Shipley-2 indices of intelligence, vocabulary, and abstraction, with a trend for perceptual reasoning. The CCHS patients scored significantly below population norms on indices of abstraction and perceptual reasoning. Patient-parent differences were significantly larger than patient-normative differences for vocabulary scores. CCHS patients scored significantly below population norms on Wechsler indices of intelligence, perceptual reasoning, working memory, and processing speed. CCHS may affect a broader range of cognitive abilities than previous research based on comparisons to population norms has indicated. Comparisons of CCHS children to their parents reveal deficits of vocabulary and abstract reasoning which have not been previously identified. A full understanding of the neurocognitive impact of CCHS requires comparisons between patients and other individuals such as friends, parents, or siblings who closely resemble them on disease-extrinsic characteristics. © 2018 Wiley Periodicals, Inc.

  19. [Contribution of dynamic electrocardiography by Holter monitoring in the evaluation of congenital long QT syndrome patients].

    PubMed

    Maia, I G; Fagundes, M L; Cruz Filho, F; Barbosa, R C; Alves, P A

    1998-07-01

    The purpose of this study was to evaluate the value of ambulatory electrocardiogram as a clinical tool to assess ventricular repolarization in patients with the congenital long QT syndrome. The study population comprised six patients and their data were compared to a control group of six patients matched in age and gender. The QT interval (ms), corrected by the heart rate, was measured in the first minute of each hour using two monitoring leads, with the mean of six consecutive complexes. The data obtained include the morphologic pattern of T wave, the mean 24-h QTc interval, relation between QT and cardiac cycle, QTc variability (assessed calculating hourly standard deviation of the interval and then obtaining the global 24-h mean), QTc dispersion (difference between the longest and shortest QTc interval). In all patients abnormal patterns of T waves were detected with frequent episodes of T wave alternans. Mean 24-h QTc--patients: 598.2 +/- 73.8 ms; controls: 436.1 +/- 8.9 ms (p = 0.000). Linear correlation and regression between QT and heart rate-patients: r = 0.812; controls: r = 0.967 (p = 0.000). QTc variability-patients: 36.9 +/- 17.2 ms; controls: 14.7 +/- 2.1 ms (p = 0.01). QTc dispersion-patients: 168.3 +/- 70.2 ms; controls: 53.3 +/- 8.1 ms (p = 0.000). The data showed increased hourly QTc variability. QTc dispersion and worse correlation between QT and heart rate. This data may reflect an abnormally augmented ventricular vulnerability.

  20. Neurogenic bladder findings in patients with Congenital Zika Syndrome: A novel condition.

    PubMed

    Costa Monteiro, Lucia Maria; Cruz, Glaura Nisya de Oliveira; Fontes, Juliana Marin; Saad Salles, Tania Regina Dias; Boechat, Marcia Cristina Bastos; Monteiro, Ana Carolina; Moreira, Maria Elizabeth Lopes

    2018-01-01

    Congenital Zika Syndrome (CZS) has been associated with microcephaly and other central nervous system abnormalities including areas that have been implicated in the control of the lower urinary tract. As such, this descriptive case series has aimed to investigate whether CZS is linked with neurogenic bladder. Identifying such an association is paramount in the effort to recognize CZS complications that have putative treatment options that could mitigate the impact of CZS in infected children. Following IRB approval, urological assessment was performed in all patients referred to our clinic between June 2016 and May 2017 who presented with confirmed CZS-associated microcephaly. The research protocol consisted of obtaining clinical history, laboratory tests, lower and upper urinary tract ultrasounds, as well as a diagnostic urodynamic evaluation. ZIKA virus infection was previously confirmed by maternal history and positive PCR in babies and mothers. Microcephaly and other central nervous system abnormalities were established based on neurological assessment and associated imaging of the central nervous system (CT head and/or Brain MRI). Twenty-two consecutive CZS patients were tested and confirmed to have neurogenic bladder. Of the 22 patients assessed, 21 presented with an overactive bladder combined with reduced bladder capacity and elevated detrusor filling pressures. Clinically significant increases in postvoid residual (PVR) were confirmed in 40% of cases while a urinary tract infection (UTI) was identified in 23% of cases. Neurogenic bladder, a known treatable health condition, was confirmed in 100% of patients tested in this study, most presenting with high-risk urodynamic patterns known to lead to renal damage when left untreated. Follow up studies are necessary to provide further insight onto long-term disease progression and to investigate the response to standard therapies for neurogenic bladder. Nonetheless, we emphasize the importance of proactive

  1. Epidemiology of rubella and congenital rubella syndrome in Japan before 1989.

    PubMed

    Ueda, Kohji

    2016-04-07

    Epidemiological studies of rubella and congenital rubella syndrome (CRS) in Japan have been conducted since the first nationwide rubella epidemic of 1965-1969 and subsequent epidemics of 1975-1977, 1982, 1987-1988, and 1992-1993. Rubella was non-endemic in Japan before the 1975-1977 epidemic, and endemic thereafter. Japan started a selective rubella vaccination program for junior high school girls in 1977, and universal rubella vaccination of children of both sexes in 1989. No nationwide rubella epidemics have occurred since 1994. Only three children with CRS were reported in Japan before 1964; however, many children with CRS were identified in 1965 when a rubella epidemic struck Okinawa, which has many the United States military bases. After the 1965-1969 and 1975-1977 rubella epidemics on the Japanese mainland, small numbers of children with CRS were identified (hospital survey). These findings led to the hypothesis that, compared to U.S. rubella virus strains, Japanese strains of rubella virus are less teratogenic. This hypothesis strongly affected the development of rubella vaccines in Japan. However, retrospective seroepidemiological studies attributed the CRS in many children in Okinawa to the high rate of rubella infection in pregnant women. According to the survey conducted at special schools for the deaf, 83, 232, 77, and 167 children were born with CRS on the Japanese mainland respectively after the 1965-1969, 1975-1977, 1982, and 1987-1988 nationwide rubella epidemics, suggesting that the incidence of CRS in Japan is in fact comparable to that in the U.S. and Europe. Rubella epidemics in children have been effectively prevented since 1994. However, a rubella outbreak among adult males and CRS occurred between 2012 and 2014. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Congenital myasthenic syndromes in Turkey: Clinical clues and prognosis with long term follow-up.

    PubMed

    Durmus, Hacer; Shen, Xin-Ming; Serdaroglu-Oflazer, Piraye; Kara, Bulent; Parman-Gulsen, Yesim; Ozdemir, Coskun; Brengman, Joan; Deymeer, Feza; Engel, Andrew G

    2017-11-28

    Congenital myasthenic syndromes (CMS) are a group of hereditary disorders affecting the neuromuscular junction. Here, we present clinical, electrophysiological and genetic findings of 69 patients from 51 unrelated kinships from Turkey. Genetic tests of 60 patients were performed at Mayo Clinic. Median follow-up time was 9.8 years (range 1-22 years). The most common CMS was primary acetylcholine receptor (AChR) deficiency (31/51) and the most common mutations in AChR were c.1219 + 2T > G (12/51) and c.1327delG (6/51) in CHRNE. Four of our 5 kinships with AChE deficiency carried p.W148X that truncates the collagen domain of COLQ, and was previously reported only in patients from Turkey. These were followed by GFPT1 deficiency (4/51), DOK7 deficiency (3/51), slow channel CMS (3/51), fast channel CMS (3/51), choline acetyltransferase deficiency (1/51) and a CMS associated with desmin deficiency (1/51). Distribution of muscle weakness was sometimes useful in giving a clue to the CMS subtype. Presence of repetitive compound muscle action potentials pointed to AChE deficiency or slow channel CMS. Our experience confirms that one needs to be cautious using pyridostigmine, since it can worsen some types of CMS. Ephedrine/salbutamol were very effective in AChE and DOK7 deficiencies and were useful as adjuncts in other types of CMS. Long follow-up gave us a chance to assess progression of the disease, and to witness 12 mainly uneventful pregnancies in 8 patients. In this study, we describe some new phenotypes and detail the clinical features of the well-known CMS. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. The cerebral cost of breathing: an FMRI case-study in congenital central hypoventilation syndrome.

    PubMed

    Sharman, Mike; Gallea, Cécile; Lehongre, Katia; Galanaud, Damien; Nicolas, Nathalie; Similowski, Thomas; Cohen, Laurent; Straus, Christian; Naccache, Lionel

    2014-01-01

    Certain motor activities--like walking or breathing--present the interesting property of proceeding either automatically or under voluntary control. In the case of breathing, brainstem structures located in the medulla are in charge of the automatic mode, whereas cortico-subcortical brain networks--including various frontal lobe areas--subtend the voluntary mode. We speculated that the involvement of cortical activity during voluntary breathing could impact both on the "resting state" pattern of cortical-subcortical connectivity, and on the recruitment of executive functions mediated by the frontal lobe. In order to test this prediction we explored a patient suffering from central congenital hypoventilation syndrome (CCHS), a very rare developmental condition secondary to brainstem dysfunction. Typically, CCHS patients demonstrate efficient cortically-controlled breathing while awake, but require mechanically-assisted ventilation during sleep to overcome the inability of brainstem structures to mediate automatic breathing. We used simultaneous EEG-fMRI recordings to compare patterns of brain activity between these two types of ventilation during wakefulness. As compared with spontaneous breathing (SB), mechanical ventilation (MV) restored the default mode network (DMN) associated with self-consciousness, mind-wandering, creativity and introspection in healthy subjects. SB on the other hand resulted in a specific increase of functional connectivity between brainstem and frontal lobe. Behaviorally, the patient was more efficient in cognitive tasks requiring executive control during MV than during SB, in agreement with her subjective reports in everyday life. Taken together our results provide insight into the cognitive and neural costs of spontaneous breathing in one CCHS patient, and suggest that MV during waking periods may free up frontal lobe resources, and make them available for cognitive recruitment. More generally, this study reveals how the active

  4. Cleft Palate, Retrognathia and Congenital Heart Disease in Velo-Cardio-Facial Syndrome: A Phenotype Correlation Study

    PubMed Central

    Friedman, Marcia A.; Miletta, Nathanial; Roe, Cheryl; Wang, Dongliang; Morrow, Bernice E.; Kates, Wendy R.; Higgins, Anne Marie; Shprintzen, Robert J.

    2011-01-01

    Objective Velo-cardio-facial syndrome (VCFS) is caused by a microdeletion of approximately 40 genes from one copy of chromosome 22. Expression of the syndrome is a variable combination of over 190 phenotypic characteristics. As of yet, little is known about how these phenotypes correlate with one another or whether there are predictable patterns of expression. Two of the most common phenotypic categories, congenital heart disease and cleft palate, have been proposed to have a common genetic relationship to the deleted T-box 1 gene (TBX1). The purpose of this study is to determine if congenital heart disease and cleft palate are correlated in a large cohort of human subjects with VCFS. Methods This study is a retrospective chart review including 316 Caucasian non-Hispanic subjects with FISH or CGH microarray confirmed chromosome 22q11.2 deletions. All subjects were evaluated by the interdisciplinary team at the Velo-Cardio-Facial Syndrome International Center at Upstate Medical University, Syracuse, NY. Each combination of congenital heart disease, cleft palates, and retrognathia was analyzed by chi square or Fisher exact test. Results For all categories of congenital heart disease and cleft palate or retrognathia no significant associations were found, with the exception of submucous cleft palate and retrognathia (nominal p=0.0325) and occult submucous cleft palate and retrognathia (nominal p=0.000013). Conclusions Congenital heart disease and cleft palate do not appear to be correlated in human subjects with VCFS despite earlier suggestions from animal models. Possible explanations include modification of the effect of TBX1 by genes outside of the 22q11.2 region that may further influence the formation of the palate or heart, or the presence of epigenetic factors that may effect genes within the deleted region, modifying genes elsewhere, or polymorphisms on the normal copy of chromosome 22. Lastly, it is possible that TBX1 plays a role in palate formation in some

  5. Cleft palate, retrognathia and congenital heart disease in velo-cardio-facial syndrome: a phenotype correlation study.

    PubMed

    Friedman, Marcia A; Miletta, Nathanial; Roe, Cheryl; Wang, Dongliang; Morrow, Bernice E; Kates, Wendy R; Higgins, Anne Marie; Shprintzen, Robert J

    2011-09-01

    Velo-cardio-facial syndrome (VCFS) is caused by a microdeletion of approximately 40 genes from one copy of chromosome 22. Expression of the syndrome is a variable combination of over 190 phenotypic characteristics. As of yet, little is known about how these phenotypes correlate with one another or whether there are predictable patterns of expression. Two of the most common phenotypic categories, congenital heart disease and cleft palate, have been proposed to have a common genetic relationship to the deleted T-box 1 gene (TBX1). The purpose of this study is to determine if congenital heart disease and cleft palate are correlated in a large cohort of human subjects with VCFS. This study is a retrospective chart review including 316 Caucasian non-Hispanic subjects with FISH or CGH microarray confirmed chromosome 22q11.2 deletions. All subjects were evaluated by the interdisciplinary team at the Velo-Cardio-Facial Syndrome International Center at Upstate Medical University, Syracuse, NY. Each combination of congenital heart disease, cleft palates, and retrognathia was analyzed by Chi square or Fisher exact test. For all categories of congenital heart disease and cleft palate or retrognathia no significant associations were found, with the exception of submucous cleft palate and retrognathia (nominal p=0.0325) and occult submucous cleft palate and retrognathia (nominal p=0.000013). Congenital heart disease and cleft palate do not appear to be correlated in human subjects with VCFS despite earlier suggestions from animal models. Possible explanations include modification of the effect of TBX1 by genes outside of the 22q11.2 region that may further influence the formation of the palate or heart, or the presence of epigenetic factors that may effect genes within the deleted region, modifying genes elsewhere, or polymorphisms on the normal copy of chromosome 22. Lastly, it is possible that TBX1 plays a role in palate formation in some species, but not in humans. In VCFS

  6. Congenital Joint Dislocations Caused by Carbohydrate Sulfotransferase 3 Deficiency in Recessive Larsen Syndrome and Humero-Spinal Dysostosis

    PubMed Central

    Hermanns, Pia; Unger, Sheila; Rossi, Antonio; Perez-Aytes, Antonio; Cortina, Hector; Bonafé, Luisa; Boccone, Loredana; Setzu, Valeria; Dutoit, Michel; Sangiorgi, Luca; Pecora, Fabio; Reicherter, Kerstin; Nishimura, Gen; Spranger, Jürgen; Zabel, Bernhard; Superti-Furga, Andrea

    2008-01-01

    Deficiency of carbohydrate sulfotransferase 3 (CHST3; also known as chondroitin-6-sulfotransferase) has been reported in a single kindred so far and in association with a phenotype of severe chondrodysplasia with progressive spinal involvement. We report eight CHST3 mutations in six unrelated individuals who presented at birth with congenital joint dislocations. These patients had been given a diagnosis of either Larsen syndrome (three individuals) or humero-spinal dysostosis (three individuals), and their clinical features included congenital dislocation of the knees, elbow joint dysplasia with subluxation and limited extension, hip dysplasia or dislocation, clubfoot, short stature, and kyphoscoliosis developing in late childhood. Analysis of chondroitin sulfate proteoglycans in dermal fibroblasts showed markedly decreased 6-O-sulfation but enhanced 4-O-sulfation, confirming functional impairment of CHST3 and distinguishing them from diastrophic dysplasia sulphate transporter (DTDST)-deficient cells. These observations provide a molecular basis for recessive Larsen syndrome and indicate that recessive Larsen syndrome, humero-spinal dysostosis, and spondyloepiphyseal dysplasia Omani type form a phenotypic spectrum. PMID:18513679

  7. Congenital joint dislocations caused by carbohydrate sulfotransferase 3 deficiency in recessive Larsen syndrome and humero-spinal dysostosis.

    PubMed

    Hermanns, Pia; Unger, Sheila; Rossi, Antonio; Perez-Aytes, Antonio; Cortina, Hector; Bonafé, Luisa; Boccone, Loredana; Setzu, Valeria; Dutoit, Michel; Sangiorgi, Luca; Pecora, Fabio; Reicherter, Kerstin; Nishimura, Gen; Spranger, Jürgen; Zabel, Bernhard; Superti-Furga, Andrea

    2008-06-01

    Deficiency of carbohydrate sulfotransferase 3 (CHST3; also known as chondroitin-6-sulfotransferase) has been reported in a single kindred so far and in association with a phenotype of severe chondrodysplasia with progressive spinal involvement. We report eight CHST3 mutations in six unrelated individuals who presented at birth with congenital joint dislocations. These patients had been given a diagnosis of either Larsen syndrome (three individuals) or humero-spinal dysostosis (three individuals), and their clinical features included congenital dislocation of the knees, elbow joint dysplasia with subluxation and limited extension, hip dysplasia or dislocation, clubfoot, short stature, and kyphoscoliosis developing in late childhood. Analysis of chondroitin sulfate proteoglycans in dermal fibroblasts showed markedly decreased 6-O-sulfation but enhanced 4-O-sulfation, confirming functional impairment of CHST3 and distinguishing them from diastrophic dysplasia sulphate transporter (DTDST)-deficient cells. These observations provide a molecular basis for recessive Larsen syndrome and indicate that recessive Larsen syndrome, humero-spinal dysostosis, and spondyloepiphyseal dysplasia Omani type form a phenotypic spectrum.

  8. Tenascin-X Haploinsufficiency Associated with Ehlers-Danlos Syndrome in Patients with Congenital Adrenal Hyperplasia

    PubMed Central

    Chen, Wuyan; Morissette, Rachel; Xu, Zhi; Van Ryzin, Carol; Sachdev, Vandana; Hannoush, Hwaida; Shanbhag, Sujata M.; Acevedo, Ana T.; Nishitani, Miki; Arai, Andrew E.; McDonnell, Nazli B.

    2013-01-01

    Context: The gene for congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, CYP21A2, is flanked by the gene encoding tenascin-X (TNXB), a connective tissue extracellular matrix protein that has been linked to both autosomal dominant and autosomal recessive Ehlers-Danlos syndrome (EDS). A contiguous deletion of CYP21A2 and TNXB has been described. Objective: The objective of the study was to determine the frequency and clinical significance of TNXB haploinsufficiency in CAH patients. Design, Setting, and Participants: A total of 192 consecutive unrelated CAH patients being seen as part of an observational study at the National Institutes of Health Clinical Center (Bethesda, MD) were prospectively studied during 2006–2010. Patients were evaluated for clinical evidence of EDS, including cardiac evaluation. DNA was analyzed by PCR, multiplex ligation-dependent probe amplification, Southern blot, and TNXB sequencing. Tenascin-X expression was evaluated by Western blot analysis of fibroblasts and immunostaining of the skin. CAH patients with TNXB haploinsufficiency were compared with age-matched CAH patients with normal TNXB (controls). Phenotyping of 7 parents with TNXB haploinsufficiency was performed. Main Outcome Measures: The frequency of TNXB haploinsufficiency among CAH patients and the frequency of EDS symptomatology among CAH patients with TNXB haploinsufficiency and controls. Results: TNXB haploinsufficiency, here termed CAH-X syndrome, was present in 7% of CAH patients. Twelve of 91 patients carrying a CYP21A2 deletion (13%) carried a contiguous deletion that extended into TNXB. One patient carried a TNXB premature stop codon. Twelve of 13 patients with CAH-X had EDS clinical features. Patients with CAH-X were more likely than age-matched controls to have joint hypermobility (P < .001), chronic joint pain (P = .003), multiple joint dislocations (P = .004), a structural cardiac valve abnormality by echocardiography (P = .02), and reduced

  9. Isolated lower limb hypoplasia secondary to congenital varicella syndrome: a rare occurrence and management of its complications.

    PubMed

    Mehta, Sneha; Schenk, Willem; Kirker, Stephen; Atrey, Amit

    2017-03-22

    Isolated lower limb hypoplasia is a rare consequence of maternal congenital varicella syndrome (CVS). The hypoplastic limb is susceptible to multiple injuries, including fractures, especially if there is associated muscle weakness and lack of sensation. We describe a unique index case of a woman aged 26 years with a background of CVS who presented with a distal femur fracture following a fall onto her insensate, hypoplastic right leg. This report highlights the complexities involved in the diagnosis and management of fractures in patients with an anaesthetic limb, and in particular describes limb amputation as a successful treatment modality for distal femur fractures. 2017 BMJ Publishing Group Ltd.

  10. Noninvasive ventilatory strategies in the management of a newborn infant and three children with congenital central hypoventilation syndrome.

    PubMed

    Tibballs, James; Henning, Robert D

    2003-12-01

    Four children with congenital central hypoventilation syndrome (CCHS) treated with noninvasive techniques of ventilation are presented. Two infants (one in the newborn period) were treated with nasal mask bilevel positive airway pressure (BiPAP), and then both were transitioned to negative pressure chamber ventilation at several years of age because of possible midface hypoplasia. Tracheostomies were not performed. Two older children were transitioned from mechanical ventilation via tracheostomy to nasal mask BiPAP, and then in one case to negative pressure chamber ventilation, and in the other to phrenic nerve pacing. Their tracheostomies were removed. Copyright 2003 Wiley-Liss, Inc.

  11. Coffin-Siris syndrome with the rarest constellation of congenital cardiac defects: A case report with review of literature.

    PubMed

    Nemani, Lalita; Barik, Ramachandra; Patnaik, Amar Narayana; Mishra, Ramesh C; Rao, Amaresh M; Kapur, Pragati

    2014-09-01

    We report a case of type-A Coffin-Siris syndrome (CSS) with a unique constellation of congenital heart defects. A 17-year-old Indian boy was referred to our hospital for central cyanosis with features of right heart failure. The cardiac abnormalities included biventricular outflow tract obstruction, small atrial septal defect (ASD), subaortic ventricular septal defect, drainage of left superior venacava to left atrial appendage, and aortic arch anomaly. Patient underwent successful right ventricular infundibular resection, subaortic membrane resection, closure of atrial and ventricular septal defect, rerouting left superior vena cava to left pulmonary artery and aortic valve replacement.

  12. Coffin-Siris syndrome with the rarest constellation of congenital cardiac defects: A case report with review of literature

    PubMed Central

    Nemani, Lalita; Barik, Ramachandra; Patnaik, Amar Narayana; Mishra, Ramesh C; Rao, Amaresh M; Kapur, Pragati

    2014-01-01

    We report a case of type-A Coffin-Siris syndrome (CSS) with a unique constellation of congenital heart defects. A 17-year-old Indian boy was referred to our hospital for central cyanosis with features of right heart failure. The cardiac abnormalities included biventricular outflow tract obstruction, small atrial septal defect (ASD), subaortic ventricular septal defect, drainage of left superior venacava to left atrial appendage, and aortic arch anomaly. Patient underwent successful right ventricular infundibular resection, subaortic membrane resection, closure of atrial and ventricular septal defect, rerouting left superior vena cava to left pulmonary artery and aortic valve replacement. PMID:25298701

  13. Congenital Heart Defects and Measures of Fetal Growth in Newborns with Down Syndrome or 22q11.2 Deletion Syndrome.

    PubMed

    Matthiesen, Niels B; Agergaard, Peter; Henriksen, Tine B; Bach, Cathrine C; Gaynor, J William; Hjortdal, Vibeke; Østergaard, John R

    2016-08-01

    To estimate the association between congenital heart defects (CHD) and indices of fetal growth in Down and 22q11.2 deletion syndromes. We established 2 Danish nationwide cohorts of newborn singletons with either Down syndrome (n = 670) or 22q11.2 deletion syndrome (n = 155), born 1997-2011. In both cohorts, we analyzed the association between CHD, CHD severity, and indices of fetal growth by multivariable linear regression adjusted for potential confounders. We report mean differences in gestational age specific z-scores compared with newborns without CHD. Down syndrome and 22q11.2 deletion syndrome were both associated with lower mean birth weight and head circumference z-scores. We found no association between CHD or CHD severity and indices of fetal growth. In Down syndrome, the association between any CHD and the mean difference in head circumference z-score was 0.03 (95% CI -0.12, 0.18), and the estimate regarding birth weight z-score was 0.09 (95% CI -0.08, 0.25). The corresponding estimates in 22q11.2 deletion syndrome were 0.00 (95% CI -0.33, 0.32) and -0.09 (95% CI -0.45, 0.26). We found no association between CHD and fetal growth measures in newborns with Down syndrome or 22q11.2 deletion syndrome. Thus, in certain subtypes of CHD, the contribution of genetic factors to prenatal growth impairment may be more important than circulatory disturbances. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Vaccination in secondary school students expedites rubella control and prevents congenital rubella syndrome.

    PubMed

    He, Hanqing; Yan, Rui; Tang, Xuewen; Zhou, Yang; Deng, Xuan; Xie, Shuyun

    2016-11-30

    In order to control the spread of rubella and reduce the risk for congenital rubella syndrome, an additional rubella vaccination program was set up for all secondary school students since 2008 in Zhejiang, China. We conducted a descriptive analysis of rubella incidence among different age groups from 2005 to 2015 and a serosurvey of female subjects aged 15-39 years to understand the possible effects of this immunization program. The average annual rubella incidence rate had decreased from 15.86 per 100,000 population (2005-2007) to 0.75 per 100,000 population (2013-2015) in Zhejiang. The decrease in the rate of rubella incidence in girls aged 15-19 years was more accelerated (from 138.30 to 0.34 per 100,000) than in the total population during 2008-2015 (from 32.20 to 0.46 per 100,000). Of 1225 female subjects in the serosurvey, 256 (20.9%) were not immune to rubella. The proportion of subjects immune to rubella was significantly different among different age groups (Wald χ2 = 22.19, p = 0.000), and subjects aged 15-19 years old had the highest immunity (88.0%). Rubella antibody levels were significantly lower in women aged 25-30 years with 26.7% of them not immune, followed by the group aged 20-24 years (25.0%) and 30-35 years (24.5%). Rubella vaccine included in the Expanded Program on Immunization together with vaccination activities for secondary school students can help in rubella control, particularly in targeted age groups in the program. Seroprevalence of antibodies to the rubella virus amongst the female population within childbearing age in Zhejiang, China, is still too low to provide immunity. In addition to vaccination programs in the secondary schools, rubella vaccination should also be encouraged in women of childbearing age, which can be done effectively combined with pre-marital examination in China.

  15. Description of 214 cases of autoimmune congenital heart block: Results of the French neonatal lupus syndrome.

    PubMed

    Levesque, Kateri; Morel, Nathalie; Maltret, Alice; Baron, Gabriel; Masseau, Agathe; Orquevaux, Pauline; Piette, Jean-Charles; Barriere, Francois; Le Bidois, Jérome; Fermont, Laurent; Fain, Olivier; Theulin, Arnaud; Sassolas, Francois; Pezard, Philippe; Amoura, Zahir; Guettrot-Imbert, Gaëlle; Le Mercier, Delphine; Georgin-Lavialle, Sophie; Deligny, Christophe; Hachulla, Eric; Mouthon, Luc; Ravaud, Philippe; Villain, Elisabeth; Bonnet, Damien; Costedoat-Chalumeau, Nathalie

    2015-12-01

    Cardiac neonatal lupus syndrome is due to anti-SSA or SSB antibodies and mainly includes congenital heart block (CHB) and dilated cardiomyopathy (DCM). Its optimal management is still debated. We report a large series of autoimmune high degree CHB. Inclusion criteria in this retrospective study were fetuses or neonates with high-degree CHB associated with maternal anti-SSA/SSB antibodies. 214 CHB were included: 202 detected in utero at a median term of 23 weeks' gestation (WG) [range 16 to 39 WG] and 12 neonatal cases diagnosed at a median age of 0 days [range birth to 8 days]. The 214 cases of CHB included 202 (94.4%) third-degree CHB, 8 (3.7%) second-degree CHB, and 4 (1.9%) intermittent CHB. In multivariate analysis, the factors associated with feto-neonatal deaths (15.7%) were hydrops (p<0.001; hazard ratio [HR] 12.4 [95% confidence interval (95%CI) 4.7-32.7]) and prematurity (p=0.002; HR 17.1 [95%CI 2.8-103.1]). During a median follow-up of 7 years [birth to 36 years], 148 of 187 children born alive (79.1%) had a pacemaker, 35 (18.8%, one missing data) had DCM, and 22 (11.8%) died. In multivariate analysis, factors associated with child death were in utero DCM (p=0.0157; HR 6.37 [95%CI: 1.25-32.44]), postnatal DCM (p<0.0001; HR 227.58[95%CI: 24.33-2128.46]) and pacemaker implantation (p=0.0035; HR 0.11[95%CI: 0.02-0.51]). The use of fluorinated steroids was neither associated with survival nor with regression of 2nd degree CHB. In this second largest series of CHB, we confirm some of the previous results. We were unable to find data supporting the routine use of in utero fluorinated steroids. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. A COLQ Missense Mutation in Sphynx and Devon Rex Cats with Congenital Myasthenic Syndrome

    PubMed Central

    Abitbol, Marie; Hitte, Christophe; Bossé, Philippe; Blanchard-Gutton, Nicolas; Thomas, Anne; Martignat, Lionel; Blot, Stéphane; Tiret, Laurent

    2015-01-01

    An autosomal recessive neuromuscular disorder characterized by skeletal muscle weakness, fatigability and variable electromyographic or muscular histopathological features has been described in the two related Sphynx and Devon Rex cat breeds (Felis catus). Collection of data from two affected Sphynx cats and their relatives pointed out a single disease candidate region on feline chromosome C2, identified following a genome-wide SNP-based homozygosity mapping strategy. In that region, we further identified COLQ (collagen-like tail subunit of asymmetric acetylcholinesterase) as a good candidate gene, since COLQ mutations were identified in affected humans and dogs with endplate acetylcholinesterase deficiency leading to a synaptic form of congenital myasthenic syndrome (CMS). A homozygous c.1190G>A missense variant located in exon 15 of COLQ, leading to a C397Y substitution, was identified in the two affected cats. C397 is a highly-conserved residue from the C-terminal domain of the protein; its mutation was previously shown to produce CMS in humans, and here we confirmed in an affected Sphynx cat that it induces a loss of acetylcholinesterase clustering at the neuromuscular junction. Segregation of the c.1190G>A variant was 100% consistent with the autosomal recessive mode of inheritance of the disorder in our cat pedigree; in addition, an affected, unrelated Devon Rex cat recruited thereafter was also homozygous for the variant. Genotyping of a panel of 333 cats from 14 breeds failed to identify a single carrier in non-Sphynx and non-Devon Rex cats. Finally, the percentage of healthy carriers in a European subpanel of 81 genotyped Sphynx cats was estimated to be low (3.7%) and 14 control Devon Rex cats were genotyped as wild-type individuals. Altogether, these results strongly support that the neuromuscular disorder reported in Sphynx and Devon Rex breeds is a CMS caused by a unique c.1190G>A missense mutation, presumably transmitted through a founder effect, which

  17. A boy with homozygous microdeletion of NEUROG1 presents with a congenital cranial dysinnervation disorder [Moebius syndrome variant

    PubMed Central

    2013-01-01

    Background We report on a 6-year-old Turkish boy with profound sensorineural deafness, balance disorder, severe disorder of oral motor function, and mild developmental delay. Further findings included scaphocephaly, plagiocephaly, long palpebral fissures, high narrow palate, low-set posteriorly rotated ears, torticollis, hypoplastic genitalia and faulty foot posture. Parents were consanguineous. Methods and results Computed tomography and magnetic resonance imaging showed bilateral single widened cochlear turn, narrowing of the internal auditory canal, and bilateral truncation of the vestibulo-cochlear nerve. Microarray analysis and next generation sequencing showed a homozygous deletion of chromosome 5q31.1 spanning 115.3 kb and including three genes: NEUROG1 (encoding neurogenin 1), DCNP1 (dendritic cell nuclear protein 1, C5ORF20) and TIFAB (TIFA-related protein). The inability to chew and swallow, deafness and balance disorder represented congenital palsies of cranial nerves V (trigeminal nerve) and VIII (vestibulo-cochlear nerve) and thus a congenital cranial dysinnervation disorder. Conclusions Based on reported phenotypes of neurog1 null mutant mice and other vertebrates, we strongly propose NEUROG1 as the causative gene in this boy. The human NEUROG1 resides within the DFNB60 locus for non-syndromic autosomal recessive deafness on chromosome 5q22-q31, but linkage data have excluded it from being causative in the DFNB60 patients. Given its large size (35 Mb, >100 genes), the 5q22-q31 area could harbor more than one deafness gene. We propose NEUROG1 as a new gene for syndromic autosomal recessive hearing loss and congenital cranial dysinnervation disorder including cranial nerves V and VIII. PMID:23419067

  18. Life and death of a child with down syndrome and a congenital heart condition: experiences of six couples.

    PubMed

    Reilly, Deirdre; Huws, Jaci; Hastings, Richard; Vaughan, Frances

    2010-12-01

    Individuals with Down syndrome are at increased risk of congenital heart conditions (CHCs), and mortality is higher in people with Down syndrome and a CHC than those without (J. C. Vis et al., 2009). As a consequence, parents of children with Down syndrome and a CHC are more likely to outlive their child. In this research, semistructured interviews were used to explore the experiences of 6 couples whose child with Down syndrome and a CHC had died. The interviews were analyzed qualitatively using interpretative phenomenological analysis (IPA), and 4 themes emerged: dilemmas associated with the dual diagnosis; treatment decisions during the life and the death of their child ("We had to make a decision"); ways couples coped when bereaved ("We weren't really going through it together"); and ripples from the child's life. There was a high degree of similarity of experience within couples. Differences between couples existed in their experiences of coping and supporting each other. Practical implications include the importance of considering the specific needs of couples, individuals, and fathers within partnerships.

