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Sample records for congenital horner syndrome

  1. Horner Syndrome

    MedlinePlus

    ... at birth Tumor of the hormonal and nervous systems (neuroblastoma) Unknown causes In some cases the cause of Horner syndrome cannot be identified. This is known as idiopathic Horner syndrome. By Mayo Clinic Staff . Mayo Clinic Footer Legal Conditions and Terms Any use of this site ...

  2. 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

  3. 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. ...

  4. [Irreversible Horner's syndrome after bilateral thoracoscopic sympathectomy].

    PubMed

    Vicente, P; Canelles, E; Díaz, A; Fons, A

    2014-02-01

    A 19 year-old boy who developed a right Horner's syndrome after a bilateral sympathectomy as a treatment for palmoplantar hyperhidrosis. Horner's syndrome is defined by the occurrence of miosis, ptosis and enophthalmos as a result of involvement of sympathetic innervation. This is quite rare, but identification is very important because it may also be an ominous sign secondary to a neoplasm, neurological diseases, or surgery of the sympathetic chain, as in our case. Copyright © 2010 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  5. First Rib Fracture Resulting in Horner's Syndrome.

    PubMed

    Lin, You-Cheng; Chuang, Ming-Tsung; Hsu, Chin-Hao; Tailor, Al-Rahim Abbasali; Lee, Jung-Shun

    2015-12-01

    First rib fractures and traumatic Horner's syndrome are both quite rare, which can make it difficult to properly diagnose the combination of these 2 conditions in the emergency department. These conditions may be associated with severe medical emergencies, such as ongoing carotid dissection. We present the case of a 33-year-old man who sustained fractures to his right second, third, and fourth ribs and a delay in the diagnosis of left Horner's syndrome after he was involved in a traffic accident. Left Horner's syndrome was caused by a left transverse fracture of the first rib. This fracture was not detected on chest radiographs and required a 3-dimensional reconstructed neck computed tomography scan for detection. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: In the diagnosis of carotid artery dissection, conventional angiography is the criterion standard but is considered invasive. CTA is less invasive, time-saving, and can show more anatomic structures in the neck in addition to the carotid arteries. It is a good screening diagnostic modality in the traumatology department. Although the treatments for Horner's syndrome and first rib fracture are conservative, the early diagnosis of both conditions can resolve the anxiety and uncertainty experienced by both doctors and patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. 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.

  7. Postganglionic horner syndrome in three patients with coincident middle ear infection.

    PubMed

    Spector, Robert H

    2008-09-01

    Three patients developed a postganglionic Horner syndrome during the course of an ipsilateral uncomplicated middle ear infection. The mechanism may be an effect on the middle ear caroticotympanic sympathetic plexus, for which there is considerable anatomic and physiologic evidence. Why Horner syndrome does not occur more often after middle ear infection is a mystery.

  8. 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.

  9. 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.

  10. Skin vasomotor hemiparesis followed by overactivity: characteristic thermography findings in a patient with Horner syndrome due to spinal cord infarction.

    PubMed

    Kobayashi, Makoto

    2016-04-01

    We present a 21-year-old female with Horner syndrome due to spinal cord infarction. In this patient, infrared thermography revealed a hemibody skin temperature increase followed by excessive focal decreases, indicating skin vasomotor hemiparesis and overactivity.

  11. Horner syndrome after unsuccessful venous port implantation by cannulation of the right internal jugular vein.

    PubMed

    Nowak, Łukasz R; Duda, Krzysztof; Mizianty, Marek; Wilczek, Małgorzata; Bieda, Tomasz

    2015-01-01

    Horner syndrome is a rare but likely underdiagnosed complication of internal jugular vein cannulation. We present a case of a young woman undergoing chemotherapy for gestational trophoblastic disease for whom venous port implantation was attempted due to poor peripheral vein access. Despite ultrasound guidance, the procedure was unsuccessful and complicated by a local haematoma, causing compression of the sympathetic nerves with Horner syndrome. The symptoms subsided within 3 weeks without treatment. The possible pathomechanisms of Horner syndrome after central venous cannulation are presented with suggested diagnostic and therapeutic approaches. Special emphasis must be placed on excluding carotid artery dissection because it carries the risk of subsequent cerebral vascular incidents. In the event of a carotid dissection, a multidisciplinary team must choose a pharmacological (antiplatelet drugs/anticoagulation) or interventional approach. Even with ultrasonography, central venous cannulation is not free of serious risks. In case of anisocoria following an uneventful procedure, diagnostic imaging of the vascular structures in the neck is mandatory for the exclusion of potentially serious complications, such as carotid dissection or venous thrombosis.

  12. Trigemino-autonomic headache and Horner syndrome as a first sign of granulomatous hypophysitis

    PubMed Central

    Kreitschmann-Andermahr, Ilonka; Fisse, Anna Lena; Börnke, Christian; Schroeder, Christoph; Pitarokoili, Kalliopi; Müller, Oliver; Lukas, Carsten; van de Nes, Johannes; Buslei, Rolf; Gold, Ralf; Ayzenberg, Ilya

    2017-01-01

    Objective: To report a rare case of incipient granulomatous hypophysitis presenting by atypical trigemino-autonomic cephalalgia (TAC) and Horner syndrome. Methods: The patient was investigated with repeated brain MRI, CSF examination, thoracic CT, Doppler and duplex ultrasound of the cerebral arteries, and extensive serologic screening for endocrine and autoimmune markers. Written informed consent was obtained from the patient for access to clinical files for research purposes and for publication. Results: We present a middle-aged woman with a history of an autoimmune pancreatitis type 2 who had therapy-refractory TAC with Horner syndrome. Initial cerebral MRI showed only indistinct and unspecific signs of a pathologic process. A biopsy revealed a granulomatous hypophysitis. The symptoms disappeared after transsphenoidal subtotal resection of the pituitary mass and anti-inflammatory therapy. Conclusions: This case elucidates that inflammatory pituitary diseases must be taken into account in case of atypical and refractory TAC, especially in patients with a history of autoimmune diseases. To our knowledge, the association between TAC accompanied by Horner syndrome and hypophysitis has not yet been described before. PMID:28243612

  13. Horner's syndrome in patients admitted to the intensive care unit that have undergone central venous catheterization: a prospective study.

    PubMed

    Butty, Z; Gopwani, J; Mehta, S; Margolin, E

    2016-01-01

    PurposeCentral venous catheterization (CVC) is estimated to be performed in millions of patients per year. Swan-Ganz catheters used for CVC are most often inserted into the internal jugular vein and during this procedure they may come into contact with the sympathetic chain. This study aims to determine the incidence of Horner's syndrome in patients admitted to intensive care unit that have undergone internal jugular CVC insertion during their admission and to determine whether ultrasonography-assisted insertion has decreased the frequency of this complication.Patients and methodsA total of 100 prospective patients admitted to the ICU were examined for the presence of anisocoria and ptosis after undergoing recent CVC. Presence of Horner's syndrome was confirmed by testing with 0.5% apraclonidine and looking for the reversal of anisocoria.ResultsFrequency of Horner's syndrome after CVC was 2% in a sample of 100 prospectively examined patients.ConclusionHorner's syndrome remains a relatively rare but definitive complication of CVC. ICU physicians should be educated about its existence and prevalence and ophthalmologists should inquire about any history of ICU admission necessitating CVC insertion in any patient presenting with Horner's 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. Horner syndrome

    MedlinePlus

    ... to a part of the brain called the brainstem Tumor in the top of the lung Injections ... 424. Thurtell MJ, Rucker JC. Pupillary and eyelid abnormalities. In: Daroff RB, Jankovic J, Mazziotta JC, Pomeroy ...

  16. 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

  17. 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 ...

  18. Congenital nephrotic syndrome.

    PubMed

    Hamed, Radi Ma

    2003-01-01

    The congenital nephrotic syndrome (CNS) is an uncommon disorder with onset of the nephrotic syndrome usually in the first three months of life. Several different diseases may cause the syndrome. These may be inherited, sporadic, acquired or part of a general malformation syndrome. The clinical course is marked by failure to thrive, recurrent life threatening bacterial infections, and early death from sepsis and/or uremia. A characteristic phenotype may be seen in children with CNS. The majority of reported cases of CNS are of the Finnish type (CNF). Although the role of the glomerular basement membrane has been emphasized as the barrier for retaining plasma proteins, recent studies have clearly shown that the slit diaphragm is the structure most likely to be the barrier in the glomerular capillary wall. The gene (NPHS1) was shown to encode a novel protein that was termed nephrin, due to its specific location in the kidney filter barrier, where it seems to form a highly organized filter structure. Nephrin is a transmembrane protein that probably forms the main building block of an isoporous zipper-like slit diaphragm filter structure. Defects in nephrin lead to the abnormal or absent slit diaphragm resulting in massive proteinuria and renal failure.

  19. Morning glory disk anomaly with ipsilateral capillary hemangioma, agenesis of the internal carotid artery, and Horner syndrome: a variant of PHACES syndrome?

    PubMed

    Puvanachandra, Narman; Heran, Manraj K; Lyons, Christopher J

    2008-10-01

    We describe a 6-week-old girl with a right upper lid capillary hemangioma, ipsilateral morning glory disk anomaly, microphthalmos, Mittendorf dot, and Horner syndrome. The ipsilateral internal carotid artery was also found to be absent. To our knowledge, this is the first patient to be reported with this group of findings. We suggest that this represents an overlap between morning glory disk and intracranial vascular abnormalities, a recognized association, and PHACES syndrome (posterior fossa malformations, hemangiomas, arterial anomalies, cardiac defects, eye, and sternal abnormalities). We discuss the common embryological basis for these abnormalities, which point to a widespread but highly variable disorder of mesodermal differentiation.

  20. Cervical Sympathetic Chain Schwannoma Masquerading as a Vagus Nerve Schwannoma Complicated by Postoperative Horner's Syndrome and Facial Pain: A Case Report.

    PubMed

    Baker, Austin T; Homewood, Tyler J; Baker, Terry R

    2018-06-09

    Cervical Sympathetic Chain Schwannomas (CSCS) of the carotid sheath are rare neoplasms that can be misdiagnosed on imaging. The following case documents a rare incident of a misdiagnosed CSCS with unusual outcomes of permanent Horner's syndrome and facial pain. A 36-year-old female presented with a slow-growing neck mass. CT and MRI led to a preoperative diagnosis of vagus nerve schwannoma (VNS). However, surgical treatment revealed the mass to be involved with the cervical sympathetic chain rather than the vagus nerve. The diagnosis was corrected to CSCS and the nerve was resected with the mass. The patient presented postoperatively with Horner's syndrome and severe facial pain. These symptoms persisted despite two years of medical management. Studies indicate that imaging trends used for distinction between VNS and CSCS show inconsistencies in making preoperative diagnoses. Recent literature reveals helpful criteria for improving diagnostic standards that assist with preoperative patient counseling. In addition, postoperative outcomes, such as temporary, asymptomatic Horner's syndrome are common in CSCS. The following case report exemplifies the difficulties in diagnosis and addresses the unique complications of facial pain and permanent Horner's syndrome. This case report examines postoperative outcomes and improves clinician awareness of the potential for misdiagnosis of a rare neoplasm and the recently improved diagnostic measures, providing for higher quality preoperative counseling. Future research is recommended to confirm and improve diagnostic guidelines and accuracy. Additional studies may focus on evaluating the effects of incorrect preoperative diagnosis on postoperative complication rates. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  1. Genetics Home Reference: congenital nephrotic syndrome

    MedlinePlus

    ... eventually leading to end-stage renal disease. NPHS1 gene mutations cause all cases of congenital nephrotic syndrome of ... is found in people of Finnish ancestry. NPHS1 gene mutations can cause congenital nephrotic syndrome in non-Finnish ...

  2. Anisocoria and Horner's Syndrome

    MedlinePlus

    ... and how they react to bright and dim lighting. Based on the evaluation, the doctor may wish ... the difference in pupil size increases in bright lighting, then the larger (mydriatic) pupil may be the ...

  3. [Congenital sensorineural deafness and associated syndromes].

    PubMed

    Moatti, L; Garabedian, E N; Lacombe, H; Spir-Jacob, C

    1990-01-01

    The etiology of perceptive deafness, especially the congenital variety, requires investigation. The presence of a variety of signs associated with deafness constitutes an "associated syndrome" and helps to define a possible genetic origin. These syndromes only represent a small percentage of overall causes of deafness in children, since at most they account for only 10% of cases. Certain syndromes are encountered more often or are well known, others are extremely rare or have only been described recently. The authors report six of these very rare syndromes discovered among their patients: a KID syndrome, a Leopard syndrome, a Norrie syndrome, a Jervell and Lange Nielsen syndrome, a recently described entity called CEE with deafness and an External Neuro-Cochleo-Pancreatic syndrome which would not appear to have been previously described.

  4. Congenital central hypoventilation syndrome mimicking mitochondrial disease.

    PubMed

    Rojnueangnit, Kitiwan; Descartes, Maria

    2018-03-01

    Later-onset congenital central hypoventilation syndrome (LO-CCHS) does not present only breathing problems but can be present as episodic multiple organs involvement. Our unique case demonstrated LO-CCHS should be considered in the differential diagnosis of mitochondrial diseases and having nontypical polysomnography result.

  5. Genetics Home Reference: congenital myasthenic syndrome

    MedlinePlus

    ... 1196/annals.1405.049. Citation on PubMed Engel AG, Shen XM, Selcen D, Sine SM. What have ... PubMed or Free article on PubMed Central Engel AG. Current status of the congenital myasthenic syndromes. Neuromuscul ...

  6. Genetics Home Reference: congenital central hypoventilation syndrome

    MedlinePlus

    ... M, Stevens CA, Berry-Kravis EM, Weese-Mayer DE. PHOX2B mutation-confirmed congenital central hypoventilation syndrome: presentation ... on PubMed Axelrod FB, Chelimsky GG, Weese-Mayer DE. Pediatric autonomic disorders. Pediatrics. 2006 Jul;118(1): ...

  7. Magnetic resonance imaging in congenital Brown syndrome.

    PubMed

    Kim, Jae Hyoung; Hwang, Jeong-Min

    2015-08-01

    Our aim was to elucidate the etiology of Brown syndrome by evaluating the trochlea position, morphologic characteristics of the extraocular muscles including superior oblique muscle/tendon complex, and the presence of the cranial nerves (CN) III, IV, and VI using magnetic resonance imaging (MRI) in eight patients with unilateral congenital Brown syndrome and one patient with bilateral congenital Brown syndrome. Nine consecutive patients diagnosed with congenital Brown syndrome had a comprehensive ocular examination and MRI for the CN III, CN VI, and the extraocular muscles. Five of the nine patients underwent additional high resolution MRI for CN IV. The distance from the annulus of Zinn to the trochlea was measured. Normal sized CN III, IV, and VI, as well as all extraocular muscles, could be identified bilaterally in all patients with available MRI. The distance from the annulus of Zinn to the trochlea was the same in both eyes. The findings for our patients, particularly in those who underwent additional high resolution MRI, did not provide evidence of a lack of CN IV as a cause of Brown syndrome.

  8. 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)

  9. Isolated and syndromic forms of congenital anosmia.

    PubMed

    Karstensen, H G; Tommerup, N

    2012-03-01

    Loss of smell (anosmia) is common in the general population and the frequency increases with age. A much smaller group have no memory of ever being able to smell and are classified as having isolated congenital anosmia (ICA). Families are rare, and tend to present in a dominant inheritance pattern. Despite a strong degree of heritability, no human disease-causing mutations have been identified. Anosmia is part of the clinical spectrum in various diseases, as seen in Kallmann syndrome, various ciliopathies and congenital insensitivity to pain. This review will focus on ICA through already published families and cases as well as syndromes where anosmia is part of the clinical disease spectrum. Furthermore, olfactory signal transduction pathway genes and animal models may shed light on potential candidate genes and pathways involved in ICA. © 2011 John Wiley & Sons A/S.

  10. Congenital Nephrotic Syndrome – Finish Type

    PubMed Central

    Spahiu, Lidvana; Merovci, Besart; Jashari, Haki; Këpuska, Arbnore Batalli; Rugova, Blerta Elezi

    2016-01-01

    Introduction: Identification of the NPHS1 gene, which encodes nephrin, was followed by many studies demonstrating its mutation as a frequent cause of congenital nephrotic syndrome (CNS). While this gene is found in 98% of Finnish children with this syndrome, non-Finnish cases have lower level of incidence ranging from 39 to 80%. Case report: This report describes the clinical presentation of a two-week-old neonate who presented with periorbital and lower extremities edema, abdominal distention, heavy proteinuria, serum hypoproteinemia and failure to thrive. Genetic analysis revealed NHPS1 gene mutation leading to CNS-Finnish type diagnosis. Conclusion: Through this case we want to create awareness about diagnosis and treatment challenges in developing countries for rare congenital diseases. PMID:27594755

  11. Poland syndrome a rare congenital anomaly.

    PubMed

    Ibrahim, Aliyu; Ramatu, Abdallah; Helen, Akhiwu

    2013-07-01

    Poland syndrome is a rare congenital anomaly classically consisting of unilateral hypoplasia of the sternocostal head of the pectoralis major muscle and ipsilateral brachysyndactyly. It was first described by Alfred Poland in 1840 and may occur with different gravity. Our patient is an eight-year-old Nigerian girl with left-sided anterior chest wall defect with no detectable structural heart abnormality but presented with repeated episodes of syncopal attacks following minor trauma to the anterior chest wall.

  12. Congenital heart defects in Williams syndrome.

    PubMed

    Yuan, Shi-Min

    2017-01-01

    Yuan SM. Congenital heart defects in Williams syndrome. Turk J Pediatr 2017; 59: 225-232. Williams syndrome (WS), also known as Williams-Beuren syndrome, is a rare genetic disorder involving multiple systems including the circulatory system. However, the etiologies of the associated congenital heart defects in WS patients have not been sufficiently elucidated and represent therapeutic challenges. The typical congenital heart defects in WS were supravalvar aortic stenosis, pulmonary stenosis (both valvular and peripheral), aortic coarctation and mitral valvar prolapse. The atypical cardiovascular anomalies include tetralogy of Fallot, atrial septal defects, aortic and mitral valvular insufficiencies, bicuspid aortic valves, ventricular septal defects, total anomalous pulmonary venous return, double chambered right ventricle, Ebstein anomaly and arterial anomalies. Deletion of the elastin gene on chromosome 7q11.23 leads to deficiency or abnormal deposition of elastin during cardiovascular development, thereby leading to widespread cardiovascular abnormalities in WS. In this article, the distribution, treatment and surgical outcomes of typical and atypical cardiac defects in WS are discussed.

  13. Hyperthyroidism hidden by congenital central hypoventilation syndrome.

    PubMed

    Fox, Danya A; Weese-Mayer, Debra E; Wensley, David F; Stewart, Laura L

    2015-05-01

    Congenital central hypoventilation syndrome (CCHS) is a rare neurocristopathy with severe central hypoventilation. CCHS results from a mutation in the paired-like homeobox 2B gene (PHOX2B). In addition to hypoventilation, patients with CCHS display a wide array of autonomic nervous system abnormalities, including decreased heart rate variability and abrupt sinus pauses, esophageal dysmotility, abnormal pupillary light response, and temperature dysregulation, to name a few. To date, there has been no documentation of a child with both CCHS and hyperthyroidism. We report the case of a young child with CCHS who presented with tachycardia, which was later found to be due to Grave's disease, after many months of investigation.

  14. Responses to Horner and Carr.

    ERIC Educational Resources Information Center

    Durand, V. Mark; And Others

    1997-01-01

    Five special educators (Durand, Bambara, Dunlap, Kennedy, and Wacker) respond to an article in the same issue by Horner and Carr entitled "Behavioral Support for Students with Severe Disabilities: Functional Assessment and Comprehensive Intervention." Respondents raise concerns regarding the range of intervention options, the behavioral…

  15. Congenital rubella syndrome in Haiti (Short communication).

    PubMed

    Golden, Nancy; Kempker, Russell; Khator, Parul; Summerlee, Robert; Fournier, Arthur

    2002-10-01

    To determine if there is an unrecognized problem of congenital rubella syndrome (CRS) in Haiti, a country without a national rubella immunization program. During March 2001 and June 2001, screening physicals were conducted on approximately 80 orphans at three orphanages in Haiti that accept disabled children. Children were classified as probable CRS cases based on established clinical criteria. Photo documentation of findings was obtained whenever possible. Six children met the criteria for probable CRS. Using data from surrounding Caribbean countries and from the United States of America prior to rubella immunization, we estimated that there are between 163 and 440 new cases of CRS per year in Haiti. CRS exists in Haiti, but its presence is generally unrecognized. A national rubella immunization policy should be considered.

  16. 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.

  17. Current Status of the Congenital Myasthenic Syndromes

    PubMed Central

    Engel, Andrew G.

    2011-01-01

    Congenital myasthenic syndromes (CMS) are heterogeneous disorders in which the safety margin of neuromuscular transmission is compromised by one or more specific mechanisms. Clinical, electrophysiologic, and morphologic studies have paved the way for detecting CMS-related mutations in proteins residing in the nerve terminal, the synaptic basal lamina, and in the postsynaptic region of the motor endplate. The disease proteins identified to date include choline acetyltransferase (ChAT), the endplate species of acetylcholinesterase (AChE), β2-laminin, the acetylcholine receptor (AChR), rapsyn, plectin, Nav1.4, the muscle specific protein kinase (MuSK), agrin, downstream of tyrosine kinase 7 (Dok-7), and glutamine-fructose-6-phosphate transaminase 1 (GFPT1). Myasthenic syndromes associated with centronuclear myopathies were recently recognized. Analysis of properties of expressed mutant proteins contributed to finding improved therapy for most CMS. Despite these advances, the molecular basis of some phenotypically characterized CMS remains elusive. Moreover, other types of CMS and disease genes likely exist and await discovery. PMID:22104196

  18. Congenital central hypoventilation syndrome: four families.

    PubMed

    Trivedi, Amit; Waters, Karen; Suresh, Sadasivam; Nair, Rashmi

    2011-12-01

    Congenital central hypoventilation syndrome (CCHS) is a rare condition that usually presents soon after birth and is potentially life-shortening if not treated. The defining abnormality is hypoventilation during sleep which requires life-long treatment with artificial ventilation. This syndrome may also be associated with generalised dysfunction of the autonomic nervous system and a sub-group with associated Hirschsprung's disease. The genetic basis of CCHS has been identified as mutations in the PHOX2B gene. We present four families, three with autosomal dominant inheritance and familial clustering, and one with a de novo mutation resulting in CCHS. We demonstrate that nasal mask ventilation from birth can provide adequate treatment and improved quality of life for these children. Phenotypic variability in expression of disease is seen in families with the same mutations in PHOX2B gene. The psychosocial costs of the disease and the unrecognised 'morbidity barter' that is part of current management needs to be factored into in all stages of management from childhood to adolescence to adulthood.

  19. Burden and impact of congenital syndromes and comorbidities among adults with congenital heart disease.

    PubMed

    Bracher, Isabelle; Padrutt, Maria; Bonassin, Francesca; Santos Lopes, Bruno; Gruner, Christiane; Stämpfli, Simon F; Oxenius, Angela; De Pasquale, Gabriella; Seeliger, Theresa; Lüscher, Thomas F; Attenhofer Jost, Christine; Greutmann, Matthias

    2017-08-01

    Our aim was to assess the overall burden of congenital syndromes and non-cardiac comorbidities among adults with congenital heart disease and to assess their impact on circumstances of living and outcomes. Within a cohort of 1725 adults with congenital heart defects (65% defects of moderate or great complexity) followed at a single tertiary care center, congenital syndromes and comorbidities were identified by chart review. Their association with arrhythmias, circumstances of living and survival was analyzed. Within the study cohort, 232 patients (13%) had a genetic syndrome, 51% at least one comorbidity and 23% ≥2 comorbidities. Most prevalent comorbidities were systemic arterial hypertension (11%), thyroid dysfunction (9%), psychiatric disorders (9%), neurologic disorders (7%), chronic lung disease (7%), and previous stroke (6%). In contrast to higher congenital heart defect complexity, the presence of comorbidities had no impact on living circumstances but patients with comorbidities were less likely to work full-time. Atrial arrhythmias were more common among patients with moderate/great disease complexity and those with comorbidities but were less common among patients with congenital syndromes (p<0.01 for all comparisons). Patients with ≥2 comorbidities had lower survival estimates compared to those with ≤1 comorbidity (p=0.013). Congenital syndromes and comorbidities are highly prevalent in adults with congenital heart disease followed at specialist centers and add to the overall complexity of care. The presence of these additional factors has an impact on living circumstances, is associated with arrhythmias and needs to be further explored as prognostic markers. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Congenital rubella syndrome surveillance in Honduras.

    PubMed

    Molina, Ida Berenice; Mendoza, Lourdes Otilia; Palma, María Aparicia

    2011-09-01

    Congenital rubella syndrome (CRS) surveillance was established in Honduras to determine the scope of the problem and assess the impact of vaccination. Implementation of the surveillance system required the drafting of national CRS epidemiological surveillance guidelines, the development of a laboratory diagnostic method, and training of physicians, nurses, and microbiologists in the Honduran hospital network and social security system on CRS surveillance guidelines. Honduras' experience with the surveillance of other vaccine-preventable diseases facilitated the implementation of hospital-based CRS surveillance. The surveillance system operates in 23 of the 25 public hospitals that offer services to children and at 2 social security hospitals; the private sector has not been integrated into this system. Clinical and technical staff, including representatives from various disciplines such as pediatrics, neonatology, general medicine, epidemiology, nursing, and microbiology, participate in the hospital network, as well as follow up on cases in accordance with the standardized guidelines, depending on their areas of expertise. Implementation of the CRS surveillance system requires technical guidelines, laboratory diagnostic capacity, and trained multidisciplinary human resources for its systematization and operation.

  1. 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.

  2. Rapsyn congenital myasthenic syndrome worsened by fluoxetine.

    PubMed

    Visser, Amy C; Laughlin, Ruple S; Litchy, William J; Benarroch, Eduardo E; Milone, Margherita

    2017-01-01

    Fluoxetine is a selective serotonin reuptake inhibitor and long-lived open channel blocker of the acetylcholine receptor, often used in the treatment of slow-channel congenital myasthenic syndromes (CMS). We report a 42-year-old woman who had a history of episodic limb weakness that worsened after initiation of fluoxetine for treatment of depression. Genetic testing for CMS revealed a homozygous pathogenic mutation in the rapsyn (RAPSN) gene (p.Asn88Lys). Electrodiagnostic testing was performed before and 1 month after discontinuation of fluoxetine. The 2 Hz repetitive nerve stimulation of the fibular and spinal accessory nerves showed a baseline decrement of 36% and 14%, respectively. One month after discontinuing fluoxetine, the spinal accessory nerve decrement was no longer present, and the decrement in the fibular nerve was improved at 17%. This case demonstrates worsening of both clinical and electrophysiologic findings in a patient with CMS secondary to a RAPSN mutation treated with fluoxetine. Muscle Nerve 55: 131-135, 2017. © 2016 Wiley Periodicals, Inc.

  3. Congenital hypoventilation syndrome and Hirschsprung's disease - Haddad syndrome: A neonatal case presentation.

    PubMed

    Jaiyeola, P; El-Metwally, D; Viscardi, R; Greene, C; Woo, H

    2015-01-01

    Congenital central hypoventilation syndrome (CCHS) is an uncommon cause of apnea in the newborn characterized by the occurrence of apnea predominantly during sleep. Haddad syndrome is CCHS with Hirschsprung's disease. We report a newborn with Haddad syndrome that had a family history of spinal muscular atrophy and discuss aspects of CCHS and important considerations in the evaluation of apnea in the term newborn.

  4. Spine deformities in rare congenital syndromes: clinical issues.

    PubMed

    Campbell, Robert M

    2009-08-01

    A focused review of the literature with regard to the important system abnormalities of patients with spinal deformities associated with exotic congenital syndromes with additional data from the author's own experience in assessment of patients with rare syndromes treated for thoracic insufficiency syndrome. The objectives of this study are to emphasize important medical considerations that influence the choice of surgical treatment of spinal deformity in patients with exotic congenital syndromes and point out preoperative strategies that reduce treatment morbidity and mortality of these patients. Individual experience is limited in the treatment of spine abnormality in rare exotic syndromes and the medical aspects of these syndromes that may impact spinal treatment are seldom discussed in detail in the orthopedic literature. For a successful outcome in the treatment of spinal deformity in these unique patients, a working knowledge of the unique pitfalls in their medical care is necessary in order to avoid morbidity and mortality during their treatment. The literature was reviewed for 6 exotic congenital syndromes with known or unreported spinal abnormalities and the author's personal 22-years experience of the treatment of thoracic insufficiency syndrome in the relevant congenital syndromes was summarized. Children with Marfan syndrome and spinal deformity may have serious cardiac abnormalities. Spontaneous dissection of the aortic root is a clear danger and patients should be monitored by serial echocardiograms. Prophylactic cardiac surgery may be necessary before spinal surgery is to be performed. Patients with Jeune syndrome have a high rate of proximal cervical stenosis and should undergo screening with cervical spine films at birth. Significant stenosis or instability may require decompression and cervical-occipital fusion. Arthrogryposis may be associated with a severe scoliosis and jaw contracture may make intubation difficult. Larsen syndrome may have

  5. 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

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

    PubMed Central

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

    2017-01-01

    Importance 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. Objective To report the ocular manifestations of congenital Zika syndrome with microcephaly in Colombia and Venezuela. Design, Setting, and Participants 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. Interventions 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. Main Outcomes and Measures Ophthalmic manifestations of congenital Zika syndrome. Results 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

  7. [Exudative enteropathy in congenital lymphedema-lymphangiectasia syndrome].

    PubMed

    Heruth, M; Müller, P; Liebscher, L; Kurze, G; Richter, T

    2006-01-01

    Congenital peripheral elephantiasiformic alterations are very rare in paediatric patients. In a patient with lymphangiectasia-lymphedema syndrome we demonstrate over a 8-year follow-up that not only cosmetic and social indications for surgical treatments but also internal care become important during the course. We report on a boy with congenital lymphedemas of the extremities and the genital region, which were several times surgically treated. The patient became symptomatic firstly with tetanic cramps caused by malabsorption syndrome due to intestinal lymphangiectasia at the age of 6 years. Synopsis of clinical and laboratory findings and the patient's course are pointing to a mild Hennekam syndrome with still unknown aetiology. The boy developed adequately with permanent oral substitution of electrolytes and vitamins, protein-rich diet, supplementation of medium-chain fatty acids and compressing bandages. Infusions of human albumin to correct persistent hypalbuminemia as well as cytostatic treatment with cyclophosphamide as a formal trial were ineffective and are not advisable, therefore.

  8. [Congenital syphillis presenting congenital nephrotic syndrome in two children and related data review].

    PubMed

    Xiao, Hui-jie; Liu, Jing-cheng; Zhong, Xu-hui

    2011-12-18

    To study the clinical features of congenital syphillis presenting congenital nephrotic syndrome (CNS) in children. Two cases diagnosed as congenital syphillis presenting CNS in our hospital were retrospectively analyzed and related data reviewed. The two children had edema, gross proteinuria, haematuria, hepatosplenomegaly, abdominal distention and anaema. Rapid plasmin regain (RPR) and treponema palidum hemagglutination assay (TPHA) were all positive. One chiild was also had renal biopsy and showed membraous nephropathy. Adequate penicillin therapy got satisfatory effects without steroid treatment. For children with early occurrence of proteinuria, edema accompanied by anaema, and hepatosplenomegaly, we should conside the possibility of syphillis nephropathy, which should be treated with enough dosage of penicillin in instead of steroid. Early diagnosis and treatmen could get complete recovery of CNS.

  9. Thromboembolism and congenital malformations: from Duane syndrome to thalidomide embryopathy.

    PubMed

    Parsa, Cameron F; Robert, Matthieu P

    2013-04-01

    To propose a pathophysiologic mechanism to unify a variety of disparate sporadic congenital malformations. Inductive and deductive analyses to correlate malformation laterality with asymmetries in thoracic anatomy, critical analysis of malformations with female predominance, and concepts of hydrodynamic pressure gradients in vascular growth were applied to the ensuing development of guiding tissue scaffolds for cellular proliferation, differentiation, and apoptosis. Duane syndrome may develop following a focal vascular insult to the sixth nerve trunk with axonal degeneration, allowing for substitutive innervation from third nerve axons to the lateral rectus muscle. Causative fibrin clots may originate from the venous system and paradoxically migrate through physiological right-to left shunts, or they may arise directly from the heart. Hence, the unilateral, left-sided, and female predominance of Duane syndrome results from the asymmetry in the thoracic anatomy and from thrombosis risk factors. Embolic occlusions may also alter local hemodynamic pressure gradients, leading to the compensatory enlargement and persistence of the fetal vasculature and may dysregulate tissue growth. Within the eye, this results in forms of Peters anomaly, unilateral congenital cataracts, and the morning glory disc anomaly, all in the vascular territory of the carotid arteries that also share a propensity for left-sided involvement in girls. Most aberrant misinnervation phenomena (eg, jaw-winking syndrome, crocodile tear syndrome, Brown syndrome, and congenital fibrosis syndrome) and, by extrapolation, the hypoplasia or dysgenesis of noncephalic anatomical structures (including limbs) may be similarly explained. Such malformations will occur more frequently under thrombogenic conditions, such as those induced by thalidomide. Fibrin emboli and focal hypoperfusion may explain the development of many sporadic congenital malformations.

  10. 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

  11. [Basan's syndrome: Congenital absence of dermatoglyphs and milia].

    PubMed

    Gagey-Caron, V; Stalder, J-F; Barbarot, S

    2009-05-01

    White micropapules are uncommon on the face newborns and are mainly due to sebaceous hyperplasia, or more rarely to milia. In some cases they may result from milia and profuse milia suggest rare diseases. We report the case of a newborn presenting with profuse congenital milia on the face that resolved spontaneously within a few months. This eruption revealed Basan's syndrome, a rare, autosomal dominant inherited dermatosis described as the association of profuse facial milia, acral bullae, absence of dermatoglyphs, and palmoplantar hypohydrosis.

  12. The syndrome of perisylvian polymicrogyria with congenital arthrogryposis.

    PubMed

    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

    2010-08-01

    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. 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. 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. 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. Copyright 2009 Elsevier B.V. All rights reserved.

  13. 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.

  14. [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.

  15. Congenital Zika syndrome: Pitfalls in the placental barrier.

    PubMed

    Robinson, Nia; Mayorquin Galvan, Evangelina E; Zavala Trujillo, Isidro G; Zavala-Cerna, Maria G

    2018-05-15

    Much progress with respect to congenital Zika virus (ZIKV) pathogenesis has been achieved after the 2015 outbreak in Brazil. It is now accepted that ZIKV is vertically transmitted, infects cells of the developing central nervous system and the placenta, yet it is unclear to what extent placental affection contributes to the development of congenital ZIKV. The association between fulminant villitis and severe fetal involvement emerges as a possibility. ZIKV is unique among the Flaviviruses in its ability to be sexually transmitted, possibly responsible for its teratogenicity. Furthermore, there is controversy over the participation of antibody dependent enhancement (ADE) in patients with non-neutralizing anti-Flavivirus antibodies, a phenomenon previously recognized in serious DENV infections. Our aim was to analyze information regarding the contribution of the placental barrier as an actual player in neonatal ZIKV. Therefore, we underwent a systematic review with keywords "Zika virus" and "ZIKV". Articles were screened for relevance concerning the topics of microcephaly, transplacental transmission, sexual transmission, and ADE. We identified variables that affect the severity of congenital Zika syndrome: age of gestation at maternal infection, the extent of placental disruption (villitis), sexual transmission, initial viral replication at the uterine wall, anti-DENV antibodies, and the possibility of antibody-mediated transcytosis of ZIKV through the placenta. These questions may not seem relevant when Zika becomes endemic, and we are no longer witness to the extreme clinical sequelae seen when the virus moves through an immunologically naïve population; however, characterizing the pathogenesis of congenital Zika syndrome will continue to further our understanding. Copyright © 2018 John Wiley & Sons, Ltd.

  16. 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.

  17. Keratitis-Ichthyosis-Deafness syndrome: A rare congenital disorder

    PubMed Central

    Shanker, Vinay; Gupta, Mudita; Prashar, Aditi

    2012-01-01

    Keratitis-Icthyosis-Deafness syndrome is a rare congenital disorder characterized by keratitis, ichthyosis, and deafness. We report a 13 year old female child who presented with diffuse alopecia of the scalp and body. There was erythrokeratoderma of face and discrete hyperkeratotic hyperpigmented papulo plaque lesions on the body. Patient also had reticulate hyperkeratosis of palms and soles. There was history of recurrent episodes of folliculitis over the scalp and body. There was no evidence of any malignancy. Eye involvement in the form of bilateral vascularising keratitis was present. There was bilateral mixed hearing loss. PMID:23130264

  18. Leigh syndrome with Fukuyama congenital muscular dystrophy: a case report.

    PubMed

    Kondo, Hidehito; Tanda, Koichi; Tabata, Chihiro; Hayashi, Kohei; Kihara, Minako; Kizaki, Zenro; Taniguchi-Ikeda, Mariko; Mori, Masato; Murayama, Kei; Ohtake, Akira

    2014-09-01

    We report the first case of Leigh syndrome (LS) with Fukuyama congenital muscular dystrophy (FCMD). A neonate suffered from lactic acidosis and subsequently presented with poor feeding, muscle weakness, hypotonia, cardiopulmonary dysfunction, and hydrocephalus. He died at 17 months. The findings of brain magnetic resonance imaging indicated some specific features of both LS and FCMD, and FCMD gene mutation was detected. Decreased mitochondrial respiratory complex I and II activity was noted. Mitochondrial DNA sequencing showed no pathogenic mutation. A case with complex I+II deficiency has rarely been reported, suggesting a nuclear gene mutation. Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  19. Characterization of dermatoglyphics in PHOX2B-confirmed congenital central hypoventilation syndrome.

    PubMed

    Todd, Emily S; Scott, Nicole M; Weese-Mayer, Debra E; Weinberg, Seth M; Berry-Kravis, Elizabeth M; Silvestri, Jean M; Kenny, Anna S; Hauptman, Susan A; Zhou, Lili; Marazita, Mary L

    2006-08-01

    Individuals with congenital central hypoventilation syndrome have characteristic variants in the PHOX2B gene (primarily polyalanine expansion mutations). The PHOX2B gene acts as a transcriptional activator in the promotion of pan-neuronal differentiation in the autonomic nervous system during early embryologic development, with a primary role in the sympathetic noradrenergic phenotype in vertebrates. Because sympathetic innervation has been hypothesized to affect the development of dermatoglyphic pattern types, we hypothesized that individuals with PHOX2B-confirmed congenital central hypoventilation syndrome would have characteristic dermatoglyphic patterning and that the dermatoglyphic phenotype would be related to the disease-defining PHOX2B genotype. Dermatoglyphic pattern type frequency, left/right symmetry, and genotype/phenotype correlation were assessed for 33 individuals with PHOX2B-confirmed congenital central hypoventilation syndrome and compared with published control data. Dermatoglyphic pattern type frequencies were altered in congenital central hypoventilation syndrome cases versus controls. In particular, there was an increase of arches in females and ulnar loops in males, with the largest differences for the left hand and for individuals with both congenital central hypoventilation syndrome and Hirschsprung disease. Dissimilarity scores between the congenital central hypoventilation syndrome and congenital central hypoventilation syndrome + Hirschsprung disease cases were not significantly different, nor were dissimilarity scores between all of the female and all of the male cases. No significant association was found between the number of polyalanine repeats in the PHOX2B genotypic category and dermatoglyphic pattern frequencies in the congenital central hypoventilation syndrome study groups. These results represent the first report describing specific dermatoglyphic patterning in congenital central hypoventilation syndrome and suggest a

  20. 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.

  1. 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

  2. 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

  3. 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

  4. Neonatal diabetes mellitus, congenital hypothyroidism, hepatic fibrosis, polycystic kidneys, and congenital glaucoma: a new autosomal recessive syndrome?

    PubMed

    Taha, Doris; Barbar, Maha; Kanaan, Hassan; Williamson Balfe, John

    2003-10-15

    We report on two sibs (of 4) with a syndrome of minor facial anomalies, proportionate IUGR, neonatal non-autoimmune diabetes mellitus (NDM), severe congenital hypothyroidism (CH), cholestasis, congenital glaucoma, and polycystic kidneys. Liver disease progressed to hepatic fibrosis. The renal disease was characterized by large kidneys and multiple small cysts with deficient corticomedullary junction differentiation and normal kidney function. The phenotype observed in the two sibs was identical. Although a combination of liver, kidney, and pancreatic involvement has been described in Ivemark syndrome (hepato-renal-pancreatic syndrome), the coexistence of NDM, CH, and glaucoma in both sibs suggests the possibility that this combination of manifestations describes a new autosomal recessive syndrome. Mutation analysis for several candidate genes is warranted. Copyright 2003 Wiley-Liss, Inc.

  5. Heterogeneity in Phenotype of Usher-Congenital Hyperinsulinism Syndrome

    PubMed Central

    Al Mutair, Angham N.; Brusgaard, Klaus; Bin-Abbas, Bassam; Hussain, Khalid; Felimban, Naila; Al Shaikh, Adnan; Christesen, Henrik T.

    2013-01-01

    OBJECTIVE To evaluate the phenotype of 15 children with congenital hyperinsulinism (CHI) and profound hearing loss, known as Homozygous 11p15-p14 Deletion syndrome (MIM #606528). RESEARCH DESIGN AND METHODS Prospective clinical follow-up and genetic analysis by direct sequencing, multiplex ligation-dependent probe amplification, and microsatellite markers. RESULTS Genetic testing identified the previous described homozygous deletion in 11p15, USH1C:c.(90+592)_ABCC8:c.(2694–528)del. Fourteen patients had severe CHI demanding near-total pancreatectomy. In one patient with mild, transient neonatal hypoglycemia and nonautoimmune diabetes at age 11 years, no additional mutations were found in HNF1A, HNF4A, GCK, INS, and INSR. Retinitis pigmentosa was found in two patients aged 9 and 13 years. No patients had enteropathy or renal tubular defects. Neuromotor development ranged from normal to severe delay with epilepsy. CONCLUSIONS The phenotype of Homozygous 11p15-p14 Deletion syndrome, or Usher-CHI syndrome, includes any severity of neonatal-onset CHI and severe, sensorineural hearing loss. Retinitis pigmentosa and nonautoimmune diabetes may occur in adolescence. PMID:23150283

  6. 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.

  7. 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.

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

    PubMed Central

    Sakallı, Hale; Bucak, Hakan İbrahim

    2012-01-01

    Summary Background: 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. Case Report: 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 30th 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. Conclusions: Because of the clinical and laboratory simulations between the various diseases that lead to hypokalemic-hypochloremic metabolic alkalosis, patients must be evaluated carefully. PMID:23569535

  9. 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…

  10. Spastic quadriplegia in Down syndrome with congenital duodenal stenosis/atresia.

    PubMed

    Kurosawa, Kenji; Enomoto, Keisuke; Tominaga, Makiko; Furuya, Noritaka; Sameshima, Kiyoko; Iai, Mizue; Take, Hiroshi; Shinkai, Masato; Ishikawa, Hiroshi; Yamanaka, Michiko; Matsui, Kiyoshi; Masuno, Mitsuo

    2012-06-01

    Down syndrome is an autosomal chromosome disorder, characterized by intellectual disability and muscle hypotonia. Muscle hypotonia is observed from neonates to adulthood in Down syndrome patients, but muscle hypertonicity is extremely unusual in this syndrome. During a study period of nine years, we found three patients with severe spastic quadriplegia among 20 cases with Down syndrome and congenital duodenal stenosis/atresia (3/20). However, we could find no patient with spastic quadriplegia among 644 cases with Down syndrome without congenital duodenal stenosis/atresia during the same period (0/644, P < 0.05). Further, we did not find any cases with spastic quadriplegia among 17 patients with congenital duodenal stenosis/atresia without Down syndrome admitted during the same period to use as a control group (0/17, P < 0.05). Our results suggest that congenital duodenal stenosis/atresia is a potential risk factor for spastic quadriplegia in patients with Down syndrome. Long-term survival is improving, and the large majority of people with Down syndrome are expected to live well into adult life. Management and further study for the various problems, representing a low prevalence but serious and specific to patients with Down syndrome, are required to improve their quality of life. © 2012 The Authors. Congenital Anomalies © 2012 Japanese Teratology Society.