  19. Novel syndrome with conductive hearing loss and congenital glaucoma in three generations.

    PubMed

    Takeuchi, Kazuhiko; Kitano, Masako; Sakaida, Hiroshi; Masuda, Sawako

    2017-08-01

    The objective of this paper was to describe the clinical and otological findings in multiple members of a family with congenital glaucoma, cardiac anomaly, and conductive hearing loss due to ossicular chain anomalies. We performed a retrospective review of the medical charts and otological materials of multiple members of the same family. Congenital glaucoma and hearing loss were inherited by the proband and her daughter, son, and mother, suggesting autosomal dominant inheritance. The son and daughter also showed atrial septal defects. Exploratory tympanotomies revealed anomalies of the long process of the incus in the proband and her daughter, and tympanoplasty improved hearing loss in both patients. This represents the first description of coexisting congenital glaucoma and conductive hearing loss due to ossicular chain anomalies in multiple members of a single family. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. Juvenile-Onset Diabetes and Congenital Cataract: “Double-Gene” Mutations Mimicking a Syndromic Diabetes Presentation

    PubMed Central

    Lenfant, Caroline; Baz, Patrick; Degavre, Anne; Philippi, Anne; Senée, Valérie; Derbois, Céline; Nicolino, Marc; Zalloua, Pierre; Julier, Cécile

    2017-01-01

    Monogenic forms of diabetes may account for 1–5% of all cases of diabetes, and may occur in the context of syndromic presentations. We investigated the case of a girl affected by insulin-dependent diabetes, diagnosed at 6 years old, associated with congenital cataract. Her consanguineous parents and her four other siblings did not have diabetes or cataract, suggesting a recessive syndrome. Using whole exome sequencing of the affected proband, we identified a heterozygous p.R825Q ABCC8 mutation, located at the exact same amino-acid position as the p.R825W recurring diabetes mutation, hence likely responsible for the diabetes condition, and a homozygous p.G71S mutation in CRYBB1, a gene known to be responsible for congenital cataract. Both mutations were predicted to be damaging and were absent or extremely rare in public databases. Unexpectedly, we found that the mother was also homozygous for the CRYBB1 mutation, and both the mother and one unaffected sibling were heterozygous for the ABCC8 mutation, suggesting incomplete penetrance of both mutations. Incomplete penetrance of ABCC8 mutations is well documented, but this is the first report of an incomplete penetrance of a CRYBB1 mutation, manifesting between susceptible subjects (unaffected mother vs. affected child) and to some extent within the patient herself, who had distinct cataract severities in both eyes. Our finding illustrates the importance of family studies to unmask the role of confounding factors such as double-gene mutations and incomplete penetrance that may mimic monogenic syndromes including in the case of strongly evocative family structure with consanguinity. PMID:29112131

  1. Congenital Hypopituitarism.

    PubMed

    Parks, John S

    2018-03-01

    Mutations of growth hormone genes and pituitary transcription factors account for a small proportion of cases of severe congenital hypopituitarism. Most cases show characteristic MRI findings of pituitary stalk interruption syndrome. Clinical suspicion should prompt assessment of cortisol, free T4, thyroid-stimulating hormone, and growth hormone levels together with MRI of the hypothalamic and pituitary regions. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. [Vasopressin V2 receptor-related pathologies: congenital nephrogenic diabetes insipidus and nephrogenic syndrome of inappropiate antidiuresis].

    PubMed

    Morin, Denis

    2014-12-01

    Congenital nephrogenic diabetes insipidus is a rare hereditary disease with mainly an X-linked inheritance (90% of the cases) but there are also autosomal recessive and dominant forms. Congenital nephrogenic diabetes insipidus is characterized by a resistance of the renal collecting duct to the action of the arginine vasopressin hormone responsible for the inability of the kidney to concentrate urine. The X-linked form is due to inactivating mutations of the vasopressin 2 receptor gene leading to a loss of function of the mutated receptors. Affected males are often symptomatic in the neonatal period with a lack of weight gain, dehydration and hypernatremia but mild phenotypes may also occur. Females carrying the mutation may be asymptomatic but, sometimes, severe polyuria is found due to the random X chromosome inactivation. The autosomal recessive and dominant forms, occurring in both genders, are linked to mutations in the aquaporin-2 gene. The treatment remains difficult, especially in infants, and is based on a low osmotic diet with increased water intake and the use of thiazides and indomethacin. The main goal is to avoid hypernatremic episodes and maintain a good hydration state. Potentially, specific treatment, in some cases of X-linked congenital nephrogenic diabetes insipidus, with pharmacological chaperones such as non-peptide vasopressin-2 receptor antagonists will be available in the future. Conversely, the nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is linked to a constitutive activation of the V(2)-receptor due to activating mutations with clinical and biological features of inappropriate antidiuresis but with low or undetectable plasma arginine vasopressin hormone levels. Copyright © 2014 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

  3. Usher syndrome and Leber congenital amaurosis are molecularly linked via a novel isoform of the centrosomal ninein-like protein

    PubMed Central

    van Wijk, Erwin; Kersten, Ferry F.J.; Kartono, Aileen; Mans, Dorus A.; Brandwijk, Kim; Letteboer, Stef J.F.; Peters, Theo A.; Märker, Tina; Yan, Xiumin; Cremers, Cor W.R.J.; Cremers, Frans P.M.; Wolfrum, Uwe; Roepman, Ronald; Kremer, Hannie

    2009-01-01

    Usher syndrome (USH) and Leber congenital amaurosis (LCA) are autosomal recessive disorders resulting in syndromic and non-syndromic forms of blindness. In order to gain insight into the pathogenic mechanisms underlying retinal degeneration, we searched for interacting proteins of USH2A isoform B (USH2AisoB) and the LCA5-encoded protein lebercilin. We identified a novel isoform of the centrosomal ninein-like protein, hereby named Nlp isoform B (NlpisoB), as a common interactor. Although we identified the capacity of this protein to bind calcium with one of its three EF-hand domains, the interacton with USH2AisoB did not depend on this. Upon expression in ARPE-19 cells, recombinant NlpisoB, lebercilin and USH2AisoB were all found to co-localize at the centrosomes. Staining of retinal sections with specific antibodies against all three proteins revealed their co-localization at the basal bodies of the photoreceptor-connecting cilia. Based on this subcellular localization and the nature of their previously identified binding partners, we hypothesize that the pathogenic mechanisms for LCA and USH show significant overlap and involve defects in ciliogenesis, cilia maintenance and intraflagellar and/or microtubule-based transport. The direct association of NlpisoB with USH2AisoB and lebercilin indicates that Nlp can be considered as a novel candidate gene for USH, LCA and allied retinal ciliopathies. PMID:18826961

  4. The Application of Root Mean Square Electrocardiography (RMS ECG) for the Detection of Acquired and Congenital Long QT Syndrome

    PubMed Central

    Lux, Robert L.; Sower, Christopher Todd; Allen, Nancy; Etheridge, Susan P.; Tristani-Firouzi, Martin; Saarel, Elizabeth V.

    2014-01-01

    Background Precise measurement of the QT interval is often hampered by difficulty determining the end of the low amplitude T wave. Root mean square electrocardiography (RMS ECG) provides a novel alternative measure of ventricular repolarization. Experimental data have shown that the interval between the RMS ECG QRS and T wave peaks (RTPK) closely reflects the mean ventricular action potential duration while the RMS T wave width (TW) tracks the dispersion of repolarization timing. Here, we tested the precision of RMS ECG to assess ventricular repolarization in humans in the setting of drug-induced and congenital Long QT Syndrome (LQTS). Methods RMS ECG signals were derived from high-resolution 24 hour Holter monitor recordings from 68 subjects after receiving placebo and moxifloxacin and from standard 12 lead ECGs obtained in 97 subjects with LQTS and 97 age- and sex-matched controls. RTPK, QTRMS and RMS TW intervals were automatically measured using custom software and compared to traditional QT measures using lead II. Results All measures of repolarization were prolonged during moxifloxacin administration and in LQTS subjects, but the variance of RMS intervals was significantly smaller than traditional lead II measurements. TW was prolonged during moxifloxacin and in subjects with LQT-2, but not LQT-1 or LQT-3. Conclusion These data validate the application of RMS ECG for the detection of drug-induced and congenital LQTS. RMS ECG measurements are more precise than the current standard of care lead II measurements. PMID:24454918

  5. The application of root mean square electrocardiography (RMS ECG) for the detection of acquired and congenital long QT syndrome.

    PubMed

    Lux, Robert L; Sower, Christopher Todd; Allen, Nancy; Etheridge, Susan P; Tristani-Firouzi, Martin; Saarel, Elizabeth V

    2014-01-01

    Precise measurement of the QT interval is often hampered by difficulty determining the end of the low amplitude T wave. Root mean square electrocardiography (RMS ECG) provides a novel alternative measure of ventricular repolarization. Experimental data have shown that the interval between the RMS ECG QRS and T wave peaks (RTPK) closely reflects the mean ventricular action potential duration while the RMS T wave width (TW) tracks the dispersion of repolarization timing. Here, we tested the precision of RMS ECG to assess ventricular repolarization in humans in the setting of drug-induced and congenital Long QT Syndrome (LQTS). RMS ECG signals were derived from high-resolution 24 hour Holter monitor recordings from 68 subjects after receiving placebo and moxifloxacin and from standard 12 lead ECGs obtained in 97 subjects with LQTS and 97 age- and sex-matched controls. RTPK, QTRMS and RMS TW intervals were automatically measured using custom software and compared to traditional QT measures using lead II. All measures of repolarization were prolonged during moxifloxacin administration and in LQTS subjects, but the variance of RMS intervals was significantly smaller than traditional lead II measurements. TW was prolonged during moxifloxacin and in subjects with LQT-2, but not LQT-1 or LQT-3. These data validate the application of RMS ECG for the detection of drug-induced and congenital LQTS. RMS ECG measurements are more precise than the current standard of care lead II measurements.

  6. Coffin-Siris syndrome with multiple congenital malformations and intrauterine death: towards a better delineation of the severe end of the spectrum.

    PubMed

    Coulibaly, Béma; Sigaudy, Sabine; Girard, Nadine; Popovici, Cornel; Missirian, Chantal; Heckenroth, Hélène; Tasei, Anne-Marie; Fernandez, Carla

    2010-01-01

    Coffine-Siris syndrome or "fifth digit" syndrome is a multiple congenital anomaly-mental retardation syndrome with severe developmental delay, coarse facial features, hirsutism and absent fifth fingernails or toenails or fifth distal phalanges. The etiology of this syndrome remains uncertain. Here we report a stillborn male baby born from consanguineous parents who might represent a very severe form of Coffine-Siris syndrome with cardiac defect and multiple brain malformations including corpus callosum agenesis and Dandy Walker malformation. To the best of our knowledge, it is the first case leading to intrauterine death. Karyotype and array comparative genomic hybridization were normal; these results give additional support to mendelian inheritance for this syndrome. In our family, the most likely mode of inheritance is autosomal recessive and the recurrence is probably as high as 25%. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  7. Prenatal ultrasound findings observed in the Wolf-Hirschhorn syndrome: data from the registry of congenital malformations in Auvergne.

    PubMed

    Debost-Legrand, Anne; Goumy, Carole; Laurichesse-Delmas, Hélène; Déchelotte, Pierre; Beaufrère, Anne-Marie; Lémery, Didier; Francannet, Christine; Gallot, Denis

    2013-12-01

    Wolf-Hirschhorn syndrome (WHS) is associated with facial dysmorphism including high forehead, high nasal bridge, hypertelorism and severe mental retardation. WHS results from a 4p16.3 deletion. Only a small number of reports have been made on the prenatal ultrasound findings observed in WHS. Here we report our experience on 10 cases of WHS ascertained prenatally between 1983 and 2009 through the CEMC-Auvergne registry of congenital malformations. The assumption that a "Greek warrior helmet" facies is pathognomonic of WHS could lead to misdiagnosis. Other clinical findings such as severe and early onset intrauterine growth retardation, facial dysmorphism (high forehead, high nasal bridge, low-set ears, micrognathia, hypertelorism), atrial or ventricular septal defect, and renal dysplasia should help obstetricians to suspect the diagnosis of WHS prenatally. Copyright © 2013 Wiley Periodicals, Inc.

  8. Combined laparoscopic and open technique for repair of congenital abdominal hernia: A case report of prune belly syndrome.

    PubMed

    Ye, Qinghuang; Chen, Yan; Zhu, Jinhui; Wang, Yuedong

    2017-10-01

    Prune belly syndrome (PBS) is a rare congenital disorder among adults, and the way for repairing abdominal wall musculature has no unified standard. We described combining laparoscopic and open technique in an adult male who presented with PBS. Physical examination and radiological imaging verified the case of PBS. The deficiency of abdominal wall musculature was repaired by combining laparoscopic and open technique using a double-deck complex patch. The patient successfully underwent abdominal wall repair by combining laparoscopic and open technique. Postoperative recovery was uneventful, and improvement in symptom was significant in follow-up after 3, 6, 12, and 24 months. Combining laparoscopic and open technique for repair of deficiency of abdominal wall musculature in PBS was an exploratory way to improve life quality.

  9. Therapy-resistant anaemia in congenital nephrotic syndrome of the Finnish type--implication of EPO, transferrin and transcobalamin losses.

    PubMed

    Toubiana, Julie; Schlageter, Marie-Hélène; Aoun, Bilal; Dunand, Olivier; Vitkevic, Renata; Bensman, Albert; Ulinski, Tim

    2009-04-01

    Congenital nephrotic syndrome of the Finnish type (CNF) is due to NPHS1 mutation and is responsible for a variety of urinary protein losses. We report the case of a 4-month-old girl with a particularly severe form (proteinuria approximately 150 g/l) of CNF. She developed severe non-regenerative anaemia requiring bi-monthly blood transfusions despite daily EPO (600 UI/kg) and iron supplementation. Epoetin pharmacokinetics revealed a urinary loss of 27% of the given dose within the first 24 h after IV injection. However, plasma levels remained increased after 24 h (228 UI/l). Plasma transferrin and transcobalamin levels were undetectable. Atransferrinaemia and atranscobalaminaemia seem to be responsible for disturbed erythropoiesis.

  10. Novel PIGT Variant in Two Brothers: Expansion of the Multiple Congenital Anomalies-Hypotonia Seizures Syndrome 3 Phenotype.

    PubMed

    Skauli, Nadia; Wallace, Sean; Chiang, Samuel C C; Barøy, Tuva; Holmgren, Asbjørn; Stray-Pedersen, Asbjørg; Bryceson, Yenan T; Strømme, Petter; Frengen, Eirik; Misceo, Doriana

    2016-11-29

    Biallelic PIGT variants were previously reported in seven patients from three families with Multiple Congenital Anomalies-Hypotonia Seizures Syndrome 3 (MCAHS3), characterized by epileptic encephalopathy, hypotonia, global developmental delay/intellectual disability, cerebral and cerebellar atrophy, craniofacial dysmorphisms, and skeletal, ophthalmological, cardiac, and genitourinary abnormalities. We report a novel homozygous PIGT missense variant c.1079G>T (p.Gly360Val) in two brothers with several of the typical features of MCAHS3, but in addition, pyramidal tract neurological signs. Notably, they are the first patients with MCAHS3 without skeletal, cardiac, or genitourinary anomalies. PIGT encodes a crucial subunit of the glycosylphosphatidylinositol (GPI) transamidase complex, which catalyzes the attachment of proteins to GPI-anchors, attaching the proteins to the cell membrane. In vitro studies in cells from the two brothers showed reduced levels of GPI-anchors and GPI-anchored proteins on the cell surface, supporting the pathogenicity of the novel PIGT variant.

  11. NPHS1 gene mutations confirm congenital nephrotic syndrome in four Brazilian cases: A novel mutation is described.

    PubMed

    Guaragna, Mara S; Cleto, Thaís Lira; Souza, Marcela Lopes; Lutaif, Anna Cristina G B; de Castro, Luiz Cláudio Gonçalves; Penido, Maria Goretti Moreira Guimarães; Maciel-Guerra, Andréa T; Belangero, Vera M S; Guerra-Junior, Gil; De Mello, Maricilda P

    2016-09-01

    Autosomal recessive mutations in NPHS1 gene are a common cause of congenital nephrotic syndrome (CNS). The disorder is characterized by massive proteinuria that manifests in utero or in the neonatal period during the first 3 months of life. NPHS1 encodes nephrin, a member of the immunoglobulin family of cell adhesion molecules and the main protein expressed at the renal slit diaphragm. Currently, there are approximately 250 mutations described in the NPHS1 gene distributed among all nephrin domains. The main objective of this study was to perform the analysis of the NPHS1 gene in patients with congenital nephrotic syndrome in order to determine the molecular cause of the disease. Direct sequencing of NPHS1 gene in four children was performed. Each patient was heterozygous for two pathogenic mutations disclosing the molecular cause of the disease in 100% of the cases. We identified six different mutations, consisting of one in-frame deletion, one frameshift, and four missense substitutions. The p.Val736Met mutation that is described here for the first time was considered pathogenic by different mutation predictive algorithms. Regardless of the type of mutation, three patients had a bad outcome and died Despite the small size of the cohort, this study contributed to the increasing number of deleterious mutations in the NPHS1 gene by describing a new mutation. Also, since we identified NPHS1 pathogenic mutations as the cause of the disease in all cases analyzed, it might be a frequent cause of CNS in the South Eastern region of Brazil, although the analysis of a larger sample is required to obtain more indicative epidemiological data. © 2015 Asian Pacific Society of Nephrology.

  12. Infantile spinal muscular atrophy (SMA) and multiple congenital bone fractures in sibs: a lethal new syndrome.

    PubMed Central

    Borochowitz, Z; Glick, B; Blazer, S

    1991-01-01

    Acute infantile spinal muscular atrophy (SMA type I, Werdnig-Hoffmann disease) has generally been accepted as an autosomal recessive disorder. However, several investigators have noted a slightly increased male to female ratio. We describe here a family with two affected male sibs who had a form of acute infantile SMA with congenital bone fractures, whose parents were first cousins. Pedigree analysis strongly suggested autosomal recessive inheritance, but X linked recessive inheritance could not be ruled out. In view of the heterogeneity of the SMAs, and the distinct clinical features found in our patients, we suggest that their infantile SMA might well be a distinct entity. We suggest that SMA I with congenital contractures and bone fractures appears to be a recognisable disorder that can be distinguished from the more common classic form of SMA I. PMID:1865475

  13. Assessment of cardiac function in absence of congenital and acquired heart disease in patients with Down syndrome.

    PubMed

    Balli, Sevket; Yucel, Ilker Kemal; Kibar, Ayse Esin; Ece, Ibrahim; Dalkiran, Eylem Sen; Candan, Sukru

    2016-11-01

    Extra genetic material in patients with Down syndrome (DS) may affect the function of any organ system. We evaluated cardiac functions using conventional tissue Doppler and two-dimensional speckle tracking echocardiography in patients with DS in the absence of congenital and acquired heart disease in patients. A total of 115 patients with DS between 6 and 13 years of age with clinically and anatomically normal heart and 55 healthy children were included in this cross-sectional study. DS was diagnosed by a karyotype test. Patients with mosaic type were not included in this study. Systolic and diastolic functions were evaluated by echocardiography. Pulsed waved Doppler transmitral early/late inflow velocity (E/A), tissue Doppler mitral annular early/late diastolic peak velocity (Ea/Aa), transtricuspid E/A and tricuspid valve annulus Ea/Aa, pulmonary venous Doppler systolic/diastolic (S/D) wave ratio were lower in patients with Down syndrome than in the control group (P=0.04, P=0.001, P<0.05, P<0.001, P<0.001, respectively). Mitral and tricuspid annular Ea were lower in patients with DS (P<0.001). The right and left ventricular myocardial performance indexes were higher in patients with DS than in the controls (P<0.01). They had significantly higher left ventricular mass, ejection fraction, the mitral annular plane systolic excursion values. However, the Down syndrome group compared with the controls had a lower strain values examined by two-dimensional longitudinal speckle-tracking strain echocardiography. These findings suggest conventional tissue Doppler and two-dimensional longitudinal speckletracking strain echocardiography were useful methods of investigating ventricular function and identifying a higher incidence of biventricular dysfunction in patients with Down syndrome compared with the healthy controls.

  14. Zika Virus Infection as a Cause of Congenital Brain Abnormalities and Guillain–Barré Syndrome: Systematic Review

    PubMed Central

    Reveiz, Ludovic; Oladapo, Olufemi T.; Martínez-Vega, Ruth; Haefliger, Anina

    2017-01-01

    Background The World Health Organization (WHO) stated in March 2016 that there was scientific consensus that the mosquito-borne Zika virus was a cause of the neurological disorder Guillain–Barré syndrome (GBS) and of microcephaly and other congenital brain abnormalities based on rapid evidence assessments. Decisions about causality require systematic assessment to guide public health actions. The objectives of this study were to update and reassess the evidence for causality through a rapid and systematic review about links between Zika virus infection and (a) congenital brain abnormalities, including microcephaly, in the foetuses and offspring of pregnant women and (b) GBS in any population, and to describe the process and outcomes of an expert assessment of the evidence about causality. Methods and Findings The study had three linked components. First, in February 2016, we developed a causality framework that defined questions about the relationship between Zika virus infection and each of the two clinical outcomes in ten dimensions: temporality, biological plausibility, strength of association, alternative explanations, cessation, dose–response relationship, animal experiments, analogy, specificity, and consistency. Second, we did a systematic review (protocol number CRD42016036693). We searched multiple online sources up to May 30, 2016 to find studies that directly addressed either outcome and any causality dimension, used methods to expedite study selection, data extraction, and quality assessment, and summarised evidence descriptively. Third, WHO convened a multidisciplinary panel of experts who assessed the review findings and reached consensus statements to update the WHO position on causality. We found 1,091 unique items up to May 30, 2016. For congenital brain abnormalities, including microcephaly, we included 72 items; for eight of ten causality dimensions (all except dose–response relationship and specificity), we found that more than half the

  15. Zika Virus Infection as a Cause of Congenital Brain Abnormalities and Guillain-Barré Syndrome: Systematic Review.

    PubMed

    Krauer, Fabienne; Riesen, Maurane; Reveiz, Ludovic; Oladapo, Olufemi T; Martínez-Vega, Ruth; Porgo, Teegwendé V; Haefliger, Anina; Broutet, Nathalie J; Low, Nicola

    2017-01-01

    The World Health Organization (WHO) stated in March 2016 that there was scientific consensus that the mosquito-borne Zika virus was a cause of the neurological disorder Guillain-Barré syndrome (GBS) and of microcephaly and other congenital brain abnormalities based on rapid evidence assessments. Decisions about causality require systematic assessment to guide public health actions. The objectives of this study were to update and reassess the evidence for causality through a rapid and systematic review about links between Zika virus infection and (a) congenital brain abnormalities, including microcephaly, in the foetuses and offspring of pregnant women and (b) GBS in any population, and to describe the process and outcomes of an expert assessment of the evidence about causality. The study had three linked components. First, in February 2016, we developed a causality framework that defined questions about the relationship between Zika virus infection and each of the two clinical outcomes in ten dimensions: temporality, biological plausibility, strength of association, alternative explanations, cessation, dose-response relationship, animal experiments, analogy, specificity, and consistency. Second, we did a systematic review (protocol number CRD42016036693). We searched multiple online sources up to May 30, 2016 to find studies that directly addressed either outcome and any causality dimension, used methods to expedite study selection, data extraction, and quality assessment, and summarised evidence descriptively. Third, WHO convened a multidisciplinary panel of experts who assessed the review findings and reached consensus statements to update the WHO position on causality. We found 1,091 unique items up to May 30, 2016. For congenital brain abnormalities, including microcephaly, we included 72 items; for eight of ten causality dimensions (all except dose-response relationship and specificity), we found that more than half the relevant studies supported a causal

  16. The case for early use of rapid whole genome sequencing in management of critically ill infants: Late diagnosis of Coffin-Siris syndrome in an infant with left congenital diaphragmatic hernia, congenital heart disease and recurrent infections.

    PubMed

    Sweeney, Nathaly M; Nahas, Shareef A; Chowdhury, Shimul; Del Campo, Miguel; Jones, Marilyn C; Dimmock, David P; Kingsmore, Stephen F; Investigators, Rcigm

    2018-03-16

    Congenital diaphragmatic hernia (CDH) results from incomplete formation of the diaphragm leading to herniation of abdominal organs into the thoracic cavity. CDH is associated with pulmonary hypoplasia, congenital heart disease and pulmonary hypertension. Genetically, it is associated with aneuploidies, chromosomal copy number variants, and single gene mutations. CDH is the most expensive non-cardiac congenital defect: Management frequently requires implementation of Extracorporeal Membrane Oxygenation (ECMO), which increases management expenditures 2.4 - 3.5-fold. The cost of management of CDH has been estimated to exceed $250 million per year. Despite in hospital survival of 80-90%, current management is imperfect, as a great proportion of surviving children have long-term functional deficits. We report the case of a premature infant prenatally diagnosed with CDH and congenital heart disease, who had a protracted and complicated course in the intensive care unit with multiple surgical interventions, including post-cardiac surgery ECMO, gastrostomy tube placement with Nissen fundoplication, tracheostomy for respiratory failure, recurrent infections and developmental delay. Rapid whole genome sequencing (rWGS) identified a de novo, likely pathogenic, c.3096_3100delCAAAG (p.Lys1033Argfs*32) variant in ARID1B, providing a diagnosis of Coffin-Siris syndrome. Her parents elected palliative care and she died later that day. Had rWGS been performed as a neonate, eight months of suffering and futile healthcare utilization may have been avoided. Cold Spring Harbor Laboratory Press.

  17. Exome Sequencing Discerns Syndromes in Patients from Consanguineous Families with Congenital Anomalies of the Kidneys and Urinary Tract.

    PubMed

    Vivante, Asaf; Hwang, Daw-Yang; Kohl, Stefan; Chen, Jing; Shril, Shirlee; Schulz, Julian; van der Ven, Amelie; Daouk, Ghaleb; Soliman, Neveen A; Kumar, Aravind Selvin; Senguttuvan, Prabha; Kehinde, Elijah O; Tasic, Velibor; Hildebrandt, Friedhelm

    2017-01-01

    Congenital anomalies of the kidneys and urinary tract (CAKUT) are the leading cause of CKD in children, featuring a broad variety of malformations. A monogenic cause can be detected in around 12% of patients. However, the morphologic clinical phenotype of CAKUT frequently does not indicate specific genes to be examined. To determine the likelihood of detecting causative recessive mutations by whole-exome sequencing (WES), we analyzed individuals with CAKUT from 33 different consanguineous families. Using homozygosity mapping and WES, we identified the causative mutations in nine of the 33 families studied (27%). We detected recessive mutations in nine known disease-causing genes: ZBTB24, WFS1, HPSE2, ATRX, ASPH, AGXT, AQP2, CTNS, and PKHD1 Notably, when mutated, these genes cause multiorgan syndromes that may include CAKUT as a feature (syndromic CAKUT) or cause renal diseases that may manifest as phenocopies of CAKUT. None of the above monogenic disease-causing genes were suspected on clinical grounds before this study. Follow-up clinical characterization of those patients allowed us to revise and detect relevant new clinical features in a more appropriate pathogenetic context. Thus, applying WES to the diagnostic approach in CAKUT provides opportunities for an accurate and early etiology-based diagnosis and improved clinical management. Copyright © 2016 by the American Society of Nephrology.

  18. Exome Sequencing Discerns Syndromes in Patients from Consanguineous Families with Congenital Anomalies of the Kidneys and Urinary Tract

    PubMed Central

    Vivante, Asaf; Hwang, Daw-Yang; Kohl, Stefan; Chen, Jing; Shril, Shirlee; Schulz, Julian; van der Ven, Amelie; Daouk, Ghaleb; Soliman, Neveen A.; Kumar, Aravind Selvin; Senguttuvan, Prabha; Kehinde, Elijah O.; Tasic, Velibor

    2017-01-01

    Congenital anomalies of the kidneys and urinary tract (CAKUT) are the leading cause of CKD in children, featuring a broad variety of malformations. A monogenic cause can be detected in around 12% of patients. However, the morphologic clinical phenotype of CAKUT frequently does not indicate specific genes to be examined. To determine the likelihood of detecting causative recessive mutations by whole-exome sequencing (WES), we analyzed individuals with CAKUT from 33 different consanguineous families. Using homozygosity mapping and WES, we identified the causative mutations in nine of the 33 families studied (27%). We detected recessive mutations in nine known disease–causing genes: ZBTB24, WFS1, HPSE2, ATRX, ASPH, AGXT, AQP2, CTNS, and PKHD1. Notably, when mutated, these genes cause multiorgan syndromes that may include CAKUT as a feature (syndromic CAKUT) or cause renal diseases that may manifest as phenocopies of CAKUT. None of the above monogenic disease–causing genes were suspected on clinical grounds before this study. Follow-up clinical characterization of those patients allowed us to revise and detect relevant new clinical features in a more appropriate pathogenetic context. Thus, applying WES to the diagnostic approach in CAKUT provides opportunities for an accurate and early etiology–based diagnosis and improved clinical management. PMID:27151922

  19. Congenital crocodile tears: a key to the aetiology of Duane's syndrome.

    PubMed Central

    Ramsay, J; Taylor, D

    1980-01-01

    The occurrence from birth of copious lacrimation on eating in some patients with Duane's syndrome suggests that both are caused by dysgenesis or a lesion in the vicinity of the abducens nucleus in the pons. PMID:7426566

  20. [Intrathoracic kidney in a newborn with breathing difficulty syndrome secondary to congenital diaphragmatic hernia].

    PubMed

    Urdaneta-Carruyo, Eliexer; Méndez-Parra, Alexander; Palencia-Molina, María Alejandra; Urdaneta-Contreras, Adriana; Urdaneta-Morales, Aubin

    2004-01-01

    Congenital diaphragmatic hernia (CDH) is found frequently in from 0.17 to 0.57 among 1000 newborns and is associated with intrathoracic kidney (IK) in 0.25%. The objective of the present work was to describe both present pathologies in a newborn and to review the literature in this respect. male newborns, who presented tachypnea sudden and persistent for the first 24 h of life. For the that was physical exam, we included breathing difficult, (eight points of Silverman's) and cyanosis; initial arterial gases: hypoxemia and hypocapnia (acute respiratory failure type I); thorax X-ray; increase of bronchial plot and of parahiliary density; normal lungs, pleuro-peritoneal membrane and solid mass superimposed on heart silhouette were observed and confirmed by echocardiogram. Computed axial tomography (CAT) revealed left kidney and part of spleen inside thorax, beside inferior lobe of left lung. Immediately, the patient was mechanically ventilated and after 2 days, was operated surgically for correction of CDH and descent of left kidney. After surgical intervention, initial symtomatology disappeared and evolution was satisfactory. The present case illustrates how the kidney on occasion can emigrate due to congenital default to the thorax of the wall of the diaphragm and be a casual discovery at the moment of radiologic exploration.

  1. Multiple branchial cleft anomalies in conjunction with a congenital dermal fistula of the lower extremity: first report of the Guarisco-Winters syndrome.

    PubMed

    Winters, Ryan; Guarisco, J Lindhe

    2012-03-01

    Branchial cleft anomalies are congenital remnants of the embryologic branchial clefts persisting past the embryo stage. Most occur singly and sporadically, though syndromic associations are described. Multiple branchial cleft anomalies coincident in the same patient are exceptionally rare, and rarer still are peripheral dermal sinus tracts on the extremities, with one prior documented case. We report the first case of multiple branchial cleft anomalies with a peripheral dermal sinus of the ipsilateral lower extremity. Numerous concurrent congenital anomalies exist in the patient, representing the first description of the Guarisco-Winters syndrome. The patient is intellectually and developmentally age-appropriate in all other regards. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  2. Congenital Long QT Syndrome: An Update and Present Perspective in Saudi Arabia

    PubMed Central

    Bhuiyan, Zahurul A.; Al-Shahrani, Safar; Al-Aama, Jumana; Wilde, Arthur A. M.; Momenah, Tarek S.

    2013-01-01

    Primary cardiac arrhythmias are often caused by defects, predominantly in the genes responsible for generation of cardiac electrical potential, i.e., cardiac rhythm generation. Due to the variability in underlying genetic defects, type, and location of the mutations and putative modifiers, clinical phenotypes could be moderate to severe, even absent in many individuals. Clinical presentation and severity could be quite variable, syncope, or sudden cardiac death could also be the first and the only manifestation in a patient who had previously no symptoms at all. Despite usual familial occurrence of such cardiac arrhythmias, disease causal genetic defects could also be de novo in significant number of patients. Long QT syndrome (LQTS) is the most eloquently investigated primary cardiac rhythm disorder. A genetic defect can be identified in ∼70% of definitive LQTS patients, followed by Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) and Brugada syndrome (BrS), where a genetic defect is found in <40% cases. In addition to these widely investigated hereditary arrhythmia syndromes, there remain many other relatively less common arrhythmia syndromes, where researchers also have unraveled the genetic etiology, e.g., short QT syndrome (SQTS), sick sinus syndrome (SSS), cardiac conduction defect (CCD), idiopathic ventricular fibrillation (IVF), early repolarization syndrome (ERS). There exist also various other ill-defined primary cardiac rhythm disorders with strong genetic and familial predisposition. In the present review we will focus on the genetic basis of LQTS and its clinical management. We will also discuss the presently available genetic insight in this context from Saudi Arabia. PMID:24400285

  3. Neuroimaging findings associated with congenital Zika virus syndrome: case series at the time of first epidemic outbreak in Pernambuco State, Brazil.

    PubMed

    Pires, Pedro; Jungmann, Patricia; Galvão, Jully Moura; Hazin, Adriano; Menezes, Luiza; Ximenes, Ricardo; Tonni, Gabriele; Araujo Júnior, Edward

    2018-05-01

    This study aimed to describe the prenatal and postnatal neuroimaging and clinical findings in a clinical series following congenital Zika virus syndrome during the first epidemic Zika virus (ZIKV) outbreak in the State of Pernambuco, Brazil. We (the authors) conducted a retrospective study of a prospectively collected case series of fetuses and neonates with microcephaly born to mothers with presumed/confirmed congenital ZIKV syndrome. Prenatal ultrasound findings were reviewed to identify potential central nervous system (CNS) abnormalities. Neonates underwent postnatal neuroimaging follow up by computed tomography (CT)-scan or magnetic resonance (MR) imaging. The prenatal and postnatal outcomes of eight fetuses/neonates born to mothers with presumed/confirmed congenital ZIKV syndrome were examined. The mean gestational age at ultrasound was 31.3 weeks. Severe microcephaly was identified in seven fetuses (87.5%), while ventriculomegaly and brain calcifications were detected in all fetuses. The mean gestational age at delivery and head circumference were 38 weeks and 30.2 cm, respectively. All cases of microcephaly but one was confirmed postnatally. Brain CT scans or MRIs were performed in seven newborns, and all had periventricular and/or parenchymal calcifications, symmetrical or asymmetrical ventriculomegaly, pachygyria, and reduced sulcation and gyration. MR imaging aided the detection of one undetected case of corpus callosum dysgenesis and was essential in documenting reduced mantel of the cerebral cortex and reduced gyration and sulcation, especially involving the parietal lobe. In addition, MR imaging was also able to display irregular interfaces with the subcortical white matter, a finding consistent with polymicrogyria, more frequently seen at the level of the frontal lobe and atrophic and thinned pons. Severe microcephaly and CNS abnormalities may be associated with congenital ZIKV syndrome.

  4. The impact of rubella immunisation on the incidence of rubella, congenital rubella syndrome and rubella-related terminations of pregnancy in South Australia.