  11. 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)

  12. 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.

  13. [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.

  14. Congenital myopathy associated with the triadin knockout syndrome

    PubMed Central

    Redhage, Keeley R.; Tester, David J.; Ackerman, Michael J.; Selcen, Duygu

    2017-01-01

    Objective: Triadin is a component of the calcium release complex of cardiac and skeletal muscle. Our objective was to analyze the skeletal muscle phenotype of the triadin knockout syndrome. Methods: We performed clinical evaluation, analyzed morphologic features by light and electron microscopy, and immunolocalized triadin in skeletal muscle. Results: A 6-year-old boy with lifelong muscle weakness had a triadin knockout syndrome caused by compound heterozygous null mutations in triadin. Light microscopy of a deltoid muscle specimen shows multiple small abnormal spaces in all muscle fibers. Triadin immunoreactivity is absent from type 1 fibers and barely detectable in type 2 fibers. Electron microscopy reveals focally distributed dilation and degeneration of the lateral cisterns of the sarcoplasmic reticulum and loss of the triadin anchors from the preserved lateral cisterns. Conclusions: Absence of triadin in humans can result in a congenital myopathy associated with profound pathologic alterations in components of the sarcoplasmic reticulum. Why only some triadin-deficient patients develop a skeletal muscle phenotype remains an unsolved question. PMID:28202702

  15. Congenital diaphragmatic hernia as a part of Nance-Horan syndrome?

    PubMed

    Kammoun, Molka; Brady, Paul; De Catte, Luc; Deprest, Jan; Devriendt, Koenraad; Vermeesch, Joris Robert

    2018-03-01

    Nance-Horan syndrome is a rare X-linked developmental disorder characterized by bilateral congenital cataract, dental anomalies, facial dysmorphism, and intellectual disability. Here, we identify a patient with Nance-Horan syndrome caused by a new nonsense NHS variant. In addition, the patient presented congenital diaphragmatic hernia. NHS gene expression in murine fetal diaphragm was demonstrated, suggesting a possible involvement of NHS in diaphragm development. Congenital diaphragmatic hernia could result from NHS loss of function in pleuroperitoneal fold or in somites-derived muscle progenitor cells leading to an impairment of their cells migration.

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

    PubMed Central

    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. PMID:29085165

  17. Congenital rubella syndrome in a child born to Liberian refugees: clinical and public health perspectives.

    PubMed

    Plotinsky, Rachel N; Talbot, Elizabeth A; Kellenberg, Joan E; Reef, Susan E; Buseman, Sandra K; Wright, Karen D; Modlin, John F

    2007-05-01

    We describe a case of congenital rubella syndrome with typical stigmata in an infant born in New Hampshire to Liberian refugees. The infant's clinical specimens were tested for rubella. Rubella immunity status was sought for contacts. The infant's specimen cultures grew wild-type rubella virus; serum immunoglobulin M and G were positive. Eighteen of 20 contacts were rubella-immune. Family's transit history, mother's vaccination history, and infant's estimated gestational age supported congenital infection acquired overseas. Clinicians should maintain vigilance for congenital rubella syndrome in infants with relevant stigmata, particularly those whose mothers are from countries with nonexistent or recently implemented rubella vaccination programs.

  18. 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.

  19. Ethical considerations with the management of congenital central hypoventilation syndrome.

    PubMed

    Massie, John; Gillam, Lynn

    2015-05-01

    Congenital central hypoventilation syndrome (CCHS) is a well-recognized disorder of the autonomic nervous system caused by mutations in the PHOX2B gene. The most characteristic feature is failure of ventilatory control, resulting in the need for respiratory support while asleep, and in some cases when awake also. Most cases present in infancy or early childhood. Technological advances allow patients with mild to moderate phenotypesto receive adequate support by non-invasive ventilation (NIV), or diaphragm pacing (or combination of the two) avoiding the need for long-term ventilation by tracheostomy. Daytime functioning of patients with CCHS who require sleep-time ventilation only is expected to be good, with some additional surveillance to ensure they don't accidentally fall asleep without respiratory support available. Some children with CCHS have other complications, such as Hirschprung's disease, learning difficulties, and cardiac arrhythmias (leading in some instances to heart block and the requirement for a pacemaker). In a few cases, patients can develop neurogenic malignancies. Parents bear a significant burden for the care of their child with CCHS including provision of NIV at home, close monitoring, and regular surveillance for complications. Information about patients with CCHS comes from databases in the United States and Europe, but these don't include infants or children for whom ventilator support was not offered. In this paper we use a case study to explore the ethical issues of provision of treatment, or non-treatment, of children with CCHS. © 2014 Wiley Periodicals, Inc.

  20. Congenital central hypoventilation syndrome: diagnostic and management challenges.

    PubMed

    Kasi, Ajay S; Perez, Iris A; Kun, Sheila S; Keens, Thomas G

    2016-01-01

    Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder with failure of central control of breathing and of the autonomic nervous system function due to a mutation in the paired-like homeobox 2B (PHOX2B) gene. Affected patients have absent or negligible ventilatory sensitivity to hypercapnia and hypoxemia, and they do not exhibit signs of respiratory distress when challenged with hypercarbia or hypoxia. The diagnosis of CCHS must be confirmed with PHOX2B gene mutation. Generally, the PHOX2B mutation genotype can aid in anticipating the severity of the phenotype. They require ventilatory support for life. Home assisted ventilation options include positive pressure ventilation via tracheostomy, noninvasive positive pressure ventilation, and diaphragm pacing via phrenic nerve stimulation, but each strategy has its associated limitations and challenges. Since all the clinical manifestations of CCHS may not manifest at birth, periodic monitoring and early intervention are necessary to prevent complications and improve outcome. Life-threatening arrhythmias can manifest at different ages and a normal cardiac monitoring study does not exclude future occurrences leading to the dilemma of timing and frequency of cardiac rhythm monitoring and treatment. Given the rare incidence of CCHS, most health care professionals are not experienced with managing CCHS patients, particularly those with diaphragm pacers. With early diagnosis and advances in home mechanical ventilation and monitoring strategies, many CCHS children are surviving into adulthood presenting new challenges in their care.

  1. 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.

  2. 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.

  3. Genetic Landscape of Congenital Myasthenic Syndromes From Turkey: Novel Mutations and Clinical Insights.

    PubMed

    Yiş, Uluç; Becker, Kerstin; Kurul, Semra Hız; Uyanik, Gökhan; Bayram, Erhan; Haliloğlu, Göknur; Polat, Ayşe İpek; Ayanoğlu, Müge; Okur, Derya; Tosun, Ayşe Fahriye; Serdaroğlu, Gül; Yilmaz, Sanem; Topaloğlu, Haluk; Anlar, Banu; Cirak, Sebahattin; Engel, Andrew G

    2017-07-01

    Congenital myasthenic syndromes are clinically and genetically heterogeneous disorders of neuromuscular transmission. Most are treatable, but certain subtypes worsen with cholinesterase inhibitors. This underlines the importance of genetic diagnosis. Here, the authors report on cases with genetically proven congenital myasthenic syndromes from Turkey. The authors retrospectively reviewed their experience of all patients with congenital myasthenic syndromes, referred over a 5-year period (2011-2016) to the Child Neurology Department of Dokuz Eylül University, Izmir, Turkey. In addition, PubMed was searched for published cases of genetically proven congenital myasthenic syndromes originating from Turkey. In total, the authors identified 43 (8 new patients, 35 recently published patients) cases. Defects in the acetylcholine receptor (n = 15; 35%) were the most common type, followed by synaptic basal-lamina associated (n = 14; 33%) and presynaptic syndromes (n = 10; 23%). The authors had only 3 cases (7%) who had defects in endplate development. One patient had mutation GFPT1 gene (n = 1; 2%). Knowledge on congenital myasthenic syndromes and related genes in Turkey will lead to prompt diagnosis and treatment of these rare neuromuscular disorders.

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

    PubMed

    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; Beeson, David

    2015-09-01

    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

  5. 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

  6. The Perlman syndrome: familial renal dysplasia with Wilms tumor, fetal gigantism and multiple congenital anomalies.

    PubMed

    Neri, G; Martini-Neri, M E; Katz, B E; Opitz, J M

    1984-09-01

    We describe a familial syndrome of renal dysplasia, Wilms tumor, hyperplasia of the endocrine pancreas, fetal gigantism, multiple congenital anomalies and mental retardation. This condition was previously described by Perlman et al [1973, 1975] and we propose to call it the "Perlman syndrome." It appears to be transmitted as an autosomal recessive trait. The possible relationships between dysplasia, neoplasia and malformation are discussed.

  7. 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.

  8. 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

  9. 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

  10. Congenital Mirror Movements in Gorlin Syndrome: A Case Report With DTI and Functional MRI Features.

    PubMed

    Sag, Erdal; Gocmen, Rahsan; Yildiz, F Gokcem; Ozturk, Zeynelabidin; Temucin, Cagri; Teksam, Ozlem; Utine, Eda

    2016-03-01

    Congenital mirror movements are rare conditions that define the inability to perform unimanual movements. Gorlin syndrome, also known as nevoid basal cell carcinoma syndrome, is a genetic disorder with multiple nevi predisposing to basal cell carcinoma, odontogenic keratocysts, and skeletal malformations. Herein we report on an adolescent patient with Gorlin syndrome and coexisting congenital mirror movements. To our knowledge, this is the first patient in the literature who has both of these very rare conditions. Copyright © 2016 by the American Academy of Pediatrics.

  11. Congenital yellow nail syndrome: a case report and its relationship to nonimmune fetal hydrops.

    PubMed

    Nanda, Arti; Al-Essa, Fahad H; El-Shafei, Wael M; Alsaleh, Qasem A

    2010-01-01

    Yellow nail syndrome (YNS) is an uncommon disorder characterized by a triad of nail dystrophy, lymphedema, and pleural effusion. It is rare in children and congenital occurrence of YNS has been very rarely described. We report a 2-year-old Arab boy having congenital yellow nail syndrome with mild facial dysmorphism and bilateral conjunctival pigmentation born to consanguineous parents. One of his older siblings had died of nonimmune fetal hydrops (NIFH). The case supports the genetic basis of yellow nail syndrome with a possible relationship to nonimmune fetal hydrops. © 2010 Wiley Periodicals, Inc.

  12. 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.

  13. Echocardiographic findings in infants with presumed congenital Zika syndrome: Retrospective case series study

    PubMed Central

    Santos, Cleusa C.; Feitosa, Fabiana G.; Ribeiro, Maria C.; Menge, Paulo; Lira, Izabelle M.

    2017-01-01

    Objective To report the echocardiographic evaluation of 103 infants with presumed congenital Zika syndrome. Methods An observational retrospective study was performed at Instituto de Medicina Integral Prof. Fernando Figueira (IMIP), Recife, Brazil. 103 infants with presumed congenital Zika syndrome. All infants had microcephaly and head computed tomography findings compatible with congenital Zika syndrome. Zika IgM antibody was detected in cerebrospinal fluid samples of 23 infants. In 80 infants, the test was not performed because it was not available at that time. All infants had negative serology for HIV, syphilis, rubella, cytomegalovirus and toxoplasmosis. A complete transthoracic two-dimensional, M-mode, continuous wave and pulsed wave Doppler and color Doppler echocardiographic (PHILIPS HD11XE or HD15) examination was performed on all infants. Results 14/103 (13.5%) echocardiograms were compatible with congenital heart disease: 5 with an ostium secundum atrial septal defect, 8 had a hemodynamically insignificant small apical muscular ventricular septal defect and one infant with dyspnea had a large membranous ventricular septal defect. The echocardiograms considered normal included 45 infants with a persistent foramen ovale and 16 with a minimum patent ductus arteriosus. Conclusions Preliminarily this study suggests that congenital Zika syndrome may be associated with an increase prevalence of congenital heart disease. However the types of defects noted were septal defects, a proportion of which would not be hemodynamically significant. PMID:28426680

  14. 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

  15. 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.

  16. Bartter syndrome type III and congenital anomalies of the kidney and urinary tract: an antenatal presentation.

    PubMed

    Westland, Rik; Hack, Wilfried W; van der Horst, Henricus J R; Uittenbogaard, Lukas B; van Hagen, Johanna M; van der Valk, Paul; Kamsteeg, Erik J; van den Heuvel, Lambert P; van Wijk, Joanna A E

    2012-12-01

    Bartter syndrome encompasses a variety of inheritable renal tubular transport disorders characterized by hypokalemia and hypochloremic metabolic alkalosis. Bartter syndrome Type III is caused by genetic alterations in the chloride channel kidney B (CLCNKB) gene and often presents in the first 2 years of life, known as classic Bartter syndrome. However, in rare cases Bartter syndrome Type III has an antenatal presentation with polyhydramnios, premature delivery and severe dehydration in the first weeks of life. Associations between congenital anomalies of the kidney and urinary tract and Bartter syndrome are extremely rare. This case report presents a girl with Bartter syndrome Type III due to a homozygous CLCNKB mutation and bilateral congenital anomalies of the kidney and urinary tract. In addition, we describe the antenatal presentation as well as its perinatal management.

  17. Syndromes with salivary dysfunction predispose to tooth wear: Case reports of congenital dysfunction of major salivary glands, Prader-Willi, congenital rubella, and Sjögren's syndromes.

    PubMed

    Young, W; Khan, F; Brandt, R; Savage, N; Razek, A A; Huang, Q

    2001-07-01

    Four cases-of congenital dysfunction of the major salivary glands as well as of Prader-Willi, congenital rubella, and Sjögren's syndromes-were identified in a series of 500 patients referred for excessive tooth wear. Although there was evidence of consumption of highly acidic drinks, some occlusal parafunction, and unacceptable toothbrushing habits, salivary dysfunction was the salient factor predisposing a patient to tooth wear in these syndromal cases. The 500 subjects have been characterized either as having medical conditions and medications that predispose them to xerostomia or lifestyles in which workplace- and sports-related dehydration lead to reduced salivary flow. Normal salivation, by buffering capacity, clearance by swallowing, pellicle formation, and capacity for remineralization of demineralized enamel, protects the teeth from extrinsic and intrinsic acids that initiate dental erosion. Thus, the syndromes, unrelated in many respects, underline the importance of normal salivation in the protection of teeth against tooth wear by erosion, attrition, and abrasion.

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

    PubMed

    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; Lochmüller, Hanns

    2016-08-01

    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. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

  19. 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

  20. [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.

  1. Unit 6, downstream from Horner Street Bridge Johnstown Local ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Unit 6, downstream from Horner Street Bridge - Johnstown Local Flood Protection Project, Beginning on Conemaugh River approx 3.8 miles downstream from confluence of Little Conemaugh & Stony Creek Rivers at Johnstown, Johnstown, Cambria County, PA

  2. [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.

  3. Percutaneous Embolization of Congenital Portosystemic Venous Fistula in an Infant with Down Syndrome

    PubMed Central

    Tanya Chun, Pattaraporn; Files, Matthew; Vo, Nghia; McAdams, Ryan M.

    2013-01-01

    Congenital intrahepatic portosystemic venous shunts are rare vascular malformations often associated with severe complications. We describe a term male infant with Down syndrome with high output heart failure secondary to a congenital arterial to portal venous fistula that was diagnosed by Doppler ultrasound. Percutaneous embolizations of the left hepatic vein, portal vein, and communicating fistulas were performed without complications, resulting in clinical improvement. A subsequent hepatic ultrasound demonstrated resolution of the pathologic fistulous communication and shunting effects. PMID:24171135

  4. 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.

  5. 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

    2018-06-01

    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% versus 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% versus 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 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

  6. 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

  7. 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

  8. 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)

  9. [Congenital Heart Disease in Children with Down Syndrome: What Has Changed in the Last Three Decades?

    PubMed

    Dias, Filipa Mestre; Cordeiro, Susana; Menezes, Isabel; Nogueira, Graça; Teixeira, Ana; Marques, Marta; Abecasis, Miguel; Anjos, Rui

    2016-10-01

    The prevalence of Down syndrome has increased in the last 30 years; 55% of these children have congenital heart disease. A retrospective longitudinal cohort study; clinical data from 1982 to 2013 databases with the diagnosis of Down syndrome or trisomy 21 in a reference hospital in pediatric cardiology and cardiac surgery. to assess the progress in the last three decades of cardiological care given to children with Down syndrome and congenital heart disease. We studied 102 patients with Down syndrome and congenital heart disease subjected to invasive therapy: corrective or palliative cardiac surgery and therapeutic catheterization. The referral age was progressively earlier in patients referred in the first year of life. The most frequent diagnosis was complete atrioventricular sptal defect (41%). There was a trend towards increasingly early corrective surgery in patients under 12 months (p < 0.001). Since 2000, the large majority of patients were operated before reaching six months of age. The main cardiac complications were rhythm dysfunction and low output. More frequent noncardiac complications were pulmonary and infectious. The 30-day mortality rate was 3/102 cases (2.9%). Of patients in follow-up, 89% are in NYHA class I. The early surgical correction seen over the past 15 years follows the approach suggested in the literature. The observed 30-day mortality rate is overlapping international results. Patients with Down syndrome subjected to corrective surgery of congenital heart disease have an excellent long-term functional capacity.

  10. Agrin mutations lead to a congenital myasthenic syndrome with distal muscle weakness and atrophy.

    PubMed

    Nicole, Sophie; Chaouch, Amina; Torbergsen, Torberg; Bauché, Stéphanie; de Bruyckere, Elodie; Fontenille, Marie-Joséphine; Horn, Morten A; van Ghelue, Marijke; Løseth, Sissel; Issop, Yasmin; Cox, Daniel; Müller, Juliane S; Evangelista, Teresinha; Stålberg, Erik; Ioos, Christine; Barois, Annie; Brochier, Guy; Sternberg, Damien; Fournier, Emmanuel; Hantaï, Daniel; Abicht, Angela; Dusl, Marina; Laval, Steven H; Griffin, Helen; Eymard, Bruno; Lochmüller, Hanns

    2014-09-01

    Congenital myasthenic syndromes are a clinically and genetically heterogeneous group of rare diseases resulting from impaired neuromuscular transmission. Their clinical hallmark is fatigable muscle weakness associated with a decremental muscle response to repetitive nerve stimulation and frequently related to postsynaptic defects. Distal myopathies form another clinically and genetically heterogeneous group of primary muscle disorders where weakness and atrophy are restricted to distal muscles, at least initially. In both congenital myasthenic syndromes and distal myopathies, a significant number of patients remain genetically undiagnosed. Here, we report five patients from three unrelated families with a strikingly homogenous clinical entity combining congenital myasthenia with distal muscle weakness and atrophy reminiscent of a distal myopathy. MRI and neurophysiological studies were compatible with mild myopathy restricted to distal limb muscles, but decrement (up to 72%) in response to 3 Hz repetitive nerve stimulation pointed towards a neuromuscular transmission defect. Post-exercise increment (up to 285%) was observed in the distal limb muscles in all cases suggesting presynaptic congenital myasthenic syndrome. Immunofluorescence and ultrastructural analyses of muscle end-plate regions showed synaptic remodelling with denervation-reinnervation events. We performed whole-exome sequencing in two kinships and Sanger sequencing in one isolated case and identified five new recessive mutations in the gene encoding agrin. This synaptic proteoglycan with critical function at the neuromuscular junction was previously found mutated in more typical forms of congenital myasthenic syndrome. In our patients, we found two missense mutations residing in the N-terminal agrin domain, which reduced acetylcholine receptors clustering activity of agrin in vitro. Our findings expand the spectrum of congenital myasthenic syndromes due to agrin mutations and show an unexpected

  11. Congenital myasthenic syndromes due to mutations in ALG2 and ALG14.

    PubMed

    Cossins, Judith; Belaya, Katsiaryna; Hicks, Debbie; Salih, Mustafa A; Finlayson, Sarah; Carboni, Nicola; Liu, Wei Wei; Maxwell, Susan; Zoltowska, Katarzyna; Farsani, Golara Torabi; Laval, Steven; Seidhamed, Mohammed Zain; Donnelly, Peter; Bentley, David; McGowan, Simon J; Müller, Juliane; Palace, Jacqueline; Lochmüller, Hanns; Beeson, David

    2013-03-01

    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 linkage analysis, whole-exome and whole-genome sequencing to determine the underlying defect in patients with an inherited limb-girdle pattern of myasthenic weakness. We identify ALG14 and ALG2 as novel genes in which mutations cause a congenital myasthenic syndrome. Through analogy with yeast, ALG14 is thought to form a multiglycosyltransferase complex with ALG13 and DPAGT1 that catalyses the first two committed steps of asparagine-linked protein glycosylation. We show that ALG14 is concentrated at the muscle motor endplates and small interfering RNA silencing of ALG14 results in reduced cell-surface expression of muscle acetylcholine receptor expressed in human embryonic kidney 293 cells. ALG2 is an alpha-1,3-mannosyltransferase that also catalyses early steps in the asparagine-linked glycosylation pathway. Mutations were identified in two kinships, with mutation ALG2p.Val68Gly found to severely reduce ALG2 expression both in patient muscle, and in cell cultures. Identification of DPAGT1, ALG14 and ALG2 mutations as a cause of congenital myasthenic syndrome underscores the importance of asparagine-linked protein glycosylation for proper functioning of the neuromuscular junction. These syndromes form part of the wider spectrum of congenital disorders of glycosylation caused by impaired asparagine-linked glycosylation. It is likely that further genes encoding components of this pathway will be associated with congenital myasthenic syndromes or impaired neuromuscular transmission as part of a more severe multisystem disorder. Our findings suggest that treatment with cholinesterase inhibitors may improve muscle function in many of the congenital disorders of glycosylation.