    PubMed

    Cheffins, T; Chan, A; Keane, R J; Haan, E A; Hall, R

    1998-09-01

    To describe the impact of rubella immunisation on the incidence of rubella, congenital rubella syndrome and rubella-related terminations of pregnancy in South Australia, and to identify factors associated with a re-emerging problem. A population-based descriptive study using data from South Australian notifications of disease, births and terminations of pregnancy, the rubella immunisation programme, antenatal rubella antibody screening and paediatric hospital case records. South Australia (population 1.48 million people; 20,000 births per year). Incidence of rubella (age-sex specific), congenital rubella syndrome and rubella-related terminations of pregnancy; antenatal rubella sero-positive rates; rubella immunisation uptake rates. Rubella notification rates in 1990-1996 were significantly higher for males than females for ages 15-34 years. There were five cases of congenital rubella syndrome notified in 1980-1996 compared with at least 20 confirmed or compatible cases in 1965-1979. Rubella-related terminations of pregnancy are now rare, with the last termination for maternal rubella being in 1993. The antenatal rubella sero-positive rate in 1995 was 96.7%, but was significantly lower among Asian women born overseas (78.6% among those 30 years or older). Vaccination uptake rates in schoolgirls decreased between 1990 and 1994 (91.2% to 86.9%). Since the introduction of rubella immunisation, the incidence of rubella infection among women of reproductive age, and of rubella-related terminations, has fallen. Congenital rubella syndrome has not been notified since 1990 but its risk persists with a recent increase in rubella notifications, a fall in school immunisation rates, a relatively low antenatal sero-positive rate among older Asian women born overseas and the trend towards giving birth at older ages. Effective immunisation programmes must be maintained, particularly in schools and for young children and migrant women.

  5. Learning from the Histories of Rhetoric: Essays in Honor of Winifred Bryan Horner.

    ERIC Educational Resources Information Center

    Enos, Theresa, Ed.

    This collection of 11 essays honors Winifred Bryan Horner for her sustained effort to establish that the special nature of rhetoric and composition leads teachers to theorize practice and to apply theory in their own classrooms. The collection urges those in the field to learn from histories of rhetoric in order to draw rhetoric and composition…

  6. Congenital lymphatic dysplasia in Kabuki syndrome: first report of an unusual association.

    PubMed

    Morcaldi, G; Boccardo, F; Campisi, C; Bellini, T; Massocco, D; Bonioli, E

    2010-12-01

    Kabuki syndrome was first described in Japan in 1981 as a rare disorder of unknown cause. Its main features include characteristic facies, postnatal growth retardation, and mental delay. To date, there is no molecular marker for Kabuki syndrome, which is considered genetically heterogeneous and still is a clinically-based diagnosis. Here we describe the first case of a patient affected by Kabuki syndrome associated with lymphatic dysplasia. We suggest accurate evaluation of all Kabuki patients as early as possible in order to diagnose lymphedema or other clinical manifestations of lymphatic system involvement. Early identification of lymphatic system maldevelopment provides the best chance for reducing the risk of developing progressive lymphedema with associated tissue changes (fibrosis, sclerosis, and fat deposition).

  7. A case of 22q11.2 deletion syndrome with Peters anomaly, congenital glaucoma, and heterozygous mutation in CYP1B1.

    PubMed

    Reis, Linda M; Tyler, Rebecca C; Zori, Roberto; Burgess, Jennifer; Mueller, Jennifer; Semina, Elena V

    2015-03-01

    We read with interest the recent publication by Tarlan and colleagues 1 describing a patient with 22q11.2 deletion syndrome and ocular features of right microphthalmia and left anterior segment dysgenesis. While anterior segment dysgenesis disorders are occasionally reported with 22q11.2 deletions, 2-5 this remains a rare association. We report here an 8-year-old patient with 22q11.2 deletion syndrome and bilateral Peters anomaly with congenital glaucoma; in addition, our patient was found to have a single heterozygous mutation in CYP1B1, c.83C > T, p.(Ser28Trp).

  8. Congenital hypertrichosis, osteochondrodysplasia, and cardiomegaly: further delineation of a new genetic syndrome.

    PubMed

    Garcia-Cruz, D; Sánchez-Corona, J; Nazará, Z; Garcia-Crúz, M O; Figuera, L E; Castañeda, V; Cantú, J M

    1997-03-17

    The hypertrichosis and osteochondrodysplasia syndrome is a rare entity with clinical findings including macrosomia at birth cardiomegaly. Autosomal recessive inheritance is presumed based on the report of two affected sibs born to healthy parents. Here we report on four new patients with their follow-up data, as well as on one of the four cases from the original report. Comparison of all eight cases indicates that they share 50% of clinical and radiological changes. This report contributes to the further delineation of this newly recognized syndrome.

  9. Autonomic modulation in patients with congenital generalized lipodystrophy (Berardinelli-Seip syndrome).

    PubMed

    Faria, Carlos A; Moraes, Ruy S; Sobral-Filho, Dário C; Rego, Antônio G; Baracho, Maria F P; Egito, Eryvaldo S T; Brandão-Neto, José

    2009-06-01

    This study was designed to assess cardiac autonomic regulation in congenital generalized lipodystrophy (CGL) patients using 24 h heart rate variability (HRV). A cross-sectional study was carried out to evaluate 18 patients with CGL and 19 healthy controls matched by sex and age. We measured blood pressure, plasma concentrations of glucose, triglycerides, cholesterol, high-density lipoprotein-cholesterol, insulin resistance by the homeostatic model assessment (HOMA-R), left ventricular mass (LVM) (by two-dimensional echocardiography), and 24 h HRV (by the time domain indices MeanRR, SDNN, and rMSSD). Compared with controls, CGL patients had higher blood pressure (systolic, 131.1 vs. 106.3 mmHg, P < 0.05; diastolic, 85.0 vs. 68.2 mmHg, P < 0.05) and 10 patients met criteria for arterial hypertension and concentric left ventricular hypertrophy (LVM index > or =115 g/m(2)and relative left ventricular wall thickness > or =0.42). Patients with CGL had higher levels of glucose, triglycerides, cholesterol, and HOMA-R and 12 met criteria for type 2 diabetes mellitus. Compared with controls, CGL patients had lower MeanRR (639.8 vs. 780.5 ms, P < 0.001), SDNN (79.2 vs. 168.5 ms, P < 0.001), and rMSSD (15.8 vs. 59.6 ms, P < 0.001). In CGL patients, the reduction in HRV was independent of the metabolic and haemodynamic disturbances. Congenital generalized lipodystrophy patients have abnormal autonomic modulation, reflected by increased heart rate and pronounced reduction in HRV, independent of the metabolic and haemodynamic disturbances observed in this disorder.

  10. A new syndrome: multiple congenital abnormalities and mental retardation in two brothers.

    PubMed

    Dundar, M; Ozdemir, S Y; Fryns, J P

    2012-01-01

    In this report we present two brothers with abnormal neurological development, hypotonia, short stature, pylorus stenosis, pectus excavatum, brachycephaly due to craniosynostosis, frontal bossing, depressed nasal bridge, high arched-wide palate, downslant palpebral fissures, low-set, large ears, thin upper lip and bilateral cryptorchidism. The brothers were born to a couple of second cousins and were the third and fourth pregnancies of the mother. The father, the mother and the eldest sibling were phenotypically and chromosomally normal. The clinical findings of the brothers were found to be similar. These clinical findings were compared with syndromes showing some of the symptoms, namely Apert, FG, Floating-Harbor, Shprintzen-Goldberg and Rett Syndromes. However, when the findings were detailed, we observed that they did not match completely any of the syndromes in a discernable way. The MECP2 gene mutation was analysed because of mental retardation, poor neurological evolution and large ears, but no mutation was found. So these cases are presented as a new syndrome with apparent autosomal recessive inheritance.

  11. Epidemiological characteristics of rubella and congenital rubella syndrome in the 2012-2013 epidemics in Tokyo, Japan.

    PubMed

    Sugishita, Yoshiyuki; Shimatani, Naotaka; Katow, Shigetaka; Takahashi, Takuri; Hori, Narumi

    2015-01-01

    A large rubella outbreak has been observed since June 2012 in Tokyo, Japan, and a rapid increase in the number of congenital rubella syndrome (CRS) cases have also been reported in Japan since October 2012. All the clinically diagnosed and laboratory-confirmed rubella cases reported in Tokyo from January 2012 to December 2013 and all the laboratory-confirmed CRS cases from January 2012 to March 2014 were analyzed. In total, 4,116 rubella cases were reported in Tokyo. Of these, 77.2% (n=3,176) were male; the highest number of cases occurred in males aged 35-39 years and in females aged 20-24 years. Complications included arthralgia/arthritis (19.4%), thrombocytopenic purpura (0.5%), hepatic dysfunction (0.3%), and encephalitis (0.1%). The circulating rubella virus in Tokyo was genotype 2B. The most possible site of transmission was the workplace. Because of the rubella epidemic, 16 CRS cases were reported in Tokyo from March 2013 to February 2014. Domestic infection with rubella was proven for all mothers of 16 cases. This situation suggests that Japan is still working to achieve rubella elimination.

  12. Shedding of Rubella Virus among Infants with Congenital Rubella Syndrome Born in Tokyo, Japan, 2013-2014.

    PubMed

    Sugishita, Yoshiyuki; Akiba, Tetsuya; Sumitomo, Masami; Hayata, Noriko; Hasegawa, Michiya; Tsunoda, Tokuko; Okazaki, Terue; Murauchi, Konomi; Hayashi, Yukinao; Kai, Akemi; Seki, Naomi; Kayebeta, Aya; Iwashita, Yuuko; Kurita, Masayuki; Tahara, Narumi

    2016-09-21

    Rubella is usually a mild illness, with febrile rash being its main symptom. However, serious consequences of rubella infection can result when the infection occurs during the early stages of pregnancy. After the occurrence of a rubella outbreak in Japan that was observed from 2012 to 2013, 45 infants were reportedly born with congenital rubella syndrome (CRS). We prospectively followed the 15 CRS cases reported in Tokyo to determine the virus shedding periods by using nested reverse transcriptase-polymerase chain reaction to detect rubella virus genes. Throast swabs were used for virus detection. The virus shedding period was measured from birth until the time when the sample last tested positive followed by 2 consecutive negative samples. Kaplan-Meier method was used to estimate the proportion of cases remaining positive for rubella virus genes over time. The proportion of CRS cases shedding virus dropped steadily after birth, dropping to 33.8% at 6 months and 16.9% at 12 months. Our findings also suggested that the earlier the mother's onset of rubella during pregnancy, the longer the infant remained positive. Based on our findings, we believe that infants with CRS should be monitored for rubella virus shedding until 1 year of age.

  13. Sexual orientation and medical history among Iranian people with Complete Androgen Insensitivity Syndrome and Congenital Adrenal Hyperplasia.

    PubMed

    Khorashad, Behzad S; Roshan, Ghasem M; Reid, Alistair G; Aghili, Zahra; Hiradfar, Mehran; Afkhamizadeh, Mozhgan; Talaei, Ali; Aarabi, Azadeh; Ghaemi, Nosrat; Taghehchian, Negin; Saberi, Hedieh; Farahi, Nazanin; Abbaszadegan, Mohammad Reza

    2017-01-01

    To report sexual orientation, relationship status and medical history of Iranian people with Differences of Sex Development (DSD) who were raised female. Our participants consisted of nineteen 46,XY individuals with Complete Androgen Insensitivity Syndrome (CAIS) and eighteen 46,XX individuals with Congenital Adrenal Hyperplasia (CAH) who were raised as females and older than 13years. As well as their relationship status and detailed medical history, an expert psychiatrist assessed their sexual orientation by a semi-structured psychiatric interview with them and, where applicable, their parents. Five percent of CAH participants and 42% of CAIS participants were in a relationship, which was significantly different. All CAH individuals had been diagnosed at birth; 89% of CAIS had been diagnosed after puberty and due to primary amenorrhea and 11% were diagnosed in childhood due to inguinal hernia. Genital reconstructive surgery had been performed in 100% of CAH participants and 37% of CAIS. Regarding sexual contact experiences and sexual fantasies (androphilic, gynephilic or both), no significant differences were found. However, CAH females had significantly more gynephilic dreams (P=0.045). This study, notable as one of the rare from a non-western culture, described sexual, medical and socioeconomic status of 46,XX CAH and 46,XY CAIS individuals living in Iran. Although broadly in line with previous findings from Western cultures, Iranian CAH individuals had fewer romantic relationships, but in contrast to previous studies their sexual orientation was only different from CAIS in the contents of sexual dreams. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Syndrome-Related Stigma in the General Social Environment as Reported by Women with Classical Congenital Adrenal Hyperplasia.

    PubMed

    Meyer-Bahlburg, Heino F L; Reyes-Portillo, Jazmin A; Khuri, Jananne; Ehrhardt, Anke A; New, Maria I

    2017-02-01

    Stigma defined as "undesired differentness" (Goffman, 1963) and subtyped as "experienced" or "enacted," "anticipated," and "internalized" has been documented for patients with diverse chronic diseases. However, no systematic data exist on the association of stigma with somatic intersexuality. The current report concerns women with classical congenital adrenal hyperplasia (CAH), the most prevalent intersex syndrome, and provides descriptive data on CAH-related stigma as experienced in the general social environment (excluding medical settings and romantic/sexual partners) during childhood, adolescence, and adulthood. A total of 62 adult women with classical CAH [41 with the salt-wasting (SW) variant and 21 with the simple-virilizing (SV) variant] underwent a qualitative retrospective interview, which focused on the impact of CAH and its medical treatment on many aspects of women's lives. Deductive content analysis was performed on the transcribed texts. The women's accounts of CAH-related stigma were identified and excerpted as vignettes, and the vignettes categorized according to social context, stigma type, and the associated features of the CAH condition. Nearly two-thirds of women with either variant of CAH provided stigma vignettes. The vignettes included all three stigma types, and most involved some somatic or behavioral feature related to sex or gender. Stigma situations were reported for all ages and all social contexts of everyday life: family, peers, colleagues at work, strangers, and the media. We conclude that there is a need for systematic documentation of stigma in intersexuality as a basis for the development of improved approaches to prevention and intervention.

  15. Mild recessive mutations in six Fraser syndrome-related genes cause isolated congenital anomalies of the kidney and urinary tract.

    PubMed

    Kohl, Stefan; Hwang, Daw-Yang; Dworschak, Gabriel C; Hilger, Alina C; Saisawat, Pawaree; Vivante, Asaf; Stajic, Natasa; Bogdanovic, Radovan; Reutter, Heiko M; Kehinde, Elijah O; Tasic, Velibor; Hildebrandt, Friedhelm

    2014-09-01

    Congenital anomalies of the kidney and urinary tract (CAKUT) account for approximately 40% of children with ESRD in the United States. Hitherto, mutations in 23 genes have been described as causing autosomal dominant isolated CAKUT in humans. However, >90% of cases of isolated CAKUT still remain without a molecular diagnosis. Here, we hypothesized that genes mutated in recessive mouse models with the specific CAKUT phenotype of unilateral renal agenesis may also be mutated in humans with isolated CAKUT. We applied next-generation sequencing technology for targeted exon sequencing of 12 recessive murine candidate genes in 574 individuals with isolated CAKUT from 590 families. In 15 of 590 families, we identified recessive mutations in the genes FRAS1, FREM2, GRIP1, FREM1, ITGA8, and GREM1, all of which function in the interaction of the ureteric bud and the metanephric mesenchyme. We show that isolated CAKUT may be caused partially by mutations in recessive genes. Our results also indicate that biallelic missense mutations in the Fraser/MOTA/BNAR spectrum genes cause isolated CAKUT, whereas truncating mutations are found in the multiorgan form of Fraser syndrome. The newly identified recessive biallelic mutations in these six genes represent the molecular cause of isolated CAKUT in 2.5% of the 590 affected families in this study. Copyright © 2014 by the American Society of Nephrology.

  16. Cryo-EM Structure of a KCNQ1/CaM Complex Reveals Insights into Congenital Long QT Syndrome.

    PubMed

    Sun, Ji; MacKinnon, Roderick

    2017-06-01

    KCNQ1 is the pore-forming subunit of cardiac slow-delayed rectifier potassium (I Ks ) channels. Mutations in the kcnq1 gene are the leading cause of congenital long QT syndrome (LQTS). Here, we present the cryoelectron microscopy (cryo-EM) structure of a KCNQ1/calmodulin (CaM) complex. The conformation corresponds to an "uncoupled," PIP 2 -free state of KCNQ1, with activated voltage sensors and a closed pore. Unique structural features within the S4-S5 linker permit uncoupling of the voltage sensor from the pore in the absence of PIP 2 . CaM contacts the KCNQ1 voltage sensor through a specific interface involving a residue on CaM that is mutated in a form of inherited LQTS. Using an electrophysiological assay, we find that this mutation on CaM shifts the KCNQ1 voltage-activation curve. This study describes one physiological form of KCNQ1, depolarized voltage sensors with a closed pore in the absence of PIP 2 , and reveals a regulatory interaction between CaM and KCNQ1 that may explain CaM-mediated LQTS. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. The prevalence of congenital varicella syndrome after a maternal infection, but before 20 weeks of pregnancy: a prospective cohort study.

    PubMed

    Sanchez, Maria Angeles; Bello-Munoz, Juan Carlos; Cebrecos, Isaac; Sanz, Teresa Higueras; Martinez, Juan Sagalá; Moratonas, Elena Carreras; Roura, Lluis Cabero

    2011-02-01

    To describe the prevalence of congenital varicella syndrome (CVS) within the population of presumably infected pregnant women. From 1993 to 2006, all women who presented vesicular rash or a suspicious contact were referred and evaluated in a special unit at our center. Those with residual immunity or were serologically negative were precluded from this study. Positive IgM cases underwent monthly ultrasound scans (US), fetal blood (FB) sampling (including IgM anti VZV and virus culture). Amniotic fluid sample for PCR was added to the diagnosis of positive IgM cases after 1997. A total of 276, of the 566 consulted women, tested positive for IgM anti VZV. Seventeen (6%) were excluded because of an unadvised termination of pregnancy and seven (2.55%) miscarried. Only seven (2.7%) were considered highly likely to have a VZV fetal infection. One case showed positive IgM in FB but developed normally. Another fetus showed positive PCR and infection was confirmed post TOP. Four cases that underwent TOP and histochemistry confirmed no more cases. Complete post-natal follow-up was carried out. The asymptomatic infected child grew healthy until the completion of screening tests when it reached 5 years old. The fetal infection rate in this cohort was 0.8%, but the best expected prevalence of CVS, according to our findings, should be 0.39% among infected women. This data should be considered and used during parental counselling.

  18. Effects of inhaled iloprost on congenital heart disease with Eisenmenger syndrome.

    PubMed

    Yang, Song I; Chung, Wook Jin; Jung, Sung Hwan; Choi, Deok Young

    2012-06-01

    Identification of the pathophysiology associated with Eisenmenger syndrome has led to the evaluation of targeted therapies. Iloprost is one such targeted therapy used for patients with Eisenmenger syndrome. This study aimed to assess the efficacy and safety of iloprost used for patients with Eisenmenger syndrome. In this study, 12 patients with Eisenmenger syndrome (mean age, 33.2 ± 12.1 years; 75% female) started receiving iloprost 10 μg/dose administered six times a day. Of the 12 patients, 9 were classified as New York Heart Association (NYHA) functional class 3, and three were categorized as functional class 4. Changes in 6-min walk distance, NYHA functional class, oxygen saturation at resting, and results after the 6-min walk test were checked, as well as changes in right ventricle diameter and pulmonary arterial pressure shown by echocardiography. The distance during a 6-min walk increased from 255.8 ± 120.4 to 349.4 ± 134.7 m (p = 0.013), and 10 patients improved their NYHA functional class by one grade (p = 0.007). The mean resting oxygen saturation (SpO(2)) increased from 80.6 ± 14.2 to 84.9 ± 13.0% (p = 0.040), and after the 6-min walk test, it increased from 63.8 ± 22.9 to 68.8 ± 21.5% (p = 0.007). The mean right ventricle diameter during the diastolic phase changed from 53.7 ± 4.8 to 51.4 ± 3.9 mm (p = 0.068), and the mean pulmonary arterial pressure changed from 62.8 ± 13.7 to 58.9 ± 11.7 mmHg (p = 0.059). Neither death nor critical adverse effects occurred for any patients. Mild headache and dyspnea were common reports during the iloprost treatments. No patients stopped the therapy due to these adverse effects. Iloprost is well tolerated and appears to be beneficial in the management of patients with Eisenmenger syndrome.

  19. Branchio-oto-renal syndrome plus; a contiguous gene constellation of congenital anomalies?

    SciTech Connect

    Kelly, T.E.

    1994-09-01

    A term female infant was referred to the University Hospital because of respiratory distress secondary to bilateral choanal stenosis. Her examination revealed bilateral pre-auricular pits, branchial fistulae, cupped shaped ears, and bilateral athelia. She failed ABR screening; her creatinine was elevated to 1.5 mgs% and renal ultra-sonography showed reduced kidney size bilaterally. She was the product of her mother`s third pregnancy. The first produced a now normal 5 year old son. The second pregnancy was complicated by oligohydramnios and resulted in a premature delivery at 27 weeks gestation. The infant expired secondary to pulmonary hypoplasia. The mother had bilateral neurosensorymore » deafness, pre-auricular pits, cupped shaped ears, lacrimal stenois and bilateral athelia. She wore dentures having earlier been diagnosed with dentogeneis imperfecta. She was shorter than her three normal sisters and had experienced academic problems throughout her school years. The maternal grandfather had an adult onset neurosensory hearing loss, but he and the maternal grandmother exhibited no other features of the BOR syndrome. Althelia was present only in the mother and daughter. The mother clearly has BOR syndrome transmitted to one, and possibly two, of her three offspring. The additional features of athelia, choanal stenosis and dentogenesis imperfecta are thought to represent additional autosomal dominant traits. Greenberg described an infant with athelia and choanal atresia. By family linkage studies, the BOR syndrome has been mapped to 8q13-21 with no recombination observed with loci D8S530 and D8S279. Given a normal prophase karyotype in the proband, it is speculated that a sub-microscopic deletion at 8q13-21 is the likely basis for the constellation of birth defects seen in this mother and daughter. Analysis of D8S530 and D8S279 is currently underway in this family.« less

  20. Lymphoma Secondary to Congenital and Acquired Immunodeficiency Syndromes at a Turkish Pediatric Oncology Center.

    PubMed

    Tanyildiz, Hikmet G; Dincaslan, Handan; Yavuz, Gulsan; Unal, Emel; Ikinciogulları, Aydan; Dogu, Figen; Tacyildiz, Nurdan

    2016-10-01

    The prevalence of lymphoma in primary immunodeficiency cases and autoimmune diseases, as well as on a background of immunodeficiency following organ transplants, is increasing. The lymphoma treatment success rate is known to be a low prognosis. Our study aimed to emphasize the low survival rates in immunodeficient vs. immunocompetent lymphoma patients and also to investigate the effect of rituximab in patients with ataxia telangiectasia and other immunodeficiencies. We summarized the clinical characteristics and treatment results of 17 cases with primary immunodeficiency that developed non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) retrospectively. Seven patients were diagnosed with ataxia-telangiectasia, two with common variable immunodeficiency, two with selective IgA deficiency, one with X-related lymphoproliferative syndrome, one with Wiskott-Aldrich syndrome, one with Epstein-Barr virus-related lymphoproliferative syndrome, one with interleukin-2-inducible T-cell kinase (ITK) deficiency, and one with lymphoma developing after autoimmune lymphoproliferative syndrome (ALPS). One patient underwent a renal transplant. Of the nine males and eight females (aged 3-12 years, median = 7) that developed lymphoma, seven were diagnosed with HL and ten with NHL (seven B-cell, three T-cell). The NHL patients were started on the Berlin-Frankfurt-Münster, POG9317, LMB-96, or R-CHOP treatment protocols with reduced chemotherapy dosages. HL cases were started on the doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and/or cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) protocol, also with modified dosages. Importantly, all seven cases of HL are alive and in remission, while six of the ten NHL patients have died. Primary immunodeficiency is a strong predisposing factor for developing lymphoma. Low treatment success rates relative to other lymphomas and difficulties encountered during treatment indicate that new treatment agents are needed

  1. Neurally adjusted ventilatory assist (NAVA) mode as an adjunct diagnostic tool in congenital central hypoventilation syndrome.

    PubMed

    Rahmani, Aiman; Ur Rehman, Naveed; Chedid, Fares

    2013-02-01

    A full term female newborn was admitted to the neonatal intensive care unit (NICU) for continuous observation of apnea. Infant was noted to have apnea while asleep requiring intubation and mechanical ventilation. A video EEG was performed which demonstrated normal awake background without any seizure activity. Neurally adjusted ventilatory assist (NAVA) demonstrated the absence of electrical activity of the diaphragm (Edi) when the patient was in quiet phase of sleep. This finding on NAVA monitor raised the suspicion of central hypoventilation syndrome (CCHS) which was confirmed by genetic identification of the PHOX2B mutation.

  2. Physical Fitness and Metabolic Syndrome in Children with Repaired Congenital Heart Disease Compared with Healthy Children.

    PubMed

    Zaqout, Mahmoud; Vandekerckhove, Kristof; Michels, Nathalie; Bove, Thierry; François, Katrien; De Wolf, Daniel

    2017-12-01

    To determine whether children who underwent surgery for congenital heart disease (CHD) are as fit as their peers. We studied 66 children (6-14 years) who underwent surgery for ventricular septal defect (n = 19), coarctation of aorta (n = 10), tetralogy of Fallot (n = 15), and transposition of great arteries (n = 22); and 520 healthy children (6-12 years). All children performed physical fitness tests: cardiorespiratory fitness, muscular strength, balance, flexibility, and speed. Metabolic score was assessed through z-score standardization using 4 components: waist circumference, blood pressure, blood lipids, and insulin resistance. Assessment also included self-reported and accelerometer-measured physical activity. Linear regression analyses with group (CHD vs control) as a predictor were adjusted for age, body mass index, physical activity, and parental education. Measured physical activity level, body mass index, cardiorespiratory fitness, flexibility, and total metabolic score did not differ between children with CHD and controls, whereas reported physical activity was greater in the CHD group than control group. Boys with CHD were less strong in upper muscular strength, speed, and balance, whereas girls with CHD were better in lower muscular strength and worse in balance. High-density lipoprotein was greater in boys and girls with CHD, whereas boys with CHD showed unhealthier glucose homeostasis. Appropriate physical fitness was achieved in children after surgery for CHD, especially in girls. Consequently, children with CHD were not at increased total metabolic risk. Lifestyle counseling should be part of every patient interaction. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Brown Syndrome

    MedlinePlus

    ... Does Brown syndrome cause eye problems besides abnormal eye movements? In the more severely affected cases of Brown ... acquired and congenital cases. In congenital cases, the eye movement problem is usually constant and unlikely to resolve ...

  4. Natural history of Brugada syndrome in a patient with congenital heart disease.

    PubMed

    Silva, Doroteia; Martins, Fernando Maymone; Cavaco, Diogo; Adragão, Pedro; Silva, Margarida Matos; Anjos, Rui; Ferreira, Álvaro; Gaspar, Isabel Mendes

    2015-01-01

    Risk stratification of sudden death in patients with Brugada syndrome (BrS) is a controversial issue, and there is currently no consensus on the best method. Examination of data from the natural history of the disease is of fundamental importance and may help to identify relatives at risk. At the same time, study of the genetic mutations responsible for the disease may also contribute to risk stratification of the syndrome, enabling identification of asymptomatic relatives carrying mutations. This paper presents the case of a young man, aged 26, monitored as a pediatric cardiology outpatient from birth for a simple structural heart defect not requiring surgery. Analysis of the evolution of the patient's electrocardiogram revealed the appearance, at the age of 20, of a pattern compatible with type I BrS. Following an episode of syncope and induction of polymorphic ventricular tachycardia in the electrophysiological study, a cardioverter-defibrillator was implanted. One year later, a single shock terminated an episode of ventricular fibrillation. A molecular study of the SCN5A gene identified a rare mutation, c.3622G>T (p.Glu1208X), recently described and associated with more severe phenotypes in patients with BrS, as in the case presented. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  5. Decreased CDKN1C Expression in Congenital Alveolar Rhabdomyosarcoma Associated with Beckwith-Wiedemann Syndrome.

    PubMed

    Piersigilli, Fiammetta; Auriti, Cinzia; Mondì, Vito; Francalanci, Paola; Salvatori, Guglielmo; Danhaive, Olivier

    2016-11-01

    The Beckwith-Wiedemann syndrome (BWS) is a genetic disorder characterized by somatic overgrowth and predisposition to embryonal tumors, such as Wilm's tumor, hepatoblastoma, neuroblastoma and rhabdomyosarcoma (RMS). BWS is associated with various genetic alterations: a variety of molecular lesions are described on the chromosome 11p15, affecting gene expression for IGF2, H19, CDKN1C and KCNQ1OT1. Alveolar RMS also recognises characteristic genetic alterations: two types of translocations, t(2,13) or t(1,13), that generate the PAX3-FKHR or PAX7-FKHR fusion proteins. It has been postulated however, that in BWS this kind of tumor occurs without this characteristic chromosomal rearrangement. The authors describe case of a neonate with BWS that presented at birth with cutaneous metastasis due to alveolar RMS. Genetic analysis showed lack of the two characteristic translocations in the tumor tissue, supporting a different oncogenic pathway of alveolar RMS in children with BWS.

  6. Associations Between TGFA/TGFB3/MSX1 Gene Polymorphisms and Congenital Non-Syndromic Hearing Impairment in a Chinese Population.

    PubMed

    Du, Jihong; Deng, Jianhua

    2016-06-29

    BACKGROUND The aim of this study was to investigate whether the TGFA/TGFB3/MSX1 gene polymorphisms and haplotypes lead to individual differences between congenital non-syndromic hearing impairment (NSHI) patients and normal people in a Chinese population and to analyze the risk factors for NSHI. MATERIAL AND METHODS Between December 2010 and September 2014, 343 congenital NSHI patients were recruited as cases, and 272 healthy subjects were recruited as controls. Denaturing high-performance liquid chromatography (DHPLC) was used to identify genotypes, SHEsis software was used to conduct gene linkage disequilibrium and haplotype analyses, and regression analysis was performed to identify risk factors for congenital NSHI. RESULTS The distribution of genotype frequencies and allele frequencies of TGFA rs3771494, TGFB3 rs3917201 and rs2268626, and MSX1 rs3821949 and rs62636562 were significantly different between the case and the control groups (all P<0.05). TGFA/TGFB3/MSX1 gene rs3771494, rs1058213, rs3917201, rs2268626, rs3821949, and rs62636562 haplotype analysis showed that haplotype CCGTAC and TTACGT might be protective factors (both P<0.001), while TTGCGC might be a risk factor for the normal population (P<0.001). The other risk factors include paternal smoking, advanced maternal age, maternal sickness history, maternal contact with pesticides or similar drugs, maternal abortion history, maternal medication history, maternal passive smoking history during pregnancy, rs3771494 CT, rs2268626 CC and TC, and rs3821949 GG and AG genotypes were risk factors (all P<0.05), while maternal vitamin supplements during pregnancy, rs3917201 GA, rs62636562 TT and CT genotypes were protective factors for congenital NSHI (all P<0.05). CONCLUSIONS rs3771494, rs3917201, rs2268626, rs3821949 and rs62636562 might be associated with congenital NSHI.

  7. Congenital Abnormalities of the Temporomandibular Joint.

    PubMed

    Galea, Christopher J; Dashow, Jason E; Woerner, Jennifer E

    2018-02-01

    Congenital deformities of the temporomandibular joint (TMJ) complex can present as a heterogeneous continuum of growth disturbances of the mandibular condyle, articular eminence, and temporal bone. This article describes several syndromes with congenital condylar deformity, including mandibulofacial dysostosis (Treacher Collins syndrome), hemifacial microsomia, oculoauriculovertebral syndrome, oculomandibulodyscephaly (Hallermann-Streiff syndrome), and Nager syndrome. Variations in the extent of TMJ deficiency seen in each individual case influence the timing and techniques of TMJ reconstruction. Published by Elsevier Inc.

  8. Congenital hypogonadotropic hypogonadism and Kallmann syndrome as models for studying hormonal regulation of human testicular endocrine functions.

    PubMed

    Trabado, Séverine; Lamothe, Sophie; Maione, Luigi; Bouvattier, Claire; Sarfati, Julie; Brailly-Tabard, Sylvie; Young, Jacques

    2014-05-01

    Men with Kallmann syndrome (KS) and those with congenital isolated hypogonadotropic hypogonadism with normal olfaction share a chronic, usually profound deficit, in FSH and LH, the two pituitary gonadotropins. Many studies indicate that this gonadotropin deficiency is already present during fetal life, thus explaining the micropenis, cryptorchidism and marked testicular hypotrophy already present at birth. In addition, neonatal activation of gonadotropin secretion is compromised in boys with severe CHH/Kallmann, preventing the first phase of postnatal testicular activation. Finally, CHH is characterized by the persistence, in the vast majority of cases, of gonadotropin deficiency at the time of puberty and during adulthood. This prevents the normal pubertal testicular reactivation required for physiological sex steroid and testicular peptide production, and for spermatogenesis. CHH/KS thus represents a pathological paradigm that can help to unravel, in vivo, the role of each gonadotropin in human testicular exocrine and endocrine functions at different stages of development. Recombinant gonadotropins with pure LH or FSH activity have been used to stimulate Leydig's cells and Sertoli's cells, respectively, and thereby to clarify their paracrine interaction in vivo. The effects of these pharmacological probes can be assessed by measuring the changes they provoke in circulating testicular hormone concentrations. This review discusses the impact of chronic gonadotropin deficiency on the endocrine functions of the interstitial compartment, which contains testosterone-, estradiol- and INSL3-secreting Leydig's cells. It also examines the regulation of inhibin B and anti-Mullerian hormone (AMH) secretion in the seminiferous tubules, and the insights provided by studies of human testicular stimulation with recombinant gonadotropins, used either individually or in combination. Copyright © 2014. Published by Elsevier Masson SAS.