  12. 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.

  13. The Perlman syndrome: familial renal dysplasia with Wilms tumor, fetal gigantism and multiple congenital anomalies. 1984.

    PubMed

    Neri, Giovanni; Martini-Neri, Maria Enrica; Katz, Ben E; Opitz, John M

    2013-11-01

    The ensuing paper by Professor Giovanni Neri and colleagues was originally published in 1984, American Journal of Medical Genetics 19:195–207. The original article described a new family with a condition that the authors designated as the Perlman syndrome. This disorder, while uncommon, is an important multiple congenital anomaly and dysplasia syndrome; the causative gene was recently identified. This paper is a seminal work and is graciously republished by Wiley-Blackwell in the Special Festschrift issue honoring Professor Neri. We describe a familial syndrome of renal dysplasia, Wilms tumor, hyperplasia of the endocrine pancreas, fetal gigantism, multiple congenital anomalies and mental retardation. This condition was previously described by Perlman et al. [1973, 1975] and we propose to call it the "Perlman syndrome." It appears to be transmitted as an autosomal recessive trait. The possible relationships between dysplasia, neoplasia and malformation are discussed. © 2013 Wiley Periodicals, Inc.

  14. Syndromic Hirschsprung's disease and associated congenital heart disease: a systematic review.

    PubMed

    Duess, Johannes W; Puri, Prem

    2015-08-01

    Hirschsprung's disease (HD) occurs as an isolated phenotype in 70% of infants and is associated with additional congenital anomalies or syndromes in approximately 30% of patients. The cardiac development depends on neural crest cell proliferation and is closely related to the formation of the enteric nervous system. HD associated with congenital heart disease (CHD) has been reported in 5-8% of cases, with septation defects being the most frequently recorded abnormalities. However, the prevalence of HD associated with CHD in infants with syndromic disorders is not well documented. This systematic review was designed to determine the prevalence of CHD in syndromic HD. A systematic review of the literature using the keywords "Hirschsprung's disease", "aganglionosis", "congenital megacolon", "congenital heart disease" and "congenital heart defect" was performed. Resulting publications were reviewed for epidemiology and morbidity. Reference lists were screened for additional relevant studies. A total of fifty-two publications from 1963 to 2014 reported data on infants with HD associated with CHD. The overall reported prevalence of HD associated with CHD in infants without chromosomal disorders was 3%. In infants with syndromic disorders, the overall prevalence of HD associated with CHD ranged from 20 to 80 % (overall prevalence 51%). Septation defects were recorded in 57% (atrial septal defects in 29%, ventricular septal defects in 32%), a patent ductus arteriosus in 39%, vascular abnormalities in 16%, valvular heart defects in 4% and Tetralogy of Fallot in 7%. The prevalence of HD associated with CHD is much higher in infants with chromosomal disorders compared to infants without associated syndromes. A routine echocardiogram should be performed in all infants with syndromic HD to exclude cardiac abnormalities.

  15. A unique case of Shwachman-Diamond syndrome presenting with congenital hypopituitarism.

    PubMed

    Jivani, Nurin; Torrado-Jule, Carmen; Vaiselbuh, Sarah; Romanos-Sirakis, Eleny

    2016-11-01

    Shwachman-Diamond syndrome (SDS) is an autosomal recessive bone marrow failure syndrome typically characterized by neutropenia and pancreatic dysfunction, although phenotypic presentations vary, and the endocrine phenotype is not well-described. We report a unique case of a patient with SDS who initially presented with hypoglycemia and micropenis in the newborn period and was diagnosed with congenital hypopituitarism. We are not aware of any other cases of SDS documented with this combination of complex endocrinopathies.

  16. Impact of noncardiac congenital and genetic abnormalities on outcomes in hypoplastic left heart syndrome.

    PubMed

    Patel, Angira; Hickey, Edward; Mavroudis, Constantine; Jacobs, Jeffrey P; Jacobs, Marshall L; Backer, Carl L; Gevitz, Melanie; Mavroudis, Constantine D

    2010-06-01

    Hypoplastic left heart syndrome may coexist with noncardiac congenital defects or genetic syndromes. We explored the impact of such lesions on outcomes after staged univentricular palliation. Society of Thoracic Surgeons database 2002 to 2006: Children diagnosed with hypoplastic left heart syndrome who underwent stage 1 Norwood (n = 1,236), stage 2 superior cavopulmonary anastamosis (n = 702) or stage 3 Fontan (n = 553) procedures were studied. In-hospital mortality, postoperative complications, and length of stay were compared at each stage between those with and without noncardiac-genetic defects. Congenital Heart Surgeons' Society database 1994 to 2001: All 703 infants enrolled in the Congenital Heart Surgeons' Society critical left ventricular outflow tract obstruction study who underwent primary stage 1 palliation were reviewed. The impact of noncardiac defects-syndromes on survival was explored using multivariable parametric models with bootstrap bagging. Society of Thoracic Surgeons database: Stage 1 in-hospital mortality (26% vs 20%, p = 0.04) and mean postoperative length of stay (42 versus 31 days, p < 0.0001) were greater, and postoperative complications significantly more prevalent in infants with noncardiac-genetic defects. Congenital Heart Surgeons' Society database: Noncardiac-genetic defects were present in 55 (8%). Early hazard for death after Norwood was significantly worse in infants with noncardiac defects-syndromes (p = 0.008). Chromosomal defects (n = 14) were highly unfavorable: the early risk of death was doubled (10-year survival 25 +/- 9% vs 54 +/- 2%, p = 0.005). Turner syndrome accounted for the majority of chromosomal defects in this population (11 of 14, 79%). Mode of death was rarely attributable to the noncardiac-genetic defect. Survival in hypoplastic left heart syndrome is strongly influenced by the presence of noncardiac abnormalities. Strategies to improve mortality in infants with noncardiac abnormalities should be explored

  17. 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…

  18. Perioperative considerations in a newly described subtype of congenital long QT syndrome.

    PubMed

    Joseph-Reynolds, Ann; Auden, Steve; Sobczyzk, Walter

    1997-05-01

    An infant with a newly-described subtype of congenital long QT syndrome is presented, along with her perioperative management on three separate occasions. During each anaesthetic characteristic arrhythmias occurred. The available literature and rational approaches to these high risk patients are reviewed. 1997 Blackwell Science Ltd.

  19. Perioperative considerations in a newly described subtype of congenital long QT syndrome.

    PubMed

    Joseph-Reynolds, A M; Auden, S M; Sobczyzk, W L

    1997-01-01

    An infant with a newly-described subtype of congenital long QT syndrome is presented, along with her perioperative management on three separate occasions. During each anaesthetic characteristic arrhythmias occurred. The available literature and rational approaches to these high risk patients are reviewed.

  20. 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.

  1. 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.

  2. Improving multivariate Horner schemes with Monte Carlo tree search

    NASA Astrophysics Data System (ADS)

    Kuipers, J.; Plaat, A.; Vermaseren, J. A. M.; van den Herik, H. J.

    2013-11-01

    Optimizing the cost of evaluating a polynomial is a classic problem in computer science. For polynomials in one variable, Horner's method provides a scheme for producing a computationally efficient form. For multivariate polynomials it is possible to generalize Horner's method, but this leaves freedom in the order of the variables. Traditionally, greedy schemes like most-occurring variable first are used. This simple textbook algorithm has given remarkably efficient results. Finding better algorithms has proved difficult. In trying to improve upon the greedy scheme we have implemented Monte Carlo tree search, a recent search method from the field of artificial intelligence. This results in better Horner schemes and reduces the cost of evaluating polynomials, sometimes by factors up to two.

  3. Profuse congenital familial milia with absent dermatoglyphics (Basan's Syndrome): description of a new family.

    PubMed

    Luna, Paula Carolina; Larralde, Margarita

    2012-01-01

    Milia are common, small, keratin-containing cysts frequently seen in all age groups. They may arise spontaneously or develop after a variety of stimuli. They can be found alone or as part of syndromes. We present a female neonate born not only with profuse facial milia, but also with acral bullae and absent dermatoglyphics. Similar features were seen in several members of her family. These findings correspond to the syndrome known as Basan's syndrome, a rare autosomal-dominant inherited dermatosis characterized by profuse congenital milia, transient neonatal acral bullae, and absence of dermatoglyphics. © 2011 Wiley Periodicals, Inc.

  4. Congenital leukemoid reaction followed by fatal leukemia. A case with Down's syndrome.

    PubMed

    Lin, H P; Menaka, H; Lim, K H; Yong, H S

    1980-10-01

    A serial clinical, hematologic, and cytogenetic study was done on a baby with Down's syndrome in whom a myeloid leukemoid reaction developed at birth that spontaneously regressed within a month only to relapse two years later to an acute undifferentiated stem cell leukemia. He died 1 1/2 months after onset. The unresolved controversy of the diagnosis of the congenital leukemia-like state is discussed. The importance of following up such patients with apparent remission of their congenital leukemia-like disorder is emphasized.

  5. Congenital hepatic fibrosis in a child with Prader-Willi syndrome: a novel association.

    PubMed

    Al Sarkhy, Ahmed; Hassan, Saeed; Alasmi, Mona; Assiri, Asaad Muhammed; Alkuraya, Fowzan S

    2014-01-01

    Prader-Willi syndrome (PWS) is a rare genetic disorder caused by deletion or unexpression of the chromosome 15 (q 11-13). Symptomatologies include hypotonia, hyperphagia, cognitive impairment, and characteristic dysmorphic profile. Here, we report a 4-year-old boy with PWS who presented with complications of congenital hepatic fibrosis. The uniparental heterodisomy makes it unlikely that the hepatic fibrosis was caused by unmasking of a recessive mutation on the maternal chromosome 15 although we cannot exclude the possibility of a recessively inherited mutation elsewhere given the parental consanguinity. This is the first report of congenital hepatic fibrosis in PWS.

  6. 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…

  7. 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.

  8. [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.

  9. Antenatal diagnosis of congenital heart disease and Down's syndrome: the potential effect on the practice of paediatric cardiology.

    PubMed Central

    Abu-Harb, M.; Wyllie, J.; Hey, E.; Richmond, S.; Wren, C.

    1995-01-01

    OBJECTIVE--To predict the effect of antenatal ultrasound screening for congenital heart disease and maternal serum screening of Down's syndrome on the practice of paediatric cardiology and paediatric cardiac surgery. DESIGN--A retrospective and prospective ascertainment of all congenital heart disease diagnosed in infancy in 1985-1991. SETTING--One English health region. PATIENTS--All congenital heart disease diagnosed in infancy by echocardiography, cardiac catheterisation, surgery, or necropsy was classified as "complex", "significant", or "minor" and as "detectable" or "not detectable" on a routine antenatal ultrasound scan. RESULTS--1347 infants had congenital heart disease which was "complex" in 13%, "significant" in 55%, and "minor" in 32%. 15% of cases were "detectable" on routine antenatal ultrasound. Assuming 20% detection and termination of 67% of affected pregnancies, liveborn congenital heart disease would be reduced by 2%, infant mortality from congenital heart disease by 5%, and paediatric cardiac surgical activity by 3%. Maternal screening for Down's syndrome, assuming 75% uptake, 60% detection, and termination of all affected pregnancies, would reduce liveborn cases of Down's syndrome by 45%, liveborn cases of congenital heart disease by 3.5%, and cardiac surgery by 2.6%. CONCLUSIONS--Screening for congenital heart disease using the four chamber view in routine obstetric examinations and maternal serum screening for Down's syndrome is likely to have only a small effect on the requirements for paediatric cardiology services and paediatric cardiac surgery. PMID:7547001

  10. 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.

  11. A Rare Cause of Cyanosis: Hepatopulmonary Syndrome Caused by Congenital Extrahepatic Portosystemic Shunt

    PubMed Central

    Ding, Xue-Yan; Chen, Feng; Zhao, Xian-Xian; Wu, Hong; Chen, Shao-Ping; Qin, Yong-Wen

    2011-01-01

    A 19-year-old male patient presented cyanosis and dyspnoea because of the presence of multiple pulmonary arteriovenous fistulas resulting in oxygen desaturation. The CTA revealed that intestinal and splenic venous blood bypasses the liver and drains into the inferior vena cava. This is the first reported case of hepatopulmonary syndrome caused by congenital extrahepatic portosystemic shunt in which intestinal and splenic venous blood bypasses the liver and drains into the inferior vena cava. PMID:22937464

  12. Variants in SLC18A3, vesicular acetylcholine transporter, cause congenital myasthenic syndrome

    PubMed Central

    O'Grady, Gina L.; Verschuuren, Corien; Yuen, Michaela; Webster, Richard; Menezes, Manoj; Fock, Johanna M.; Pride, Natalie; Best, Heather A.; Benavides Damm, Tatiana; Turner, Christian; Lek, Monkol; Engel, Andrew G.; North, Kathryn N.; Clarke, Nigel F.; MacArthur, Daniel G.; Kamsteeg, Erik-Jan

    2016-01-01

    Objective: To describe the clinical and genetic characteristics of presynaptic congenital myasthenic syndrome secondary to biallelic variants in SLC18A3. Methods: Individuals from 2 families were identified with biallelic variants in SLC18A3, the gene encoding the vesicular acetylcholine transporter (VAChT), through whole-exome sequencing. Results: The patients demonstrated features seen in presynaptic congenital myasthenic syndrome, including ptosis, ophthalmoplegia, fatigable weakness, apneic crises, and deterioration of symptoms in cold water for patient 1. Both patients demonstrated moderate clinical improvement on pyridostigmine. Patient 1 had a broader phenotype, including learning difficulties and left ventricular dysfunction. Electrophysiologic studies were typical for a presynaptic defect. Both patients showed profound electrodecrement on low-frequency repetitive stimulation followed by a prolonged period of postactivation exhaustion. In patient 1, this was unmasked only after isometric contraction, a recognized feature of presynaptic disease, emphasizing the importance of activation procedures. Conclusions: VAChT is responsible for uptake of acetylcholine into presynaptic vesicles. The clinical and electrographic characteristics of the patients described are consistent with previously reported mouse models of VAChT deficiency. These findings make it very likely that defects in VAChT due to variants in SLC18A3 are a cause of congenital myasthenic syndrome in humans. PMID:27590285

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

    PubMed Central

    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

    2017-01-01

    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. PMID:29030384

  14. Congenital hyperinsulinism and Poland syndrome in association with 10p13-14 duplication.

    PubMed

    Giri, Dinesh; Patil, Prashant; Hart, Rachel; Didi, Mohammed; Senniappan, Senthil

    2017-01-01

    Poland syndrome (PS) is a rare congenital condition, affecting 1 in 30 000 live births worldwide, characterised by a unilateral absence of the sternal head of the pectoralis major and ipsilateral symbrachydactyly occasionally associated with abnormalities of musculoskeletal structures. A baby girl, born at 40 weeks' gestation with birth weight of 3.33 kg (-0.55 SDS) had typical phenotypical features of PS. She had recurrent hypoglycaemic episodes early in life requiring high concentration of glucose and glucagon infusion. The diagnosis of congenital hyperinsulinism (CHI) was biochemically confirmed by inappropriately high plasma concentrations of insulin and C-peptide and low plasma free fatty acids and β-hydroxyl butyrate concentrations during hypoglycaemia. Sequencing of ABCC8 , KCNJ11 and HNF4A did not show any pathogenic mutation. Microarray analysis revealed a novel duplication in the short arm of chromosome 10 at 10p13-14 region. This is the first reported case of CHI in association with PS and 10p duplication. We hypothesise that the HK1 located on the chromosome 10 encoding hexokinase-1 is possibly linked to the pathophysiology of CHI. Congenital hyperinsulinism (CHI) is known to be associated with various syndromes.This is the first reported association of CHI and Poland syndrome (PS) with duplication in 10p13-14.A potential underlying genetic link between 10p13-14 duplication, PS and CHI is a possibility.

  15. Congenital hyperinsulinism and Poland syndrome in association with 10p13–14 duplication

    PubMed Central

    Giri, Dinesh; Patil, Prashant; Hart, Rachel; Didi, Mohammed

    2017-01-01

    Summary Poland syndrome (PS) is a rare congenital condition, affecting 1 in 30 000 live births worldwide, characterised by a unilateral absence of the sternal head of the pectoralis major and ipsilateral symbrachydactyly occasionally associated with abnormalities of musculoskeletal structures. A baby girl, born at 40 weeks’ gestation with birth weight of 3.33 kg (−0.55 SDS) had typical phenotypical features of PS. She had recurrent hypoglycaemic episodes early in life requiring high concentration of glucose and glucagon infusion. The diagnosis of congenital hyperinsulinism (CHI) was biochemically confirmed by inappropriately high plasma concentrations of insulin and C-peptide and low plasma free fatty acids and β-hydroxyl butyrate concentrations during hypoglycaemia. Sequencing of ABCC8, KCNJ11 and HNF4A did not show any pathogenic mutation. Microarray analysis revealed a novel duplication in the short arm of chromosome 10 at 10p13–14 region. This is the first reported case of CHI in association with PS and 10p duplication. We hypothesise that the HK1 located on the chromosome 10 encoding hexokinase-1 is possibly linked to the pathophysiology of CHI. Learning points: Congenital hyperinsulinism (CHI) is known to be associated with various syndromes. This is the first reported association of CHI and Poland syndrome (PS) with duplication in 10p13–14. A potential underlying genetic link between 10p13–14 duplication, PS and CHI is a possibility. PMID:28458900

  16. Ocular abnormalities in congenital Zika syndrome: a case report, and review of the literature.

    PubMed

    Guevara, Jade Gieseke; Agarwal-Sinha, Swati

    2018-06-09

    As the number of children with Zika virus-related complications grows, the long-term developmental trajectory and its effects on families are unknown. We present the first known case of congenital Zika syndrome seen at our institution with significant fundus findings. A 3-day-old Hispanic baby girl presented with severe microcephaly of 24 cm and temperature instability at birth. Her mother had traveled to Honduras early in pregnancy and testing of amniotic fluid was positive for Zika virus via polymerase chain reaction. A dilated fundus examination was significant for bilateral severe colobomatous chorioretinal atrophy of the macula and pigmentary changes. Neonatal magnetic resonance imaging revealed diffuse lissencephaly with decreased brain volume, atrophic corpus callosum and brainstem, periventricular calcifications, and ventriculomegaly of the lateral ventricles. Our patient, who presented with the first known case of congenital Zika syndrome in Northern Florida, demonstrated profound bilateral colobomatous chorioretinal atrophy of the macula. The ophthalmologic findings along with severe microcephaly emphasize the neurotropism of the Zika virus, and ultimately are indicative of poor developmental and visual prognosis for affected infants. With the increased prevalence of Zika virus, ophthalmologists should be aware of the associated findings and the importance of an eye-screening examination with a dilated fundus examination within 1 month of life of infants in which congenital Zika syndrome is suspected. A multidisciplinary care approach is essential for the care of affected infants and their families.

  17. FOXG1 Is Responsible for the Congenital Variant of Rett Syndrome

    PubMed Central

    Ariani, Francesca; Hayek, Giuseppe; Rondinella, Dalila; Artuso, Rosangela; Mencarelli, Maria Antonietta; Spanhol-Rosseto, Ariele; Pollazzon, Marzia; Buoni, Sabrina; Spiga, Ottavia; Ricciardi, Sara; Meloni, Ilaria; Longo, Ilaria; Mari, Francesca; Broccoli, Vania; Zappella, Michele; Renieri, Alessandra

    2008-01-01

    Rett syndrome is a severe neurodevelopmental disease caused by mutations in the X-linked gene encoding for the methyl-CpG-binding protein MeCP2. Here, we report the identification of FOXG1-truncating mutations in two patients affected by the congenital variant of Rett syndrome. FOXG1 encodes a brain-specific transcriptional repressor that is essential for early development of the telencephalon. Molecular analysis revealed that Foxg1 might also share common molecular mechanisms with MeCP2 during neuronal development, exhibiting partially overlapping expression domain in postnatal cortex and neuronal subnuclear localization. PMID:18571142

  18. Congenital heart disease and genetic syndromes: new insights into molecular mechanisms.

    PubMed

    Calcagni, Giulio; Unolt, Marta; Digilio, Maria Cristina; Baban, Anwar; Versacci, Paolo; Tartaglia, Marco; Baldini, Antonio; Marino, Bruno

    2017-09-01

    Advances in genetics allowed a better definition of the role of specific genetic background in the etiology of syndromic congenital heart defects (CHDs). The identification of a number of disease genes responsible for different syndromes have led to the identification of several transcriptional regulators and signaling transducers and modulators that are critical for heart morphogenesis. Understanding the genetic background of syndromic CHDs allowed a better characterization of the genetic basis of non-syndromic CHDs. In this sense, the well-known association of typical CHDs in Down syndrome, 22q11.2 microdeletion and Noonan syndrome represent paradigms as chromosomal aneuploidy, chromosomal microdeletion and intragenic mutation, respectively. Area covered: For each syndrome the anatomical features, distinctive cardiac phenotype and molecular mechanisms are discussed. Moreover, the authors include recent genetic findings that may shed light on some aspects of still unclear molecular mechanisms of these syndromes. Expert commentary: Further investigations are needed to enhance the translational approach in the field of genetics of CHDs. When there is a well-established definition of genotype-phenotype (reverse medicine) and genotype-prognosis (predictive and personalized medicine) correlations, hopefully preventive medicine will make its way in this field. Subsequently a reduction will be achieved in the morbidity and mortality of children with CHDs.