  9. The Cerebral Cost of Breathing: An fMRI Case-Study in Congenital Central Hypoventilation Syndrome

    PubMed Central

    Sharman, Mike; Gallea, Cécile; Lehongre, Katia; Galanaud, Damien; Nicolas, Nathalie; Similowski, Thomas; Cohen, Laurent; Straus, Christian; Naccache, Lionel

    2014-01-01

    Certain motor activities - like walking or breathing - present the interesting property of proceeding either automatically or under voluntary control. In the case of breathing, brainstem structures located in the medulla are in charge of the automatic mode, whereas cortico-subcortical brain networks - including various frontal lobe areas - subtend the voluntary mode. We speculated that the involvement of cortical activity during voluntary breathing could impact both on the “resting state” pattern of cortical-subcortical connectivity, and on the recruitment of executive functions mediated by the frontal lobe. In order to test this prediction we explored a patient suffering from central congenital hypoventilation syndrome (CCHS), a very rare developmental condition secondary to brainstem dysfunction. Typically, CCHS patients demonstrate efficient cortically-controlled breathing while awake, but require mechanically-assisted ventilation during sleep to overcome the inability of brainstem structures to mediate automatic breathing. We used simultaneous EEG-fMRI recordings to compare patterns of brain activity between these two types of ventilation during wakefulness. As compared with spontaneous breathing (SB), mechanical ventilation (MV) restored the default mode network (DMN) associated with self-consciousness, mind-wandering, creativity and introspection in healthy subjects. SB on the other hand resulted in a specific increase of functional connectivity between brainstem and frontal lobe. Behaviorally, the patient was more efficient in cognitive tasks requiring executive control during MV than during SB, in agreement with her subjective reports in everyday life. Taken together our results provide insight into the cognitive and neural costs of spontaneous breathing in one CCHS patient, and suggest that MV during waking periods may free up frontal lobe resources, and make them available for cognitive recruitment. More generally, this study reveals how the active

  10. Alanine Expansions Associated with Congenital Central Hypoventilation Syndrome Impair PHOX2B Homeodomain-mediated Dimerization and Nuclear Import*

    PubMed Central

    Di Lascio, Simona; Belperio, Debora

    2016-01-01

    Heterozygous mutations of the human PHOX2B gene, a key regulator of autonomic nervous system development, lead to congenital central hypoventilation syndrome (CCHS), a neurodevelopmental disorder characterized by a failure in the autonomic control of breathing. Polyalanine expansions in the 20-residues region of the C terminus of PHOX2B are the major mutations responsible for CCHS. Elongation of the alanine stretch in PHOX2B leads to a protein with altered DNA binding, transcriptional activity, and nuclear localization and the possible formation of cytoplasmic aggregates; furthermore, the findings of various studies support the idea that CCHS is not due to a pure loss of function mechanism but also involves a dominant negative effect and/or toxic gain of function for PHOX2B mutations. Because PHOX2B forms homodimers and heterodimers with its paralogue PHOX2A in vitro, we tested the hypothesis that the dominant negative effects of the mutated proteins are due to non-functional interactions with the wild-type protein or PHOX2A using a co-immunoprecipitation assay and the mammalian two-hybrid system. Our findings show that PHOX2B forms homodimers and heterodimerizes weakly with mutated proteins, exclude the direct involvement of the polyalanine tract in dimer formation, and indicate that mutated proteins retain partial ability to form heterodimers with PHOX2A. Moreover, in this study, we investigated the effects of the longest polyalanine expansions on the homeodomain-mediated nuclear import, and our data clearly show that the expanded C terminus interferes with this process. These results provide novel insights into the effects of the alanine tract expansion on PHOX2B folding and activity. PMID:27129232

  11. Neuropsychological profile and social cognition in congenital central hypoventilation syndrome (CCHS): Correlation with neuroimaging in a clinical case.

    PubMed

    Esteso Orduña, Borja; Seijas Gómez, Raquel; García Esparza, Elena; Briceño, Emily M; Melero Llorente, Javier; Fournier Del Castillo, María de la Concepción

    2018-02-01

    Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder due to paired-like homeobox gene (PHOX2B) mutations. CCHS patients suffer from dysregulation of the autonomic nervous system characterized by the absence of or extremely reduced response to hypercapnia and hypoxia, with neuropsychological deficits. The aim of this exploratory study is to describe the longitudinal neuropsychological profile and its correlations with magnetic resonance imaging (MRI) of a child with CCHS with a PHOX2B mutation. A comprehensive neuropsychological evaluation was conducted serially at age 7 years 4 months and 10 years 3 months, including assessment of intellectual functioning (IQ), motor functioning, perception, attention, executive functions, language, memory, social cognition, academic skills, and psychopathology. Reliable change index (RCI) scores were used to assess changes between assessments. We collected spin lattice relaxation time (T1)-weighted, fluid-attenuated inversion recovery (FLAIR), and spin spin lattice relaxation time (T2)-weighted images from the child at age 10 years 3 months using a 1.5-tesla MRI scanner. IQ, processing speed index (PSI), social cognition (theory of mind and facial emotion recognition), selective attention, naming, academic skills (reading/comprehension), and manual speed with right hand declined in the second evaluation relative to the initial evaluation, while visuoconstructional praxis, receptive vocabulary, working memory, and arithmetic skill improved. The patient showed a remarkable global deterioration in executive functions (planning, task flexibility, behavioral regulation, and metacognition) as revealed by parental report and clinical evaluation. MRI revealed gliosis from the head to tail of the hippocampus and thinning of parahippocampal gyri. In a clinical case of CCHS, serial evaluation revealed deterioration of executive functions and social cognition over a 3-year interval. These changes corresponded to

  12. Mutations in TKT Are the Cause of a Syndrome Including Short Stature, Developmental Delay, and Congenital Heart Defects.

    PubMed

    Boyle, Lia; Wamelink, Mirjam M C; Salomons, Gajja S; Roos, Birthe; Pop, Ana; Dauber, Andrew; Hwa, Vivian; Andrew, Melissa; Douglas, Jessica; Feingold, Murray; Kramer, Nancy; Saitta, Sulagna; Retterer, Kyle; Cho, Megan T; Begtrup, Amber; Monaghan, Kristin G; Wynn, Julia; Chung, Wendy K

    2016-06-02

    Whole-exome sequencing (WES) is increasingly being utilized to diagnose individuals with undiagnosed disorders. Developmental delay and short stature are common clinical indications for WES. We performed WES in three families, using proband-parent trios and two additional affected siblings. We identified a syndrome due to an autosomal-recessively inherited deficiency of transketolase, encoded by TKT, on chromosome 3p21. Our series includes three families with a total of five affected individuals, ranging in age from 4 to 25 years. Two families of Ashkenazi Jewish ancestry were homozygous for an 18 base pair in-frame insertion in TKT. The third family was compound heterozygous for nonsense and missense variants in TKT. All affected individuals had short stature and were developmentally delayed. Congenital heart defects were noted in four of the five affected individuals, and there was a history of chronic diarrhea and cataracts in the older individuals with the homozygous 18 base pair insertion. Enzymatic testing confirmed significantly reduced transketolase activity. Elevated urinary excretion of erythritol, arabitol, ribitol, and pent(ul)ose-5-phosphates was detected, as well as elevated amounts of erythritol, arabitol, and ribitol in the plasma of affected individuals. Transketolase deficiency reduces NADPH synthesis and nucleic acid synthesis and cell division and could explain the problems with growth. NADPH is also critical for maintaining cerebral glutathione, which might contribute to the neurodevelopmental delays. Transketolase deficiency is one of a growing list of inborn errors of metabolism in the non-oxidative part of the pentose phosphate pathway. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  13. PHOX2B mutation-confirmed congenital central hypoventilation syndrome in a Chinese family: presentation from newborn to adulthood.

    PubMed

    Lee, Peilin; Su, Yi-Ning; Yu, Chong-Jen; Yang, Pan-Chyr; Wu, Huey-Dong

    2009-02-01

    Congenital central hypoventilation syndrome (CCHS) is characterized by compromised chemoreflexes resulting in sleep hypoventilation. We report a Chinese family with paired-like homeobox 2B (PHOX2B) mutation-confirmed CCHS, with a clinical spectrum from newborn to adulthood, to increase awareness of its various manifestations. After identifying central hypoventilation in an adult man (index case), clinical evaluation was performed on the complete family, which consisted of the parents, five siblings, and five offspring. Pulmonary function tests, overnight polysomnography, arterial blood gas measurements, hypercapnia ventilatory response, and PHOX2B gene mutation screening were performed on living family members. Brain MRI, 24-h Holter monitoring, and echocardiography were performed on members with clinically diagnosed central hypoventilation. The index patient and four offspring manifested clinical features of central hypoventilation. The index patients had hypoxia and hypercapnia while awake, polycythemia, and hematocrit levels of 70%. The first and fourth children had frequent cyanotic spells, and both died of respiratory failure. The second and third children remained asymptomatic until adulthood, when they experienced impaired hypercapnic ventilatory response. The third child had nocturnal hypoventilation with nadir pulse oximetric saturation of 59%. Adult-onset CCHS with PHOX2B gene mutation of the + 5 alanine expansions were confirmed in the index patient and the second and third children. The index patient and the third child received ventilator support system bilevel positive airway pressure treatment, which improved the hypoxemia, hypercapnia, and polycythemia without altering their chemosensitivity. Transmission of late-onset CCHS is autosomal-dominant. Genetic screening of family members of CCHS probands allows for early diagnosis and treatment.

  14. The five-year survival of children with Down syndrome in Norway 1994-2009 differed by associated congenital heart defects and extracardiac malformations.

    PubMed

    Brodwall, Kristoffer; Greve, Gottfried; Leirgul, Elisabeth; Klungsøyr, Kari; Holmstrøm, Henrik; Vollset, Stein Emil; Øyen, Nina

    2018-01-17

    We investigated the prevalence of Down syndrome in a nationwide birth cohort, focusing on congenital heart defects (CHDs), their associations with extracardiac malformations (ECM) and survival. National registers were used to identify Norwegian births (1994-2009) and deaths (1994-2014) and updated with hospital diagnoses. We estimated birth defect frequencies in Down syndrome and the general population, the association between CHDs and ECM and hazard ratios for death from different combinations of CHDs and ECM. Down syndrome was found in 1672 of 953 450 births (17.6 per 10 000). Of the 1251 live births (13.3 per 10 000), 58% had CHD and 9% ECM. CHDs were associated with oesophageal atresia (p = 0.02) and Hirschsprung's disease (p = 0.03) but with no other malformations. The five-year survival for Down syndrome increased from 91.8% (1994-1999) to 95.8% (2000-2009) (p = 0.006), and overall survival was 92.0% with CHD and 97.4% without. Compared with Down syndrome children without CHD or ECM, the five-year mortality was similar for those with nonsevere CHDs, without or with ECM, but 4-7 times higher in those with severe CHDs without ECM and 13-28 times higher in those with severe CHDs and ECM. Down syndrome childhood survival improved, but mortality remained high with severe CHDs and extracardiac defects. ©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  15. Autosomal and X chromosome structural variants are associated with congenital heart defects in Turner syndrome: The NHLBI GenTAC registry.

    PubMed

    Prakash, Siddharth K; Bondy, Carolyn A; Maslen, Cheryl L; Silberbach, Michael; Lin, Angela E; Perrone, Laura; Limongelli, Giuseppe; Michelena, Hector I; Bossone, Eduardo; Citro, Rodolfo; Lemaire, Scott A; Body, Simon C; Milewicz, Dianna M

    2016-12-01

    Turner Syndrome (TS) is a developmental disorder caused by partial or complete loss of one sex chromosome. Bicuspid aortic valve and other left-sided congenital heart lesions (LSL), including thoracic aortic aneurysms and acute aortic dissections, are 30-50 times more frequent in TS than in the general population. In 454 TS subjects, we found that LSL are significantly associated with reduced dosage of Xp genes and increased dosage of Xq genes. We also showed that genome-wide copy number variation is increased in TS and identify a common copy number variant (CNV) in chromosome 12p13.31 that is associated with LSL with an odds ratio of 3.7. This CNV contains three protein-coding genes (SLC2A3, SLC2A14, and NANOGP1) and was previously implicated in congenital heart defects in the 22q11 deletion syndrome. In addition, we identified a subset of rare and recurrent CNVs that are also enriched in non-syndromic BAV cases. These observations support our hypothesis that X chromosome and autosomal variants affecting cardiac developmental genes may interact to cause the increased prevalence of LSL in TS. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  16. [Cytomegalovirus: congenital infection and clinical presentation in infants with respiratory distress syndrome].

    PubMed

    Martínez-Contreras, Angélica; Lira, Rosalía; Soria-Rodríguez, Carmen; Hori-Oshima, Sawako; Maldonado-Rodríguez, Angélica; Rojas-Montes, Othón; Ayala-Figueroa, Rafael; Estrada-Guzmán, Julia; Álvarez-Muñoz, Ma Teresa

    2015-01-01

    Respiratory distress syndrome (RDS) is a multifactorial and common disease that varies from 15 to 50 % in the newborn, causing 50 % of mortality. The RDS may be associated with bacterial and viral infections, and one of the most common viral agents is the cytomegalovirus (CMV). In the neonatal period the virus incidence goes from 0.4 to 2.5 % with a seroprevalence of 50 to 75 %; the incidence of infection in newborn with RDS is unknown. The objective was to determine the frequency of CMV infection in neonates with RDS and identify the risk factors associated with infection. The CMV-DNA was identified in plasma by quantitative PCR; maternal and neonatal variables that defined the clinical findings were analyzed by logistic regression.The CMV-DNA was identified in plasma by quantitative PCR; maternal and neonatal variables that defined the clinical findings were analyzed by logistic regression. The frequency of CMV infection in 197 infants with RDS was 8.6 % (95 % CI, 4.7-12.5). The significant variables in newborn were: neutropenia (p = 0.012), thrombocytopenia (p = 0.021), mottled skin (p = 0.03), and the maternal significant variable was cervicovaginitis (p = 0.05). We reported for the first time the highest frecuency of CMV infection in newborns with RDS and the association of various risk factors with CMV infection.

  17. A novel X-linked multiple congenital anomaly syndrome associated with an EBP mutation.

    PubMed

    Furtado, Larissa V; Bayrak-Toydemir, Pinar; Hulinsky, Becki; Damjanovich, Kristy; Carey, John C; Rope, Alan F

    2010-11-01

    Mutations of the gene coding for emopamil binding protein (EBP) can lead to deficient activity of 3-β-hydroxysteroid Δ(8), Δ(7) isomerase and are most commonly identified in. association with the X-linked dominant (male lethal) chondrodysplasia punctata (CDPX2), also known as Conradi-Hunermann syndrome. Our group has identified a hemizygous EBP mutation in males with a phenotype remarkable for Dandy-Walker malformation, cataracts, collodion skin and cryptorchidism. Additional findings of hydrocephalus, dysplasia of the corpus callosum, cardiovascular, craniofacial and skeletal anomalies were regularly seen in affected males and the family histories were supportive of an X-linked -recessive condition. The regularly reproducible constellation of cardinal features aligns very nicely with other disorders of sterol biosynthesis and is further distinguished by an absence of arty clinical manifestations in obligate carrier females. Biochemical analysis of blood from cases demonstrated markedly increased levels of 8(9)-cholestenol, and 8-dehydroeholesterol and a mildly increased level of 7-dehydrocholesterol; a similar pattern to what is seen in CDPX2. Sequence analysis of EJJP revealed a novel hemizygous missense mutation at position 141, predictive of a tryptophan to cysteine substitution (c.141G>T, p.W47C). The unaffected mothers were heterozygous for the c.141G>T mutation arid showed random X-inactivation pattern upon. © 2010 Wiley-Liss, Inc.

  18. [Congenital spinal malformations].

    PubMed

    Ertl-Wagner, B B; Reiser, M F

    2001-12-01

    Congenital spinal malformations form a complex and heterogeneous group of disorders whose pathogenesis is best explained embryologically. Radiologically, it is important to formulate a diagnosis when the disorder first becomes symptomatic. However, it is also crucial to detect complications of the disorder or of the respective therapeutic interventions in the further course of the disease such as hydromyelia or re-tethering after repair of a meningomyelocele. Moreover, once a congenital spinal malformation is diagnosed, associated malformations should be sought after. A possible syndromal classification such as in OEIS- or VACTERL-syndromes should also be considered.

  19. Congenital and acquired neutropenia consensus guidelines on diagnosis from the Neutropenia Committee of the Marrow Failure Syndrome Group of the AIEOP (Associazione Italiana Emato-Oncologia Pediatrica).

    PubMed

    Fioredda, Francesca; Calvillo, Michaela; Bonanomi, Sonia; Coliva, Tiziana; Tucci, Fabio; Farruggia, Piero; Pillon, Marta; Martire, Baldassarre; Ghilardi, Roberta; Ramenghi, Ugo; Renga, Daniela; Menna, Giuseppe; Barone, Angelica; Lanciotti, Marina; Dufour, Carlo

    2011-07-15

    Congenital and acquired neutropenia are rare disorders whose frequency in pediatric age may be underestimated due to remarkable differences in definition or misdiagnosed because of the lack of common practice guidelines. Neutropenia Committee of the Marrow Failure Syndrome Group (MFSG) of the AIEOP (Associazione Italiana Emato-Oncologia Pediatrica) elaborated this document following design and methodology formerly approved by the AIEOP board. The panel of experts reviewed the literature on the topic and participated in a conference producing a document which includes a classification of neutropenia and a comprehensive guideline on diagnosis of neutropenia. Copyright © 2011 Wiley-Liss, Inc.

  20. A Congenital Neutrophil Defect Syndrome Associated with Mutations in VPS45

    PubMed Central

    Vilboux, Thierry; Lev, Atar; Malicdan, May Christine V.; Simon, Amos J.; Järvinen, Päivi; Racek, Tomas; Puchalka, Jacek; Sood, Raman; Carrington, Blake; Bishop, Kevin; Mullikin, James; Huizing, Marjan; Garty, Ben Zion; Eyal, Eran; Wolach, Baruch; Gavrieli, Ronit; Toren, Amos; Soudack, Michalle; Atawneh, Osama M.; Babushkin, Tatiana; Schiby, Ginette; Cullinane, Andrew; Avivi, Camila; Polak-Charcon, Sylvie; Barshack, Iris; Amariglio, Ninette; Rechavi, Gideon; van der Werff ten Bosch, Jutte; Anikster, Yair; Klein, Christoph; Gahl, William A.; Somech, Raz

    2013-01-01

    Background Neutrophils are the predominant phagocytes that provide protection against bacterial and fungal infections. Genetically determined neutrophil disorders confer a predisposition to severe infections and reveal novel mechanisms that control vesicular trafficking, hematopoiesis, and innate immunity. Methods We clinically evaluated seven children from five families who had neutropenia, neutrophil dysfunction, bone marrow fibrosis, and nephromegaly. To identify the causative gene, we performed homozygosity mapping using single-nucleotide polymorphism arrays, whole-exome sequencing, immunoblotting, immunofluorescence, electron microscopy, a real-time quantitative polymerase–chain-reaction assay, immunohistochemistry, flow cytometry, fibroblast motility assays, measurements of apoptosis, and zebrafish models. Correction experiments were performed by transfecting mutant fibroblasts with the nonmutated gene. Results All seven affected children had homozygous mutations (Thr224Asn or Glu238Lys, depending on the child's ethnic origin) in VPS45, which encodes a protein that regulates membrane trafficking through the endosomal system. The level of VPS45 protein was reduced, as were the VPS45 binding partners rabenosyn-5 and syntaxin-16. The level of β1 integrin was reduced on the surface of VPS45-deficient neutrophils and fibroblasts. VPS45-deficient fibroblasts were characterized by impaired motility and increased apoptosis. A zebrafish model of vps45 deficiency showed a marked paucity of myeloperoxidase-positive cells (i.e., neutrophils). Transfection of patient cells with nonmutated VPS45 corrected the migration defect and decreased apoptosis. Conclusions Defective endosomal intracellular protein trafficking due to biallelic mutations in VPS45 underlies a new immunodeficiency syndrome involving impaired neutrophil function. (Funded by the National Human Genome Research Institute and others.) PMID:23738510

  1. Laparoscopic-assisted surgical reconstruction of a rare congenital abdominal wall defect in two children misdiagnosed with prune-belly syndrome.

    PubMed

    Fishman, Andrew I; Franco, Israel

    2013-08-01

    Abdominal wall laxity is typically associated with prune-belly syndrome (PBS). Incomplete forms of PBS have been rarely reported with only the abdominal wall laxity. Herein, we describe a rare congenital abdominal wall defect that has been confused with PBS and illustrate the laparoscopic-assisted surgical technique used for reconstruction. Two boys with symmetrical, bilateral absence or hypoplasia of the internal and external oblique muscles and no genitourinary abnormalities underwent a laparoscopic-assisted abdominal wall reconstruction utilizing the technique previously described by Firlit. Each patient had a Ct scan which confirmed the absence of the oblique muscles. In one patient EMG data confirmed no electrical activity of the obliques. Radiologic evaluation of the urinary tracts revealed no abnormalities. The abdominal wall was plicated utilizing bilateral subcostal incisions. Both patients had excellent cosmetic and functional results with no weakness or bulging of the lateral abdominal wall and improvement of associated symptoms. We believe these two cases and their congenital abdominal wall defects are a rare and often misdiagnosed muscular deficiency separate from PBS. The novel laparoscopic-assisted surgical technique illustrated is feasible and highly successful for these and possible other patients with similar rare congenital abdominal wall defects. Copyright © 2012 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

  2. Significance of heterozygosis M34T mutation of GJB2 gene in non-syndromic congenital deafness. Retrospective analysis of 12,472 samples of amniotic fluid

    PubMed Central

    Coco, Manuela; Salvinelli, Fabrizio; Greco, Fabio; Trivelli, Maurizio; D’Emidio, Laura; Mesoraca, Alvaro; Giorlandino, Claudio; Raffio, Raffaella; Coco, Claudio

    2013-01-01

    Summary Objective to determinate the role of heterozygosis of M34T mutation of GJB2 gene in non syndromic congenital deafness. Methods retrospective study between March 2010 and June 2013. Molecular screening for 35delG and M34T mutations of the GJB2 gene was offered to all women undergoing to second trimester genetic amniocentesis. Patients were excluded from the study group if one of the following conditions were present: infections, fetal abnormalities, family history for congenital deafness, diagnosis of chromosomal abnormalities, and consanguinity between parents. Results a total of 12.472 Caucasian women gave informed consent for this test. Seventy-seven cases were excluded. From the 12.395 amniotic fluid analysis remained, the following was found: 2 cases of 35delG homozygosis and 352 cases of heterozygous carriers (42 M34T mutation, 298 35delG mutation, 12 double heterozygosis M34T/35delG). The follow up in first year of life in the 42 newborns with heterozygosis for M34T mutation showed a mild deafness in 23 cases. Conclusions in our series, presence of heterozygosis M34T mutation is associated in more than 50% of cases to mild congenital deafness. PMID:24611097

  3. Physiological Basis for the Etiology, Diagnosis, and Treatment of Adrenal Disorders: Cushing’s Syndrome, Adrenal Insufficiency, and Congenital Adrenal Hyperplasia

    PubMed Central

    Raff, Hershel; Sharma, Susmeeta T.; Nieman, Lynnette K.

    2014-01-01

    The hypothalamic-pituitary-adrenal (HPA) axis is a classic neuroendocrine system. One of the best ways to understand the HPA axis is to appreciate its dynamics in the variety of diseases and syndromes that affect it. Excess glucocorticoid activity can be due to endogenous cortisol overproduction (spontaneous Cushing’s syndrome) or exogenous glucocorticoid therapy (iatrogenic Cushing’s syndrome). Endogenous Cushing’s syndrome can be subdivided into ACTH-dependent and ACTH-independent, the latter of which is usually due to autonomous adrenal overproduction. The former can be due to a pituitary corticotroph tumor (usually benign) or ectopic ACTH production from tumors outside the pituitary; both of these tumor types overexpress the proopiomelanocortin gene. The converse of Cushing’s syndrome is the lack of normal cortisol secretion and is usually due to adrenal destruction (primary adrenal insufficiency) or hypopituitarism (secondary adrenal insufficiency). Secondary adrenal insufficiency can also result from a rapid discontinuation of long-term, pharmacological glucocorticoid therapy because of HPA axis suppression and adrenal atrophy. Finally, mutations in the steroidogenic enzymes of the adrenal cortex can lead to congenital adrenal hyperplasia and an increase in precursor steroids, particularly androgens. When present in utero, this can lead to masculinization of a female fetus. An understanding of the dynamics of the HPA axis is necessary to master the diagnosis and differential diagnosis of pituitary-adrenal diseases. Furthermore, understanding the pathophysiology of the HPA axis gives great insight into its normal control. PMID:24715566

  4. Genotype and Phenotype Correlation in Hereditary Thrombotic Thrombocytopenic Purpura (Upshaw-Schulman Syndrome)

    ClinicalTrials.gov

    2018-02-12

    Thrombotic Thrombocytopenic Purpura; Congenital Thrombotic Thrombocytopenic Purpura; Familial Thrombotic Thrombocytopenic Purpura; Thrombotic Thrombocytopenic Purpura, Congenital; Upshaw-Schulman Syndrome

  5. Leonard Horner and an enthusiasm for Loess. [Leicester Studies in the History of Loess Research part I

    NASA Astrophysics Data System (ADS)

    Smalley, Ian; Kels, Holger

    2018-04-01

    Leonard Horner (1785-1864) made substantial contributions to the study of loess. He made field trips with J.J. Noeggerath and Charles Lyell and published useful material on the loess near Bonn. He was an unappreciated pioneer- he was the first person to direct attention to loess as a material. He pointed out that loess was intrinsically interesting. He studied the material transported by the Rhine, and the alluvial deposits in Egypt, looking for links to loess, and the problem of loess formation. He was born in Edinburgh in 1785 and directed the thoughts of young Charles Darwin towards science when he came to Edinburgh to study medicine. Circumstances placed him in Bonn in the critical years 1831-1833; in this time Charles Lyell married his eldest daughter Mary; and both Lyell and Horner encountered the loess. Lyell made it well known via vol.3 of the Principles of Geology, Horner became a loess enthusiast. In the summer of 1833 Horner & Lyell were in the crater of the Roderberg considering the more than 20 m of loess deposited there. His major paper was published in 1836 (reporting the Roderberg excursion) and he joined Lyell's list of loess investigators in the 5th edition of the Principles published in 1837. He was the last to join that select eleven: Bronn, Leonhard, Boue, Voltz, Steininger, Merian, Rozet, Hibbert, Noeggerath, von Meyer, Horner. Most of these were writing on the geology and landscapes of the Rhine valley, but Horner was drawing attention to the amazing nature of the loess itself, in particular the spectacular disaggregation on contact with water. He also published the first geological map of the Bonn region, including the Roderberg and the Siebengebirge, a region of loess and volcanoes.

  6. Lewis Base Activation of Silyl Acetals: Iridium-Catalyzed Reductive Horner-Wadsworth-Emmons Olefination.

    PubMed

    Dakarapu, Udaya Sree; Bokka, Apparao; Asgari, Parham; Trog, Gabriela; Hua, Yuanda; Nguyen, Hiep H; Rahman, Nawal; Jeon, Junha

    2015-12-04

    A Lewis base promoted deprotonative pronucleophile addition to silyl acetals has been developed and applied to the iridium-catalyzed reductive Horner-Wadsworth-Emmons (HWE) olefination of esters and the chemoselective reduction of the resulting enoates. Lewis base activation of silyl acetals generates putative pentacoordinate silicate acetals, which fragment into aldehydes, silanes, and alkoxides in situ. Subsequent deprotonative metalation of phosphonate esters followed by HWE with aldehydes furnishes enoates. This operationally convenient, mechanistically unique protocol converts the traditionally challenging aryl, alkenyl, and alkynyl esters to homologated enoates at room temperature within a single vessel.

  7. Congenital Hypothyroidism

    MedlinePlus

    ... Disease Featured Resource Find an Endocrinologist Search Congenital Hypothyroidism March 2012 Download PDFs English Espanol Editors Rosalind S. ... Resources MedlinePlus (NIH) Mayo Clinic What is congenital hypothyroidism? Newborn babies who are unable to make enough ...

  8. Congenital rubella

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/001658.htm Congenital rubella To use the sharing features on this page, please enable JavaScript. Congenital rubella is a condition that occurs in an infant ...

  9. Congenital Neutropenia Syndromes

    MedlinePlus

    ... Networks Research Conducted at NIAID Research Rules & Policies Sequencing Assay Project Specific Metadata Standards Core Sample Core ... Priority Areas of Interest Division of Microbiology and Infectious Diseases High-Priority Areas of Interest Small Business ...

  10. Stage 1 hybrid palliation for hypoplastic left heart syndrome--assessment of contemporary patterns of use: an analysis of The Society of Thoracic Surgeons Congenital Heart Surgery Database.

    PubMed

    Karamlou, Tara; Overman, David; Hill, Kevin D; Wallace, Amelia; Pasquali, Sara K; Jacobs, Jeffrey P; Jacobs, Marshall L; Caldarone, Christopher A

    2015-01-01

    Hybrid palliation is an alternative to Norwood stage 1 for the initial management of hypoplastic left heart syndrome. Contemporary multicenter hybrid use and institutional/patient factors associated with hybrid use relative to the Norwood have not been evaluated. We describe hybrid use in relation to institutional volume, patient factors, and short-term outcomes. Infants aged 60 days or less listed in The Society of Thoracic Surgeons Congenital Heart Surgery Database (2010-2012) undergoing initial palliation of hypoplastic left heart syndrome were included. Annual institutional hybrid use rates were calculated: [hybrid procedures/(Norwood + hybrid + transplant procedures)]. In-hospital outcomes for primary hybrid and primary Norwood were compared and stratified by high (defined as ≥50%) versus low (defined as ≤10%) institutional hybrid use. Of 1728 patients (100 centers), most (n = 1496, 87%) underwent an index Norwood; 232 patients (13%) underwent an index hybrid procedure. Preoperative patient risk factors were more prevalent in patients undergoing the hybrid procedure. Only 13 of 100 institutions were high hybrid users, and these tended to have lower annual hypoplastic left heart syndrome index case volume. Unadjusted in-hospital mortality was higher for the hybrid compared with the Norwood procedure (30% vs 16%; P < .001). In-hospital mortality for the hybrid procedure was not associated with hybrid use (26% among institutions with low use vs 28% among institutions with high use). However, centers with high hybrid use had higher mortality after the Norwood (43%) compared with centers with low hybrid use (16%). Few centers currently select the hybrid procedure for most infants with hypoplastic left heart syndrome. Although unadjusted in-hospital hybrid mortality is higher than Norwood mortality, potential risk factors are more prevalent among hybrid cases. Institutions with higher hybrid use have lower hypoplastic left heart syndrome case volume and

  11. A deletion in FOXN1 is associated with a syndrome characterized by congenital hypotrichosis and short life expectancy in Birman cats.

    PubMed

    Abitbol, Marie; Bossé, Philippe; Thomas, Anne; Tiret, Laurent

    2015-01-01

    An autosomal recessive syndrome characterized by congenital hypotrichosis and short life expectancy has been described in the Birman cat breed (Felis silvestris catus). We hypothesized that a FOXN1 (forkhead box N1) loss-of-function allele, associated with the nude phenotype in humans, mice and rats, may account for the syndrome observed in Birman cats. To the best of our knowledge, spontaneous mutations in FOXN1 have never been described in non-human, non-rodent mammalian species. We identified a recessive c.1030_1033delCTGT deletion in FOXN1 in Birman cats. This 4-bp deletion was associated with the syndrome when present in two copies. Percentage of healthy carriers in our French panel of genotyped Birman cats was estimated to be 3.2%. The deletion led to a frameshift and a premature stop codon at position 547 in the protein. In silico, the truncated FOXN1 protein was predicted to lack the activation domain and critical parts of the forkhead DNA binding domain, both involved in the interaction between FOXN1 and its targets, a mandatory step to promote normal hair and thymic epithelial development. Our results enlarge the panel of recessive FOXN1 loss-of-function alleles described in mammals. A DNA test is available; it will help owners avoid matings at risk and should prevent the dissemination of this morbid mutation in domestic felines.

  12. A Deletion in FOXN1 Is Associated with a Syndrome Characterized by Congenital Hypotrichosis and Short Life Expectancy in Birman Cats

    PubMed Central

    Abitbol, Marie; Bossé, Philippe; Thomas, Anne; Tiret, Laurent

    2015-01-01

    An autosomal recessive syndrome characterized by congenital hypotrichosis and short life expectancy has been described in the Birman cat breed (Felis silvestris catus). We hypothesized that a FOXN1 (forkhead box N1) loss-of-function allele, associated with the nude phenotype in humans, mice and rats, may account for the syndrome observed in Birman cats. To the best of our knowledge, spontaneous mutations in FOXN1 have never been described in non-human, non-rodent mammalian species. We identified a recessive c.1030_1033delCTGT deletion in FOXN1 in Birman cats. This 4-bp deletion was associated with the syndrome when present in two copies. Percentage of healthy carriers in our French panel of genotyped Birman cats was estimated to be 3.2%. The deletion led to a frameshift and a premature stop codon at position 547 in the protein. In silico, the truncated FOXN1 protein was predicted to lack the activation domain and critical parts of the forkhead DNA binding domain, both involved in the interaction between FOXN1 and its targets, a mandatory step to promote normal hair and thymic epithelial development. Our results enlarge the panel of recessive FOXN1 loss-of-function alleles described in mammals. A DNA test is available; it will help owners avoid matings at risk and should prevent the dissemination of this morbid mutation in domestic felines. PMID:25781316

  13. Synthesis of a [(14) C]-steroid intermediate: an application of a nonstabilized Horner-Wadsworth-Emmons olefination approach.

    PubMed

    Rivera, Nelo R; Ren, Sumei; Hesk, David

    2015-01-01

    Radiolabeled steroid derivative 1 was successfully prepared using a Horner-Wadsworth-Emmons approach: a [(14) C]-label was efficiently incorporated into the C-18 position of the molecule. Previously published procedures employing other olefination methods are either not applicable due to unavailability of [(14) C]-precursors or suffer from poor reactivity. Copyright © 2015 John Wiley & Sons, Ltd.

  14. [Congenital hypothyroidism].

    PubMed

    Castilla Peón, María Fernanda

    Congenital hypothyroidism (CH) is a cause of preventable mental retardation; therefore, timely diagnosis and treatment by the primary care physician is very important. CH screening must be performed between the second and fifth days of life with capillary blood done with a heel prick and must be confirmed by measurement of thyroid hormones in venous blood. The most common cause of CH is thyroid dysgenesis, which may be identified by a thyroid scan carried out before initiating treatment. Treatment should be with levothyroxine (10-15μg/kg/day) and should not be delayed or suspended during the first 3 years of life due to the deleterious effect on neurodevelopment in case of low thyroid hormones during this time. Preterm or sick infants or those with Down syndrome require special consideration. This article provides diagnostic and therapeutic algorithms for CH. Copyright © 2015 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  15. "Mowat-Wilson" syndrome with and without Hirschsprung disease is a distinct, recognizable multiple congenital anomalies-mental retardation syndrome caused by mutations in the zinc finger homeo box 1B gene.

    PubMed

    Zweier, Christiane; Albrecht, Beate; Mitulla, Beate; Behrens, Rolf; Beese, Maike; Gillessen-Kaesbach, Gabriele; Rott, Hans-Dieter; Rauch, Anita

    2002-03-15

    Recently mutations in the gene ZFHX1B (SIP1) were shown in patients with "syndromic Hirschsprung disease" with mental retardation (MR) and multiple congenital anomalies (MCA), but it was unclear if Hirschsprung disease is an obligate symptom of these mutations and if the distinct facial phenotype delineated by Mowat et al. [1998: J Med Genet 35: 617-623] is specific for ZFHX1B mutations. In order to address these open questions we analyzed the ZFHX1B gene in five patients, three of whom had "syndromic Hirschsprung disease" two with and one without the facial phenotype described by Mowat et al. [1998], and two of whom had the distinct facial gestalt without Hirschsprung disease. Analyses of microsatellite markers and newly identified SNPs, and/or FISH with BACs from the ZFHX1B region excluded large deletions in all five patients. Direct sequencing demonstrated truncating ZFHX1B mutations in all four patients with the characteristic facial phenotype, but not in the patient with syndromic Hirschsprung disease without the distinct facial appearance. We demonstrate that there is a specific clinical entity with a recognizable facial gestalt, mental retardation and variable MCAs which we propose be called the "Mowat-Wilson syndrome."

  16. Congenital Hypothyroidism.

    PubMed

    Wassner, Ari J

    2018-03-01

    Congenital hypothyroidism is common and can cause severe neurodevelopmental morbidity. Prompt diagnosis and treatment are critical to optimizing long-term outcomes. Universal newborn screening is an important tool for detecting congenital hypothyroidism, but awareness of its limitations, repeated screening in high-risk infants, and a high index of clinical suspicion are needed to ensure that all affected infants are appropriately identified and treated. Careful evaluation will usually reveal the etiology of congenital hypothyroidism, which may inform treatment and prognosis. Early and adequate treatment with levothyroxine results in excellent neurodevelopmental outcomes for most patients with congenital hypothyroidism. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Delayed diagnosis of a patient with Usher syndrome 1C in a Louisiana Acadian family highlights the necessity of timely genetic testing for the diagnosis and management of congenital hearing loss.

    PubMed

    Umrigar, Ayesha; Musso, Amanda; Mercer, Danielle; Hurley, Annette; Glausier, Cassondra; Bakeer, Mona; Marble, Michael; Hicks, Chindo; Tsien, Fern

    2017-01-01

    Advances in sequencing technologies and increased understanding of the contribution of genetics to congenital sensorineural hearing loss have led to vastly improved outcomes for patients and their families. Next-generation sequencing and diagnostic panels have become increasingly reliable and less expensive for clinical use. Despite these developments, the diagnosis of genetic sensorineural hearing loss still presents challenges for healthcare providers. Inherited sensorineural hearing loss has high levels of genetic heterogeneity and variable expressivity. Additionally, syndromic hearing loss (hearing loss and additional clinical abnormalities) should be distinguished from non-syndromic (hearing loss is the only clinical symptom). Although the diagnosis of genetic sensorineural hearing loss can be challenging, the patient's family history and ethnicity may provide critical information, as certain genetic mutations are more common in specific ethnic populations. The early identification of the cause of deafness can benefit patients and their families by estimating recurrence risks for future family planning and offering the proper interventions to improve their quality of life. Collaboration between pediatricians, audiologists, otolaryngologists, geneticists, and other specialists are essential in the diagnosis and management of patients with hearing disorders. An early diagnosis is vital for proper management and care, as some clinical manifestations of syndromic sensorineural hearing loss are not apparent at birth and have a delayed age of onset. We present a case of Usher syndrome (congenital deafness and childhood-onset blindness) illustrating the challenges encountered in the diagnosis and management of children presenting with congenital genetic sensorineural hearing loss, along with helpful resources for clinicians and families.

  18. New compound heterozygous variants of the cholinergic receptor nicotinic delta subunit gene in a Chinese male with congenital myasthenic syndrome: A case report.

    PubMed

    Feng, Huiru; Zhou, Hongyu

    2017-12-01

    Congenital myasthenic syndromes (CMS) are a group of genetic disorders that stem mostly from molecular defects in nicotinic acetylcholine receptors (AChRs). Defects in the cholinergic receptor nicotinic delta subunit (CHRND) gene can cause a series of myasthenic syndromes. Here, we report 2 new compound heterozygous variants of the CHRND gene in a Chinese male with CMS. A 43-year-old Chinese male presented with progressive muscle weakness, difficulty chewing, and an inability to lift his head from the time he was 8 years old. He was treated with pyridostigmine, which was partially effective. Two weeks prior, he was hospitalized for dyspnea. Upon examination, he was unable to drum his cheeks and exhibited fatigable muscle weakness and facial muscle atrophy. Sequencing of his exome revealed 2 previously unreported mutations in CHRND, c.59G>A (exon2) and c.423G>C (exon5). We identified a new mutational site that contributes to the onset of CMS. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  19. Genetic characterization of congenital tufting enteropathy: epcam associated phenotype and involvement of SPINT2 in the syndromic form.

    PubMed

    Salomon, Julie; Goulet, Olivier; Canioni, Danielle; Brousse, Nicole; Lemale, Julie; Tounian, Patrick; Coulomb, Aurore; Marinier, Evelyne; Hugot, Jean-Pierre; Ruemmele, Frank; Dufier, Jean-Louis; Roche, Olivier; Bodemer, Christine; Colomb, Virginie; Talbotec, Cécile; Lacaille, Florence; Campeotto, Florence; Cerf-Bensussan, Nadine; Janecke, Andreas R; Mueller, Thomas; Koletzko, Sibylle; Bonnefont, Jean-Paul; Lyonnet, Stanislas; Munnich, Arnold; Poirier, Françoise; Smahi, Asma

    2014-03-01

    Congenital tufting enteropathy (CTE) is a rare and severe enteropathy recently ascribed to mutations in the epcam gene. Here we establish SPINT2, previously ascribed to congenital sodium diarrhea, as a second gene associated with CTE and report molecular and immunohistochemistry data in 57 CTE patients. Inclusion criteria were early onset diarrhea and intestinal insufficiency with the typical histological CTE abnormalities. The clinical phenotype was registered, the entire coding regions of epcam and SPINT2 sequenced, and immunostaining of EpCAM and SPINT2 performed on intestinal biopsies. An epcam mutation was involved in 41 patients (73 %) who mainly displayed isolated digestive symptoms. Mutations severely affected gene expression since the EpCAM signal on intestinal tissues was either undetectable or low and irregular. Twelve other patients (21 %) carried mutations in SPINT2, and were phenotypically characterized by systematic association with keratitis (p < 10(-4)) and, for half of them, with choanal atresia (p < 10(-4)). Dependency on parenteral nutrition (PN) was comparable in patients with epcam or SPINT2 mutations, but the frequent epcam mutation c.556-14A>G (abnormal splicing) was significantly associated with a better outcome (p = 0.032) with milder PN dependency to weaning in some cases. Finally, four patients (7 %) with isolated digestive symptoms had no detectable epcam or SPINT2 mutation. Two candidate genes, Elf3 and Claudin7, were excluded from this population. Our study allows us to separate CTE patients into at least three genetic classes, each with specific phenotypes. The genetics approach raises the question of the distinction between two congenital enteropathies. Our findings should help improve the diagnosis of CTE, guide toward strategies of long-term PN management, and limit indications for intestinal transplantation to life-threatening PN complications.

  20. Transient unilateral brachial plexopathy and partial Horner's syndrome following spinal anesthesia for cesarean section

    PubMed Central

    Anson, Jonathan A; McQuillan, Patrick M

    2014-01-01

    A healthy 21-year-old primigravida presented for elective cesarean section. At 45 min after intrathecal (IT) injection of bupivacaine, morphine and fentanyl she developed dysphagia, right sided facial droop, ptosis and ulnar nerve weakness. This constellation of signs and symptoms resolved 2 h later. Based on the time course and laterality of her symptoms, as well as the pharmacologic properties of spinal opioids, we believe her symptoms can be attributed to the IT administration of fentanyl. PMID:24803773

  1. Prophylactic levosimendan for the prevention of low cardiac output syndrome and mortality in paediatric patients undergoing surgery for congenital heart disease.

    PubMed

    Hummel, Johanna; Rücker, Gerta; Stiller, Brigitte

    2017-08-02

    Low cardiac output syndrome remains a serious complication, and accounts for substantial morbidity and mortality in the postoperative course of paediatric patients undergoing surgery for congenital heart disease. Standard prophylactic and therapeutic strategies for low cardiac output syndrome are based mainly on catecholamines, which are effective drugs, but have considerable side effects. Levosimendan, a calcium sensitiser, enhances the myocardial function by generating more energy-efficient myocardial contractility than achieved via adrenergic stimulation with catecholamines. Thus potentially, levosimendan is a beneficial alternative to standard medication for the prevention of low cardiac output syndrome in paediatric patients after open heart surgery. To review the efficacy and safety of the postoperative prophylactic use of levosimendan for the prevention of low cardiac output syndrome and mortality in paediatric patients undergoing surgery for congenital heart disease. We identified trials via systematic searches of CENTRAL, MEDLINE, Embase, and Web of Science, as well as clinical trial registries, in June 2016. Reference lists from primary studies and review articles were checked for additional references. We only included randomised controlled trials (RCT) in our analysis that compared prophylactic levosimendan with standard medication or placebo, in infants and children up to 18 years of age, who were undergoing surgery for congenital heart disease. Two review authors independently extracted data and assessed risk of bias according to a pre-defined protocol. We obtained additional information from all but one of the study authors of the included studies. We used the five GRADE considerations (study limitations, consistency of effect, imprecision, indirectness, and publication bias) to assess the quality of evidence from the studies that contributed data to the meta-analyses for the prespecified outcomes. We created a 'Summary of findings' table to

  2. [Clinical and genetic characteristics of congenital myasthenia syndrome with episodic apnea caused by CHAT gene mutation: a report of 2 cases].

    PubMed

    Liu, Z M; Fang, F; Ding, C H; Zhang, W H; Deng, J; Chen, C H; Wang, X; Liu, J; Li, Z; Jia, X L; Zeng, J S; Qian, S Y

    2018-03-02

    Objective: To investigate the clinical and genetic features of congenital myasthenia syndrome with episodic apnea (CMS-EA) caused by gene mutation of choline acetyltransferase (CHAT) Methods: The clinical data of 2 patients with congenital myasthenia syndrome were collected, and both were diagnosed from 2013 to 2015 in Beijing Children's Hospital, Capital Medical University. The clinical features and gene mutation characteristics were analyzed, and the patients were followed-up for therapeutic efficacy. Results: The two patients (case 1 and case 2) had the onset soon after birth and at 3 months after birth respectively. The two patients were admitted to the PICU due to dyspnea, cyanotic episodes that required intubation. The patients had repeated apnea and became ventilator dependent. Case 1 died due to refusal of any treatment. Case 2 had a tracheotomy, and gradually weaned from ventilator after using pyridostigmine. The hospitalization of case 2 lasted 162 days. Case 2 was followed up to the age of 3 years and 4 months, and was extubated and was maintained on oral neostigmine but still had fluctuating ptosis and minor physical and mental retardation. Both cases were negative for anti-AChR, anti-acetylcholinesterase, anti-MuSK antibodies. Neostigmine test was negative in case 1 and suspiciously positive in case 2. Low-frequency repetitive nerve stimulation testing of case 2 was negative. Cranial MRI scans of both cases showed brain atrophy-like change. Genetic testing showed compound heterozygous deletions (exon 4, 5, 6) and pathogenic variant c.914T>C (p.I305T) in CHAT in case 1, compound heterozygous variants c.1007T>C (p.I336T) and c.64C>T (p.Q22X) in CHAT in case 2. To our knowledge, compound heterozygous deletions (exon 4, 5, 6) and p.Q22X were novel, previously unreported variants. Conclusion: CMS-EA usually presents at birth or in the neonatal period with hypotonia, ptosis, dysphagia due to severe bulbar weakness, and respiratory insufficiency with cyanosis

  3. Congenital sixth nerve palsy with associated anomalies.

    PubMed

    Kasturi, Nirupama

    2017-10-01

    Congenital abduction deficit is most likely due to Duane's retraction syndrome as congenital abducens nerve palsy is very rare. We report two cases of infantile abduction deficit due to sixth nerve palsy associated with other anomalies to highlight the importance of including neuroimaging in the evaluation of an infant presenting with a limitation of abduction.

  4. Ehlers Danlos syndrome, kyphoscoliotic type due to Lysyl Hydroxylase 1 deficiency in two children without congenital or early onset kyphoscoliosis.

    PubMed

    van Dijk, Fleur S; Mancini, Grazia M S; Maugeri, Alessandra; Cobben, Jan M

    2017-10-01

    We report two children with Ehlers Danlos, kyphoscoliotic type confirmed by Lysyl Hydroxylase 1 deficiency due to bi-allelic PLOD1 mutations (kEDS-PLOD1) who were initially thought to have either a diagnosis of classical EDS (cEDS) or a neuromuscular disorder due to absence of (congenital) scoliosis. As the two patients reported here illustrate, patients with kEDS-PLOD1 do not always have a kyphoscoliosis present at birth or in the first year of life, neither do they necessarily develop kyphoscoliosis later in infancy. Using the past criteria for kEDS there was considerable overlap with the clinical diagnostic criteria for EDS classical type. In the patients reported here without (kypho) scoliosis this has delayed the diagnosis, which is unfortunate as the diagnosis of kEDS-PLOD1 results in a different recurrence risk and has management consequences. Interestingly, the new criteria for kEDS would not have prevented this diagnostic delay as congenital or early onset kyphoscoliosis (progressive or non-progressive) is deemed obligatory for the diagnosis of kEDS. Being aware of the limitations of clinical diagnostic criteria, we recommend that (i) in patients without a positive family history nor identified COL5A1/2 mutations, lysyl hydroxylase deficiency or biallelic PLOD1 mutations should be excluded before the diagnosis classical EDS can be made and (ii) PLOD1 and COL5A1/2 should be included in the same Next Generation Sequencing (NGS) gene panel. Copyright © 2017. Published by Elsevier Masson SAS.

  5. Genetic Studies of Strabismus, Congenital Cranial Dysinnervation Disorders (CCDDs), and Their Associated Anomalies

    ClinicalTrials.gov

    2018-03-21

    Congenital Fibrosis of Extraocular Muscles; Duane Retraction Syndrome; Duane Radial Ray Syndrome; Mobius Syndrome; Brown Syndrome; Marcus Gunn Syndrome; Strabismus Congenital; Horizontal Gaze Palsy; Horizontal Gaze Palsy With Progressive Scoliosis; Facial Palsy; Facial Paresis, Hereditary, Congenital; Third Nerve Palsy; Fourth Nerve Palsy; Sixth Nerve Palsy; Synkinesis; Ocular Motility Disorders; Levator-Medial Rectus Synkinesis; Athabaskan Brainstem Dysgenesis; Tongue Paralysis; Ninth Nerve Disorder; Fifth Nerve Palsy; Seventh Nerve Palsy; Eleventh Nerve Disorder; Twelfth Nerve Disorder; Vagus Nerve Paralysis; Moebius Sequence

  6. Genetics Home Reference: congenital hepatic fibrosis

    MedlinePlus

    ... health and development? More about Mutations and Health Inheritance Pattern The various syndromes that include congenital hepatic fibrosis can have different inheritance patterns. Most of these disorders are inherited in an ...

  7. A Case of Epidermal Nervous Syndrome with a Novel Association of Congenital Cystic Dysplastic Kidney with Numerous Nephroblastic Proliferations

    DTIC Science & Technology

    2016-04-19

    Epidermal nevus syndrome is a broad term encompassing several disease processes. These entities are united by their association with epidermal nevi...However, there are no well-described, documented cases of dysplastic kidney with cystic nephroblastic proliferation associated with epidermal nevus

  8. Gustatory lid retraction: an unusual congenital cranial dysinnervation disorder.

    PubMed

    Khan, Arif O; Khan, Zabila

    2017-12-01

    Congenital cranial dysinnervation disorders are developmental abnormalities of cranial nerves that often include abnormal synkinesis. Among the most common ophthalmic congenital cranial dysinnervation disorders are Duane retraction syndrome and the Marcus-Gunn jaw-winking phenomenon. This report documents gustatory lid retraction as an unusual congenital cranial dysinnervation. Copyright © 2017 American Association for Pediatric Ophthalmology and Strabismus. All rights reserved.

  9. A novel homozygous AP4B1 mutation in two brothers with AP-4 deficiency syndrome and ocular anomalies.

    PubMed

    Accogli, Andrea; Hamdan, Fadi F; Poulin, Chantal; Nassif, Christina; Rouleau, Guy A; Michaud, Jacques L; Srour, Myriam

    2018-04-01

    Adaptor protein complex-4 (AP-4) is a heterotetrameric protein complex which plays a key role in vesicle trafficking in neurons. Mutations in genes affecting different subunits of AP-4, including AP4B1, AP4E1, AP4S1, and AP4M1, have been recently associated with an autosomal recessive phenotype, consisting of spastic tetraplegia, and intellectual disability (ID). The overlapping clinical picture among individuals carrying mutations in any of these genes has prompted the terms "AP-4 deficiency syndrome" for this clinically recognizable phenotype. Using whole-exome sequencing, we identified a novel homozygous mutation (c.991C>T, p.Q331*, NM_006594.4) in AP4B1 in two siblings from a consanguineous Pakistani couple, who presented with severe ID, progressive spastic tetraplegia, epilepsy, and microcephaly. Sanger sequencing confirmed the mutation was homozygous in the siblings and heterozygous in the parents. Similar to previously reported individuals with AP4B1 mutations, brain MRI revealed ventriculomegaly and white matter loss. Interestingly, in addition to the typical facial gestalt reported in other AP-4 deficiency cases, the older brother presented with congenital left Horner syndrome, bilateral optic nerve atrophy and cataract, which have not been previously reported in this condition. In summary, we report a novel AP4B1 homozygous mutation in two siblings and review the phenotype of AP-4 deficiency, speculating on a possible role of AP-4 complex in eye development. © 2018 Wiley Periodicals, Inc.

  10. Congenital Myopathy

    MedlinePlus

    ... arms and legs, droopy eyelids, and problems with eye movements. Weakness often gets worse with time. Central core ... difficulties occur as well. Some children have weakened eye movements. Congenital fiber-type disproportion myopathy is a rare ...

  11. Tracheomalacia - congenital

    MedlinePlus

    Babies born with tracheomalacia may have other congenital abnormalities, such as heart defects, developmental delay, or gastroesophageal reflux. Aspiration pneumonia can occur from inhaling food into the lungs or windpipe.

  12. Risk of recurrent cardiac events after onset of menopause in women with congenital long-QT syndrome types 1 and 2.

    PubMed

    Buber, Jonathan; Mathew, Jehu; Moss, Arthur J; Hall, W Jackson; Barsheshet, Alon; McNitt, Scott; Robinson, Jennifer L; Zareba, Wojciech; Ackerman, Michael J; Kaufman, Elizabeth S; Luria, David; Eldar, Michael; Towbin, Jeffrey A; Vincent, Michael; Goldenberg, Ilan

    2011-06-21

    Women with congenital long-QT syndrome experience an increased risk for cardiac events after the onset of adolescence that is more pronounced among carriers of the LQT2 genotype. We hypothesized that the hormonal changes associated with menopause may affect clinical risk in this population. We used a repeated-events analysis to evaluate the risk for recurrent syncope during the menopause transition and postmenopausal periods (5 years before and after the age at onset of menopause, respectively) among 282 LQT1 (n=151) and LQT2 (n=131) women enrolled in the Long-QT Syndrome Registry. Multivariate analysis showed that the risk for recurrent syncope (n=150) among LQT2 women was significantly increased during both menopause transition (hazard ratio, 3.38; P=0.005) and the postmenopausal period (hazard ratio, 8.10; P<0.001) compared with the reproductive period. The risk increase was evident among women who did or did not receive estrogen therapy. In contrast, among LQT1 women, the onset of menopause was associated with a reduction in the risk for recurrent syncope (hazard ratio, 0.19; P=0.05; P=0.02 for genotype-by-menopause interaction). Only 22 women (8%) experienced aborted cardiac arrest or sudden cardiac death during follow-up. The frequency of aborted cardiac arrest/sudden cardiac death showed a similar genotype-specific association with the onset of menopause. The onset of menopause is associated with a significant increase in the risk of cardiac events (dominated by recurrent episodes of syncope) in LQT2 women, suggesting that careful follow-up and continued long-term therapy are warranted in this population.

  13. Parents' perceptions during the transition to home for their child with a congenital heart defect: How can we support families of children with hypoplastic left heart syndrome?

    PubMed

    March, Sarita

    2017-07-01

    The aim of the study was to explore the literature related to transitions in healthcare between the hospital and home that caregivers experience with a child who has a congenital heart defect (CHD), specifically related to hypoplastic left heart syndrome (HLHS). A systematic literature review was conducted searching OVID Medline, CINAHL, and PubMed to discover the caregivers' perceptions on their transitions between hospital care and home care of their child with a CHD. Articles included those with focus on the transitions of caregivers between hospital and home care for children with CHD. Excluded articles were studies focused on adolescents, transition to adult healthcare, mortality results, other diseases associated with CHDs, comparison of CHD treatments, feasibility studies, differences in care between hospitals, home monitoring, and comparison of videoconference and telephone home communication. Ten articles were selected. Many parents voiced their concerns with feeding their child, learning medical skills and knowledge, reported a disrupted relationship between parents and their child, and identified stress and anxiety associated with taking care of a child with a CHD. There were limited studies on caregivers' transitions with a child with HLHS, but there also was limited focus on the caregivers' experiences with transitions between hospital and home care for their child with any CHD. Research on the transition experience between hospital care and home care for caregivers of children born with a CHD, and a specific focus on HLHS from the caregivers' viewpoint, would provide insight into the perspective of caregivers during the numerous transitions. © 2017 Wiley Periodicals, Inc.

  14. Gene of a new X-linked syndrome with multiple congenital anomalies and severe mental retardation maps in Xp22-pter

    SciTech Connect

    Wittwer, B.; Kircheisen, R.; Leutelt, J.

    1994-09-01

    We report on a family with 3 males presenting with a not yet described new X-chromosomal syndrome of multiple congenital anomalies and severe mental retardation. Two sisters have (with 3 different partners) 3 severely handicapped sons. In each case, oligohydramnios and intrauterine growth retardation were observed. Delivery was in the 34th, 31st, and 38th gestational week, respectively. Two of the patients had microcephaly (head circumference of the third case at birth is unknown). On physical examination, high and broad forehead, frontal bossing, downslanting palpebral fissures, long philtrum, thin upper lip, high arched palate, and deeply set anteverted ears were seen.more » One of the boys has microphthalmos and sclerocornea, while his cousin shows atrophy of the optic nerve. All three patients show a severe statomotor and mental retardation, they are most likely deaf and blind, have pathologic EEG, and seizures. Important additional findings are hydronephrosis, renal duplication, vesicorenal reflux, and agenesis of corpus callosum. The karyotype is normal (46,XY). We performed a segregation analysis in the family using more than 20 DNA polymorphisms distributed over the X chromosome. Linkage without recombination was found to KAL, DXS278, and DXS16 in Xp22. Analysis of multiple informative meioses suggested a location of the disease locus distal to DXS207. Recombinants were identified with all other marker loci from Xp22-Xpter.« less

  15. Immunity to polio, measles and rubella in women of child-bearing age and estimated congenital rubella syndrome incidence, Cambodia, 2012.

    PubMed

    Mao, B; Chheng, K; Wannemuehler, K; Vynnycky, E; Buth, S; Soeung, S C; Reef, S; Weldon, W; Quick, L; Gregory, C J

    2015-07-01

    Significant gaps in immunity to polio, measles, and rubella may exist in adults in Cambodia and threaten vaccine-preventable disease (VPD) elimination and control goals, despite high childhood vaccination coverage. We conducted a nationwide serological survey during November-December 2012 of 2154 women aged 15-39 years to assess immunity to polio, measles, and rubella and to estimate congenital rubella syndrome (CRS) incidence. Measles and rubella antibodies were detected by IgG ELISA and polio antibodies by microneutralization testing. Age-structured catalytic models were fitted to rubella serological data to predict CRS cases. Overall, 29.8% of women lacked immunity to at least one poliovirus (PV); seroprevalence to PV1, PV2 and PV3 was 85.9%, 93.4% and 83.3%, respectively. Rubella and measles antibody seroprevalence was 73.3% and 95.9%, respectively. In the 15-19 years age group, 48.2% [95% confidence interval (CI) 42.4-54.1] were susceptible to either PV1 or PV3, and 40.3% (95% CI 33.0-47.5) to rubella virus. Based on rubella antibody seroprevalence, we estimate that >600 infants are born with CRS in Cambodia annually. Significant numbers of Cambodian women are still susceptible to polio and rubella, especially those aged 15-19 years, emphasizing the need to include adults in VPD surveillance and a potential role for vaccination strategies targeted at adults.

  16. Congenital central hypoventilation syndrome: a bedside-to-bench success story for advancing early diagnosis and treatment and improved survival and quality of life.

    PubMed

    Weese-Mayer, Debra E; Rand, Casey M; Zhou, Amy; Carroll, Michael S; Hunt, Carl E

    2017-01-01

    The "bedside-to-bench" Congenital Central Hypoventilation Syndrome (CCHS) research journey has led to increased phenotypic-genotypic knowledge regarding autonomic nervous system (ANS) regulation, and improved clinical outcomes. CCHS is a neurocristopathy characterized by hypoventilation and ANS dysregulation. Initially described in 1970, timely diagnosis and treatment remained problematic until the first large cohort report (1992), delineating clinical presentation and treatment options. A central role of ANS dysregulation (2001) emerged, precipitating evaluation of genes critical to ANS development, and subsequent 2003 identification of Paired-Like Homeobox 2B (PHOX2B) as the disease-defining gene for CCHS. This breakthrough engendered clinical genetic testing, making diagnosis exact and early tracheostomy/artificial ventilation feasible. PHOX2B genotype-CCHS phenotype relationships were elucidated, informing early recognition and timely treatment for phenotypic manifestations including Hirschsprung disease, prolonged sinus pauses, and neural crest tumors. Simultaneously, cellular models of CCHS-causing PHOX2B mutations were developed to delineate molecular mechanisms. In addition to new insights regarding genetics and neurobiology of autonomic control overall, new knowledge gained has enabled physicians to anticipate and delineate the full clinical CCHS phenotype and initiate timely effective management. In summary, from an initial guarantee of early mortality or severe neurologic morbidity in survivors, CCHS children can now be diagnosed early and managed effectively, achieving dramatically improved quality of life as adults.

  17. Microduplication of 7q36.3 encompassing the SHH long-range regulator (ZRS) in a patient with triphalangeal thumb-polysyndactyly syndrome and congenital heart disease

    PubMed Central

    Liu, Zhenghua; Yin, Ni; Gong, Lianghui; Tan, Zhiping; Yin, Bangliang; Yang, Yifeng; Luo, Cheng

    2017-01-01

    Triphalangeal thumb-polysyndactyly syndrome (TPT-PS) is an autosomal dominant disorder with complete penetrance and a variable expression consisting of opposable triphalangeal thumbs, duplication of the distal thumb phalanx, pre-axial polydactyly and duplication of the big toes (hallux). The causative gene of TPT-PS has been mapped to 7q36.3. Sonic hedgehog (SHH) expressed in the zone of polarizing activity (ZPA) has an important role in defining the anterior-posterior axis and numbers of digits in limb bud development. Point mutation or duplication in the ZPA regulatory sequence (ZRS), a cis-regulator of SHH, will lead to TPT-PS. The present study describes a 1-year-old female congenital heart disease (CHD) patient with TPT-PS phenotype. In this Han Chinese family with TPT-PS, high resolution single nucleotide polymorphism array technology identified a novel 0.29 Mb duplication comprising ZRS at 7q36.3 where LMBR1 is located. Additionally, a novel deletion of 22q11.21 was detected in the proband with Tetralogy of Fallot. However, the parents and other relatives of the patient did not harbor this genomic lesion nor CHD. The findings supported the hypothesis that an increased copy number variation of ZRS is the genetic mechanism underlying the phenotype of TPT-PS, and corroborated that 22q11.21 deletion is a genetic cause of CHD. PMID:28035386

  18. Prenatal diagnosis of Wolf-Hirschhorn syndrome (4p-) in association with congenital hypospadias and foot deformity

    PubMed Central

    Aslan, Halil; Karaca, Nilay; Basaran, Seher; Ermis, Hayri; Ceylan, Yavuz

    2003-01-01

    Background Wolf-Hirschhorn syndrome is caused by distal deletion of the short arm of chromosome 4 (4p-). We report a case in which intrauterine growth restriction, hypospadias and foot deformity were detected by prenatal ultrasound examination at 29 weeks of gestation. Case Presentation A 31-year-old gravida 2 partus 1 woman was referred at 29 weeks' gestation with suspicion of intrauterine growth restriction. Sonographic examination revealed deformity of the right lower limb and undescended testes with an irregular distal penis. A cordocentesis was performed and chromosome analysis revealed a 46,XY,del(4)(p14) karyotype. Conclusion The prenatal detection of intrauterine growth restriction, hypospadias and foot deformity should lead doctors to suspect the presence of Wolf-Hirschhorn syndrome. PMID:12546710

  19. Constellation of congenital abnormalities in an infant: A new syndrome or tissue-specific mosaicism for trisomy 18?

    SciTech Connect

    Shashi, V.; Golden, W.L.; von Kap-Herr, C.

    1996-03-01

    A newborn infant born to consanguineous (first cousin) parents was noted to have complex cogenital heart defect and minor anomalies suggestive of trisomy 18. Blood lymphocyte and skin fibroblast karyotypes were normal. He died in the neonatal period of postoperative complications. On interphase fluorescence in-situ hybridization (FISH) using autopsy specimens, a significant number of cells in the liver (17%) were trisomic for chromosome 18, compared to normal control liver tissue. However, interphase FISH analyses of blood lymphocytes, skin fibroblasts, and kidney tissue were normal. It is our opinion that this apparent mosaicism for trisomy 18 in the patient`s liver maymore » be spurious, though it brings into focus the issue of possible tissue/organ-specific mosaicism. The anomalies in this infant do not resemble a previously described malformation syndrome. Parental consanguinity raises the possibility that this represents a new autosomal recessive malformation syndrome. 15 refs., 3 figs., 3 tabs.« less

  20. Germline mutations in ABL1 cause an autosomal dominant syndrome characterized by congenital heart defects and skeletal malformations

    PubMed Central

    Wang, Xia; Charng, Wu-Lin; Chen, Chun-An; Rosenfeld, Jill A.; Shamsi, Aisha Al; Al-Gazali, Lihadh; McGuire, Marianne; Mew, Nicholas Ah; Arnold, Georgianne L.; Qu, Chunjing; Ding, Yan; Muzny, Donna M.; Gibbs, Richard A.; Eng, Christine M.; Walkiewicz, Magdalena; Xia, Fan; Plon, Sharon E.; Lupski, James R.; Schaaf, Christian P.; Yang, Yaping

    2017-01-01

    ABL1 is a proto-oncogene well known as part of the fusion gene BCR-ABL in the Philadelphia chromosome of leukemia cancer cells1. Inherited germline ABL1 changes have not been associated with genetic disorders. Here we report ABL1 germline variants co-segregating with an autosomal dominant disorder characterized by congenital heart disease, skeletal abnormalities, and failure to thrive. The variant c.734A>G (p.Tyr245Cys) was found as de novo or co-segregating with disease in five individuals (families 1-3). Additionally, a de novo c.1066G>A (p.Ala356Thr) variant was identified in the sixth individual (family 4). We overexpressed the mutant constructs in HEK 293T cells and observed increased tyrosine phosphorylation, suggesting increased ABL1 kinase activities associated with both p.Tyr245Cys and p.Ala356Thr substitutions. Our clinical and laboratory findings, together with previously reported teratogenic effects of selective BCR-ABL inhibitors in humans2-5 and developmental defects in Abl1 knock-out mice6,7, suggest ABL1 plays an important role during organismal development. PMID:28288113

  1. PBIS Is (Not) Behavior Analysis: a Response to Horner and Sugai (2015).

    PubMed

    Loukus, Amy K

    2015-05-01

    I comment on Horner's and Sugai's article regarding the lessons learned from implementing Positive Behavioral Interventions and Support (PBIS)-that is, the things to consider when attempting to extend other works in behavior analysis to the likes of mainstream society. In adopting a critical eye toward the PBIS model, I comment first on the need for dissemination of behavioral principles to a public audience, and then outline the suggestions made by the authors for enhancing acceptance across disciplines. I clarify the definition of PBIS presented by the authors, and summarize the benefits and drawbacks associated with the conceptual argument surrounding the contention that PBIS is a behavior analytic approach to system-wide change, and argue instead for the distinction of elements in the PBIS model and their respective empirical effectiveness. I refer to other works in behavior analysis that are relevant to the current discussion and offer additional considerations for behavior analysts interested in forging ahead with endeavors that aim increase dissemination, particularly those that incorporate a culmination of alternative professional practices.

  2. Heterochromia

    PubMed Central

    Rehman, Habib Ur

    2008-01-01

    Abstract: A patient was noted to have 2 different eye colours and miosis in her left eye. She ultimately received a diagnosis of congenital Horner syndrome. Determinants of eye colour and possible clinical significance are discussed. PMID:18725617

  3. Heterochromia.

    PubMed

    Ur Rehman, Habib

    2008-08-26

    A patient was noted to have 2 different eye colours and miosis in her left eye. She ultimately received a diagnosis of congenital Horner syndrome. Determinants of eye colour and possible clinical significance are discussed.