  19. Does canal wall down mastoidectomy benefit syndromic children with congenital aural stenosis?

    PubMed

    Sjogren, Phayvanh P; Gurgel, Richard K; Park, Albert H

    2016-11-01

    To determine whether a canal wall down mastoidectomy can provide long-term benefit for children with aural stenosis. Retrospective case series of children with congenital aural stenosis having undergone a canal wall down mastoidectomy over a twelve-year period at a tertiary children's hospital. Data from thirteen children who underwent a total of twenty canal wall down mastoidectomies for aural stenosis were reviewed. The mean age at surgery was 7.1 years (range, 3.3-12.3 years). All patients had genetic syndromes including Trisomy 21 (n = 7), Trisomy 21 and Pierre Robin sequence (n = 1), Angelmann (n = 1), Cri-du-chat (n = 1), Branchio-oto-renal syndrome (n = 1), Spina bifida (n = 1) and Nager syndrome (n = 1). Seven (54%) children underwent bilateral canal wall down mastoidectomies. All thirteen ears that could not be visualized preoperatively had improved ease of office examination following surgery. Only one patient required revision surgery and all canals were patent at the last clinic visit. The mean follow-up was 4.9 years. There were no cases of facial nerve injury or cerebrospinal fluid leak. Syndromic children with congenital aural stenosis with poorly pneumatized mastoids may benefit from canal wall down mastoidectomy to improve ease of office examinations. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. Private multiple congenital anomaly syndromes may result from unbalanced subtle translocations: t(2q;4p) explains the Lambotte syndrome.

    PubMed

    Herens, C; Jamar, M; Alvarez-Gonzalez, M L; Lesenfants, S; Lombet, J; Bonnivert, J; Koulischer, L; Verloes, A

    1997-12-12

    In 1990, Lambotte syndrome was reported as an apparently autosomal recessive multiple congenital anomaly/mental retardation (MCA/MR) syndrome observed in 4 of 12 sibs from a probably consanguineous mating [Verloes et al., Am J Med Genet 1990; 37:119-123]. Major manifestations included intrauterine growth retardation (IUGR), microcephaly, large soft pinnae, hypertelorism, beaked nose, and extremely severe neurologic impairment, with holoprosencephaly in one instance. After the observation of a further affected child born of one unaffected sister, in situ hybridization analysis and chromosome painting techniques demonstrated a subtle t(2;4)(q37.1; p16.2) translocation in the mother, suggesting a combination of 2q/4p trisomy/monosomy in all of the affected children of the family. Many private sporadic or recurrent MCA/MR syndromes maybe due to similar symmetric translocations, undetectable by conventional banding techniques.

  1. Congenital pseudarthrosis of the clavicle causing thoracic outlet syndrome

    PubMed Central

    Watson, Hannah Isabella; Hopper, Graeme Philip; Kovacs, Peter

    2013-01-01

    A 7-year-old girl presented with an asymptomatic right supraclavicular swelling. Radiographs were interpreted as showing a non-union of her clavicle. No treatment was given at this time. However, she represented 12 years later with right upper limb pain and altered sensation. Examination revealed a positive Allen's test on the right. Repeat radiographs demonstrated a pseudarthrosis of the clavicle, associated with a secondary complication of thoracic outlet syndrome with vascular and neurological complications present. Non-operative management failed to relieve her symptoms. Operative intervention successfully treated her symptoms. PMID:23975919

  2. Lumbo-costo-vertebral syndrome with congenital lumbar hernia.

    PubMed

    Gupta, Lucky; Mala, Tariq Ahmed; Gupta, Rahul; Malla, Shahid Amin

    2014-01-01

    Lumbo-costo-vertebral syndrome (LCVS) is a set of rare abnormalities involving vertebral bodies, ribs, and abdominal wall. We present a case of LCVS in a 2-year-old girl who had a progressive swelling over left lumbar area noted for the last 12 months. Clinical examination revealed a reducible swelling with positive cough impulse. Ultrasonography showed a defect containing bowel loops in the left lumbar region. Chest x-ray showed scoliosis and hemivertebrae with absent lower ribs on left side. Meshplasty was done.

  3. Lumbo-Costo-Vertebral Syndrome with Congenital Lumbar Hernia

    PubMed Central

    Gupta, Lucky; Gupta, Rahul; Malla, Shahid Amin

    2014-01-01

    Lumbo-costo-vertebral syndrome (LCVS) is a set of rare abnormalities involving vertebral bodies, ribs, and abdominal wall. We present a case of LCVS in a 2-year-old girl who had a progressive swelling over left lumbar area noted for the last 12 months. Clinical examination revealed a reducible swelling with positive cough impulse. Ultrasonography showed a defect containing bowel loops in the left lumbar region. Chest x-ray showed scoliosis and hemivertebrae with absent lower ribs on left side. Meshplasty was done. PMID:24834386

  4. Craniofacial and dental manifestations of triple X syndrome associated with congenital hypothyroidism: a case report.

    PubMed

    Ferrazzo, Kívia Linhares; Payeras, Marcia Rodrigues; Ferrazzo, Vilmar Antonio; Mezomo, Maurício Barbieri

    2014-01-01

    Triple X syndrome (47,XXX) is a numerical chromosomal alteration that affects 1/1,000 women, in which the woman is born with an extra X chromosome. Some oral changes have been reported in the literature, as hypodontia, influence on deposition of crown enamel and discrepancies in cephalometric measurements. Other systemic complications may lead to oral abnormalities similar to those seen in triple X patients, such as congenital hypothyroidism (CH). This paper reports a triple X syndrome case associated with CH later treated. Besides delay in cognitive and intellectual development, the patient had changes in teeth development and in cephalometric measurements with deficiencies in the maxilla and mandible. This is the first report of a triple X syndrome associated with CH. Both conditions may result in changes in dentofacial development. © 2013 Special Care Dentistry Association and Wiley Periodicals, Inc.

  5. 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.

  6. Congenital non-syndromal autosomal recessive deafness in Bengkala, an isolated Balinese village.

    PubMed Central

    Winata, S; Arhya, I N; Moeljopawiro, S; Hinnant, J T; Liang, Y; Friedman, T B; Asher, J H

    1995-01-01

    Bengkala is an Indonesian village located on the north shore of Bali that has existed for over 700 years. Currently, 2.2% of the 2185 people in this village have profound congenital deafness. In response to the high incidence of deafness, the people of Bengkala have developed a village specific sign language which is used by many of the hearing and deaf people. Deafness in Bengkala is congenital, sensorineural, non-syndromal, and caused by a fully penetrant autosomal recessive mutation at the DFNB3 locus. The frequency of the DFNB3 mutation is estimated to be 9.4% among hearing people who have a 17.2% chance of being heterozygous for DFNB3. PMID:7616538

  7. Inflammation and Rupture of a Congenital Pericardial Cyst Manifesting Itself as an Acute Chest Pain Syndrome.

    PubMed

    Aertker, Robert A; Cheong, Benjamin Y C; Lufschanowski, Roberto

    2016-12-01

    We present the case of a 63-year-old woman with a remote history of supraventricular tachycardia and hyperlipidemia, who presented with recurrent episodes of acute-onset chest pain. An electrocardiogram showed no evidence of acute coronary syndrome. A chest radiograph revealed a prominent right-sided heart border. A suspected congenital pericardial cyst was identified on a computed tomographic chest scan, and stranding was noted around the cyst. The patient was treated with nonsteroidal anti-inflammatory drugs, and the pain initially abated. Another flare-up was treated similarly. Cardiac magnetic resonance imaging was then performed after symptoms had resolved, and no evidence of the cyst was seen. The suspected cause of the patient's chest pain was acute inflammation of a congenital pericardial cyst with subsequent rupture and resolution of symptoms.

  8. Identification of a novel locus for a USH3 like syndrome combined with congenital cataract.

    PubMed

    Dad, S; Østergaard, E; Thykjaer, T; Albrectsen, A; Ravn, K; Rosenberg, T; Møller, L B

    2010-10-01

    Usher syndrome (USH) is the most common genetic disease that causes both deafness and blindness. USH is divided into three types, USH1, USH2 and USH3, depending on the age of onset, the course of the disease, and on the degree of vestibular dysfunction. By homozygosity mapping of a consanguineous Danish family of Dutch descent, we have identified a novel locus for a rare USH3-like syndrome. The affected family members have a unique association of retinitis pigmentosa, progressive hearing impairment, vestibular dysfunction, and congenital cataract. The phenotype is similar, but not identical to that of USH3 patients, as congenital cataract has not been reported for USH3. By homozygosity mapping, we identified a 7.3 Mb locus on chromosome 15q22.2-23 with a maximum multipoint LOD score of 2.0. The locus partially overlaps with the USH1 locus, USH1H, a novel unnamed USH2 locus, and the non-syndromic deafness locus DFNB48. © 2010 John Wiley & Sons A/S.

  9. Sleeping problems in mothers and fathers of patients suffering from congenital central hypoventilation syndrome.

    PubMed

    Paddeu, Erika Maria; Giganti, Fiorenza; Piumelli, Raffaele; De Masi, Salvatore; Filippi, Luca; Viggiano, Maria Pia; Donzelli, Gianpaolo

    2015-09-01

    Advanced medical technology has resulted in an increased survival rate of children suffering from congenital central hypoventilation syndrome. After hospitalization, these technology-dependent patients require special home care for assuring ventilator support and the monitoring of vital parameters mainly during sleep. The daily challenges associated with caring for these children can place primary caregivers under significant stress, especially at night. Our study aimed at investigating how this condition affects mothers and fathers by producing poor sleep quality, high-level diurnal sleepiness, anxiety, and depression. The study included parents of 23 subjects with congenital central hypoventilation syndrome and 23 healthy subjects. All parents filled out the Pittsburgh Sleep Quality Index (PSQI) questionnaire, Epworth Sleepiness Scale (ESS), Beck Depression Inventory (BDI-II), and Beck Anxiety Inventory (BAI). A comparison between the two groups showed that parents of patients had poorer sleep quality, greater sleepiness, and higher BDI-II scores compared to that of parents of healthy subjects (respectively, PSQI score 6.5 vs 3.8, ESS score 6.2 vs 4.3, BDI-II score 8.4 vs 5.7). Specifically, mothers of patients showed poorer sleep quality and higher BDI-II scores compared to that of mothers of controls (respectively, PSQI score 7.5 vs 3.8, BDI-II score 9.3 vs 5.9), whereas fathers of patients showed greater levels of sleepiness with respect to fathers of healthy children (respectively, ESS score 6.8 vs 4.0). These differences emerged in parents of younger children. Congenital central hypoventilation syndrome impacts the family with different consequences for mothers and fathers. Indeed, while the patients' sleep is safeguarded, sleeping problems may occur in primary caregivers often associated with other psychological disorders. Specifically, this disease affects sleep quality and mood in the mothers and sleepiness levels in the fathers.

  10. 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.

  11. Congenital cytomegalovirus infection and Wiskott-Aldrich syndrome successfully treated with unrelated cord blood transplantation.

    PubMed

    Almagor, Yotam; Revel-Vilk, Shoshana; Averbuch, Diana; Mechoulam, Hadas; Engelhard, Dan; Resnick, Igor B; Weintraub, Michael; Stepensky, Polina

    2011-10-01

    We report a successful umbilical cord blood transplantation (UCBT) in an 8-month male with Wiskott-Aldrich syndrome (WAS) and congenital cytomegalovirus (CMV) infection. The child presented at 3 months of age with symptomatic thrombocytopenia and CMV infection. Despite appropriate antiviral treatment no rise in the platelet count was observed. Genetic analysis confirmed the diagnosis of WAS. The clinical course was complicated by severe CMV retinitis with bilateral retinal hemorrhages and renal vasculitis. He underwent unrelated UCBT resulting in a rapid resolution of autoimmunity and thrombocytopenia. Copyright © 2011 Wiley-Liss, Inc.

  12. Branchial cleft anomaly, congenital heart disease, and biliary atresia: Goldenhar complex or Lambert syndrome?

    PubMed

    Cohen, J; Schanen, N C

    2000-01-01

    The features of Goldenhar complex have been well-described and classically include branchial arch abnormalities, epibulbar dermoid and vertebral abnormalities. We have identified an infant with these features in association with complex congenital heart disease and intrahepatic biliary atresia. Although Lambert described an autosomal recessive disorder with an association of biliary atresia and branchial arch abnormalities, none of those cases had epibulbar dermoid. Diagnostic considerations in this case include inclusion of biliary atresia as a new feature in the expanding spectrum of the Goldenhar complex, versus Lambert syndrome with epibulbar dermoid.

  13. Diabetic retinopathy in two patients with congenital IGF-I deficiency (Laron syndrome).

    PubMed

    Laron, Zvi; Weinberger, Dov

    2004-07-01

    Animal and clinical studies have shown that excessive amounts of growth hormone or insulin-like growth factor-I (IGF-I) promote the development of diabetes and diabetic retinopathy. Forthwith, we present two patients with congenital IGF-I deficiency who developed type II diabetes and subsequently retinopathy. Eighteen adult patients with classical Laron syndrome (8 males, 10 females, aged 20-62 years) were followed by us since childhood or underwent fundus photography with a Nikon NF 505 instrument. Three had been treated in childhood with IGF-I, the rest were never treated, including the two patients reported. Two never-treated patients were diagnosed with type II diabetes (DM) at ages 39 and 41 respectively. There was no diabetes in the families. Oral treatment was followed by insulin injections. Metabolic control was not optimal and one patient developed proliferative diabetic retinopathy, necessitating laser surgery. He also has nephropathy and severe neuropathy. The other patient has background diabetic retinopathy and has developed, progressively, exudates, microaneurisms, hemorrhages and clinically significant macular edema. He also has subacute ischemic heart disease. Our findings show that congenital IGF-I deficiency, similar to excess, causes vascular complications of DM, denoting also that vascular endothelial growth factor can induce neovascularization in the presence of congenital IGF-I deficiency.

  14. 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.

  15. Gastric heterotopia with extensive involvement of the small intestine associated with congenital short bowel syndrome and intestinal malrotation.

    PubMed

    Shehata, Bahig; Chang, Tiffany; Greene, Courtney; Steelman, Charlotte; McHugh, Mary; Zarroug, Abdalla; Ricketts, Richard

    2011-01-01

    We present a case of extensive gastric heterotopia involving the small intestine associated with congenital short bowel syndrome and malrotation. The infant showed a normal mesenteric artery, without signs of "apple peel" deformity. Gastric heterotopia extended from the duodenum to the mid-ileum involving the short bowel. Gastric mucosa heterotopia may involve any segment of the gastrointestinal tract. It can be associated with pancreatic heterotopia and Meckel diverticulum. However, our case showed involvement of two-thirds of the small intestine without pancreatic heterotopia. To our knowledge, this is the first report of gastric heterotopia with congenital short gut syndrome and malrotation.

  16. 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.

  17. Effects of movement and work load in patients with congenital central hypoventilation syndrome.

    PubMed

    Hager, Alfred; Koch, Walter; Stenzel, Heike; Hess, John; Schöber, Johannes

    2007-04-01

    Patients with congenital central hypoventilation syndrome lack ventilatory chemosensitivity and depend at least in part on the ergoreceptor function during exercise. In these patients a substantial increase of ventilation has been reported for passive movement during sleep as well as active movement on a treadmill. The aim of the study was to investigate ventilatory response to an increasing work load with constant movement. Eighteen patients and 17 healthy volunteers performed a cardiopulmonary exercise test on a bicycle pedaling at a constant rate of about 60 revolutions per minute throughout the entire test. The patients were able to exercise adequately and showed normal peak oxygen uptake. There was a steep rise in minute ventilation in both groups at the start of exercise, yet there was only a minor increase in both groups during the increase of workload up to the anaerobic threshold. After the anaerobic threshold, there was again an increase in ventilation in both groups, but the increase was less prominent in the patient group. Ventilation in patients with congenital central hypoventilation syndrome is increased during exercise caused both by movement (mechanoreceptors) and by anaerobic workload. This facilitates a normal ventilatory drive up to the anaerobic threshold and a normal exercise capacity in these patients.

  18. Congenital extrahepatic portosystemic shunt: an underdiagnosed but treatable cause of hepatopulmonary syndrome.

    PubMed

    Fu, Lijun; Wang, Qian; Wu, Jinjin; Guo, Ying; Huang, Meirong; Liu, Tingliang; Chen, Qimin; Li, Fen

    2016-02-01

    Congenital extrahepatic portosystemic shunt (CEPS) is a rare malformation of the mesenteric vasculature, which may lead to severe complications. In this report, we describe a case series of three children with type II CEPS (presenting as hypoxemia) and hepatopulmonary syndrome (HPS). The first patient was a 4-year-old male who did not receive any specific treatment and subsequently died of brain abscess 5 years after the diagnosis. The second patient was a 10-year-old female with a 5-year history of cyanosis and dyspnea on exertion. She had partial regression of hypoxemia and improved exercise tolerance at 8 months after a surgical shunt closure. The third patient was a 4-year-old male with a 3-year history of cyanosis and decreased exercise tolerance. He had full regression of hypoxemia at 3 months after a transcatheter shunt closure. These results indicate that CEPS may present in children with unexplained hypoxemia, which may lead to devastating clinical consequences. Closure of portosystemic shunts may result in resolution of HPS in type II CEPS and the length of period for resolution varies depending on the severity of HPS. Congenital extrahepatic portosystemic shunt (CEPS) is a rare cause of hepatopulmonary syndrome (HPS). There have been few reports in the literature about the management and outcome of HPS in children with CEPS. CEPS may present in children with unexplained hypoxemia, which may lead to devastating clinical consequences. Closure of portosystemic shunts may result in resolution of HPS in type II CEPS.

  19. 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

  20. Duane Syndrome

    MedlinePlus

    ... is Duane Syndrome? Duane syndrome, also called Duane retraction syndrome (DRS), is a congenital and non-progressive ... Is Duane syndrome congenital (present from birth)? Duane retraction syndrome is present from birth, even if it ...

  1. "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,"…

  2. 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…

  3. Congenital sensori-neural deafness associated with onycho-osteo dystrophy and mental retardation (D.O.O.R. syndrome).

    PubMed

    Cantwell, R J

    1975-01-01

    A characteristic syndrome is described in which congenital sensori-neural deafness is associated not only with onychodystrophy but also with congenital bony anomalies the most characteristic of which are tri-phalangeal thumbs, bi-phalangeal digits of hands and feet, and dystrophic terminal phalanges of some of the fingers and toes. In addition, there is mental retardation and the dermatoglyphics are characterized by the presence of 10 arches and elevation of the atd angles. The syndrome is inherited as an autosomal recessive. It is suggested that this entity be named the D.O.O.R. Syndrome because of the deafness, onychodystrophy, osteodystrophy and retardation. A similar syndrome without retardation as described by Goodman et al. (1969) appears to be inherited as an autosomal dominant.

  4. Novel de novo mutations in ZBTB20 in Primrose syndrome with congenital hypothyroidism.

    PubMed

    Mattioli, Francesca; Piton, Amelie; Gérard, Bénédicte; Superti-Furga, Andrea; Mandel, Jean-Louis; Unger, Sheila

    2016-06-01

    The cardinal features of Primrose syndrome (MIM 259050) are dysmorphic facial features, macrocephaly, and intellectual disability, as well as large body size, height and weight, and calcified pinnae. A variety of neurological signs and symptoms have been reported including hearing loss, autism, behavioral abormalities, hypotonia, cerebral calcifications, and hypoplasia of the corpus callosum. Recently, heterozygous de novo missense mutations in ZBTB20, coding for a zing finger protein, have been identified in Primrose syndrome patients. We report a boy with intellectual disability carrying two de novo missense mutations in the last exon of ZBTB20 (Ser616Phe and Gly741Arg; both previously unreported). One of them, Ser616Phe, affects an amino acid located in one of the C2H2 zing-fingers involved in DNA-binding and close to other missense mutations already described. Reverse phenotyping showed that this patient presents with classic features of Primrose syndrome (dysmorphic facies, macrocephaly, hearing loss, hypotonia, hypoplasia of the corpus callosum) and, in addition, congenital hypothyroidism. Review of the literature reveals another Primrose syndrome patient with hypothyroidism and thus, this may represent an under recognized component that should be investigated in other patients. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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

    PubMed

    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

    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. 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. 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. 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%). 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.

  6. 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

  7. 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

  8. Platelet abnormalities in adults with severe pulmonary arterial hypertension related to congenital heart defects (Eisenmenger syndrome).

    PubMed

    Remková, Anna; Šimková, Iveta; Valkovičová, Tatiana; Kaldarárová, Monika

    2016-12-01

    Patients with severe pulmonary arterial hypertension suffer from life-threatening thrombotic and bleeding complications. The aim of this study was to compare selected platelet, endothelial, and coagulation parameters in healthy volunteers and patients with severe pulmonary arterial hypertension because of congenital heart defects. The study included healthy volunteers (n = 50) and patients with cyanotic congenital heart defects classified as Eisenmenger syndrome (n = 41). We investigated platelet count, mean platelet volume, and platelet aggregation - spontaneous and induced by various concentrations of five agonists. Von Willebrand factor (vWF), fibrinogen, factor VIII and XII, plasminogen activator inhibitor, antithrombin, D-dimer, and antiphospholipid antibodies were also investigated. We found a decreased platelet count [190 (147-225) vs. 248 (205-295) 10 l, P < 0.0001], higher mean platelet volume [10.9 (10.1-12.0) vs. 10.2 (9.4-10.4) fl, P < 0.0001], and significantly decreased platelet aggregation (induced by five agonists, in various concentrations) in patients with Eisenmenger syndrome compared with controls. These changes were accompanied by an increase of plasma vWF antigen [141.6 (108.9-179.1) vs. 117.4 (9.2-140.7) IU/dl, P = 0.022] and serum anti-β2-glycoprotein [2.07 (0.71-3.41) vs. 0.47 (0.18-0.99) U/ml, P < 0.0001]. Eisenmenger syndrome is accompanied by platelet abnormalities. Thrombocytopenia with increased platelet size is probably due to a higher platelet turnover associated with platelet activation. Impaired platelet aggregation can reflect specific platelet behaviour in patients with Eisenmenger syndrome. These changes can be related both to bleeding and to thrombotic events. A higher vWF antigen may be a consequence of endothelial damage in Eisenmenger syndrome, but the cause for an increase of anti-β2-glycoprotein is unknown.