  4. De Novo Loss-of-Function Mutations in USP9X Cause a Female-Specific Recognizable Syndrome with Developmental Delay and Congenital Malformations

    PubMed Central

    Reijnders, Margot R.F.; Zachariadis, Vasilios; Latour, Brooke; Jolly, Lachlan; Mancini, Grazia M.; Pfundt, Rolph; Wu, Ka Man; van Ravenswaaij-Arts, Conny M.A.; Veenstra-Knol, Hermine E.; Anderlid, Britt-Marie M.; Wood, Stephen A.; Cheung, Sau Wai; Barnicoat, Angela; Probst, Frank; Magoulas, Pilar; Brooks, Alice S.; Malmgren, Helena; Harila-Saari, Arja; Marcelis, Carlo M.; Vreeburg, Maaike; Hobson, Emma; Sutton, V. Reid; Stark, Zornitza; Vogt, Julie; Cooper, Nicola; Lim, Jiin Ying; Price, Sue; Lai, Angeline Hwei Meeng; Domingo, Deepti; Reversade, Bruno; Gecz, Jozef; Gilissen, Christian; Brunner, Han G.; Kini, Usha; Roepman, Ronald; Nordgren, Ann; Kleefstra, Tjitske

    2016-01-01

    Mutations in more than a hundred genes have been reported to cause X-linked recessive intellectual disability (ID) mainly in males. In contrast, the number of identified X-linked genes in which de novo mutations specifically cause ID in females is limited. Here, we report 17 females with de novo loss-of-function mutations in USP9X, encoding a highly conserved deubiquitinating enzyme. The females in our study have a specific phenotype that includes ID/developmental delay (DD), characteristic facial features, short stature, and distinct congenital malformations comprising choanal atresia, anal abnormalities, post-axial polydactyly, heart defects, hypomastia, cleft palate/bifid uvula, progressive scoliosis, and structural brain abnormalities. Four females from our cohort were identified by targeted genetic testing because their phenotype was suggestive for USP9X mutations. In several females, pigment changes along Blaschko lines and body asymmetry were observed, which is probably related to differential (escape from) X-inactivation between tissues. Expression studies on both mRNA and protein level in affected-female-derived fibroblasts showed significant reduction of USP9X level, confirming the loss-of-function effect of the identified mutations. Given that some features of affected females are also reported in known ciliopathy syndromes, we examined the role of USP9X in the primary cilium and found that endogenous USP9X localizes along the length of the ciliary axoneme, indicating that its loss of function could indeed disrupt cilium-regulated processes. Absence of dysregulated ciliary parameters in affected female-derived fibroblasts, however, points toward spatiotemporal specificity of ciliary USP9X (dys-)function. PMID:26833328

  5. Fatal Cardiac Arrhythmia and Long-QT Syndrome in a New Form of Congenital Generalized Lipodystrophy with Muscle Rippling (CGL4) Due to PTRF-CAVIN Mutations

    PubMed Central

    McCann, Liza J.; Seelow, Dominik; Varon, Raymonda; Barresi, Rita; Schulze, Anne; Lucke, Barbara; Lützkendorf, Susanne; Karbasiyan, Mohsen; Bachmann, Sebastian; Spuler, Simone; Schuelke, Markus

    2010-01-01

    We investigated eight families with a novel subtype of congenital generalized lipodystrophy (CGL4) of whom five members had died from sudden cardiac death during their teenage years. ECG studies revealed features of long-QT syndrome, bradycardia, as well as supraventricular and ventricular tachycardias. Further symptoms comprised myopathy with muscle rippling, skeletal as well as smooth-muscle hypertrophy, leading to impaired gastrointestinal motility and hypertrophic pyloric stenosis in some children. Additionally, we found impaired bone formation with osteopenia, osteoporosis, and atlanto-axial instability. Homozygosity mapping located the gene within 2 Mbp on chromosome 17. Prioritization of 74 candidate genes with GeneDistiller for high expression in muscle and adipocytes suggested PTRF-CAVIN (Polymerase I and transcript release factor/Cavin) as the most probable candidate leading to the detection of homozygous mutations (c.160delG, c.362dupT). PTRF-CAVIN is essential for caveolae biogenesis. These cholesterol-rich plasmalemmal vesicles are involved in signal-transduction and vesicular trafficking and reside primarily on adipocytes, myocytes, and osteoblasts. Absence of PTRF-CAVIN did not influence abundance of its binding partner caveolin-1 and caveolin-3. In patient fibroblasts, however, caveolin-1 failed to localize toward the cell surface and electron microscopy revealed reduction of caveolae to less than 3%. Transfection of full-length PTRF-CAVIN reestablished the presence of caveolae. The loss of caveolae was confirmed by Atomic Force Microscopy (AFM) in combination with fluorescent imaging. PTRF-CAVIN deficiency thus presents the phenotypic spectrum caused by a quintessential lack of functional caveolae. PMID:20300641

  6. Adverse cardiac events in children with Williams syndrome undergoing cardiovascular surgery: An analysis of the Society of Thoracic Surgeons Congenital Heart Surgery Database.

    PubMed

    Hornik, Christoph P; Collins, Ronnie Thomas; Jaquiss, Robert D B; Jacobs, Jeffrey P; Jacobs, Marshall L; Pasquali, Sara K; Wallace, Amelia S; Hill, Kevin D

    2015-06-01

    Patients with Williams syndrome (WS) undergoing cardiac surgery are at risk for major adverse cardiac events (MACE). Prevalence and risk factors for such events have not been well described. We sought to define frequency and risk of MACE in patients with WS using a multicenter clinical registry. We identified cardiac operations performed in patients with WS using the Society of Thoracic Surgeons Congenital Heart Surgery Database (2000-2012). Operations were divided into 4 groups: isolated supravalvular aortic stenosis, complex left ventricular outflow tract (LVOT), isolated right ventricular outflow tract (RVOT), and combined LVOT/RVOT procedures. The proportion of patients with MACE (in-hospital mortality, cardiac arrest, or postoperative mechanical circulatory support) was described and the association with preoperative factors was examined. Of 447 index operations (87 centers), median (interquartile range) age and weight at surgery were 2.4 years (0.6-7.4 years) and 10.6 kg (6.5-21.5 kg), respectively. Mortality occurred in 20 patients (5%). MACE occurred in 41 patients (9%), most commonly after combined LVOT/RVOT (18 out of 87; 21%) and complex LVOT (12 out of 131; 9%) procedures, but not after isolated RVOT procedures. Odds of MACE decreased with age (odds ratio [OR], 0.99; 95% confidence interval [CI], 0.98-0.99), weight (OR, 0.97; 95% CI, 0.93-0.99), but increased in the presence of any preoperative risk factor (OR, 2.08; 95% CI, 1.06-4.00), and in procedures involving coronary artery repair (OR, 5.37; 95% CI, 2.05-14.06). In this multicenter analysis, MACE occurred in 9% of patients with WS undergoing cardiac surgery. Demographic and operative characteristics were associated with risk. Further study is needed to elucidate mechanisms of MACE in this high-risk population. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  7. GENETICS IN ENDOCRINOLOGY: Genetic counseling for congenital hypogonadotropic hypogonadism and Kallmann syndrome: new challenges in the era of oligogenism and next-generation sequencing.

    PubMed

    Maione, Luigi; Dwyer, Andrew A; Francou, Bruno; Guiochon-Mantel, Anne; Binart, Nadine; Bouligand, Jérôme; Young, Jacques

    2018-03-01

    Congenital hypogonadotropic hypogonadism (CHH) and Kallmann syndrome (KS) are rare, related diseases that prevent normal pubertal development and cause infertility in affected men and women. However, the infertility carries a good prognosis as increasing numbers of patients with CHH/KS are now able to have children through medically assisted procreation. These are genetic diseases that can be transmitted to patients' offspring. Importantly, patients and their families should be informed of this risk and given genetic counseling. CHH and KS are phenotypically and genetically heterogeneous diseases in which the risk of transmission largely depends on the gene(s) responsible(s). Inheritance may be classically Mendelian yet more complex; oligogenic modes of transmission have also been described. The prevalence of oligogenicity has risen dramatically since the advent of massively parallel next-generation sequencing (NGS) in which tens, hundreds or thousands of genes are sequenced at the same time. NGS is medically and economically more efficient and more rapid than traditional Sanger sequencing and is increasingly being used in medical practice. Thus, it seems plausible that oligogenic forms of CHH/KS will be increasingly identified making genetic counseling even more complex. In this context, the main challenge will be to differentiate true oligogenism from situations when several rare variants that do not have a clear phenotypic effect are identified by chance. This review aims to summarize the genetics of CHH/KS and to discuss the challenges of oligogenic transmission and also its role in incomplete penetrance and variable expressivity in a perspective of genetic counseling. © 2018 European Society of Endocrinology.

  8. Global N-linked Glycosylation is Not Significantly Impaired in Myoblasts in Congenital Myasthenic Syndromes Caused by Defective Glutamine-Fructose-6-Phosphate Transaminase 1 (GFPT1)

    PubMed Central

    Chen, Qiushi; Müller, Juliane S.; Pang, Poh-Choo; Laval, Steve H.; Haslam, Stuart M.; Lochmüller, Hanns; Dell, Anne

    2015-01-01

    Glutamine-fructose-6-phosphate transaminase 1 (GFPT1) is the first enzyme of the hexosamine biosynthetic pathway. It transfers an amino group from glutamine to fructose-6-phosphate to yield glucosamine-6-phosphate, thus providing the precursor for uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) synthesis. UDP-GlcNAc is an essential substrate for all mammalian glycosylation biosynthetic pathways and N-glycan branching is especially sensitive to alterations in the concentration of this sugar nucleotide. It has been reported that GFPT1 mutations lead to a distinct sub-class of congenital myasthenic syndromes (CMS) termed “limb-girdle CMS with tubular aggregates”. CMS are hereditary neuromuscular transmission disorders in which neuromuscular junctions are impaired. To investigate whether alterations in protein glycosylation at the neuromuscular junction might be involved in this impairment, we have employed mass spectrometric strategies to study the N-glycomes of myoblasts and myotubes derived from two healthy controls, three GFPT1 patients, and four patients with other muscular diseases, namely CMS caused by mutations in DOK7, myopathy caused by mutations in MTND5, limb girdle muscular dystrophy type 2A (LGMD2A), and Pompe disease. A comparison of the relative abundances of bi-, tri-, and tetra-antennary N-glycans in each of the cell preparations revealed that all samples exhibited broadly similar levels of branching. Moreover, although some differences were observed in the relative abundances of some of the N-glycan constituents, these variations were modest and were not confined to the GFPT1 samples. Therefore, GFPT1 mutations in CMS patients do not appear to compromise global N-glycosylation in muscle cells. PMID:26501342

  9. Global N-linked Glycosylation is Not Significantly Impaired in Myoblasts in Congenital Myasthenic Syndromes Caused by Defective Glutamine-Fructose-6-Phosphate Transaminase 1 (GFPT1).

    PubMed

    Chen, Qiushi; Müller, Juliane S; Pang, Poh-Choo; Laval, Steve H; Haslam, Stuart M; Lochmüller, Hanns; Dell, Anne

    2015-10-16

    Glutamine-fructose-6-phosphate transaminase 1 (GFPT1) is the first enzyme of the hexosamine biosynthetic pathway. It transfers an amino group from glutamine to fructose-6-phosphate to yield glucosamine-6-phosphate, thus providing the precursor for uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) synthesis. UDP-GlcNAc is an essential substrate for all mammalian glycosylation biosynthetic pathways and N-glycan branching is especially sensitive to alterations in the concentration of this sugar nucleotide. It has been reported that GFPT1 mutations lead to a distinct sub-class of congenital myasthenic syndromes (CMS) termed "limb-girdle CMS with tubular aggregates". CMS are hereditary neuromuscular transmission disorders in which neuromuscular junctions are impaired. To investigate whether alterations in protein glycosylation at the neuromuscular junction might be involved in this impairment, we have employed mass spectrometric strategies to study the N-glycomes of myoblasts and myotubes derived from two healthy controls, three GFPT1 patients, and four patients with other muscular diseases, namely CMS caused by mutations in DOK7, myopathy caused by mutations in MTND5, limb girdle muscular dystrophy type 2A (LGMD2A), and Pompe disease. A comparison of the relative abundances of bi-, tri-, and tetra-antennary N-glycans in each of the cell preparations revealed that all samples exhibited broadly similar levels of branching. Moreover, although some differences were observed in the relative abundances of some of the N-glycan constituents, these variations were modest and were not confined to the GFPT1 samples. Therefore, GFPT1 mutations in CMS patients do not appear to compromise global N-glycosylation in muscle cells.

  10. A zebrafish model of lethal congenital contracture syndrome 1 reveals Gle1 function in spinal neural precursor survival and motor axon arborization.

    PubMed

    Jao, Li-En; Appel, Bruce; Wente, Susan R

    2012-04-01

    In humans, GLE1 is mutated in lethal congenital contracture syndrome 1 (LCCS1) leading to prenatal death of all affected fetuses. Although the molecular roles of Gle1 in nuclear mRNA export and translation have been documented, no animal models for this disease have been reported. To elucidate the function of Gle1 in vertebrate development, we used the zebrafish (Danio rerio) model system. gle1 mRNA is maternally deposited and widely expressed. Altering Gle1 using an insertional mutant or antisense morpholinos results in multiple defects, including immobility, small eyes, diminished pharyngeal arches, curved body axis, edema, underdeveloped intestine and cell death in the central nervous system. These phenotypes parallel those observed in LCCS1 human fetuses. Gle1 depletion also results in reduction of motoneurons and aberrant arborization of motor axons. Unexpectedly, the motoneuron deficiency results from apoptosis of neural precursors, not of differentiated motoneurons. Mosaic analyses further indicate that Gle1 activity is required extrinsically in the environment for normal motor axon arborization. Importantly, the zebrafish phenotypes caused by Gle1 deficiency are only rescued by expressing wild-type human GLE1 and not by the disease-linked Fin(Major) mutant form of GLE1. Together, our studies provide the first functional characterization of Gle1 in vertebrate development and reveal its essential role in actively dividing cells. We propose that defective GLE1 function in human LCCS1 results in both neurogenic and non-neurogenic defects linked to the apoptosis of proliferative organ precursors.

  11. Risk of Recurrent Cardiac Events after Onset of Menopause in Women with Congenital Long-QT Syndrome Types 1 and 2

    PubMed Central

    Buber, Jonathan; Mathew, Jehu; Moss, Arthur J.; Hall, W. Jackson; Barsheshet, Alon; McNitt, Scott; Robinson, Jennifer L.; Zareba, Wojciech; Ackerman, Michael J.; Kaufman, Elizabeth S.; Luria, David; Eldar, Michael; Towbin, Jeffrey A.; Vincent, Michael; Goldenberg, Ilan

    2011-01-01

    Background Women with congenital long-QT syndrome (LQTS) experience increased risk for cardiac events after the onset of adolescence, that is more pronounced among carriers of the LQT2 genotype. We hypothesized that the hormonal changes associated with menopause may affect clinical risk in this population. Methods and Results We used a repeated events analysis to evaluate the risk for recurrent syncope during the menopause-transition and post-menopausal periods (5-years before and after the age at onset of menopause, respectively) among 282 LQT1 (n=151) and LQT2 (n=131) women enrolled in the LQTS Registry. Multivariate analysis showed that the risk for recurrent syncope (n=150) among LQT2 women was significantly increased during both menopause-transition (HR = 3.38 [p = 0.005]) and the post-menopausal period (HR = 8.10 [p < 0.001]) as compared with the reproductive period. The risk increase was evident among women who did or did not receive estrogen therapy. In contrast, among LQT1 women the onset of menopause was associated with a reduction in the risk for recurrent syncope (HR = 0.19 [p = 0.05]; p-value for genotype-by-menopause interaction = 0.02). Only 22 women (8%) experienced aborted cardiac arrest (ACA) or sudden cardiac death (SCD) during follow-up. The frequency of ACA/SCD showed a similar genotype-specific association with the onset of menopause. Conclusions The onset of menopause is associated with a significant increase in the risk of cardiac events (dominated by recurrent episodes of syncope) in LQT2 women, suggesting that careful follow-up and continued long-term therapy are warranted in this population. PMID:21632495

  12. Serological evidence of acute rubella infection among under-fives in Mwanza: a threat to increasing rates of congenital rubella syndrome in Tanzania.

    PubMed

    Mirambo, Mariam M; Aboud, Said; Mushi, Martha F; Seugendo, Mwanaisha; Majigo, Mtebe; Groß, Uwe; Mshana, Stephen E

    2016-05-25

    Control of rubella infection is essential for preventing congenital rubella syndrome (CRS) and one of the important steps is to define a target population for vaccination. Therefore this study was done to determine serological evidence of acute rubella infection among under-fives in order to anticipate the magnitude of rubella virus transmission in Tanzania. A cross-sectional study involving children aged between 1 and 59 months was conducted between September and October 2014 before national rubella vaccination campaigns commenced. Rubella IgM antibodies were detected using commercial indirect enzyme-linked immunosorbent assay (ELISA). Data were analyzed using STATA version 11. A total of230 under-fives were enrolled, their median age was 14 (Interquartile range (IQR) 7-26) months. The overall seroprevalence of rubella IgM antibodies was 10.9 % (25/230) with two confirmed cases of CRS. Two-sample Wilcoxon rank-sum test showed that the median age of rubella IgM seropositive children was significantly higher than that of IgM seronegative children (39 IQR: 18-51months vs. 14 IQR: 7-24 months, P < 0.001). On multivariate logistic regression analysis increase in age (OR: 1.07, 95 % CI; 1.03-1.1, P < 0.001) and residing in rural areas (OR: 8.07, 95 % CI; 1.43-45.6, P = 0.018) were independently found to predict acute rubella infection among under-fives. Our findings indicate that rubella virus is prevalent in our setting posing a risk of transmitting to childbearing aged women hence increasing the risk of CRS. Increasing prevalence of acute infection with age in under-fives indicates the protective role of maternal antibodies among infants. The sustained vaccination programme of under-fives as effective measure to control CRS should be emphasized in developing countries.

  13. Mental Health and Disorders of Sex Development/Intersex Conditions in Iranian Culture: Congenital Adrenal Hyperplasia, 5-α Reductase Deficiency-Type 2, and Complete Androgen Insensitivity Syndrome.

    PubMed

    Khorashad, Behzad S; Aghili, Zahra; Kreukels, Baudewijntje P C; Reid, Alistair G; Roshan, Ghasem M; Hiradfar, Mehran; Talaei, Ali; Cohen Kettenis, Peggy T

    2018-05-01

    Sixty-one patients (22 patients with congenital adrenal hyperplasia [CAH] with a mean age of 14.86 years [range, 5-23], 20 patients with 5-α reductase deficiency type 2 [5α-RD-2] with a mean age of 19.5 years [range, 5-29], and 19 patients with complete androgen insensitivity syndrome [CAIS] with a mean age of 18.26 years [range, 5-28]) were evaluated using the Kiddie Schedule for Affective Disorders and Schizophrenia, the Structured Clinical Interview for DSM-IV Axis I, Axis II, and the Global Assessment Functioning Scale. All participants were female-assigned at birth. Ten patients (16.4%) transitioned to the male gender. Overall, 68% of patients had one or more lifetime Axis I disorders, including 63.6% of the CAH participants, 90% of 5α-RD-2 participants, and 52.6% of the CAIS participants. The most commonly observed were affective disorders (27.9%), gender identity disorder (27.9%), and anxiety (16.4%). Our study demonstrates that mental health of Iranian patients with DSD is at risk. This might be due to the fact that patients with DSD conditions are mostly treated medically and their mental health is often superficially addressed in developing countries such as Iran, at least in the past. We argue that it is important to pay attention to the mental health issues of patients with DSD and focus on specific issues, which may vary cross-culturally.

  14. Ocular pathology in congenital heart disease.

    PubMed

    Mansour, A M; Bitar, F F; Traboulsi, E I; Kassak, K M; Obeid, M Y; Megarbane, A; Salti, H I

    2005-01-01

    To describe the ocular findings in subjects with congenital heart disease (CHD). In a prospective study, the same observer examined 240 consecutive patients with CHD admitted to the medical centre. Two independent geneticists performed identification of syndromes. The commonest anatomic cardiac anomalies were ventricular or atrial septal defects (62), tetralogy of Fallot (39), pulmonary stenosis (25), and transposition of the great arteries (24). The heart lesions were divided physiologically into volume overload (90), cyanotic (87), and obstructive (63). In all, 105 syndromic subjects included the velocardiofacial syndrome (18), Down's syndrome (17), CHARGE association (6), DiGeorge syndrome (5), Williams syndrome (3), Edwards syndrome (3), Noonan syndrome (3), VACTERL association (2), and Patau syndrome (trisomy 13) (2). The paediatric team recognized 51 patients as syndromic. Two independent geneticists recognized additional 54 patients as syndromic. Positive eye findings were present in 55% (132) and included retinal vascular tortuosity (46), optic disc hypoplasia (30), trichomegaly (15), congenital ptosis (12), strabismus (11), retinal haemorrhages (8), prominent eyes (7), and congenital cataract (6). There was a strong correlation between the retinal vascular tortuosity and both a low haematocrit (P=0.000) and a low arterial oxygen saturation (P=0.002). Patients with CHD are at a high risk for ocular pathology and need screening for various ocular abnormalities.

  15. Congenital amusias.

    PubMed

    Tillmann, B; Albouy, P; Caclin, A

    2015-01-01

    In contrast to the sophisticated music processing reported in the general population, individuals with congenital amusia show deficits in music perception and production. Congenital amusia occurs without brain damage, sensory or cognitive deficits, and has been suggested as a lifelong deficit with genetic origin. Even though recognized for a long time, this disorder has been systematically studied only relatively recently for its behavioral and neural correlates. The currently most investigated hypothesis about the underlying deficits concerns the pitch dimension, notably with impaired pitch discrimination and memory. Anatomic and functional investigations of pitch processing revealed that the amusic brain presents abnormalities in the auditory and inferior frontal cortices, associated with decreased connectivity between these structures. The deficit also impairs processing of pitch in speech material and processing of the time dimension in music for some of the amusic individuals, but does not seem to affect spatial processing. Some studies suggest at least partial dissociation in the disorder between perception and production. Recent studies revealed spared implicit pitch perception in congenital amusia, supporting the power of implicit cognition in the music domain. Current challenges consist in defining different subtypes of congenital amusia as well as developing rehabilitation programs for this "musical handicap." © 2015 Elsevier B.V. All rights reserved.

  16. Congenital Defects.

    ERIC Educational Resources Information Center

    Goldman, Allen S.; And Others

    There are two general categories (not necessarily mutually exclusive) of congenital defects: (1) abnormalities that have an hereditary basis, such as single and multiple genes, or chromosomal abberration; and (2) abnormalities that are caused by nonhereditary factors, such as malnutrition, maternal disease, radiation, infections, drugs, or…

  17. Surgical management of aortic root disease in Marfan syndrome and other congenital disorders associated with aortic root aneurysms.

    PubMed

    Treasure, Tom; Takkenberg, J J M; Pepper, John

    2014-10-01

    Elective root replacement in Marfan syndrome has improved life expectancy in affected patients. Three forms of surgery are now available: total root replacement (TRR) with a valved conduit, valve sparing root replacement (VSRR) and personalised external aortic root support (PEARS) with a macroporous mesh sleeve. TRR can be performed irrespective of aortic dimensions and a mechanical replacement valve is a secure and near certain means of correcting aortic valve regurgitation but has thromboembolic and bleeding risks. VSRR offers freedom from anticoagulation and attendant risks of bleeding but reoperation for aortic regurgitation runs at 1.3% per annum. A prospective multi-institutional study has found this to be an underestimate of the true rate of valve-related adverse events. PEARS conserves the aortic root anatomy and optimises the chance of maintaining valve function but average follow-up is under 5 years and so the long-term results are yet to be determined. Patients are on average in their 30s and so the cumulative lifetime need for reoperation, and of any valve-related complications, are consequently substantial. With lowering surgical risk of prophylactic root replacement, the threshold for intervention has reduced progressively over 30 years to 4.5 cm and so an increasing number of patients who are not destined to have a dissection are now having root replacement. In evaluation of these three forms of surgery, the number needed to treat to prevent dissection and the balance of net benefit and harm in future patients must be considered.

  18. Congenital aural atresia.

    PubMed

    Abdel-Aziz, Mosaad

    2013-07-01

    Congenital aural atresia is a spectrum of ear deformities present at birth that involves some degree of failure of the development of the external auditory canal. This malformation may be associated with other congenital anomalies; it occurs as a result of abnormal development of the first and second branchial arches and the first branchial cleft and most often occurs sporadically, although the disease may be manifested in different syndromes. Congenital aural atresia is considered one of the most difficult and challenging surgeries for the otologic surgeon. The goals of atresia surgery are to restore functional hearing, preferably without the requirement of a hearing aid, and to reconstruct a patent, infection-free external auditory canal. The repair is usually done at the age of 6 years, so children with bilateral atresia may need hearing amplification in the first few weeks of life until the age at surgery. To optimize the surgical outcome, careful audiological and radiological evaluation of the patient should be performed preoperatively. Also, postoperative frequent packing and regular follow-up are mandatory to avoid restenosis and infection of the newly created canal. With careful intraoperative dissection and regular follow-up, complications of surgery can be avoided.

  19. Oculoauriculovertebral dysplasia (Goldenhar's syndrome).

    PubMed

    Nkrumah, F K

    1971-03-01

    A case of Goldenhar's Syndrome or Oculoauriculovertebral dysplasia in a Ghanaian infant is described. Significant were the additional findings of congenital esophageal atresia and arthrogryposis which have so far not been reported in association with the syndrome.

  20. Surgical management of aortic root disease in Marfan syndrome and other congenital disorders associated with aortic root aneurysms

    PubMed Central

    Treasure, Tom; Takkenberg, J J M; Pepper, John

    2014-01-01

    Elective root replacement in Marfan syndrome has improved life expectancy in affected patients. Three forms of surgery are now available: total root replacement (TRR) with a valved conduit, valve sparing root replacement (VSRR) and personalised external aortic root support (PEARS) with a macroporous mesh sleeve. TRR can be performed irrespective of aortic dimensions and a mechanical replacement valve is a secure and near certain means of correcting aortic valve regurgitation but has thromboembolic and bleeding risks. VSRR offers freedom from anticoagulation and attendant risks of bleeding but reoperation for aortic regurgitation runs at 1.3% per annum. A prospective multi-institutional study has found this to be an underestimate of the true rate of valve-related adverse events. PEARS conserves the aortic root anatomy and optimises the chance of maintaining valve function but average follow-up is under 5 years and so the long-term results are yet to be determined. Patients are on average in their 30s and so the cumulative lifetime need for reoperation, and of any valve-related complications, are consequently substantial. With lowering surgical risk of prophylactic root replacement, the threshold for intervention has reduced progressively over 30 years to 4.5 cm and so an increasing number of patients who are not destined to have a dissection are now having root replacement. In evaluation of these three forms of surgery, the number needed to treat to prevent dissection and the balance of net benefit and harm in future patients must be considered. PMID:24986892

  1. Republished review: Surgical management of aortic root disease in Marfan syndrome and other congenital disorders associated with aortic root aneurysms

    PubMed Central

    Treasure, Tom; Takkenberg, J J M; Pepper, John

    2016-01-01

    Elective root replacement in Marfan syndrome has improved life expectancy in affected patients. Three forms of surgery are now available: total root replacement (TRR) with a valved conduit, valve sparing root replacement (VSRR) and personalised external aortic root support (PEARS) with a macroporous mesh sleeve. TRR can be performed irrespective of aortic dimensions and a mechanical replacement valve is a secure and near certain means of correcting aortic valve regurgitation but has thromboembolic and bleeding risks. VSRR offers freedom from anticoagulation and attendant risks of bleeding but reoperation for aortic regurgitation runs at 1.3% per annum. A prospective multi-institutional study has found this to be an underestimate of the true rate of valve-related adverse events. PEARS conserves the aortic root anatomy and optimises the chance of maintaining valve function but average follow-up is under 5 years and so the long-term results are yet to be determined. Patients are on average in their 30s and so the cumulative lifetime need for reoperation, and of any valve-related complications, are consequently substantial. With lowering surgical risk of prophylactic root replacement, the threshold for intervention has reduced progressively over 30 years to 4.5 cm and so an increasing number of patients who are not destined to have a dissection are now having root replacement. In evaluation of these three forms of surgery, the number needed to treat to prevent dissection and the balance of net benefit and harm in future patients must be considered. PMID:26811510

  2. Republished review: Surgical management of aortic root disease in Marfan syndrome and other congenital disorders associated with aortic root aneurysms.

    PubMed

    Treasure, Tom; Takkenberg, J J M; Pepper, John

    2016-02-01

    Elective root replacement in Marfan syndrome has improved life expectancy in affected patients. Three forms of surgery are now available: total root replacement (TRR) with a valved conduit, valve sparing root replacement (VSRR) and personalised external aortic root support (PEARS) with a macroporous mesh sleeve. TRR can be performed irrespective of aortic dimensions and a mechanical replacement valve is a secure and near certain means of correcting aortic valve regurgitation but has thromboembolic and bleeding risks. VSRR offers freedom from anticoagulation and attendant risks of bleeding but reoperation for aortic regurgitation runs at 1.3% per annum. A prospective multi-institutional study has found this to be an underestimate of the true rate of valve-related adverse events. PEARS conserves the aortic root anatomy and optimises the chance of maintaining valve function but average follow-up is under 5 years and so the long-term results are yet to be determined. Patients are on average in their 30s and so the cumulative lifetime need for reoperation, and of any valve-related complications, are consequently substantial. With lowering surgical risk of prophylactic root replacement, the threshold for intervention has reduced progressively over 30 years to 4.5 cm and so an increasing number of patients who are not destined to have a dissection are now having root replacement. In evaluation of these three forms of surgery, the number needed to treat to prevent dissection and the balance of net benefit and harm in future patients must be considered. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  3. Congenital Hydrocephalus.

    PubMed

    Estey, Chelsie M

    2016-03-01

    There are several types of hydrocephalus, which are characterized based on the location of the cerebrospinal fluid (CSF) accumulation. Physical features of animals with congenital hydrocephalus may include a dome-shaped skull, persistent fontanelle, and bilateral ventrolateral strabismus. Medical therapy involves decreasing the production of CSF. The most common surgical treatment is placement of a ventriculoperitoneal shunt. Postoperative complications may include infection, blockage, drainage abnormalities, and mechanical failure. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. [Congenital aniridia].

    PubMed

    Chiruţa, Daria; Stan, Cristina

    2014-01-01

    Aniridia is a rare congenital, hereditary, bilateral disease which is associated with various systemic and ocular defects. We present the case of a 61 year old patient who was admitted in the hospital of ophthalmology Cluj Napoca, for the symptoms caused by the ocular defects associated with aniridia. In this case, aniridia is autosomal dominant transmitted with incomplete penetrance and it is not accompanied by any systemic defects. The disease also affects three of her sons and two nephews of the patient.

  5. Congenital toxoplasmosis.

    PubMed

    Kieffer, François; Wallon, Martine

    2013-01-01

    Congenital toxoplasmosis results from the transplacental transmission of the parasite Toxoplasma gondii after a maternal infection acquired in pregnancy. Prevalence of congenital infection ranges from 0.1 to 0.3 per 1000 live births. The maternal-fetal transmission rate increases with gestational age at maternal seroconversion, from less than 15% at 13 weeks of gestation to over 70% at 36 weeks. Conversely, the later the maternal infection, the lower the risk of symptomatic congenital infection (infections acquired during the third trimester are most often asymptomatic at birth). Prenatal diagnosis is currently performed by PCR analysis in amniotic fluid. Antenatal management and treatment vary considerably among countries. In some European countries, maternal infections are detected through serological screening allowing a prompt treatment with spiramycin, which is expected to reduce the risk of vertical transmission. If PCR analysis in amniotic fluid is positive or if maternal infection was acquired in the third trimester of pregnancy, a combination with pyrimethamine and sulphonamide is given until delivery. Benefits of antenatal treatments remain controversial. Infected newborns are prescribed pyrimethamine and sulphonamide for 12 months. Despite antenatal and postnatal treatment, chorioretinitis can occur at any age (prevalence>20% at 10 years of age): long-term ophthalmological follow-up remains necessary. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Renal abnormalities in congenital chloride diarrhea.

    PubMed

    Al-Hamad, Nadia M; Al-Eisa, Amal A

    2004-05-01

    Congenital chloride diarrhea (CLD) is a rare autosomal recessive disorder caused by a defect in the chloride/ bicarbonate exchange in the ileum and colon. It is characterized by watery diarrhea, abdominal distension, hypochloremic hypokalemic metabolic alkalosis with high fecal content of chloride (>90 mmol/l). We report 3 patients with CLD associated with various renal abnormalities including chronic renal failure secondary to renal hypoplasia, nephrocalcinosis and congenital nephrotic syndrome.

  7. Review of Bruce Horner, Brice Nordquist, and Susan M. Ryan's "Economies of Writing: Revaluations in Rhetoric and Composition"

    ERIC Educational Resources Information Center

    Johnson, Cynthia

    2017-01-01

    In 2012, Bruce Horner guest edited a special issue of "JAC" focused on "Economies of Writing" ("JAC" n3-4 p453-778 2012). In his introduction, he explains that the included essays originated from an October 2011 symposium at the University of Louisville, held in preparation for the similarly-themed 2012 Thomas R.…

  8. Renal complications in 6p duplication syndrome: microarray-based investigation of the candidate gene(s) for the development of congenital anomalies of the kidney and urinary tract (CAKUT) and focal segmental glomerular sclerosis (FSGS).

    PubMed

    Yoshimura-Furuhata, Megumi; Nishimura-Tadaki, Akira; Amano, Yoshiro; Ehara, Takashi; Hamasaki, Yuko; Muramatsu, Masaki; Shishido, Seiichiro; Aikawa, Atsushi; Hamada, Riku; Ishikura, Kenji; Hataya, Hiroshi; Hidaka, Yoshihiko; Noda, Shunsuke; Koike, Kenichi; Wakui, Keiko; Fukushima, Yoshimitsu; Matsumoto, Naomichi; Awazu, Midori; Miyake, Noriko; Kosho, Tomoki

    2015-03-01

    6p duplication syndrome is a rare chromosomal disorder that frequently manifests renal complications, including proteinuria, hypoplastic kidney, and hydronephrosis. We report a girl with the syndrome, manifesting left hydronephrosis, proteinuria/hematuria, and focal segmental glomerular sclerosis (FSGS) resulting in chronic end-stage renal failure, successfully treated with renal transplantation. Microarray comparative genomic hybridization showed the derivative chromosome 6 to have a 6.4-Mb duplication at 6p25.3-p25.1 with 32 protein-coding genes and a 220-Kb deletion at 6p25.3 with two genes of no possible relation to the renal pathology. Review of the literature shows that variation of renal complications in the syndrome is compatible with congenital anomalies of the kidney and urinary tract (CAKUT). FSGS, observed in another patient with 6p duplication syndrome, could be a non-coincidental complication. FOXC1, located within the 6.4-Mb duplicated region at 6p25.3-p25.2, could be a candidate gene for CAKUT, but its single gene duplication effect would not be sufficient. FSGS would be a primary defect associated with duplicated gene(s) albeit no candidate could be proposed, or might occur in association with CAKUT. © 2015 Wiley Periodicals, Inc.