  9. Congenital rubella syndrome: a review of laboratory data from 2002 to 2011.

    PubMed

    Saraswathy, T S; Rozainanee, M Z; Asshikin, R Nurul; Zainah, S

    2013-05-01

    Rubella infection in pregnant women during the first trimester of pregnancy can lead to fetal anomalies, commonly known as congenital rubella syndrome (CRS). The objective of our study was to analyze the serological test results among infants suspected of having CRS aged < or = 12 months compared with their clinical status. Between January 2002 and December 2011, 3,279 serum samples from infants aged < or = 12 months from government hospitals in Malaysia were examined for rubella specific IgM and IgG antibodies using a Axsym, automated analyzer (Abbott Laboratories). Forty-eight samples were positive for rubella specific IgM antibodies and 494 samples were positive for rubella specific IgG antibodies. These were then age stratified and their clinical history reviewed for any CRS symptoms. Fifteen of 38 rubella IgM positive infants (39.5%) aged < 3 months, had a clinical appearance compatible with CRS. However, only 1 IgM positive infant aged 3 to 6 months and one infant aged 7 to 11 months had clinical appearance compatible with CRS. The most common abnormal findings in these cases were congenital heart defects and cataracts. Forty-eight point eight percent of IgM positive cases and 53.1% of IgG positive cases, had inadequate information in the chart to determine the presence of CRS. Clinical findings and timely laboratory diagnosis to determine the presence of CRS are important in infants born with congenital defects. Physicians should also be aware of the appropriate interpretation of these findings.

  10. Congenital Hyperinsulinism in Infants with Turner Syndrome: Possible Association with Monosomy X and KDM6A Haploinsufficiency.

    PubMed

    Gibson, Christopher E; Boodhansingh, Kara E; Li, Changhong; Conlin, Laura; Chen, Pan; Becker, Susan A; Bhatti, Tricia; Bamba, Vaneeta; Adzick, N Scott; De Leon, Diva D; Ganguly, Arupa; Stanley, Charles A

    2018-06-14

    Previous case reports have suggested a possible association of congenital hyperinsulinism with Turner syndrome. We examined the clinical and molecular features in girls with both congenital hyperinsulinism and Turner syndrome seen at The Children's Hospital of Philadelphia (CHOP) between 1974 and 2017. Records of girls with hyperinsulinism and Turner syndrome were reviewed. Insulin secretion was studied in pancreatic islets and in mouse islets treated with an inhibitor of KDM6A, an X chromosome gene associated with hyperinsulinism in Kabuki syndrome. Hyperinsulinism was diagnosed in 12 girls with Turner syndrome. Six were diazoxide-unresponsive; 3 had pancreatectomies. The incidence of Turner syndrome among CHOP patients with hyperinsulinism (10 of 1,050 from 1997 to 2017) was 48 times more frequent than expected. The only consistent chromosomal anomaly in these girls was the presence of a 45,X cell line. Studies of isolated islets from 1 case showed abnormal elevated cytosolic calcium and heightened sensitivity to amino acid-stimulated insulin release; similar alterations were demonstrated in mouse islets treated with a KDM6A inhibitor. These results demonstrate a higher than expected frequency of Turner syndrome among children with hyperinsulinism. Our data suggest that haploinsufficiency for KDM6A due to mosaic X chromosome monosomy may be responsible for hyperinsulinism in Turner syndrome. © 2018 S. Karger AG, Basel.

  11. Congenital chloride diarrhea needs to be distinguished from Bartter and Gitelman syndrome.

    PubMed

    Matsunoshita, Natsuki; Nozu, Kandai; Yoshikane, Masahide; Kawaguchi, Azusa; Fujita, Naoya; Morisada, Naoya; Ishimori, Shingo; Yamamura, Tomohiko; Minamikawa, Shogo; Horinouchi, Tomoko; Nakanishi, Keita; Fujimura, Junya; Ninchoji, Takeshi; Morioka, Ichiro; Nagase, Hiroaki; Taniguchi-Ikeda, Mariko; Kaito, Hiroshi; Iijima, Kazumoto

    2018-05-30

    Pseudo-Bartter/Gitelman syndrome (p-BS/GS) encompasses a clinically heterogeneous group of inherited or acquired disorders similar to Bartter syndrome (BS) or Gitelman syndrome (GS), both renal salt-losing tubulopathies. Phenotypic overlap frequently occurs between p-BS/GS and BS/GS, which are difficult to diagnose based on their clinical presentation and require genetic tests for accurate diagnosis. In addition, p-BS/GS can occur as a result of other inherited diseases such as cystic fibrosis, autosomal dominant hypocalcemia, Dent disease, or congenital chloride diarrhea (CCD). However, the detection of the variants in genes other than known BS/GS-causing genes by conventional Sanger sequencing requires substantial time and resources. We studied 27 cases clinically diagnosed with BS/GS, but with negative genetic tests for known BS/GS genes. We conducted targeted sequencing for 22 genes including genes responsible for tubulopathies and other inherited diseases manifesting with p-BS/GS symptoms. We detected the SLC26A3 gene variants responsible for CCD in two patients. In Patient 1, we found the SLC26A3 compound heterozygous variants: c.354delC and c.1008insT. In Patient 2, we identified the compound heterozygous variants: c.877G > A, p.(Glu293Lys), and c.1008insT. Our results suggest that a comprehensive genetic screening system using targeted sequencing is useful for the diagnosis of patients with p-BS/GS with alternative genetic origins.

  12. 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.

  13. 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

  14. Unlikely culprit: congenital middle aortic syndrome diagnosed in the sixth decade of life.

    PubMed

    Ali, Muhammad Sajawal; Tchernodrinski, Stefan; Mohananey, Divyanshu; Ali, Ahya Sajawal

    2016-08-16

    A 58-year-old woman was admitted with acute heart failure. She had a long history of resistant hypertension, with an unremarkable work up for secondary causes in the past. Her brachial blood pressure was 210/70 mm Hg, with ankle blood pressure of 100/70 mm Hg. CT angiogram revealed marked narrowing of the descending thoracic aorta between the left subclavian artery and the diaphragm, consistent with middle aortic syndrome (MAS). She was initially managed with diuretics and antihypertensives. Subsequently thoracotomy revealed a severely hypoplastic segment of the descending aorta. The diseased segment was resected and aortic reconstruction performed. Histopathology showed fragmentation of the medial elastic fibres and fibrosis of the medial and intimal layers. These findings along with gross aortic hypoplasia and absence of features of Takayasu's arteritis, suggest that our patient had congenital MAS. The patient has done well since her surgery. We believe this is the first case of congenital MAS reported in the sixth decade of life. 2016 BMJ Publishing Group Ltd.

  15. 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

  16. 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.

  17. Neonatal Bartter Syndrome in association with congenital adrenal hyperplasia in a neonate - a rare combination.

    PubMed

    Hussain, Shabbir

    2016-05-01

    Neonatal Bartter syndrome (NBS) is an autosomal recessive renal tubulopathy characterized by hypokalaemic, hypochloraemic metabolic alkalosis associated with increased urinary loss of sodium, potassium, calcium and chloride. There is hyperreninaemia and hyperaldosteronaemia but normotension. Congenital adrenal hyperplasia (CAH), another autosomal recessive condition, may present in the neonatal period with vomiting, hypovolaemia, failure to gain weight or ambiguous genitalia. We report a case of NBS and CAH combination in a neonate. A male neonate born at term was admitted with history of recurrent vomiting and dehydration episodes. Investigations revealed electrolytes imbalance, metabolic alkalosis, raised aldosterone and renin levels suggestive of NBS. He was treated successfully and discharged. He was re-admitted with the same symptoms. Further evaluation confirmed the presence of CAH as well. We report this case because of the rarity of this combination (NBS plus CAH) and to the best of our knowledge this is the first such case report from Pakistan.

  18. Congenital Perisylvian Syndrome presenting as Post-partum Seizures with Preeclampsia.

    PubMed

    Agarwal, Arun; Goyal, Manju; Jain, Jainendra; Agarwal, Aakanksha

    2017-06-01

    Whether preceded by preeclampsia, or occuring without antecedent warning symptoms, eclamptic seizures usually occur in the antepartum period between 20 and 40 weeks of gestation or within a few hours to 2 days postpartum. We report the case of a patient with pre-eclampsia who developed seizures after more than 2 days of delivery. In view of late onset postpartum seizures and non-responsiveness to magnesium sulphate, she was further evaluated and diagnosed to have congenital perisylvian syndrome(CPS). In CPS, polymicrogyric cortex is distributed in variable extensions around the sylvian fissure i.e. a structural malformation of the brain with underlying anomaly of polymicrogyria. © Journal of the Association of Physicians of India 2011.

  19. 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.

  20. Macroscopic hematuria caused by congenital portosystemic shunt and concomitant nutcracker syndrome.

    PubMed

    Lee, Sang Hyub; Lee, Dong-Gi

    2015-06-01

    Nutcracker syndrome (NCS) is an uncommon vascular abnormality that causes a variety of symptoms that range from asymptomatic microscopic hematuria to severe pelvic congestion. Congenital portosystemic shunt (CPSS) is an extremely rare anomaly that causes serious complications. Many cases of NCS and CPSS that have presented separately have been reported, but no cases of concomitant NCS and CPSS have been reported. We present a case of intermittent macroscopic hematuria in a patient with both NCS and CPSS. We diagnosed NCS on pressure gradient between the left renal vein (LRV) and the inferior vena cava. The presence of CPSS, which emerged from the LRV and connected to the extrahepatic portal vein, was confirmed on computed tomography. The interaction between NCS and CPSS resulted in mild intermittent macroscopic hematuria only, rather than the more common symptoms that occur when NCS or CPSS present separately. © 2015 Japan Pediatric Society.

  1. 22q11.2 microduplication syndrome with congenital aural atresia: a family report.

    PubMed

    Boudewyns, An; van den Ende, Jenneke; Boiy, Tine; Van de Heyning, Paul; Declau, Frank

    2012-06-01

    22q11.2 microduplication syndrome is characterized by a large phenotypic variability including facial dysmorphism, developmental delay, and hearing loss. We describe a family in whom 5 of 11 children were affected by a unilateral or bilateral congenital aural atresia. Four of these 5 carried a 22q11.2 microduplication and had typical dysmorphic features. Computed tomography with 3-D reconstructions allowed for a detailed examination of the middle ear structures and classification of the atresia type. Audiometry revealed a moderately severe conductive hearing loss in accordance with the clinical and computed tomography findings. Detailed examination of the ear is warranted in patients with a 22q11.2 microduplication. When outer ear abnormalities are encountered, an additional workup including audiometry and computed tomography with 3-D reconstructions is required.

  2. 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.

  3. Choline transporter mutations in severe congenital myasthenic syndrome disrupt transporter localization.

    PubMed

    Wang, Haicui; Salter, Claire G; Refai, Osama; Hardy, Holly; Barwick, Katy E S; Akpulat, Ugur; Kvarnung, Malin; Chioza, Barry A; Harlalka, Gaurav; Taylan, Fulya; Sejersen, Thomas; Wright, Jane; Zimmerman, Holly H; Karakaya, Mert; Stüve, Burkhardt; Weis, Joachim; Schara, Ulrike; Russell, Mark A; Abdul-Rahman, Omar A; Chilton, John; Blakely, Randy D; Baple, Emma L; Cirak, Sebahattin; Crosby, Andrew H

    2017-11-01

    The presynaptic, high-affinity choline transporter is a critical determinant of signalling by the neurotransmitter acetylcholine at both central and peripheral cholinergic synapses, including the neuromuscular junction. Here we describe an autosomal recessive presynaptic congenital myasthenic syndrome presenting with a broad clinical phenotype due to homozygous choline transporter missense mutations. The clinical phenotype ranges from the classical presentation of a congenital myasthenic syndrome in one patient (p.Pro210Leu), to severe neurodevelopmental delay with brain atrophy (p.Ser94Arg) and extend the clinical outcomes to a more severe spectrum with infantile lethality (p.Val112Glu). Cells transfected with mutant transporter construct revealed a virtually complete loss of transport activity that was paralleled by a reduction in transporter cell surface expression. Consistent with these findings, studies to determine the impact of gene mutations on the trafficking of the Caenorhabditis elegans choline transporter orthologue revealed deficits in transporter export to axons and nerve terminals. These findings contrast with our previous findings in autosomal dominant distal hereditary motor neuropathy of a dominant-negative frameshift mutation at the C-terminus of choline transporter that was associated with significantly reduced, but not completely abrogated choline transporter function. Together our findings define divergent neuropathological outcomes arising from different classes of choline transporter mutation with distinct disease processes and modes of inheritance. These findings underscore the essential role played by the choline transporter in sustaining acetylcholine neurotransmission at both central and neuromuscular synapses, with important implications for treatment and drug selection. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. Congenital myasthenic syndrome with tubular aggregates caused by GFPT1 mutations.

    PubMed

    Guergueltcheva, Velina; Müller, Juliane S; Dusl, Marina; Senderek, Jan; Oldfors, Anders; Lindbergh, Christopher; Maxwell, Susan; Colomer, Jaume; Mallebrera, Cecilia Jimenez; Nascimento, Andres; Vilchez, Juan J; Muelas, Nuria; Kirschner, Janbernd; Nafissi, Shahriar; Kariminejad, Ariana; Nilipour, Yalda; Bozorgmehr, Bita; Najmabadi, Hossein; Rodolico, Carmelo; Sieb, Jörn P; Schlotter, Beate; Schoser, Benedikt; Herrmann, Ralf; Voit, Thomas; Steinlein, Ortrud K; Najafi, Abdolhamid; Urtizberea, Andoni; Soler, Doriette M; Muntoni, Francesco; Hanna, Michael G; Chaouch, Amina; Straub, Volker; Bushby, Kate; Palace, Jacqueline; Beeson, David; Abicht, Angela; Lochmüller, Hanns

    2012-05-01

    Congenital myasthenic syndrome (CMS) is a clinically and genetically heterogeneous group of inherited disorders of the neuromuscular junction. A difficult to diagnose subgroup of CMS is characterised by proximal muscle weakness and fatigue while ocular and facial involvement is only minimal. DOK7 mutations have been identified as causing the disorder in about half of the cases. More recently, using classical positional cloning, we have identified mutations in a previously unrecognised CMS gene, GFPT1, in a series of DOK7-negative cases. However, detailed description of clinical features of GFPT1 patients has not been reported yet. Here we describe the clinical picture of 24 limb-girdle CMS (LG-CMS) patients and pathological findings of 18 of them, all carrying GFPT1 mutations. Additional patients with CMS, but without tubular aggregates, and patients with non-fatigable weakness with tubular aggregates were also screened. In most patients with GFPT1 mutations, onset of the disease occurs in the first decade of life with characteristic limb-girdle weakness and fatigue. A common feature was beneficial and sustained response to acetylcholinesterase inhibitor treatment. Most of the patients who had a muscle biopsy showed tubular aggregates in myofibers. Analysis of endplate morphology in one of the patients revealed unspecific abnormalities. Our study delineates the phenotype of CMS associated with GFPT1 mutations and expands the understanding of neuromuscular junction disorders. As tubular aggregates in context of a neuromuscular transmission defect appear to be highly indicative, we suggest calling this condition congenital myasthenic syndrome with tubular aggregates (CMS-TA).

  5. Prenatal detection of congenital bilateral cataract leading to the diagnosis of Nance-Horan syndrome in the extended family.

    PubMed

    Reches, Adi; Yaron, Yuval; Burdon, Kathryn; Crystal-Shalit, Ornit; Kidron, Dvora; Malcov, Mira; Tepper, Ron

    2007-07-01

    To describe a family in which it was possible to perform prenatal diagnosis of Nance-Horan Syndrome (NHS). The fetus was evaluated by 2nd trimester ultrasound. The family underwent genetic counseling and ophthalmologic evaluation. The NHS gene was sequenced. Ultrasound demonstrated fetal bilateral congenital cataract. Clinical evaluation revealed other family members with cataract, leading to the diagnosis of NHS in the family. Sequencing confirmed a frameshift mutation (3908del11bp) in the NHS gene. Evaluation of prenatally diagnosed congenital cataract should include a multidisciplinary approach, combining experience and input from sonographer, clinical geneticist, ophthalmologist, and molecular geneticist.

  6. Congenital atresia of the external ear and tinnitus: a new syndrome.

    PubMed

    Shulman, Abraham; Strashun, Arnold M; Goldstein, Barbara; Lenhardt, Martin L

    2006-01-01

    Congenital atresia of the external ears and severe tinnitus has been reported by two patients to be contralateral to the atretic ear. The use of the nuclear medicine imaging technique of single-photon emission computed tomography (SPECT) of brain has demonstrated hypoperfusion in brain areas supplied by the middle cerebral artery on the side of the atretic ear. Ultrahigh-frequency audiometry (UHFA) has revealed a bilateral loss of hearing greater than expected for the age of affected patients. Quantitative electroencephalography (QEEG) has shown a significant central nervous system electrical dysfunction correlated with the SPECT of brain findings. One case is reported in detail at this time. Completion of the medical audiological tinnitus patient protocol, including SPECT of brain, UHFA, and QEEG, accurately established the clinical tinnitus diagnosis of predominantly a central-type tinnitus, a clinical hypothesis that the medical significance of the tinnitus is a "soft" sign of cerebrovascular disease, and provided a rationale for treatment directed to a presumed ischemia of brain based on a receptor-targeted therapy targeted to the GABA-A receptor, resulting in significant tinnitus relief. Questions that have arisen include (1) the incidence of occurrence of hypoperfusion of the middle cerebral artery in congenital atresia patients; (2) implications and long-term consequences of this finding in this patient population for development of cerebrovascular disease; (3) brain plasticity for tinnitus relief (i.e., neuronal reprogramming, particularly in response to treatment recommendations for complaints of the cochleovestibular system in general and specifically for tinnitus); (4) the clinical significance of the UHFA thresholds of bilateral hearing loss greater than expected for the age of the patient; and (5) whether congenital atresia of the external ear may be part of a syndrome that includes hypoperfusion in brain areas supplied by the middle cerebral artery on

  7. [New treatment concept for children with thoracic insufficiency syndrome due to congenital spine deformity].

    PubMed

    Hell, A K; Campbell, R M; Hefti, F

    2005-01-01

    Children with congenital thoracic scoliosis associated with fused ribs and unilateral unsegmented bars adjacent to convex hemivertebrae will inevitably develop thoracic insufficiency syndrome and curve progression with hemithorax compression without treatment. It is assumed that the concave side of such curves and their unilateral unsegmented bars do not grow. In the past early spinal fusion was performed with consecutive short thoracic spines and loss of lung volume. Little attention has been paid to lung function. These patients often suffered from lung failure and early death due to a small thorax. A new surgical technique is based on an indirect deformity correction and enlargement of the thorax due to a longitudinal implant, the vertical expandable prosthetic titanium rib (VEPTR). The spine is not fused, thus promoting growth of the spine, the thorax and the lungs. Elongation of the implant is done every six months. Since 2002 this method has been performed on fifteen children in Basel as the first European center. Patients (mean age 6 years; 11 months to 12 years) were suffering from thoracic insufficiency syndrome due to unilateral unsegmented bars with fused ribs (n = 4), absent ribs (n = 2), bilaterally fused ribs (n = 2), hemivertebrae (n = 3) or neuromuscular scoliosis (n = 6). Doing fifteen primarily implantations and thirteen elongations there were three complications (two hook dislocations, one skin breakage). All patients improved cosmetically, functionally and radiologically which was shown on X-rays as a reduction of the Cobb angle from an average of 76 degrees (40-110 degrees ) to 55 degrees (30-67 degrees ). Expansion thoracoplasty and VEPTR implantation is a new treatment concept for children with thoracic insufficiency syndrome due to spinal deformities, which is based on distraction and expansion of the thorax thus allowing growth of the spine, the thorax and probably lungs. Presently it seems to be superior to any other method for the

  8. Prognostic implications of mutation-specific QTc standard deviation in congenital long QT syndrome.

    PubMed

    Mathias, Andrew; Moss, Arthur J; Lopes, Coeli M; Barsheshet, Alon; McNitt, Scott; Zareba, Wojciech; Robinson, Jennifer L; Locati, Emanuela H; Ackerman, Michael J; Benhorin, Jesaia; Kaufman, Elizabeth S; Platonov, Pyotr G; Qi, Ming; Shimizu, Wataru; Towbin, Jeffrey A; Michael Vincent, G; Wilde, Arthur A M; Zhang, Li; Goldenberg, Ilan

    2013-05-01

    Individual corrected QT interval (QTc) may vary widely among carriers of the same long QT syndrome (LQTS) mutation. Currently, neither the mechanism nor the implications of this variable penetrance are well understood. To hypothesize that the assessment of QTc variance in patients with congenital LQTS who carry the same mutation provides incremental prognostic information on the patient-specific QTc. The study population comprised 1206 patients with LQTS with 95 different mutations and ≥ 5 individuals who carry the same mutation. Multivariate Cox proportional hazards regression analysis was used to assess the effect of mutation-specific standard deviation of QTc (QTcSD) on the risk of cardiac events (comprising syncope, aborted cardiac arrest, and sudden cardiac death) from birth through age 40 years in the total population and by genotype. Assessment of mutation-specific QTcSD showed large differences among carriers of the same mutations (median QTcSD 45 ms). Multivariate analysis showed that each 20 ms increment in QTcSD was associated with a significant 33% (P = .002) increase in the risk of cardiac events after adjustment for the patient-specific QTc duration and the family effect on QTc. The risk associated with QTcSD was pronounced among patients with long QT syndrome type 1 (hazard ratio 1.55 per 20 ms increment; P<.001), whereas among patients with long QT syndrome type 2, the risk associated with QTcSD was not statistically significant (hazard ratio 0.99; P = .95; P value for QTcSD-by-genotype interaction = .002). Our findings suggest that mutations with a wider variation in QTc duration are associated with increased risk of cardiac events. These findings appear to be genotype-specific, with a pronounced effect among patients with the long QT syndrome type 1 genotype. Copyright © 2013. Published by Elsevier Inc.