  9. The genetic landscape of familial congenital hydrocephalus.

    PubMed

    Shaheen, Ranad; Sebai, Mohammed Adeeb; Patel, Nisha; Ewida, Nour; Kurdi, Wesam; Altweijri, Ikhlass; Sogaty, Sameera; Almardawi, Elham; Seidahmed, Mohammed Zain; Alnemri, Abdulrahman; Madirevula, Sateesh; Ibrahim, Niema; Abdulwahab, Firdous; Hashem, Mais; Al-Sheddi, Tarfa; Alomar, Rana; Alobeid, Eman; Sallout, Bahauddin; AlBaqawi, Badi; AlAali, Wajeih; Ajaji, Nouf; Lesmana, Harry; Hopkin, Robert J; Dupuis, Lucie; Mendoza-Londono, Roberto; Al Rukban, Hadeel; Yoon, Grace; Faqeih, Eissa; Alkuraya, Fowzan S

    2017-06-01

    Congenital hydrocephalus is an important birth defect, the genetics of which remains incompletely understood. To date, only 4 genes are known to cause Mendelian diseases in which congenital hydrocephalus is the main or sole clinical feature, 2 X-linked (L1CAM and AP1S2) and 2 autosomal recessive (CCDC88C and MPDZ). In this study, we aimed to determine the genetic etiology of familial congenital hydrocephalus with the assumption that these cases represent Mendelian forms of the disease. Exome sequencing combined, where applicable, with positional mapping. We identified a likely causal mutation in the majority of these families (21 of 27, 78%), spanning 16 genes, none of which is X-linked. Ciliopathies and dystroglycanopathies were the most common etiologies of congenital hydrocephalus in our cohort (19% and 26%, respectively). In 1 family with 4 affected members, we identified a homozygous truncating variant in EML1, which we propose as a novel cause of congenital hydrocephalus in addition to its suggested role in cortical malformation. Similarly, we show that recessive mutations in WDR81, previously linked to cerebellar ataxia, mental retardation, and disequilibrium syndrome 2, cause severe congenital hydrocephalus. Furthermore, we confirm the previously reported candidacy of MPDZ by presenting a phenotypic spectrum of congenital hydrocephalus associated with 5 recessive alleles. Our study highlights the importance of recessive mutations in familial congenital hydrocephalus and expands the locus heterogeneity of this condition. Ann Neurol 2017;81:890-897. © 2017 American Neurological Association.

  10. Congenital toxoplasmosis.

    PubMed

    Jones, Jeffrey; Lopez, Adriana; Wilson, Marianna

    2003-05-15

    Approximately 85 percent of women of childbearing age in the United States are susceptible to acute infection with the protozoan parasite Toxoplasma gondii. Transmission of T. gondii to the fetus can result in serious health problems, including mental retardation, seizures, blindness, and death. Some health problems may not become apparent until the second or third decade of life. An estimated 400 to 4,000 cases of congenital toxoplasmosis occur in the United States each year. Serologic tests are used to diagnose acute T. gondii infection in pregnant women. Because false-positive tests occur frequently, serologic diagnosis must be confirmed at a Toxoplasma reference laboratory before treatment with potentially toxic drugs is considered. In many instances, congenital toxoplasmosis can be prevented by educating pregnant women and other women of childbearing age about not ingesting raw or undercooked meat, using measures to avoid cross-contamination of other foods with raw or undercooked meat, and protecting themselves against exposure to cat litter or contaminated soil.

  11. Congenital Toxoplasmosis

    PubMed Central

    McAuley, James B.

    2014-01-01

    Toxoplasmosis is caused by infection with the parasite Toxoplasma gondii. It is one of the most common parasitic infections in humans and is most typically asymptomatic. However, primary infection in a pregnant woman can cause severe and disabling disease in the developing fetus. Recent developments have included increased understanding of the role of parasite genotype in determining infectivity and disease severity. Risk factors for acquisition of infection have been better defined, and the important role of foodborne transmission has been further delineated. In addition, strategies have emerged to decrease mother-to-child transmission through prompt identification of acutely infected pregnant women followed by appropriate treatment. Refined diagnostic tools, particularly the addition of immunoglobulin G avidity testing, allow for more accurate timing of maternal infection and hence better decision making during pregnancy. Congenitally infected children can be treated, beginning in utero and continuing through the first year of life, to ameliorate the severity of disease. However, despite these many advances in our understanding of congenital toxoplasmosis prevention and treatment, significant areas of study remain: we need better drugs, well defined strategies for screening of pregnant women, improved food safety, and improved diagnostic tests. PMID:25232475

  12. Congenital Toxoplasmosis.

    PubMed

    McAuley, James B

    2014-09-01

    Toxoplasmosis is caused by infection with the parasite Toxoplasma gondii. It is one of the most common parasitic infections in humans and is most typically asymptomatic. However, primary infection in a pregnant woman can cause severe and disabling disease in the developing fetus. Recent developments have included increased understanding of the role of parasite genotype in determining infectivity and disease severity. Risk factors for acquisition of infection have been better defined, and the important role of foodborne transmission has been further delineated. In addition, strategies have emerged to decrease mother-to-child transmission through prompt identification of acutely infected pregnant women followed by appropriate treatment. Refined diagnostic tools, particularly the addition of immunoglobulin G avidity testing, allow for more accurate timing of maternal infection and hence better decision making during pregnancy. Congenitally infected children can be treated, beginning in utero and continuing through the first year of life, to ameliorate the severity of disease. However, despite these many advances in our understanding of congenital toxoplasmosis prevention and treatment, significant areas of study remain: we need better drugs, well defined strategies for screening of pregnant women, improved food safety, and improved diagnostic tests. © The Author 2014. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. Scimitar syndrome.

    PubMed

    Khalilzadeh, Soheila; Hassanzad, Maryam; Khodayari, Amir-Ali

    2009-01-01

    Scimitar syndrome or congenital pulmonary venolobar syndrome is a rare anomaly most commonly consisting of partial pulmonary venous drainage into the hepatic portion of the inferior vena cava, right lung hypoplasia, dextroposition of the heart, and anomalous systemic arterial supply from aorta or one of its branches to the right lung. We report a four-year-old girl with recurrent pneumonia and failure to thrive, who was diagnosed as having scimitar syndrome.

  14. Magnetic resonance imaging in congenital facial palsy.

    PubMed

    Sasaki, Masayuki; Imamura, Yoshihiko; Sato, Noriko

    2008-03-01

    We report magnetic resonance (MR) findings in a patient with congenital unilateral facial palsy and a patient with atypical Moebius syndrome. MR imaging showed a complete deficiency of right facial nerve in the patient with congenital unilateral facial palsy and bilateral, thin proximal facial nerves in the Moebius syndrome patient. Three-dimensional constructive interference in steady state (3D-CISS) MR imaging, especially reconstructions perpendicular to the bilateral internal auditory channel, was very useful when diagnosing patients with facial palsy due to the associated facial nerve abnormalities.

  15. Marrow hypoplasia associated with congenital neurologic anomalies in two siblings.

    PubMed

    Drachtman, R; Weinblatt, M; Sitarz, A; Gold, A; Kochen, J

    1990-10-01

    Two siblings with congenital neurologic structural anomalies and delayed-onset selective bone marrow hypoplasia in a previously undescribed constellation of symptoms are presented. Differences between these cases and other well known syndromes are discussed. The importance of this association is the implication that children with congenital neurologic abnormalities may be at increased risk for the development of hypoplastic hematopoietic conditions.

  16. Congenital cutis laxa with retardation of growth and development.

    PubMed Central

    Patton, M A; Tolmie, J; Ruthnum, P; Bamforth, S; Baraitser, M; Pembrey, M

    1987-01-01

    Seven patients with congenital cutis laxa are presented. The associated features include developmental delay, joint laxity, wide anterior fontanelle, growth retardation, dental caries, and osteopenia. The heterogeneity and inheritance of congenital cutis laxa are discussed. This particular syndrome appears distinct and is likely to be autosomal recessive in view of the two brother-sister sib pairs in this report. Images PMID:3669050

  17. Congenital paroxysmal atrial tachycardia.

    PubMed Central

    Radford, D J; Izukawa, T; Rowe, R D

    1976-01-01

    Ten infants who had paroxysmal atrial tachycardia in utero or at birth are reported. Because of apparent fetal distress, caesarean section was performed in 4 cases and labour was induced in 1. Birthweight was generally large for gestational age. Severe ascites and hydrops at birth were manifestations of cardiac failure. Atrial flutter was recorded in 4 infants and supraventricular tachycardia in 5. The WoLff-Parkinson-White syndrome became evident later in 2. Digoxin was given to all 10 infants, and cardioversion was required and was effective in 4. Known recurrences in childhood have occurred in only 1 patient. Congenital atrial tachyarrhythmias may be commoner than generally believed, and fetal electrocardiography may help to avoid unnecessary termination of pregnancy. Blood sugar determinations are important, since neonatal hypoglycaemia was found. Cardioversion should be performed promptly in severely ill infants or if there is no response to digoxin. Care is required to avoid digoxin toxicity. PMID:962371

  18. Congenital amusia.

    PubMed

    Williamson, Victoria J; Stewart, Lauren

    2013-01-01

    For most people, music, like language, is acquired effortlessly in early life. But a few percent of the population have lifelong difficulties in the perception and production of music. In this chapter we discuss psycho-acoustic and behavioral studies that have attempted to delineate the nature of the auditory perceptual deficits in this group and consider whether these difficulties extend outside the musical domain. Finally, we review structural imaging studies in this group which point to subtle anomalies in temporal and frontal areas. We suggest that amusia can be considered a disorder of neural development, which has relatively specific consequences at the behavioral level. Studies of congenital amusia provide a unique window on the neurocognitive architecture of music processing. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Mental retardation, congenital heart defect, cleft palate, short stature, and facial anomalies: A new X-linked multiple congenital anomalies/mental retardation syndrome: Clinical description and molecular studies

    SciTech Connect

    Hamel, B.C.J.; Mariman, E.C.M.; Beersum, S.E.C. van

    1994-07-15

    We report on two brothers and their two maternal uncles with severe mental retardation, congenital heart defect, cleft or highly arched palate, short stature and craniofacial anomalies consisting of microcephaly, abnormal ears, bulbous nose, broad nasal bridge, malar hypoplasia, and micro-gnathia. Three of the four patients died at an early age. The mother of the two brothers had an atrial septal defect. She is assumed to be manifesting carrier of a mutant gene, which is expressed in her two sons and two brothers. By multipoint linkage analysis it is found that the most likely location of the responsible gene ismore » the pericentromeric region Xp21.3-q21.3 with DMD and DXS3 as flanking markers. Maximum information is obtained with marker DXS453 (Z = 1.20 at {theta} = 0.0). 24 refs., 12 figs., 1 tab.« less

  20. Imaging of Cranial Nerves III, IV, VI in Congenital Cranial Dysinnervation Disorders.

    PubMed

    Kim, Jae Hyoung; Hwang, Jeong Min

    2017-06-01

    Congenital cranial dysinnervation disorders are a group of diseases caused by abnormal development of cranial nerve nuclei or their axonal connections, resulting in aberrant innervation of the ocular and facial musculature. Its diagnosis could be facilitated by the development of high resolution thin-section magnetic resonance imaging. The purpose of this review is to describe the method to visualize cranial nerves III, IV, and VI and to present the imaging findings of congenital cranial dysinnervation disorders including congenital oculomotor nerve palsy, congenital trochlear nerve palsy, Duane retraction syndrome, Möbius syndrome, congenital fibrosis of the extraocular muscles, synergistic divergence, and synergistic convergence. © 2017 The Korean Ophthalmological Society.

  1. [Genetics of congenital heart diseases].

    PubMed

    Bonnet, Damien

    2017-06-01

    Developmental genetics of congenital heart diseases has evolved from analysis of serial slices in embryos towards molecular genetics of cardiac morphogenesis with a dynamic view of cardiac development. Genetics of congenital heart diseases has also changed from formal genetic analysis of familial recurrences or population-based analysis to screening for mutations in candidates genes identified in animal models. Close cooperation between molecular embryologists, pathologists involved in heart development and pediatric cardiologists is crucial for further increase of knowledge in the field of cardiac morphogenesis and genetics of cardiac defects. The genetic model for congenital heart disease has to be revised to favor a polygenic origin rather than a monogenic one. The main mechanism is altered genic dosage that can account for heart diseases in chromosomal anomalies as well as in point mutations in syndromic and isolated congenital heart diseases. The use of big data grouping information from cardiac development, interactions between genes and proteins, epigenetic factors such as chromatin remodeling or DNA methylation is the current source for improving our knowledge in the field and to give clues for future therapies. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  2. Congenital and acquired neutropenias consensus guidelines on therapy and follow-up in childhood from the Neutropenia Committee of the Marrow Failure Syndrome Group of the AIEOP (Associazione Italiana Emato-Oncologia Pediatrica).

    PubMed

    Fioredda, Francesca; Calvillo, Michaela; Bonanomi, Sonia; Coliva, Tiziana; Tucci, Fabio; Farruggia, Piero; Pillon, Marta; Martire, Baldassarre; Ghilardi, Roberta; Ramenghi, Ugo; Renga, Daniela; Menna, Giuseppe; Pusiol, Anna; Barone, Angelica; Gambineri, Eleonora; Palazzi, Giovanni; Casazza, Gabriella; Lanciotti, Marina; Dufour, Carlo

    2012-02-01

    The management of congenital and acquired neutropenias presents some differences according to the type of the disease. Treatment with recombinant human granulocyte-colony stimulating factor (G-CSF) is not standardized and scanty data are available on the best schedule to apply. The frequency and the type of longitudinal controls in patients affected with neutropenias are not usually discussed in the literature. The Neutropenia Committee of the Marrow Failure Syndrome Group (MFSG) of the Associazione Italiana di Emato-Oncologia Pediatrica (AIEOP) elaborated this document following design and methodology formerly approved by the AIEOP board. The panel of experts reviewed the literature on the topic and participated in a conference producing a document that includes recommendations on neutropenia treatment and timing of follow-up.

  3. [Cacchi Ricci disease associated with congenital hemihypertrophy].

    PubMed

    Cuesta Alcalá, José Angel; Aldave Villanueva, Javier; Solchaga Martínez, Alfredo; Pascual Piédrola, Ignacio; Arrondo Arrondo, José Luis; Ripa Saldías, Luis; Grasa Lanau, Vicente; Ponz González, Mariano; Ipiéns Aznar, Alfredo

    2002-12-01

    An uncommon case of medullary sponge kidney with congenital hemihypertrophy complicated by nephrocalcinosis and nephrolithiasis is reported here. A 29 year old female patient with multiple episodes of renal colic is presented. Clinical features, radiological findings and differential diagnosis in a patient with Cacchi-Ricci disease are discussed. At least twenty-nine cases associated with congenital hemihypertrophy have been reported previously. A significant number of patients with medullary sponge kidney are asymptomatic. In many cases the diagnosis is made when a patient is evaluated by intravenous urography for some unrelated problem. However, medullary sponge kidney has been reported in association with rare congenital anomalies (Beckwith-Widemann syndrome and congenital hemihypertrophy) and these patients appear to be at risk of malignant neoplasms of the adrenal gland, kidney and liver, therefore they must be followed closely.

  4. Congenital hypothyroidism

    PubMed Central

    2010-01-01

    Congenital hypothyroidism (CH) occurs in approximately 1:2,000 to 1:4,000 newborns. The clinical manifestations are often subtle or not present at birth. This likely is due to trans-placental passage of some maternal thyroid hormone, while many infants have some thyroid production of their own. Common symptoms include decreased activity and increased sleep, feeding difficulty, constipation, and prolonged jaundice. On examination, common signs include myxedematous facies, large fontanels, macroglossia, a distended abdomen with umbilical hernia, and hypotonia. CH is classified into permanent and transient forms, which in turn can be divided into primary, secondary, or peripheral etiologies. Thyroid dysgenesis accounts for 85% of permanent, primary CH, while inborn errors of thyroid hormone biosynthesis (dyshormonogeneses) account for 10-15% of cases. Secondary or central CH may occur with isolated TSH deficiency, but more commonly it is associated with congenital hypopitiutarism. Transient CH most commonly occurs in preterm infants born in areas of endemic iodine deficiency. In countries with newborn screening programs in place, infants with CH are diagnosed after detection by screening tests. The diagnosis should be confirmed by finding an elevated serum TSH and low T4 or free T4 level. Other diagnostic tests, such as thyroid radionuclide uptake and scan, thyroid sonography, or serum thyroglobulin determination may help pinpoint the underlying etiology, although treatment may be started without these tests. Levothyroxine is the treatment of choice; the recommended starting dose is 10 to 15 mcg/kg/day. The immediate goals of treatment are to rapidly raise the serum T4 above 130 nmol/L (10 ug/dL) and normalize serum TSH levels. Frequent laboratory monitoring in infancy is essential to ensure optimal neurocognitive outcome. Serum TSH and free T4 should be measured every 1-2 months in the first 6 months of life and every 3-4 months thereafter. In general, the prognosis

  5. Congenital diseases of the gastrointestinal tract.

    PubMed

    Lentze, M

    2014-05-01

    With the rapid increase in knowledge on the genetic origin of diseases within the gastrointestinal tract the number of congenital diseases, which already manifest during childhood have drastically increased. Due to the large application of molecular genetics the number is steadily increasing. To make the access to these rare diseases fast and efficient the data base of the National Library of Medicine (Online Mendelian Inheritance of Man - OMIN) is a very helpful online tool, with which all these disease entities can be found easily (http://www.ncbi.nlm.nih.gov/omim). Detailed tables are given to find most of the congenitally inherited disease, which affect the gastrointestinal tract. A variety of congenital diarrheas with disturbances of digestion, hydrolysis, absorption and secretion is described in detail: lactose intolerance, sucrose intolerance, glucose-galactose malabsorption, fructose malabsorption, trehalase and enterokinase deficiency, congenital chloride and sodium diarrhea, congenital hypomagnesaemia, primary bile acid malabsorption, acrodermatitis enteropathica and Menke's syndrome. Also described in detail are diseases with structural anomalies of the intestine like microvillous inclusion disease, congenital tufting enteropathy and IPEX syndrome. The diagnosis in the disturbances of carbohydrate hydrolysis or absorption can be established by H2-breath tests after appropriate sugar challenge. Treatment consists of elimination of the responsible sugar from the diet. The diagnosis of the congenital secretory diarrheas is established by investigation of electrolytes in blood and stool. Substitution of high doses of the responsible mineral can improve the clinical outcome. In acrodermatitis enteropathica low serum zinc level together with the typical skin lesions guide to the diagnosis. High doses of oral zinc aspartate can cure the symptoms of the disease. The diagnosis of structural congenital lesions of the intestine can be established by histology and

  6. 1:1 atrioventricular conduction in congenital complete heart block

    PubMed Central

    McLeod, K; Rankin, A; Houston, A

    1998-01-01

    A female neonate with congenital complete heart block developed atrioventricular conduction through an accessory pathway. Despite sinus rhythm and an adequate heart rate she developed severe dilated cardiomyopathy and died at age 14 months. This case illustrates that underlying heart block can be present in individuals with asymptomatic Wolff-Parkinson-White syndrome and that the dilated cardiomyopathy that occasionally accompanies autoimmune congenital heart block is not primarily caused by bradycardia.

 Keywords: congenital heart disease;  complete heart block;  atrioventricular conduction;  Wolff-Parkinson-White syndrome PMID:9930058

  7. Congenital Heart Information Network

    MedlinePlus

    ... heart defects. Important Notice The Congenital Heart Information Network website is temporarily out of service. Please join ... and Uwe Baemayr for The Congenital Heart Information Network Exempt organization under Section 501(c)3. Copyright © ...

  8. Prune Belly Syndrome

    PubMed Central

    Tagore, Koyye Ravindranath; Ramineni, Asok Kumar S.; Vijaya Lakshmi, A. R.; N., Bhavani

    2011-01-01

    Prune belly syndrome is a rare congenital disorder of the urinary system, characterized by a triad of abnormalities. The aetiology is not known. Many infants are either stillborn or die within the first few weeks of life from severe lung or kidney problems, or a combination of congenital anomalies. PMID:22606508

  9. Whole Genome Sequencing Reveals Novel Non-Synonymous Mutation in Ectodysplasin A (EDA) Associated with Non-Syndromic X-Linked Dominant Congenital Tooth Agenesis

    PubMed Central

    Sarkar, Tanmoy; Bansal, Rajesh; Das, Parimal

    2014-01-01

    Congenital tooth agenesis in human is characterized by failure of tooth development during tooth organogenesis. 300 genes in mouse and 30 genes in human so far have been known to regulate tooth development. However, candidature of only 5 genes viz. PAX9, MSX1, AXIN2, WNT10A and EDA have been experimentally established for congenitally missing teeth like hypodontia and oligodontia. In this study an Indian family with multiple congenital tooth agenesis was identified. Pattern of inheritance was apparently autosomal dominant type with a rare possibility to be X-linked. Whole genome sequencing of two affected individuals was carried out which revealed 119 novel non-synonymous single nucleotide variations (SNVs) distributed among 117 genes. Out of these only one variation (c.956G>T) located at exon 9 of X-linked EDA gene was considered as pathogenic and validated among all the affected and unaffected family members and unrelated controls. This variation leads to p.Ser319Ile change in the TNF homology domain of EDA (transcript variant 1) protein. In silico analysis predicts that this Ser319 is well conserved across different vertebrate species and a part of putative receptor binding site. Structure based homology modeling predicts that this amino acid residue along with four other amino acid residues nearby, those when mutated known to cause selective tooth agenesis, form a cluster that may have functional significance. Taken together these results suggest that c.956G>T (p.Ser319Ile) mutation plausibly reduces the receptor binding activity of EDA leading to distinct tooth agenesis in this family. PMID:25203534

  10. Whole genome sequencing reveals novel non-synonymous mutation in ectodysplasin A (EDA) associated with non-syndromic X-linked dominant congenital tooth agenesis.

    PubMed

    Sarkar, Tanmoy; Bansal, Rajesh; Das, Parimal

    2014-01-01

    Congenital tooth agenesis in human is characterized by failure of tooth development during tooth organogenesis. 300 genes in mouse and 30 genes in human so far have been known to regulate tooth development. However, candidature of only 5 genes viz. PAX9, MSX1, AXIN2, WNT10A and EDA have been experimentally established for congenitally missing teeth like hypodontia and oligodontia. In this study an Indian family with multiple congenital tooth agenesis was identified. Pattern of inheritance was apparently autosomal dominant type with a rare possibility to be X-linked. Whole genome sequencing of two affected individuals was carried out which revealed 119 novel non-synonymous single nucleotide variations (SNVs) distributed among 117 genes. Out of these only one variation (c.956G>T) located at exon 9 of X-linked EDA gene was considered as pathogenic and validated among all the affected and unaffected family members and unrelated controls. This variation leads to p.Ser319Ile change in the TNF homology domain of EDA (transcript variant 1) protein. In silico analysis predicts that this Ser319 is well conserved across different vertebrate species and a part of putative receptor binding site. Structure based homology modeling predicts that this amino acid residue along with four other amino acid residues nearby, those when mutated known to cause selective tooth agenesis, form a cluster that may have functional significance. Taken together these results suggest that c.956G>T (p.Ser319Ile) mutation plausibly reduces the receptor binding activity of EDA leading to distinct tooth agenesis in this family.

  11. [Distribution of multiple congenital abnormalities including anotia and microtia].

    PubMed

    Paput, László; Falvai, Judit; Bánhidy, Ferenc

    2011-08-28

    To evaluate cases with unclassified multiple congenital abnormalities including microtia and anotia as component congenital abnormalities in order to reveal the characteristic pattern of other associated component congenital abnormalities and to make an attempt to establish a registry diagnosis on the pattern of associated congenital abnormalities and to stimulate the establishment of an international registry of cases with unclassified multiple congenital abnormalities comprising of microtia and anotia. The large population-based dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996. A total of 156 cases with unclassified multiple congenital abnormalities including microtia and anotia were analyzed according to the number of 2-9 component congenital abnormalities. The comparison of the distribution and frequency of component congenital abnormalities in these cases showed significant differences from the data of other unclassified multiple congenital abnormalities. Of the 156 cases, registry diagnosis was possible in 48 (30.8%) cases. The evaluation of available dataset of unclassified multiple anotia and microtia may help the delineation of new syndromes and associations with better prognosis and recurrence risk estimation, thus finally a better chance for their prevention.

  12. Noonan syndrome

    PubMed Central

    Roberts, Amy E; Allanson, Judith E; Tartaglia, Marco; Gelb, Bruce D

    2014-01-01

    Noonan syndrome is a genetic multisystem disorder characterised by distinctive facial features, developmental delay, learning difficulties, short stature, congenital heart disease, renal anomalies, lymphatic malformations, and bleeding difficulties. Mutations that cause Noonan syndrome alter genes encoding proteins with roles in the RAS–MAPK pathway, leading to pathway dysregulation. Management guidelines have been developed. Several clinically relevant genotype–phenotype correlations aid risk assessment and patient management. Increased understanding of the pathophysiology of the disease could help development of pharmacogenetic treatments. PMID:23312968

  13. X-linked neurodegenerative syndrome with congenital ataxia, late-onset progressive myoclonic encephalopathy and selective macular degeneration, linked to Xp22.33-pter

    SciTech Connect

    Portes, V. des; Beldjord, C.; Bruels, T.

    1996-07-12

    Linkage analysis was performed in a previously described family segregating for an X-linked progressive neurological disorder. In three generations, the disease was inherited from the mothers in seven affected males. Five had severe congenital hypotonia and died during the first year of life. Two other boys (maternal cousins) were found to have severe congenital ataxia, late-onset progressive myoclonic encephalopathy, and selective macular degeneration; brain CT-scan showed moderate cerebellar vermis hypoplasia. Linkage analysis was carried out in 12 informative relatives using 35 microsatellite markers (Genethon) evenly distributed on the X chromosome. A multipoint analysis showed a significant linkage (Z > 2)more » between the disease and three markers in the Xp22.33 region: DYS403 (Z = 2.37, {theta} = 0) which maps in the pseudoautosomal region, DXS7099 (Z = 2.45, {theta} = 0), and DXS7100 (Z = 2.48, {theta} = 0). Further linkage analysis with more telomeric markers will refine the location of this severe X-linked encephalopathy. 12 refs., 2 figs., 1 tab.« less

  14. Early diagnosis of congenital heart disease.

    PubMed

    Richmond, S; Wren, C

    2001-02-01

    Routine examination of apparently healthy newborn babies detects less than half of those with congenital cardiac malformations because they are asymptomatic and without signs. More severe cardiac malformations are not detected more easily. A normal clinical examination does not exclude serious congenital cardiac malformation. Left heart obstruction is easily overlooked but often causes serious deterioration in less than 3 weeks. It is important to arrange early echocardiography of babies with signs and to consider cardiac malformation in a sick baby even if a previous routine examination was normal. All babies with Down syndrome should have early expert cardiological assessment. Copyright 2001 Harcourt Publishers Ltd.

  15. Congenital insensitivity to pain: report of two cases.

    PubMed

    Lawoyin, J O; Lawoyin, D O

    2001-01-01

    Congenital indifference or insensitivity to pain (CIP) is a rare syndrome. It mimics a number of other syndromes categorized under peripheral sensory neuropathies, often making early diagnosis difficult. Two cases from the middle east are presented, highlighting possible diagnostic, and management difficulties.

  16. Congenital cavitary optic disc anomaly and Axenfeld's anomaly in Wolf-Hirschhorn syndrome: A case report and review of the literature.

    PubMed

    Ali, Mohsin H; Azar, Nathalie F; Aakalu, Vinay; Chau, Felix Y; Abbasian, Javaneh; Setabutr, Pete; Maumenee, Irene H

    2018-04-01

    Wolf-Hirschhorn syndrome is a rare genetic syndrome caused by a heterozygous deletion on chromosome 4p16.3 and is characterized by a "Greek warrior helmet" facies, hypotonia, developmental delay, seizures, structural central nervous system defects, intrauterine growth restriction, sketelal anomalies, cardiac defects, abnormal tooth development, and hearing loss. A variety of ocular manifestations may occur in up to 40% of patients. We report the genetic testing results, systemic findings, and complete ophthalmologic examination findings in a patient with Wolf-Hirschhorn syndrome, including external photography, RetCam3 (Clarity Medical Systems, Pleasonton, CA) goniography, and fundus photography. In addition, we review the literature on ocular manifestations of Wolf-Hirschhorn syndrome. Microarray analysis revealed an unbalanced translocation between 4p16.3-15.3 and Xp22.33-p22.2. Systemic findings included "Greek warrior helmet" facies, hypotonia, cleft palate, neonatal tooth eruption, talipes equinovarus, bilateral clinodactyly, clitoromegaly, partial agenesis of the corpus callosum, bilateral renal hypoplasia, and two atrial septal defects. Ocular findings included normal intraocular pressures and corneal diameters, large-angle exotropia, downward slanting of the palpebral fissures, absent eyelid creases, upper and lower eyelid retraction with shortage of the anterior eyelid lamellae, euryblepharon, lagophthalmos with poor Bell's reflex and exposure keratopathy, hypertelorism, Axenfeld's anomaly, megalopapillae, and cavitary optic disc anomaly. We describe the ocular phenotype of a patient with Wolf-Hirschhorn syndrome, including the rare descriptions and photographs of Axenfeld's anomaly, megalopapilla, and cavitary optic disc anomaly in this condition.

  17. Multiple congenital anomalies in a man with (X;6) translocation.

    PubMed

    Sivak, L E; Esbenshade, J; Brothman, A R; Issa, B; Lemons, R S; Carey, J C

    1994-05-15

    X;autosome translocations in humans, often associated with congenital anomalies or with gonadal dysgenesis syndromes, are informative for the study of X-linked gene expression and of the phenomenon of X chromosome inactivation. When such translocations occur in association with multiple congenital anomaly (MCA) syndromes, the observed phenotypes are not always attributable solely to disruption of specific genes, if X-inactivation spreads onto the translocated autosome, rendering some distal genes inactive. We report on a man with multiple congenital anomalies and a maternally inherited (X;6)(p22.1;p25) translocation. He has abnormalities not described in the Klinefelter or 6p deletion syndromes. His unique findings constitute a recognizable syndrome, which is likely caused by disomy for a region of Xp in conjunction with a partial 6p deletion.

  18. Congenital Diaphragmatic Hernia

    PubMed Central

    2012-01-01

    Congenital Diaphragmatic Hernia (CDH) is defined by the presence of an orifice in the diaphragm, more often left and posterolateral that permits the herniation of abdominal contents into the thorax. The lungs are hypoplastic and have abnormal vessels that cause respiratory insufficiency and persistent pulmonary hypertension with high mortality. About one third of cases have cardiovascular malformations and lesser proportions have skeletal, neural, genitourinary, gastrointestinal or other defects. CDH can be a component of Pallister-Killian, Fryns, Ghersoni-Baruch, WAGR, Denys-Drash, Brachman-De Lange, Donnai-Barrow or Wolf-Hirschhorn syndromes. Some chromosomal anomalies involve CDH as well. The incidence is < 5 in 10,000 live-births. The etiology is unknown although clinical, genetic and experimental evidence points to disturbances in the retinoid-signaling pathway during organogenesis. Antenatal diagnosis is often made and this allows prenatal management (open correction of the hernia in the past and reversible fetoscopic tracheal obstruction nowadays) that may be indicated in cases with severe lung hypoplasia and grim prognosis. Treatment after birth requires all the refinements of critical care including extracorporeal membrane oxygenation prior to surgical correction. The best hospital series report 80% survival but it remains around 50% in population-based studies. Chronic respiratory tract disease, neurodevelopmental problems, neurosensorial hearing loss and gastroesophageal reflux are common problems in survivors. Much more research on several aspects of this severe condition is warranted. PMID:22214468

  19. Xenopus: An Emerging Model for Studying Congenital Heart Disease

    PubMed Central

    Kaltenbrun, Erin; Tandon, Panna; Amin, Nirav M.; Waldron, Lauren; Showell, Chris; Conlon, Frank L.

    2011-01-01

    Congenital heart defects affect nearly 1% of all newborns and are a significant cause of infant death. Clinical studies have identified a number of congenital heart syndromes associated with mutations in genes that are involved in the complex process of cardiogenesis. The African clawed frog, Xenopus, has been instrumental in studies of vertebrate heart development and provides a valuable tool to investigate the molecular mechanisms underlying human congenital heart diseases. In this review, we discuss the methodologies that make Xenopus an ideal model system to investigate heart development and disease. We also outline congenital heart conditions linked to cardiac genes that have been well-studied in Xenopus and describe some emerging technologies that will further aid in the study of these complex syndromes. PMID:21538812

  20. Adult congenital heart disease.

    PubMed

    Moodie, D S

    1994-01-01

    There are approximately 500,000 adults in the United States with congenital heart disease, and this group is growing at 5% per year. Adult cardiologists are, for the most part, poorly trained in the treatment of congenital heart disease; pediatric cardiologists, on the other hand, work in children's hospitals where it is difficult to care for adults. It is important, therefore, to review the current literature as it relates to adult congenital heart disease. This report details the long-term follow-up of patients who were operated on in childhood for congenital heart disease and are now adults. In addition, it reviews information related to the social adaptation of adult congenital heart patients. There are a number of interesting new reports on specific adult congenital heart anomalies. Atrial septal defects as well as the relationship between a patent foramen ovale and stroke are also reviewed.

  1. Canadian Cardiovascular Society 2009 Consensus Conference on the management of adults with congenital heart disease: Outflow tract obstruction, coarctation of the aorta, tetralogy of Fallot, Ebstein anomaly and Marfan’s syndrome

    PubMed Central

    Silversides, Candice K; Beauchesne, Luc; Bradley, Timothy; Connelly, Michael; Niwa, Koichiro; Mulder, Barbara; Webb, Gary; Colman, Jack; Therrien, Judith

    2010-01-01

    With advances in pediatric cardiology and cardiac surgery, the population of adults with congenital heart disease (CHD) has increased. In the current era, there are more adults with CHD than children. This population has many unique issues and needs. Since the 2001 Canadian Cardiovascular Society Consensus Conference report on the management of adults with CHD, there have been significant advances in the field of adult CHD. Therefore, new clinical guidelines have been written by Canadian adult CHD physicians in collaboration with an international panel of experts in the field. Part II of the guidelines includes recommendations for the care of patients with left ventricular outflow tract obstruction and bicuspid aortic valve disease, coarctation of the aorta, right ventricular outflow tract obstruction, tetralogy of Fallot, Ebstein anomaly and Marfan’s syndrome. Topics addressed include genetics, clinical outcomes, recommended diagnostic workup, surgical and interventional options, treatment of arrhythmias, assessment of pregnancy risk and follow-up requirements. The complete document consists of four manuscripts that are published online in the present issue of The Canadian Journal of Cardiology. The complete document and references can also be found at www.ccs.ca or www.cachnet.org. PMID:20352138

  2. A de novo 2q35-q36.1 deletion incorporating IHH in a Chinese boy (47,XYY) with syndactyly, type III Waardenburg syndrome, and congenital heart disease.