  9. 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

  10. Diffusion tensor imaging demonstrates brainstem and cerebellar abnormalities in congenital central hypoventilation syndrome.

    PubMed

    Kumar, Rajesh; Macey, Paul M; Woo, Mary A; Alger, Jeffry R; Harper, Ronald M

    2008-09-01

    Congenital central hypoventilation syndrome (CCHS) patients show reduced breathing drive during sleep, decreased hypoxic and hypercapnic ventilatory responses, and autonomic and affective deficits, suggesting both brainstem and forebrain injuries. Forebrain damage was previously described in CCHS, but methodological limitations precluded detection of brainstem injury, a concern because genetic mutations in CCHS target brainstem autonomic nuclei. To assess brainstem and cerebellar areas, we used diffusion tensor imaging-based measures, namely axial diffusivity, reflecting water diffusion parallel to fibers, and sensitive to axonal injury, and radial diffusivity, measuring diffusion perpendicular to fibers, and indicative of myelin injury. Diffusion tensor imaging was performed in 12 CCHS and 26 controls, and axial and radial diffusivity maps were compared between groups using analysis of covariance (covariates; age and gender). Increased axial diffusivity in CCHS appeared within the lateral medulla and clusters with injury extended from the dorsal midbrain through the periaqueductal gray, raphé, and superior cerebellar decussation, ventrally to the basal-pons. Cerebellar cortex and deep nuclei, and the superior and inferior cerebellar peduncles showed increased radial diffusivity. Midbrain, pontine, and lateral medullary structures, and the cerebellum and its fiber systems are injured in CCHS, likely contributing to the characteristics found in the syndrome.

  11. Variations in NPHP5 in Patients With Nonsyndromic Leber Congenital Amaurosis and Senior-Loken Syndrome

    PubMed Central

    Stone, Edwin M.; Cideciyan, Artur V.; Aleman, Tomas S.; Scheetz, Todd E.; Sumaroka, Alexander; Ehlinger, Mary A.; Schwartz, Sharon B.; Fishman, Gerald A.; Traboulsi, Elias I.; Lam, Byron L.; Fulton, Anne B.; Mullins, Robert F.; Sheffield, Val C.; Jacobson, Samuel G.

    2014-01-01

    Objective To investigate whether mutations in NPHP5 can cause Leber congenital amaurosis (LCA) without early-onset renal disease. Methods DNA samples from 276 individuals with non-syndromic LCA were screened for variations in the NPHP5 gene. Each had been previously screened for mutations in 8 known LCA genes without identifying a disease-causing genotype. Results Nine of the 276 LCA probands (3.2%) harbored 2 plausible disease-causing mutations (7 different alleles) in NPHP5. Four of these have been previously reported in patients with Senior-Loken syndrome (F141del, R461X, H506del, and R489X) and 3 are novel (A111del, E346X, and R455X). All 9 patients had severe visual loss from early childhood but none had overt renal disease in the first decade of life. Two patients were diagnosed with nephronophthisis in the second decade. Retinal imaging studies showed retained photoreceptor nuclei and retinal pigment epithelium integrity mainly in the cone-rich central retina, a phenotype with strong similarities to that of NPHP6 disease. Conclusions Mutations in NPHP5 can cause LCA without early-onset renal disease. Abnormalities observed in the photoreceptor outer segments (a cilial structure) may explain the severe visual loss in NPHP5-associated LCA. Clinical Relevance The persistence of central photoreceptor nuclei despite severe visual loss in NPHP5 disease is encouraging for future therapeutic interventions. PMID:21220633

  12. A patient with congenital hyperlactataemia and Leigh syndrome: an uncommon mitochondrial variant.

    PubMed

    Ching, C K; Mak, Chloe M; Au, K M; Chan, K Y; Yuen, Y P; Yau, Eric K C; Ma, Louis C K; Chow, H L; Chan, Albert Y W

    2013-08-01

    We report an uncommon mitochondrial variant in a baby girl with congenital hyperlactataemia and Leigh syndrome. The patient presented with a single episode of generalised clonic convulsion at day 19, and was found to have isolated and persistent hyperlactataemia ranging from 3.34 to 9.26 mmol/L. She had elevated serum lactate-to-pyruvate ratios of up to 35 and high plasma alanine concentration, indicative of a respiratory chain defect. At the age of 8 months, she developed evolving neurological and imaging features compatible with Leigh syndrome. Genetic testing for common mitochondrial DNA mutations, large mitochondrial DNA deletions, and selected nuclear genes was negative. Further analysis of lymphocyte mitochondrial DNA by sequencing revealed an uncommon heteroplasmic variant, NC_012920.1(MT-ND5):m.13094T>C (p.Val253Ala), which was previously shown to reduce complex I activity. In patients in whom there was a high suspicion of mitochondrial disorder, entire mitochondrial DNA analysis may be warranted if initial screening of common mitochondrial DNA mutations is negative.

  13. QT Adaptation and Intrinsic QT Variability in Congenital Long QT Syndrome.

    PubMed

    Seethala, Srikanth; Singh, Prabhpreet; Shusterman, Vladimir; Ribe, Margareth; Haugaa, Kristina H; Němec, Jan

    2015-12-16

    Increased variability of QT interval (QTV) has been linked to arrhythmias in animal experiments and multiple clinical situations. Congenital long QT syndrome (LQTS), a pure repolarization disease, may provide important information on the relationship between delayed repolarization and QTV. Twenty-four-hour Holter monitor tracings from 78 genotyped congenital LQTS patients (52 females; 51 LQT1, 23 LQT2, 2 LQT5, 2 JLN, 27 symptomatic; age, 35.2±12.3 years) were evaluated with computer-assisted annotation of RR and QT intervals. Several models of RR-QT relationship were tested in all patients. A model assuming exponential decrease of past RR interval contributions to QT duration with 60-second time constant provided the best data fit. This model was used to calculate QTc and residual "intrinsic" QTV, which cannot be explained by heart rate change. The intrinsic QTV was higher in patients with long QTc (r=0.68; P<10(-4)), and in LQT2 than in LQT1/5 patients (5.65±1.28 vs 4.46±0.82; P<0.0002). Both QTc and intrinsic QTV were similar in symptomatic and asymptomatic patients (467±52 vs 459±53 ms and 5.10±1.19 vs 4.74±1.09, respectively). In LQTS patients, QT interval adaptation to heart rate changes occurs with time constant ≈60 seconds, similar to results reported in control subjects. Intrinsic QTV correlates with the degree of repolarization delay and might reflect action potential instability observed in animal models of LQTS. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  14. A Novel Homozygous Mutation in FOXC1 Causes Axenfeld Rieger Syndrome with Congenital Glaucoma

    PubMed Central

    Micheal, Shazia; Villanueva-Mendoza, Cristina; Cortés-González, Vianney; Khan, Muhammad Imran; den Hollander, Anneke I.

    2016-01-01

    Background Anterior segment dysgenesis (ASD) disorders are a group of clinically and genetically heterogeneous phenotypes in which frequently cornea, iris, and lens are affected. This study aimed to identify novel mutations in PAX6, PITX2 and FOXC1 in families with anterior segment dysgenesis disorders. Methods We studied 14 Pakistani and one Mexican family with Axenfeld Rieger syndrome (ARS; n = 10) or aniridia (n = 5). All affected and unaffected family members underwent full ophthalmologic and general examinations. Total genomic DNA was isolated from peripheral blood. PCR and Sanger sequencing were performed for the exons and intron-exon boundaries of the FOXC1, PAX6, and PITX2 genes. Results Mutations were identified in five of the 15 probands; four variants were novel and one variant was described previously. A novel de novo variant (c.225C>A; p.Tyr75*) was identified in the PAX6 gene in two unrelated probands with aniridia. In addition, a known variant (c.649C>T; p.Arg217*) in PAX6 segregated in a family with aniridia. In the FOXC1 gene, a novel heterozygous variant (c.454T>C; p.Trp152Arg) segregated with the disease in a Mexican family with ARS. A novel homozygous variant (c.92_100del; p.Ala31_Ala33del) in the FOXC1 gene segregated in a Pakistani family with ARS and congenital glaucoma. Conclusions Our study expands the mutation spectrum of the PAX6 and FOXC1 genes in individuals with anterior segment dysgenesis disorders. In addition, our study suggests that FOXC1 mutations, besides typical autosomal dominant ARS, can also cause ARS with congenital glaucoma through an autosomal recessive inheritance pattern. Our results thus expand the disease spectrum of FOXC1, and may lead to a better understanding of the role of FOXC1 in development. PMID:27463523

  15. A Novel Homozygous Mutation in FOXC1 Causes Axenfeld Rieger Syndrome with Congenital Glaucoma.

    PubMed

    Micheal, Shazia; Siddiqui, Sorath Noorani; Zafar, Saemah Nuzhat; Villanueva-Mendoza, Cristina; Cortés-González, Vianney; Khan, Muhammad Imran; den Hollander, Anneke I

    2016-01-01

    Anterior segment dysgenesis (ASD) disorders are a group of clinically and genetically heterogeneous phenotypes in which frequently cornea, iris, and lens are affected. This study aimed to identify novel mutations in PAX6, PITX2 and FOXC1 in families with anterior segment dysgenesis disorders. We studied 14 Pakistani and one Mexican family with Axenfeld Rieger syndrome (ARS; n = 10) or aniridia (n = 5). All affected and unaffected family members underwent full ophthalmologic and general examinations. Total genomic DNA was isolated from peripheral blood. PCR and Sanger sequencing were performed for the exons and intron-exon boundaries of the FOXC1, PAX6, and PITX2 genes. Mutations were identified in five of the 15 probands; four variants were novel and one variant was described previously. A novel de novo variant (c.225C>A; p.Tyr75*) was identified in the PAX6 gene in two unrelated probands with aniridia. In addition, a known variant (c.649C>T; p.Arg217*) in PAX6 segregated in a family with aniridia. In the FOXC1 gene, a novel heterozygous variant (c.454T>C; p.Trp152Arg) segregated with the disease in a Mexican family with ARS. A novel homozygous variant (c.92_100del; p.Ala31_Ala33del) in the FOXC1 gene segregated in a Pakistani family with ARS and congenital glaucoma. Our study expands the mutation spectrum of the PAX6 and FOXC1 genes in individuals with anterior segment dysgenesis disorders. In addition, our study suggests that FOXC1 mutations, besides typical autosomal dominant ARS, can also cause ARS with congenital glaucoma through an autosomal recessive inheritance pattern. Our results thus expand the disease spectrum of FOXC1, and may lead to a better understanding of the role of FOXC1 in development.

  16. Homozygous SALL1 Mutation Causes a Novel Multiple Congenital Anomaly—Mental Retardation Syndrome

    PubMed Central

    Vodopiutz, Julia; Zoller, Heinz; Fenwick, Aimée L.; Arnhold, Richard; Schmid, Max; Prayer, Daniela; Müller, Thomas; Repa, Andreas; Pollak, Arnold; Aufricht, Christoph; Wilkie, Andrew O.M.; Janecke, Andreas R.

    2013-01-01

    Objective To delineate a novel autosomal recessive multiple congenital anomaly-mental retardation (MCA-MR) syndrome in 2 female siblings of a consanguineous pedigree and to identify the disease-causing mutation. Study design Both siblings were clinically characterized and homozygosity mapping and sequencing of candidate genes were applied. The contribution of nonsense-mediated messenger RNA (mRNA) decay to the expression of mutant mRNA in fibroblasts of a healthy carrier and a control was studied by pyrosequencing. Results We identified the first homozygous SALL1 mutation, c.3160C > T (p.R1054*), in 2 female siblings presenting with multiple congenital anomalies, central nervous system defects, cortical blindness, and absence of psychomotor development (ie, a novel recognizable, autosomal recessive MCA-MR). The mutant SALL1 transcript partially undergoes nonsense-mediated mRNA decay and is present at 43% of the normal transcript level in the fibroblasts of a healthy carrier. Conclusion Previously heterozygous SALL1 mutations and deletions have been associated with dominantly inherited anal-renal-radial-ear developmental anomalies. We identified an allelic recessive SALL1-related MCA-MR. Our findings imply that quantity and quality of SALL1 transcript are important for SALL1 function and determine phenotype, and mode of inheritance, of allelic SALL1-related disorders. This novel MCA-MR emphasizes SALL1 function as critical for normal central nervous system development and warrants a detailed neurologic investigation in all individuals with SALL1 mutations. PMID:23069192

  17. Global Progress Toward Rubella and Congenital Rubella Syndrome Control and Elimination - 2000-2014.

    PubMed

    Grant, Gavin B; Reef, Susan E; Dabbagh, Alya; Gacic-Dobo, Marta; Strebel, Peter M

    2015-09-25

    Rubella virus usually causes a mild fever and rash in children and adults. However, infection during pregnancy, especially during the first trimester, can result in miscarriage, fetal death, stillbirth, or a constellation of congenital malformations known as congenital rubella syndrome (CRS). In 2011, the World Health Organization (WHO) updated guidance on the preferred strategy for introduction of rubella-containing vaccine (RCV) into national routine immunization schedules, including an initial vaccination campaign usually targeting children aged 9 months-15 years . The Global Vaccine Action Plan endorsed by the World Health Assembly in 2012 and the Global Measles and Rubella Strategic Plan (2012-2020) published by Measles and Rubella Initiative partners in 2012 both include goals to eliminate rubella and CRS in at least two WHO regions by 2015, and at least five WHO regions by 2020 (2,3). This report updates a previous report and summarizes global progress toward rubella and CRS control and elimination during 2000-2014. As of December 2014, RCV had been introduced in 140 (72%) countries, an increase from 99 (51%) countries in 2000 (for this report, WHO member states are referred to as countries). Reported rubella cases declined 95%, from 670,894 cases in 102 countries in 2000 to 33,068 cases in 162 countries in 2014, although reporting is inconsistent. To achieve the 2020 Global Vaccine Action Plan rubella and CRS elimination goals, RCV introduction needs to continue as country criteria indicating readiness are met, and rubella and CRS surveillance need to be strengthened to ensure that progress toward elimination can be measured.

  18. Prenatal diagnosis of Wolf-Hirschhorn syndrome (4p-) in association with congenital diaphragmatic hernia, cystic hygroma and IUGR.

    PubMed

    Basgul, A; Kavak, Z N; Akman, I; Basgul, A; Gokaslan, H; Elcioglu, N

    2006-01-01

    Wolf-Hirschhorn syndrome (WHS) is a rare distinct clinical entity caused by a deletion of the short arm of chromosome 4. We report a case in which intrauterine growth restriction (IUGR), severe oligohydramnios, left-sided congenital diaphragmtic hernia (CDH), and cystic hygroma were detected by prenatal ultrasound examination at 27 weeks of gestation. A 29-year-old gravida 3, para 2, woman was referred at 26 weeks' gestation with suspicion of IUGR and cystic hygroma. Sonographic examination revealed IUGR with severe oligohydramnios, increased nuchal fold with cystic hygroma (left-sided diaphragmatic defect of Bochdalek type), and congenital diaphragmatic hernia. Chromosome analysis revealed a 46, XX, del(4)(p15.2) karyotype. Autopsy confirmed the ultrasound findings. Congenital diaphragmatic hernia (CDH) has rarely been described to be associated with WHS. CDH and cystic hygroma can lead to a diagnosis of this syndrome very early in life. We recommend genetic evaluation of a fetus with cystic hygroma, IUGR and CDH taking into consideration 4p deletion syndrome.

  19. 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

  20. 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

  1. Quantitative Assessment of Microstructural Changes of the Retina in Infants With Congenital Zika Syndrome.

    PubMed

    Aleman, Tomas S; Ventura, Camila V; Cavalcanti, Milena M; Serrano, Leona W; Traband, Anastasia; Nti, Akosua A; Gois, Adriana L; Bravo-Filho, Vasco; Martins, Thayze T; Nichols, Charles W; Maia, Mauricio; Belfort, Rubens

    2017-10-01

    A better pathophysiologic understanding of the neurodevelopmental abnormalities observed in neonates exposed in utero to Zika virus (ZIKV) is needed to develop treatments. The retina as an extension of the diencephalon accessible to in vivo microcopy with spectral-domain optical coherence tomography (SD-OCT) can provide an insight into the pathophysiology of congenital Zika syndrome (CZS). To quantify the microstructural changes of the retina in CZS and compare these changes with those of cobalamin C (cblC) deficiency, a disease with potential retinal maldevelopment. This case series included 8 infants with CZS and 8 individuals with cblC deficiency. All patients underwent ophthalmologic evaluation at 2 university teaching hospitals and SD-OCT imaging in at least 1 eye. Patients with cblC deficiency were homozygous or compound heterozygotes for mutations in the methylmalonic aciduria and homocystinuria type C (MMACHC) gene. Data were collected from January 1 to March 17, 2016, for patients with CZS and from May 4, 2015, to April 23, 2016, for patients with cblC deficiency. The SD-OCT cross-sections were segmented using automatic segmentation algorithms embedded in the SD-OCT systems. Each retinal layer thickness was measured at critical eccentricities using the position of the signal peaks and troughs on longitudinal reflectivity profiles. Eight infants with CZS (5 girls and 3 boys; age range, 3-5 months) and 8 patients with cblC deficiency (3 girls and 5 boys; age range, 4 months to 15 years) were included in the analysis. All 8 patients with CZS had foveal abnormalities in the analyzed eyes (8 eyes), including discontinuities of the ellipsoid zone, thinning of the central retina with increased backscatter, and severe structural disorganization, with 3 eyes showing macular pseudocolobomas. Pericentral retina with normal lamination showed a thinned (<30% of normal thickness) ganglion cell layer (GCL) that colocalized in 7 of 8 eyes with a normal photoreceptor layer

  2. Acute Inhibition of MEK Suppresses Congenital Melanocytic Nevus Syndrome in a Murine Model Driven by Activated NRAS and Wnt Signaling.

    PubMed

    Pawlikowski, Jeffrey S; Brock, Claire; Chen, Sheau-Chiann; Al-Olabi, Lara; Nixon, Colin; McGregor, Fiona; Paine, Simon; Chanudet, Estelle; Lambie, Wendy; Holmes, William M; Mullin, James M; Richmond, Ann; Wu, Hong; Blyth, Karen; King, Ayala; Kinsler, Veronica A; Adams, Peter D

    2015-08-01

    Congenital melanocytic nevus (CMN) syndrome is the association of pigmented melanocytic nevi with extra-cutaneous features, classically melanotic cells within the central nervous system, most frequently caused by a mutation of NRAS codon 61. This condition is currently untreatable and carries a significant risk of melanoma within the skin, brain, or leptomeninges. We have previously proposed a key role for Wnt signaling in the formation of melanocytic nevi, suggesting that activated Wnt signaling may be synergistic with activated NRAS in the pathogenesis of CMN syndrome. Some familial pre-disposition suggests a germ-line contribution to CMN syndrome, as does variability of neurological phenotypes in individuals with similar cutaneous phenotypes. Accordingly, we performed exome sequencing of germ-line DNA from patients with CMN to reveal rare or undescribed Wnt-signaling alterations. A murine model harboring activated NRAS(Q61K) and Wnt signaling in melanocytes exhibited striking features of CMN syndrome, in particular neurological involvement. In the first model of treatment for this condition, these congenital, and previously assumed permanent, features were profoundly suppressed by acute post-natal treatment with a MEK inhibitor. These data suggest that activated NRAS and aberrant Wnt signaling conspire to drive CMN syndrome. Post-natal MEK inhibition is a potential candidate therapy for patients with this debilitating condition.

  3. 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.

  4. Associated genetic syndromes and extracardiac malformations strongly influence outcomes of fetuses with congenital heart diseases.

    PubMed

    Bensemlali, Myriam; Bajolle, Fanny; Ladouceur, Magalie; Fermont, Laurent; Lévy, Marilyne; Le Bidois, Jérôme; Salomon, Laurent J; Bonnet, Damien

    2016-05-01

    Congenital heart disease (CHD) is often associated with extracardiac malformations (ECMs) and genetic syndromes. To determine the effect of cytogenetic anomalies and/or ECMs associated with CHD on parental decision to choose termination of pregnancy (TOP) or compassionate care (CC), as well as on the outcome of children born alive. This 10-year retrospective study included all prenatally diagnosed cases of CHD in a single tertiary referral centre. From January 2002 to December 2011, 2036 consecutive cases of fetal CHD (798 TOPs and 1238 live births, including 59 with postnatal CC) were included. CHD was associated with a known cytogenetic anomaly in 9.8% of cases and a major ECM in 11.7% of cases. The proportion of prenatally identified associated cytogenetic anomalies was significantly lower in the live-birth group than in the TOP plus CC group (4.2% vs 17.5%; P<0.001); this was also true for ECMs (8.1% vs 16.7%; P<0.001). The mortality rate was higher in the group with an associated cytogenetic anomaly or ECM (29.1%) than in cases with isolated CHD; a 2.4-fold increase in the death rate was observed (95% confidence interval 1.34-4.38; P=0.003). These associations remained significant after multivariable analysis, including the severity of the CHD (uni- or biventricular physiology). Prenatal diagnosis of a known cytogenetic anomaly or major ECM strongly influences parental decision to choose TOP or postnatal CC. Genetic syndromes and ECMs are associated with a higher mortality rate, independent of the complexity of the CHD. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  5. 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

  6. Vocal cord collapse during phrenic nerve-paced respiration in congenital central hypoventilation syndrome.

    PubMed

    Domanski, Mark C; Preciado, Diego A

    2012-01-01

    Phrenic nerve pacing can be used to treat congenital central hypoventilation syndrome (CCHS). We report how the lack of normal vocal cord tone during phrenic paced respiration can result in passive vocal cord collapse and produce obstructive symptoms. We describe a case of passive vocal cord collapse during phrenic nerve paced respiration in a patient with CCHS. As far as we know, this is the first report of this etiology of airway obstruction. The patient, a 7-year-old with CCHS and normal waking vocal cord movement, continued to require nightly continuous positive airway pressure (CPAP) despite successful utilization of phrenic nerve pacers. On direct laryngoscopy, the patient's larynx was observed while the diaphragmatic pacers were sequentially engaged. No abnormal vocal cord stimulation was witnessed during engaging of either phrenic nerve stimulator. However, the lack of normal inspiratory vocal cord abduction during phrenic nerve-paced respiration resulted in vocal cord collapse and partial obstruction due to passive adduction of the vocal cords through the Bernoulli effect. Bilateral phrenic nerve stimulation resulted in more vocal cord collapse than unilateral stimulation. The lack of vocal cord abduction on inspiration presents a limit to phrenic nerve pacers.