    PubMed

    Wang, D; Ren, G F; Zhang, H Z; Yi, C Y; Peng, Z J

    2016-12-02

    Reports of terminal and interstitial deletions of the long arm of chromosome 2 are rare in the literature. Here, we present a case report concerning a Chinese boy with a 47,XYY karyotype and a de novo deletion comprising approximately 5 Mb between 2q35 and q36.1, along with syndactyly, type III Waardenburg syndrome, and congenital heart disease. High-resolution chromosome analysis to detect copy number variations was carried out using an Affymetrix microarray platform, and the genes affected by the patient's deletion, including IHH, were determined. However, no copy number changes were observed in his healthy parents. The present case exhibited novel syndactyly features, broadening the spectrum of clinical findings observed in individuals with 2q interstitial deletions. Our data, together with previous observations, suggest that IHH haploinsufficiency is the principal pathogenic factor in the syndactyly phenotype in this study, and that different types of variations at the IHH locus may cause divergent disease phenotypes. This is the first report of the involvement of IHH haploinsufficiency in syndactyly phenotype.

  3. Ethical Dilemmas Relating to the Management of a Newborn with Down Syndrome and Severe Congenital Heart Disease in a Resource-Poor Setting.

    PubMed

    Edwin, Ama K; Edwin, Frank; McGee, Summer J

    2015-01-01

    Decision-making regarding treatment for newborns with disabilities in resource-poor settings is a difficult process that can put parents and caregivers in conflict. Despite several guidelines that have helped to clarify some of the medical decision-making in Ghana, there is still no clear consensus on the specific moral criteria to be used. This article presents the case of a mother who expressed her wish that her child with Down syndrome should not have been resuscitated at birth. It explores the ethical issues at stake in both her misgivings about the resuscitation and her unwillingness to consider surgical repair of an atrioventricular (AV) canal defect. Knowing that children born with Down syndrome are able to pursue life's goals, should our treatment of complete AV canal defect in such children be considered morally obligatory, even in resource-poor settings like Ghana?

  4. The role of respiratory failure caused by congenital central nervous system abnormalities and the effect of β-casomorphins in sudden infant death syndrome pathogenesis.

    PubMed

    Sumińska-Ziemann, B; Gos, T; Jankowski, Z

    2015-01-01

    The aim of the paper is to discuss the role of respiratory failure caused by endogenous (both structural and functional) abnormalities in the central nervous system and exogenous food-derived opioid-like peptides in the pathogenesis of sudden infant death syndrome (SIDS). By stimulating μ-opioid receptors, opioid-like peptides may suppress the tonic activity of the respiratory centre in the brain stem.

  5. Congenital and inherited renal disease of small animals.

    PubMed

    Greco, D S

    2001-03-01

    Congenital renal diseases are present at birth and may be determined genetically; familial renal disorders occur in related animals with a higher frequency than would be expected by chance, and frequently are inherited. The most common familial disorders in cats and dogs include renal amyloidosis, renal dysplasia, polycystic kidneys, basement membrane disorders, and tubular dysfunction (Fanconi's syndrome). This article alerts the veterinarian to commonly observed congenital and hereditary conditions of the kidneys in small animals.

  6. Congenital bilateral upper eyelid eversion: report of a case.

    PubMed

    Cingü, Abdullah Kürşat; Sahin, Alparslan; Yüksel, Harun; Ozkök, Ahmet; Arı, Seyhmus; Caça, Ihsan

    2014-01-01

    Congenital bilateral upper eyelid eversion is a rare condition and the definite cause is not known. It is often seen in Black babies or babies with Down's syndrome. With early diagnosis and appropriate treatment, the condition can be managed without surgery. We report a case of congenital upper eyelid eversion in an otherwise healthy Caucasian neonate, born by normal vaginal delivery. The case responded well to conservative treatment, including eyelid repositioning, lubricants, antibiotic ointment, and eyelid patching.

  7. Genetics Home Reference: congenital hypothyroidism

    MedlinePlus

    ... Facebook Twitter Home Health Conditions Congenital hypothyroidism Congenital hypothyroidism Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Congenital hypothyroidism is a partial or complete loss of function ...

  8. [Development of highly stereoselective reactions utilizing heteroatoms--new approach to the stereoselective Horner-Wadsworth-Emmons reaction].

    PubMed

    Sano, S

    2000-05-01

    This article reviews a new approach to stereoselective Horner-Wadsworth-Emmons (HWE) reactions. The HWE reaction is one of the most efficient methods for the preparation of alpha,beta-unsaturated esters, which play an important role in the synthesis of biologically active compounds. The reactions of aldehydes with phosphonates bearing alpha-substituents which stabilize the carbanion, preferentially furnish the corresponding E-alkenes. However, the stereoselectivity of the HWE reactions with ketones has never been investigated in detail because of their low reactivity and low stereoselectivity. The conventional HWE reactions of aryl alkyl ketones with ethyl diethylphosphonoacetate in the presence of sodium hydride gave the corresponding alpha,beta-unsaturated esters with modest E-selectivity. On the other hand, the treatment of aryl alkyl ketones with ethyl diethylphosphonoacetate in the presence of Sn(OSO2CF3)2 and N-ethylpiperidine afforded alpha,beta-unsaturated esters in a highly Z-selective fashion. A significant improvement in the selectivity and yield was found when the Still's reagent, methyl bis(trifluoroethyl)phosphonoacetate, was used under Sn(II)-mediated conditions. On the basis of the experimental results, the high Z-selectivity in the Sn(II)-mediated HWE reactions of aryl alkyl ketones with these phosphonates can be rationalized in terms of six-membered transition state involving Sn(II) chelation. Similarly, the HWE reactions of aryl alkyl ketones with ethyl 2-fluoro-2-diethylphosphonoacetate in the presence of Sn(OSO2CF3)2 and N-ethylpiperidine gave the corresponding alpha-fluoro-alpha,beta-unsaturated esters in a highly E-selective manner. Finally, the Sn(II)-mediated asymmetric HWE reactions of isopropyl 2-fluoro-2-diethylphosphonoacetate with 4-tert-butylcyclohexanone in the presence of a chiral diamine is described.

  9. The emerging role of genomics in the diagnosis and workup of congenital urinary tract defects: a novel deletion syndrome on chromosome 3q13.31-22.1

    PubMed Central

    Materna-Kiryluk, Anna; Kiryluk, Krzysztof; Burgess, Katelyn E; Bieleninik, Arkadiusz; Sanna-Cherchi, Simone; Gharavi, Ali G.; Latos-Bielenska, Anna

    2014-01-01

    Background Copy number variants (CNVs) are increasingly recognized as an important cause of congenital malformations and likely explain over 16% cases of CAKUT. Here, we illustrate how a molecular diagnosis of CNV can inform the clinical management of a pediatric patient presenting with CAKUT and other organ defects. Methods We describe a 14 year-old girl with a large de novo deletion of chromosome 3q13.31-22.1 that disrupts 101 known genes and manifests with CAKUT, neurodevelopmental delay, agenesis of corpus callosum (ACC), cardiac malformations, electrolyte and endocrine disorders, skeletal abnormalities and dysmorphic features. We perform extensive annotation of the deleted region to prioritize genes for specific phenotypes and to predict future disease risk. Results Our case defined new minimal chromosomal candidate regions for both CAKUT and ACC. Moreover, the presence of the CASR gene in the deleted interval predicted a diagnosis of hypocalciuric hypercalcemia, which was confirmed by serum and urine chemistries. Our gene annotation explained clinical hypothyroidism and predicted that the index case is at increased risk of thoracic aortic aneurysm, renal cell carcinoma and myeloproliferative disorder. Conclusions Extended annotation of CNV regions refines diagnosis and uncovers previously unrecognized phenotypic features. This approach enables personalized treatment and prevention strategies in patients harboring genomic deletions. PMID:24292865

  10. Mild one-pot Horner-Wadsworth-Emmons olefination and intramolecular N-arylation for the syntheses of indoles, all regio-isomeric azaindoles, and thienopyrroles.

    PubMed

    Choi, Ji Hye; Lim, Hwan Jung

    2015-05-14

    The syntheses of various N-protected aromatic-ring fused pyrrole-2-carboxylate derivatives have been accomplished using mild one-pot Horner-Wadsworth-Emmons olefination and Cu-catalyzed intramolecular N-arylation reactions. The optimized mild one-pot reaction conditions of various 2-bromo arylcarboxaldehydes with commercially available N-protected phosphonoglycine trimethylesters gave the desired aromatic-ring fused pyrrole-2-carboxylates, such as substituted indole-, all regio-isomeric azaindole-, and thienopyrrole-2-carboxylates, in good to excellent yields. These conditions showed broad substrate compatibility, without the loss of the protecting group.

  11. Congenital hemihypertrophy and pheochromocytoma, not a coincidental combination?

    PubMed

    van den Akker, Erica L T; de Krijger, Ronald R; de Herder, Wouter W; Drop, Stenvert L S

    2002-03-01

    We describe a 19-year-old female, known to have congenital hemihypertrophy, who presented with bilateral benign pheochromocytoma. This is the second time that this combination has been reported in the literature. We speculate that the combination of congenital hemihypertrophy and pheochromocytoma is not coincidental and could be part of the clinical spectrum of the Beckwith-Wiedemann syndrome. in patients with congenital hemihypertrophy, the physician should be aware of the symptoms of pheochromocytoma. Besides screening for abdominal tumours, analysis of plasma and/or urinary catecholamines and/or their metabolites should be considered.

  12. Synaptogenesis and Myelination in the Nucleus/Tractus Solitarius: Potential Role in Apnea of Prematurity, Congenital Central Hypoventilation, and Sudden Infant Death Syndrome.

    PubMed

    Sarnat, Harvey B; Flores-Sarnat, Laura

    2016-05-01

    Fetuses as early as 15 weeks' gestation exhibit rhythmical respiratory movements shown by real-time ultrasonography. The nucleus/tractus solitarius is the principal brainstem respiratory center; other medullary nuclei also participate. The purpose was to determine temporal maturation of synaptogenesis. Delayed synaptic maturation may explain neurogenic apnea or hypoventilation of prematurity and some cases of sudden infant death syndrome. Sections of medulla oblongata were studied from 30 human fetal and neonatal brains 9 to 41 weeks' gestation. Synaptophysin demonstrated the immunocytochemical sequence of synaptogenesis. Other neuronal markers and myelin stain also were applied. The nucleus/tractus solitarius was similarly studied in fetuses with chromosomopathies, metabolic encephalopathies, and brain malformations. Synapse formation in the nucleus solitarius begins at about 12 weeks' gestation and matures by 15 weeks; myelination initiated at 33 weeks. Synaptogenesis was delayed in 3 fetuses with different conditions, but was not specific for only nucleus solitarius. Delayed synaptogenesis or myelination in the nucleus solitarius may play a role in neonatal hypoventilation, especially in preterm infants and in some sudden infant death syndrome cases. © The Author(s) 2015.

  13. Mutations in the heat-shock protein A9 (HSPA9) gene cause the EVEN-PLUS syndrome of congenital malformations and skeletal dysplasia.

    PubMed

    Royer-Bertrand, Beryl; Castillo-Taucher, Silvia; Moreno-Salinas, Rodrigo; Cho, Tae-Joon; Chae, Jong-Hee; Choi, Murim; Kim, Ok-Hwa; Dikoglu, Esra; Campos-Xavier, Belinda; Girardi, Enrico; Superti-Furga, Giulio; Bonafé, Luisa; Rivolta, Carlo; Unger, Sheila; Superti-Furga, Andrea

    2015-11-24

    We and others have reported mutations in LONP1, a gene coding for a mitochondrial chaperone and protease, as the cause of the human CODAS (cerebral, ocular, dental, auricular and skeletal) syndrome (MIM 600373). Here, we delineate a similar but distinct condition that shares the epiphyseal, vertebral and ocular changes of CODAS but also included severe microtia, nasal hypoplasia, and other malformations, and for which we propose the name of EVEN-PLUS syndrome for epiphyseal, vertebral, ear, nose, plus associated findings. In three individuals from two families, no mutation in LONP1 was found; instead, we found biallelic mutations in HSPA9, the gene that codes for mHSP70/mortalin, another highly conserved mitochondrial chaperone protein essential in mitochondrial protein import, folding, and degradation. The functional relationship between LONP1 and HSPA9 in mitochondrial protein chaperoning and the overlapping phenotypes of CODAS and EVEN-PLUS delineate a family of "mitochondrial chaperonopathies" and point to an unexplored role of mitochondrial chaperones in human embryonic morphogenesis.

  14. Abdominal vascular syndromes: characteristic imaging findings.

    PubMed

    Cardarelli-Leite, Leandro; Velloni, Fernanda Garozzo; Salvadori, Priscila Silveira; Lemos, Marcelo Delboni; D'Ippolito, Giuseppe

    2016-01-01

    Abdominal vascular syndromes are rare diseases. Although such syndromes vary widely in terms of symptoms and etiologies, certain imaging findings are characteristic. Depending on their etiology, they can be categorized as congenital-including blue rubber bleb nevus syndrome, Klippel-Trenaunay syndrome, and hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome)-or compressive-including "nutcracker" syndrome, median arcuate ligament syndrome, Cockett syndrome (also known as May-Thurner syndrome), and superior mesenteric artery syndrome. In this article, we aimed to illustrate imaging findings that are characteristic of these syndromes, through studies conducted at our institution, as well as to perform a brief review of the literature on this topic.

  15. Down Syndrome: A Cardiovascular Perspective

    ERIC Educational Resources Information Center

    Vis, J. C.; Duffels, M. G. J.; Winter, M. M.; Weijerman, M. E.; Cobben, J. M.; Huisman, S. A.; Mulder, B. J. M.

    2009-01-01

    This review focuses on the heart and vascular system in patients with Down syndrome. A clear knowledge on the wide spectrum of various abnormalities associated with this syndrome is essential for skillful management of cardiac problems in patients with Down syndrome. Epidemiology of congenital heart defects, cardiovascular aspects and…

  16. Williams Syndrome Information for Teachers.

    ERIC Educational Resources Information Center

    Levine, Karen

    This paper uses a question-and-answer format to summarize information about Williams syndrome, a neurobehavioral congenital disorder which affects development in cognitive, behavioral, and motor areas. Questions address the following topics: characteristics of Williams syndrome; medical problems associated with Williams syndrome; characteristic…

  17. Cleft palate lateral synechia syndrome

    PubMed Central

    Sybil, Deborah; Sagtani, Alok

    2013-01-01

    Cleft lip and palate are the most common congenital craniofacial anomaly in humans. The presence of oral synechia along with cleft palate is a rare syndrome. We encountered one case that had a cleft palate accompanied by congenital oral synechia due to a membranous adhesion between the floor of the mouth and the free margin of the cleft palate. PMID:24163560

  18. Cleft palate lateral synechia syndrome.

    PubMed

    Sybil, Deborah; Sagtani, Alok

    2013-01-01

    Cleft lip and palate are the most common congenital craniofacial anomaly in humans. The presence of oral synechia along with cleft palate is a rare syndrome. We encountered one case that had a cleft palate accompanied by congenital oral synechia due to a membranous adhesion between the floor of the mouth and the free margin of the cleft palate.

  19. Congenital chloridorrhea in Korean infants.

    PubMed Central

    Lee, Y. D.; Lee, H. J.; Moon, H. R.

    1988-01-01

    The present paper describes two Korean male infants, 1. 16 year old and newly born neonate from two families who were diagnosed and managed for one of very rare inborn errors of metabolism, congenital chloridorrhea (Darrow-Gamble syndrome). The diagnosis was suggested by one of the authors (HRM) from the unusual combination of metabolic alkalosis with severe gastrointestinal disorder presenting with chronic, profuse watery diarrhea in the newborn period in the first patient; and the maternal polyhydramnios, the appearance of dilated fetal bowel loops on prenatal ultrasonography and profuse watery diarrhea beginning at birth without passage of meconium in the second patient. The diagnosis was confirmed in both patients by examination of the stool chloride concentration which revealed extremely high exceeding the sum of sodium and potassium concentrations. Serum electrolytes and arterial blood gas analyses revealed hyponatremia, hypokalemia and hypochloremia with elevated bicarbonate. With replacement of fluid and electrolyte deficit and adequate dietary supplements of potassium and chloride, both patients remained well although the character of the stools waxed and waned. This is the first reported case of congenital chloridorrhea in korean population. PMID:3267361

  20. Congenital chloridorrhea in Korean infants.

    PubMed

    Lee, Y D; Lee, H J; Moon, H R

    1988-09-01

    The present paper describes two Korean male infants, 1. 16 year old and newly born neonate from two families who were diagnosed and managed for one of very rare inborn errors of metabolism, congenital chloridorrhea (Darrow-Gamble syndrome). The diagnosis was suggested by one of the authors (HRM) from the unusual combination of metabolic alkalosis with severe gastrointestinal disorder presenting with chronic, profuse watery diarrhea in the newborn period in the first patient; and the maternal polyhydramnios, the appearance of dilated fetal bowel loops on prenatal ultrasonography and profuse watery diarrhea beginning at birth without passage of meconium in the second patient. The diagnosis was confirmed in both patients by examination of the stool chloride concentration which revealed extremely high exceeding the sum of sodium and potassium concentrations. Serum electrolytes and arterial blood gas analyses revealed hyponatremia, hypokalemia and hypochloremia with elevated bicarbonate. With replacement of fluid and electrolyte deficit and adequate dietary supplements of potassium and chloride, both patients remained well although the character of the stools waxed and waned. This is the first reported case of congenital chloridorrhea in korean population.

  1. Insulin-like peptide 3 (INSL3) in men with congenital hypogonadotropic hypogonadism/Kallmann syndrome and effects of different modalities of hormonal treatment: a single-center study of 281 patients.

    PubMed

    Trabado, Séverine; Maione, Luigi; Bry-Gauillard, Hélène; Affres, Hélène; Salenave, Sylvie; Sarfati, Julie; Bouvattier, Claire; Delemer, Brigitte; Chanson, Philippe; Le Bouc, Yves; Brailly-Tabard, Sylvie; Young, Jacques

    2014-02-01

    Insulin-like factor 3 (INSL3) is a testicular hormone secreted during fetal life, the neonatal period, and after puberty. To measure INSL3 levels in a large series of men with congenital hypogonadotropic hypogonadism (CHH)/ Kallmann syndrome (KS), in order to assess its diagnostic value and to investigate its regulation. We studied 281 CHH/KS patients (91 untreated, 96 receiving T, and 94 receiving combined gonadotropin therapy [human chorionic gonadotropin, hCG, and FSH]) and 72 age-matched healthy men. Serum INSL3 was immunoassayed with a validated RIA. Mean (±SD) INSL3 levels (pg/mL) were 659 ± 279 in controls and lower (60 ± 43; P < .001) in untreated CHH/KS patients, with no overlap between the two groups, when the threshold of 250 pg/mL was used. Basal INSL3 levels were lower in both untreated CHH/KS men with cryptorchidism than in those with intrascrotal testes and in patients with testicular volumes below 4 mL. Significant positive correlations between INSL3 and both serum total T and LH levels were observed in untreated CHH/KS. Mean INSL3 levels remained low in T-treated CHH/KS patients and were significantly higher in men receiving combined hCG-FSH therapy (P < .001), but the increase was lower cryptorchid patients. FSH-hCG combination therapy or hCG monotherapy, contrary to T and FSH monotherapies, significantly increased INSL3 levels in CHH/KS. INSL3 is as sensitive a marker as T for the evaluation of altered Leydig cell function in CHH/KS patients. INSL3 levels correlate with LH levels in CHH/KS men showing, together with the rise in INSL3 levels during hCG therapy, that INSL3 secretion seems not constitutively secreted during adulthood but is dependence on pituitary LH.

  2. Giant congenital nevus

    MedlinePlus

    ... A congenital pigmented or melanocytic nevus is a dark-colored, often hairy, patch of skin. It is ... rare. Symptoms A nevus will appear as a dark-colored patch with any of the following: Brown ...

  3. Screening for congenital hypothyroidism.

    PubMed

    Henry, Gerard; Sobki, Samia H; Othman, Johara M

    2002-05-01

    To review the screening program for congenital hypothyroidism in the Riyadh Al-Kharj Hospital Programme, Riyadh, Kingdom of Saudi Arabia, and to investigate the clinical and biochemical characteristics of affected infants. The study was carried out from 1985 to 2000 in the Clinical Chemistry Division, Department of Pathology, Riyadh Armed Forces Hospital, Kingdom of Saudi Arabia. Laboratory data and case notes of infants diagnosed with congenital hypothyroidism were used to supply the relevant data and information. One hundred and twenty-one thousand, four hundred and four infants were screened over a period of nearly 15 years. The overall incidence of congenital hypothyroidism was 1:2759 live births with a female: male ratio of 1.8:1. The incidence in a rural satellite hospital was 1:1538. No seasonal variation was observed. Apart from jaundice, signs and symptoms of congenital hypothyroidism were rarely present in the neonatal period. The neonatal and maternal parameters of affected infants did not differ significantly from those of other infants. The predominant cause of congenital hypothyroidism was athyreosis (45%), followed by thyroid ectopia (24%) and dyshormonogenesis (17%). The mean age at the start of treatment of infants diagnosed in the screening program was 10.3 days. The screening program based on initial measurement of thyroid stimulating hormone in cord blood captures 97% of infants born in the Riyadh Al-Kharj Hospital Programme. The incidence of congenital hypothyroidism was 1:2759 live births with a female:male ratio of nearly 2:1. Congenital hypothyroidism infants had similar neonatal parameters as other infants. No seasonality in the incidence of congenital hypothyroidism was observed. In general, affected infants were started on thyroxine very soon after birth.

  4. [Congenital club foot].

    PubMed

    Waschak, K; Radler, C; Grill, F

    2009-01-01

    Congenital talipes equinovarus is the most common deformity of the lower limb. The adequate treatment of clubfeet is still a challenge for orthopaedic surgeons and requires well-founded knowledge of pathoanatomy and established therapeutical options. This refresher, in addition to pathoanatomical fundamentals, provides an update on diagnostic and therapeutical facilities. By reviewing the results of conservative and surgical treatment concepts and their discussion it shall contribute to optimal individual management of congenital talipes equinovarus.

  5. Heart transplantation in adults with congenital heart disease.

    PubMed

    Houyel, Lucile; To-Dumortier, Ngoc-Tram; Lepers, Yannick; Petit, Jérôme; Roussin, Régine; Ly, Mohamed; Lebret, Emmanuel; Fadel, Elie; Hörer, Jürgen; Hascoët, Sébastien

    2017-05-01

    With the advances in congenital cardiac surgery and postoperative care, an increasing number of children with complex congenital heart disease now reach adulthood. There are already more adults than children living with a congenital heart defect, including patients with complex congenital heart defects. Among these adults with congenital heart disease, a significant number will develop ventricular dysfunction over time. Heart failure accounts for 26-42% of deaths in adults with congenital heart defects. Heart transplantation, or heart-lung transplantation in Eisenmenger syndrome, then becomes the ultimate therapeutic possibility for these patients. This population is deemed to be at high risk of mortality after heart transplantation, although their long-term survival is similar to that of patients transplanted for other reasons. Indeed, heart transplantation in adults with congenital heart disease is often challenging, because of several potential problems: complex cardiac and vascular anatomy, multiple previous palliative and corrective surgeries, and effects on other organs (kidney, liver, lungs) of long-standing cardiac dysfunction or cyanosis, with frequent elevation of pulmonary vascular resistance. In this review, we focus on the specific problems relating to heart and heart-lung transplantation in this population, revisit the indications/contraindications, and update the long-term outcomes. Copyright © 2017. Published by Elsevier Masson SAS.

  6. Cavernous sinus syndrome: need for early diagnosis.

    PubMed

    Toro, Jaime; Burbano, Lisseth Estefania; Reyes, Saúl; Barreras, Paula

    2015-03-27

    Cavernous sinus syndrome (CSS) is a rare condition characterised by ophthalmoplegia, proptosis, ocular and conjunctival congestion, trigeminal sensory loss and Horner's syndrome. These signs and symptoms result from the involvement of the cranial nerves passing through the cavernous sinus. We report the case of a 53-year-old man with a history of daily stabbing headache associated with dizziness, progressive blurred vision, right ocular pain, ptosis and ophthalmoplegia. After working up the patient, a meningioma was identified as the cause of the CSS. Despite advances in neuroimaging techniques, in some cases, the aetiology of CSS remains difficult to determine. We highlight the clinical and radiological features of a meningioma, one of the causes of CSS. Early diagnosis and treatment of CSS play a key role in a better prognosis. 2015 BMJ Publishing Group Ltd.

  7. [Congenital equinovarus clubfoot].

    PubMed

    Seringe, R

    1999-06-01

    A congenital clubfoot is often associated with a neuromuscular disease, a chromosomal anomaly, or a syndrome. The present review will only study the idiopathic clubfoot seen in an otherwise normal child. It is considered nowadays that a clubfoot is secondary to a defect in the spontaneous "rotation-elevation" mechanism which should occur between the 9th and 10th week of fetal development. Several possible factors influence the embryonic development: genetic, neurologic, muscular, environmental, and toxic factors. Modern notions of anatomy and physiology of the foot allow a better understanding of the deformations seen in a clubfoot: calcaneo-forefoot block, talonavicular joint double "belonging", notion of "relative" hindfoot supination. The osteo-articular deformations involve mainly the talus, the calcaneus, the navicular. They are associated to articular stiffness secondary to soft tissue retractions like the posterolateral, anteromedial, and the anterolateral fibrous knots. Prenatal diagnosis can be made using the ultrasound which is usually performed at 20 weeks of gestation. Nevertheless, only the clinical exam at birth will evaluate the degree of severity of the clubfoot based upon its reducibility, the presence of skin creases, and the importance of muscular atrophy. Imaging techniques (especially standard x-ray) are useless diagnostic tools. They will be necessary for the follow-up, the evaluation of residual defects, and for the possible surgical indications. Conservative treatment is used first, and in the hands of experienced teams will give a sufficient correction in 70 to 80% of the patients. The surgical treatment is used to complete the correction obtained by conservative means. Surgical treatment will free the retracted soft tissues. Postoperatively the foot will be immobilized in the appropriate position for 2 to 3 months. Clubfoot treatments are associated with complications which have to be known to avoid them if possible and/or to be able to

  8. Duane retraction syndrome type 1 with Usher syndrome type 2: an unreported association.

    PubMed

    Khurana, Bhawna Piplani; Khurana, Aruj Kumar; Grover, Sumit

    2015-05-07

    Duane retraction syndrome is characterized by globe retraction and palpebral fissure narrowing on adduction, with restriction of abduction, adduction, or both. Usher syndrome type 2 consists of congenital bilateral sensorineural hearing loss and retinitis pigmentosa. The authors present a case with a yet unreported association between Duane retraction syndrome type 1 and Usher syndrome type 2. Copyright 2015, SLACK Incorporated.

  9. Craniofacial syndromes.

    PubMed

    Buchanan, Edward P; Xue, Amy S; Hollier, Larry H

    2014-07-01

    After studying this article, the participant should be able to: 1. Recognize the clinical presentations of commonly seen craniofacial syndromes. 2. Understand the most serious complications associated with each syndrome. 3. Formulate the best age-appropriate surgical plans. Craniofacial syndromes fall into two major categories-those associated with craniosynostosis, and those associated with clefts. Each has a different set of potential complications requiring a unique approach for surgical management. Craniosynostosis is a congenital disorder in which one or more of the cranial sutures fuses prematurely. The most common syndromes associated with this condition include Crouzon, Apert, Pfeiffer, Muenke, and Saethre-Chotzen syndromes. Surgical management of these children requires a multidisciplinary approach and close involvement of the family. Operations must take into consideration the growing potential of the bony structures. Common syndromes associated with clefts include Pierre Robin, Treacher Collins, Nager, Binder, and Stickler syndromes. Many of these children have severe airway issues requiring immediate address before operative reconstruction. As with syndromes associated with craniosynostosis, the key to management is a multidisciplinary approach focused on the right timing. The purpose of this article is to review the clinical presentation, care, and treatment of these patients.

  10. Congenital hand anomalies in Upper Egypt.

    PubMed

    Abulezz, Tarek; Talaat, Mohamed; Elsani, Asem; Allam, Karam

    2016-01-01

    Congenital hand anomalies are numerous and markedly variant. Their significance is attributed to the frequent occurrence and their serious social, psychological and functional impacts on patient's life. This is a follow-up study of 64 patients with hand anomalies of variable severity. All patients were presented to Plastic Surgery Department of Sohag University Hospital in a period of 24 months. This study revealed that failure of differentiation and duplication deformities were the most frequent, with polydactyly was the most common anomaly encountered. The mean age of presentation was 6 years and female to male ratio was 1.46:1. Hand anomalies were either isolated, associated with other anomalies or part of a syndrome. Incidence of congenital hand anomalies in Upper Egypt is difficult to be estimated due to social and cultural concepts, lack of education, poor registration and deficient medical survey. Management of hand anomalies should be individualised, carefully planned and started as early as possible to achieve the best outcome.

  11. Congenital lumbar vertebrae agenesis in a lamb

    PubMed Central

    Farajli Abbasi, Mohammad; Shojaei, Bahador; Azari, Omid

    2017-01-01

    Congenital agenesis of lumbar vertebrae was diagnosed in a day-old female lamb based on radiology and clinical examinations. There was no neurological deficit in hindlimb and forelimb associated with standing disability. Radiography of the abdominal region revealed absence of lumbar vertebrae. Necropsy confirmed clinical and radiographic results. No other anomaly or agenesis was seen macroscopically in the abdominal and thoracic regions as well as vertebral column. Partial absence of vertebral column has been reported in human and different animal species, as an independent occurrence or associated with other organs anomalies. The latter has been designated as caudal regression syndrome. Vertebral agenesis may arise from irregularity in the differentiation of somites to the sclerotome or sclerotome to the vertebral primordium. Most of the previously reported cases of agenesis were related to the lumbosacral region, lonely or along with other visceral absences. This case was the first report of congenital agenesis of lumbar vertebrae in a lamb. PMID:29326797

  12. Congenital lumbar vertebrae agenesis in a lamb.

    PubMed

    Farajli Abbasi, Mohammad; Shojaei, Bahador; Azari, Omid

    2017-01-01

    Congenital agenesis of lumbar vertebrae was diagnosed in a day-old female lamb based on radiology and clinical examinations. There was no neurological deficit in hindlimb and forelimb associated with standing disability. Radiography of the abdominal region revealed absence of lumbar vertebrae. Necropsy confirmed clinical and radiographic results. No other anomaly or agenesis was seen macroscopically in the abdominal and thoracic regions as well as vertebral column. Partial absence of vertebral column has been reported in human and different animal species, as an independent occurrence or associated with other organs anomalies. The latter has been designated as caudal regression syndrome. Vertebral agenesis may arise from irregularity in the differentiation of somites to the sclerotome or sclerotome to the vertebral primordium. Most of the previously reported cases of agenesis were related to the lumbosacral region, lonely or along with other visceral absences. This case was the first report of congenital agenesis of lumbar vertebrae in a lamb.

  13. The Nager acrofacial dysostosis syndrome with the tetralogy of Fallot.

    PubMed

    Thompson, E; Cadbury, R; Baraitser, M

    1985-10-01

    A male infant is described with mandibulofacial dysostosis and absent thumbs, consistent with the Nager acrofacial dysostosis syndrome. In addition, the tetralogy of Fallot was present. Major congenital heart malformations occur rarely in this syndrome.

  14. The Nager acrofacial dysostosis syndrome with the tetralogy of Fallot.

    PubMed Central

    Thompson, E; Cadbury, R; Baraitser, M

    1985-01-01

    A male infant is described with mandibulofacial dysostosis and absent thumbs, consistent with the Nager acrofacial dysostosis syndrome. In addition, the tetralogy of Fallot was present. Major congenital heart malformations occur rarely in this syndrome. Images PMID:4078872

  15. Prevalence of congenital amusia.

    PubMed

    Peretz, Isabelle; Vuvan, Dominique T

    2017-05-01

    Congenital amusia (commonly known as tone deafness) is a lifelong musical disorder that affects 4% of the population according to a single estimate based on a single test from 1980. Here we present the first large-based measure of prevalence with a sample of 20 000 participants, which does not rely on self-referral. On the basis of three objective tests and a questionnaire, we show that (a) the prevalence of congenital amusia is only 1.5%, with slightly more females than males, unlike other developmental disorders where males often predominate; (b) self-disclosure is a reliable index of congenital amusia, which suggests that congenital amusia is hereditary, with 46% first-degree relatives similarly affected; (c) the deficit is not attenuated by musical training and (d) it emerges in relative isolation from other cognitive disorder, except for spatial orientation problems. Hence, we suggest that congenital amusia is likely to result from genetic variations that affect musical abilities specifically.

  16. Prevalence of congenital amusia

    PubMed Central

    Peretz, Isabelle; Vuvan, Dominique T

    2017-01-01

    Congenital amusia (commonly known as tone deafness) is a lifelong musical disorder that affects 4% of the population according to a single estimate based on a single test from 1980. Here we present the first large-based measure of prevalence with a sample of 20 000 participants, which does not rely on self-referral. On the basis of three objective tests and a questionnaire, we show that (a) the prevalence of congenital amusia is only 1.5%, with slightly more females than males, unlike other developmental disorders where males often predominate; (b) self-disclosure is a reliable index of congenital amusia, which suggests that congenital amusia is hereditary, with 46% first-degree relatives similarly affected; (c) the deficit is not attenuated by musical training and (d) it emerges in relative isolation from other cognitive disorder, except for spatial orientation problems. Hence, we suggest that congenital amusia is likely to result from genetic variations that affect musical abilities specifically. PMID:28224991

  17. Estimating the burden of rubella virus infection and congenital rubella syndrome through a rubella immunity assessment among pregnant women in the Democratic Republic of the Congo: Potential impact on vaccination policy.

    PubMed

    Alleman, Mary M; Wannemuehler, Kathleen A; Hao, Lijuan; Perelygina, Ludmila; Icenogle, Joseph P; Vynnycky, Emilia; Fwamba, Franck; Edidi, Samuel; Mulumba, Audry; Sidibe, Kassim; Reef, Susan E

    2016-12-12

    Rubella-containing vaccines (RCV) are not yet part of the Democratic Republic of the Congo's (DRC) vaccination program; however RCV introduction is planned before 2020. Because documentation of DRC's historical burden of rubella virus infection and congenital rubella syndrome (CRS) has been minimal, estimates of the burden of rubella virus infection and of CRS would help inform the country's strategy for RCV introduction. A rubella antibody seroprevalence assessment was conducted using serum collected during 2008-2009 from 1605 pregnant women aged 15-46years attending 7 antenatal care sites in 3 of DRC's provinces. Estimates of age- and site-specific rubella antibody seroprevalence, population, and fertility rates were used in catalytic models to estimate the incidence of CRS per 100,000 live births and the number of CRS cases born in 2013 in DRC. Overall 84% (95% CI 82, 86) of the women tested were estimated to be rubella antibody seropositive. The association between age and estimated antibody seroprevalence, adjusting for study site, was not s