  7. The value of the study of natural history in genetic disorders and congenital anomaly syndromes.

    PubMed Central

    Hall, J G

    1988-01-01

    The study of the natural history of genetic disorders and syndromes with congenital anomalies and dysmorphic features is a challenging and often neglected area. There are many reasons to pursue this type of research but it requires special clinical skills and a considerable amount of hard work. Setting up protocols and collecting data is complex and time consuming. Frequently, helpful clues for a particular disorder come from the study of the natural history of other disorders. Older affected subjects and unique cases with unusual features are often most important in unravelling the 'normal' course of a disease or recognising the basic defect. The study of natural history from individual patients and their records is complementary to population or registry based studies because it identifies individual variations and clinical heterogeneity. The understanding of the natural history of a particular disorder is of importance both to the affected person and their family and to the physicians caring for them. It is also useful to the basic researcher trying to determine the pathogenetic mechanism causing the disorder. In many ways, clinical geneticists have learned the art of caring for patients, as well as the challenges of clinical genetics, by becoming apprentices to and studying in depth specific disease entities. PMID:3050091

  8. Zika fever and congenital Zika syndrome: An unexpected emerging arboviral disease.

    PubMed

    Chan, Jasper F W; Choi, Garnet K Y; Yip, Cyril C Y; Cheng, Vincent C C; Yuen, Kwok-Yung

    2016-05-01

    Unlike its mosquito-borne relatives, such as dengue, West Nile, and Japanese encephalitis viruses, which can cause severe human diseases, Zika virus (ZIKV) has emerged from obscurity by its association with a suspected "congenital Zika syndrome", while causing asymptomatic or mild exanthematous febrile infections which are dengue- or rubella-like in infected individuals. Despite having been discovered in Uganda for almost 60 years, <20 human cases were reported before 2007. The massive epidemics in the Pacific islands associated with the ZIKV Asian lineage in 2007 and 2013 were followed by explosive outbreaks in Latin America in 2015. Although increased mosquito breeding associated with the El Niño effect superimposed on global warming is suspected, genetic changes in its RNA virus genome may have led to better adaptation to mosquitoes, other animal reservoirs, and human. We reviewed the epidemiology, clinical manifestation, virology, pathogenesis, laboratory diagnosis, management, and prevention of this emerging infection. Laboratory diagnosis can be confounded by cross-reactivity with other circulating flaviviruses. Besides mosquito bite and transplacental transmission, the risk of other potential routes of transmission by transfusion, transplantation, sexual activity, breastfeeding, respiratory droplet, and animal bite is discussed. Epidemic control requires adequate clearance of mosquito breeding grounds, personal protection against mosquito bite, and hopefully a safe and effective vaccine. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  9. 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

  10. An outbreak investigation of congenital rubella syndrome in Solomon Islands, 2013

    PubMed Central

    Durski, Kara N; Tituli, Carol; Ogaoga, Divi; Joshua, Cynthia; Dofai, Alfred; Leydon, Jennie; Nilles, Eric

    2016-01-01

    Introduction During May 2012, a rubella outbreak was declared in Solomon Islands. A suspected case of congenital rubella syndrome (CRS) was reported from one hospital 11 months later in 2013. This report describes the subsequent CRS investigation, findings and measures implemented. Methods Prospective CRS surveillance was conducted at the newborn nursery, paediatric and post-natal wards, and the paediatric cardiology and ophthalmology clinics of the study hospital from April to July 2013. Retrospective case finding by reviewing medical records was also undertaken to identify additional cases born between January and March 2013 for the same wards and clinics. Cases were identified using established World Health Organization case definitions for CRS. Results A total of 13 CRS cases were identified, including two laboratory-confirmed, four clinically confirmed and seven suspected cases. Five CRS cases were retrospectively identified, including four suspected and one clinically confirmed case. There was no geospatial clustering of residences. The mothers of the cases were aged between 20 and 36 years. Three of the six mothers available for interview recalled an acute illness with rash during the first trimester of pregnancy. Discussion Additional CRS cases not captured in this investigation are likely. Caring for CRS cases is a challenge in resource-poor settings. Rubella vaccination is safe and effective and can prevent the serious consequences of CRS. Well planned and funded vaccination activities can prevent future CRS cases. PMID:27757248

  11. Congenital cervical kyphosis in an infant with Ehlers-Danlos syndrome.

    PubMed

    Kobets, Andrew J; Komlos, Daniel; Houten, John K

    2018-07-01

    Ehler-Danlos syndome (EDS) refers to a group of heritable connective tissue disorders; rare manifestations of which are cervical kyphosis and clinical myelopathy. Surgical treatment is described for the deformity in the thoracolumbar spine in adolescents but not for infantile cervical spine. Internal fixation for deformity correction in the infantile cervical spine is challenging due to the diminutive size of the bony anatomy and the lack of spinal instrumentation specifically designed for young children. We describe the first case of successful surgical treatment in an infant with a high cervical kyphotic deformity in EDS. A 15-month-old female with EDS presented with several months of regression in gross motor skills in all four extremities. Imaging demonstrated 45° of kyphosis from the C2-4 levels with spinal cord compression. Corrective surgery consisted of a C3 corpectomy and C2-4 anterior fusion with allograft block and anterior fixation with dual 2 × 2 hole craniofacial miniplates, supplemented by C2-4 posterior fusion using four craniofacial miniplates fixated to the lamina. Radiographs at 20 months post-surgery demonstrated solid fusion both anteriorly and posteriorly with maintenance of correction. Ehlers-Danlos syndrome may present in the pediatric population with congenital kyphosis from cervical deformity in addition to the more commonly seen thoracolumbar deformities.

  12. Ehlers-Danlos Syndrome Caused by Biallelic TNXB Variants in Patients with Congenital Adrenal Hyperplasia.

    PubMed

    Chen, Wuyan; Perritt, Ashley F; Morissette, Rachel; Dreiling, Jennifer L; Bohn, Markus-Frederik; Mallappa, Ashwini; Xu, Zhi; Quezado, Martha; Merke, Deborah P

    2016-09-01

    Some variants that cause autosomal-recessive congenital adrenal hyperplasia (CAH) also cause hypermobility type Ehlers-Danlos syndrome (EDS) due to the monoallelic presence of a chimera disrupting two flanking genes: CYP21A2, encoding 21-hydroxylase, necessary for cortisol and aldosterone biosynthesis, and TNXB, encoding tenascin-X, an extracellular matrix protein. Two types of CAH tenascin-X (CAH-X) chimeras have been described with a total deletion of CYP21A2 and characteristic TNXB variants. CAH-X CH-1 has a TNXB exon 35 120-bp deletion resulting in haploinsufficiency, and CAH-X CH-2 has a TNXB exon 40 c.12174C>G (p.Cys4058Trp) variant resulting in a dominant-negative effect. We present here three patients with biallelic CAH-X and identify a novel dominant-negative chimera termed CAH-X CH-3. Compared with monoallelic CAH-X, biallelic CAH-X results in a more severe phenotype with skin features characteristic of classical EDS. We present evidence for disrupted tenascin-X function and computational data linking the type of TNXB variant to disease severity. © 2016 WILEY PERIODICALS, INC.

  13. An outbreak investigation of congenital rubella syndrome in Solomon Islands, 2013.

    PubMed

    Durski, Kara N; Tituli, Carol; Ogaoga, Divi; Musto, Jennie; Joshua, Cynthia; Dofai, Alfred; Leydon, Jennie; Nilles, Eric

    2016-01-01

    During May 2012, a rubella outbreak was declared in Solomon Islands. A suspected case of congenital rubella syndrome (CRS) was reported from one hospital 11 months later in 2013. This report describes the subsequent CRS investigation, findings and measures implemented. Prospective CRS surveillance was conducted at the newborn nursery, paediatric and post-natal wards, and the paediatric cardiology and ophthalmology clinics of the study hospital from April to July 2013. Retrospective case finding by reviewing medical records was also undertaken to identify additional cases born between January and March 2013 for the same wards and clinics. Cases were identified using established World Health Organization case definitions for CRS. A total of 13 CRS cases were identified, including two laboratory-confirmed, four clinically confirmed and seven suspected cases. Five CRS cases were retrospectively identified, including four suspected and one clinically confirmed case. There was no geospatial clustering of residences. The mothers of the cases were aged between 20 and 36 years. Three of the six mothers available for interview recalled an acute illness with rash during the first trimester of pregnancy. Additional CRS cases not captured in this investigation are likely. Caring for CRS cases is a challenge in resource-poor settings. Rubella vaccination is safe and effective and can prevent the serious consequences of CRS. Well planned and funded vaccination activities can prevent future CRS cases.

  14. Turner's syndrome and other forms of congenital hypogonadism impair quality of life and sexual function.

    PubMed

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

    2013-06-01

    We sought to assess the burden of Turner's syndrome (TS) and other congenital hypogonadisms (OCH) on quality of life (QOL) and sexual function. An observational study was undertaken in a gynecological endocrinology unit of a teaching hospital. Three cohorts of women aged 20-50 years were compared: 26 TS patients, 21 women with OCH and wild-type karyotype, and 41 healthy age-matched women who were included as controls. All subjects filled out the Medical Outcome Study Short Form (SF-36) and the Female Sexual Function Index. TS subjects had significantly worse QOL scores in physical functioning (P = .026) and role physical functioning (P = .032) whereas OCH showed significantly worse scores in physical functioning (P = .027) and bodily pain (P = .025) compared to controls. In all, 80% of OCH and 50% of TS patients declared sexual activity. Sexually active TS patients had poorer arousal outcomes (P = .009) and OCH women showed significantly worse scores in arousal (P = .002), orgasm (P = .007), pain (P = .001), and Female Sexual Function Index total score (P = .004) compared with healthy controls. No differences between sexually active and inactive TS women were found in SF-36 scores, clinical characteristics, or anthropomorphic characteristics. TS and OCH subjects presented impaired physical domains in QOL. Women with TS are less likely to be involved in sexual activity, arousal dysfunctions being their main symptom. Conversely, arousal, orgasm, pain, and total score were significantly affected in OCH subjects. Copyright © 2013 Mosby, Inc. All rights reserved.

  15. 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.

  16. 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

    2018-06-01

    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.

  17. 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.

  18. 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.

  19. Echocardiography findings in clinically confirmed congenital rubella syndrome cases seen at the University of Port Harcourt Teaching Hospital, Nigeria.

    PubMed

    Otaigbe, B E; Tabansi, P N; Agbedey, G O

    2012-01-01

    Congenital rubella syndrome (CRS) is known to affect thousands of children in the developing world because rubella vaccination is not available routinely in most of these countries. Among its many manifestations only congenital heart disease is life threatening. This study was undertaken to ascertain the cases of echocardiographic determined congenital heart disease in clinically confirmed CRS cases. Data of patients with clinically confirmed CRS seen over a period of 5 years in the Paediatric cardiology clinic of the University of Port Harcourt Teaching Hospital was retrieved and analysed. Seven cases (2.8 % of total cardiac cases) were seen. 6 (85.7%) cases had at least one murmur on auscultation. Patent ductus arteriosus was the commonest cardiac defect seen either in isolation or incombination with a VSD or ASD. Only one child had no cardiac defect. 4 (57.1%) of them had been admitted for heart failure at least once and 2 (28.6 %) were on anti-failure regimen, one of whom had cardiac surgery one month ago. In view of the fact that 6 (85.7%) of the patients with CRS had at least one congenital heart defect, we advocate routine echocardiography on patients with CRS to ensure early treatment and reduce mortality and morbidity.We also advocate that rubella vaccination be given routinely in developing countries.

  20. 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

  1. 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.

  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. A Case of Bilateral Pigment Dispersion Syndrome Following Many Years of Uninterrupted Treatment With Atropine 1% for Bilateral Congenital Cataracts.

    PubMed

    Gizzi, Corrado; Mohamed-Noriega, Jibran; Murdoch, Ian

    2017-10-01

    Describe an unusual case of bilateral pigment dispersion syndrome (PDS) following years of uninterrupted treatment with atropine 1% for bilateral congenital cataracts, speculate on potential mechanisms leading to this condition. This is a case report. A 45-year-old white patient on long-term treatment with atropine 1% ointment since his infancy for bilateral congenital cataracts developed PDS with secondary ocular hypertension. The patient showed all the hallmarks of PDS with secondary ocular hypertension. An anterior segment Swept-Source optical coherence tomography was obtained to review the iris profile. The patient showed good pressure response to topical prostaglandin therapy. This is the second case report of PDS in a patient with chronic use of topical atropine. The proposed mechanisms for pigment dispersion are discussed and the possibility raised of dispersion being a potential side effect of the drug.

  4. 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

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

    PubMed

    Saad, Amin F; Ford, Kenneth L; Deprisco, Gregory; Smerud, Michael J

    2013-07-01

    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.

  6. Defective Fast Inactivation Recovery of Nav1.4 in Congenital Myasthenic Syndrome

    PubMed Central

    Arnold, W. David; Feldman, Daniel H.; Ramirez, Sandra; He, Liuyuan; Kassar, Darine; Quick, Adam; Klassen, Tara L.; Lara, Marian; Nguyen, Joanna; Kissel, John T.; Lossin, Christoph; Maselli, Ricardo A.

    2015-01-01

    Objective To describe the unique phenotype and genetic findings in a 57-year-old female with a rare form of congenital myasthenic syndrome (CMS) associated with longstanding muscle fatigability, and to investigate the underlying pathophysiology. Methods We used whole-cell voltage clamping to compare the biophysical parameters of wild-type and Arg1457His-mutant Nav1.4. Results Clinical and neurophysiological evaluation revealed features consistent with CMS. Sequencing of candidate genes indicated no abnormalities. However, analysis of SCN4A, the gene encoding the skeletal muscle sodium channel Nav1.4, revealed a homozygous mutation predicting an arginine-to-histidine substitution at position 1457 (Arg1457His), which maps to the channel’s voltage sensor, specifically D4/S4. Whole-cell patch clamp studies revealed that the mutant required longer hyperpolarization to recover from fast inactivation, which produced a profound use-dependent current attenuation not seen in the wild type. The mutant channel also had a marked hyperpolarizing shift in its voltage dependence of inactivation as well as slowed inactivation kinetics. Interpretation We conclude that Arg1457His compromises muscle fiber excitability. The mutant fast-inactivates with significantly less depolarization, and it recovers only after extended hyperpolarization. The resulting enhancement in its use dependence reduces channel availability, which explains the patient’s muscle fatigability. Arg1457His offers molecular insight into a rare form of CMS precipitated by sodium channel inactivation defects. Given this channel’s involvement in other muscle disorders such as paramyotonia congenita and hyperkalemic periodic paralysis, our study exemplifies how variations within the same gene can give rise to multiple distinct dysfunctions and phenotypes, revealing residues important in basic channel function. PMID:25707578

  7. 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

  8. 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

  9. 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.

  10. Implications of Zika virus and congenital Zika syndrome for the number of live births in Brazil

    PubMed Central

    Han, Qiuyi C.; Victora, Cesar G.; França, Giovanny V. A.

    2018-01-01

    An increase in microcephaly, associated with an epidemic of Zika virus (ZIKV) in Brazil, prompted the World Health Organization to declare a Public Health Emergency of International Concern in February 2016. While knowledge on biological and epidemiological aspects of ZIKV has advanced, demographic impacts remain poorly understood. This study uses time-series analysis to assess the impact of ZIKV on births. Data on births, fetal deaths, and hospitalizations due to abortion complications for Brazilian states, from 2010 to 2016, were used. Forecasts for September 2015 to December 2016 showed that 119,095 fewer births than expected were observed, particularly after April 2016 (a reduction significant at 0.05), demonstrating a link between publicity associated with the ZIKV epidemic and the decline in births. No significant changes were observed in fetal death rates. Although no significant increases in hospitalizations were forecasted, after the ZIKV outbreak hospitalizations happened earlier in the gestational period in most states. We argue that postponement of pregnancy and an increase in abortions may have contributed to the decline in births. Also, it is likely that an increase in safe abortions happened, albeit selective by socioeconomic status. Thus, the ZIKV epidemic resulted in a generation of congenital Zika syndrome (CZS) babies that reflect and exacerbate regional and social inequalities. Since ZIKV transmission has declined, it is unlikely that reductions in births will continue. However, the possibility of a new epidemic is real. There is a need to address gaps in reproductive health and rights, and to understand CZS risk to better inform conception decisions. PMID:29844186

  11. The spectrum of mutations that underlie the neuromuscular junction synaptopathy in DOK7 congenital myasthenic syndrome.

    PubMed

    Cossins, Judith; Liu, Wei Wei; Belaya, Katsiaryna; Maxwell, Susan; Oldridge, Michael; Lester, Tracy; Robb, Stephanie; Beeson, David

    2012-09-01

    Congenital myasthenic syndromes (CMS) are a group of inherited diseases that affect synaptic transmission at the neuromuscular junction and result in fatiguable muscle weakness. A subgroup of CMS patients have a recessively inherited limb-girdle pattern of weakness caused by mutations in DOK7. DOK7 encodes DOK7, an adaptor protein that is expressed in the skeletal muscle and heart and that is essential for the development and maintenance of the neuromuscular junction. We have screened the DOK7 gene for mutations by polymerase chain reaction amplification and bi-directional sequencing of exonic and promoter regions and performed acetylcholine receptor (AChR) clustering assays and used exon trapping to determine the pathogenicity of detected variants. Approximately 18% of genetically diagnosed CMSs in the UK have mutations in DOK7, with mutations in this gene identified in more than 60 kinships to date. Thirty-four different pathogenic mutations were identified as well as 27 variants likely to be non-pathogenic. An exon 7 frameshift duplication c.1124_1127dupTGCC is commonly found in at least one allele. We analyse the effect of the common frameshift c.1124_1127dupTGCC and show that 10/11 suspected missense mutations have a deleterious effect on AChR clustering. We identify for the first time homozygous or compound heterozygous mutations that are localized 5' to exon 7. In addition, three silent variants in the N-terminal half of DOK7 are predicted to alter the splicing of the DOK7 RNA transcript. The DOK7 gene is highly polymorphic, and within these many variants, we define a spectrum of mutations that can underlie DOK7 CMS that will inform in managing this disorder.

  12. An epidemiological assessment towards elimination of rubella and congenital rubella syndrome in Singapore.

    PubMed

    Chua, Ying Xian; Ang, Li Wei; Low, Constance; James, Lyn; Cutter, Jeffery L; Goh, Kee Tai

    2015-06-17

    In line with regional and global goals for the elimination of rubella and congenital rubella syndrome (CRS), we reviewed the epidemiological situation in Singapore, based on surveillance reports on rubella and CRS, national immunization coverage and seroprevalence surveys. The aim of our review was to identify current gaps and steps taken to achieve the targets set by the World Health Organization (WHO) Western Pacific Regional Office (WPRO). Epidemiological data on clinical and laboratory-confirmed rubella cases, including CRS, notified to the Communicable Diseases Division, Ministry of Health, Singapore, from 2003 to 2013 were collated and analyzed. Vaccination coverage against rubella was obtained from the National Immunization Registry and School Health Services of the Health Promotion Board. The changing prevalence of rubella was determined from periodic serological surveys. The incidence of indigenous rubella cases per million population decreased from 37.2 in 2008 to 7.6 in 2013 and there had been no indigenous case of CRS in 2012 and 2013. Therapeutic abortions performed due to rubella infections had become uncommon. The annual measles, mumps, and rubella (MMR) vaccination coverage in childhood population remained high ranging from 93% to 96%. The overall susceptibility to rubella in women aged 18-44 years had reduced significantly from 15.8% in 2004 to 11.0% in 2010. The prevalence of IgG antibody against rubella among Singapore children aged 1-17 years was maintained at 87.3% in 2008-2010. All available data indicated that Singapore has made good progress towards the elimination of rubella and CRS. It has attained the targets set by the WHO WPRO for 2015. In preparation for verification of rubella elimination, an enhanced surveillance system has been implemented to ensure that all reported cases are laboratory confirmed, and genotyping of rubella virus strains isolated is carried out to provide evidence for interruption of endemic transmission. Copyright

  13. Detection of chromosomal abnormalities, congenital abnormalities and transfusion syndrome in twins.

    PubMed

    Sperling, L; Kiil, C; Larsen, L U; Brocks, V; Wojdemann, K R; Qvist, I; Schwartz, M; Jørgensen, C; Espersen, G; Skajaa, K; Bang, J; Tabor, A

    2007-05-01

    To evaluate the outcome of screening for structural malformations in twins and the outcome of screening for twin-twin transfusion syndrome (TTTS) among monochorionic twins through a number of ultrasound scans from 12 weeks' gestation. Enrolled into this prospective multicenter observational study were women with twin pregnancies diagnosed before 14 + 6 gestational weeks. The monochorionic pregnancies were scanned every second week until 23 weeks in order to rule out early TTTS. All pregnancies had an anomaly scan in week 19 and fetal echocardiography in week 21 that was performed by specialists in fetal echocardiography. Zygosity was determined by DNA analysis in all twin pairs with the same sex. Among the 495 pregnancies the prenatal detection rate for severe structural abnormalities including chromosomal aneuploidies was 83% by the combination of a first-trimester nuchal translucency scan and the anomaly scan in week 19. The incidence of severe structural abnormalities was 2.6% and two-thirds of these anomalies were cardiac. There was no significant difference between the incidence in monozygotic and dizygotic twins, nor between twins conceived naturally or those conceived by assisted reproduction. The incidence of TTTS was 23% from 12 weeks until delivery, and all those monochorionic twin pregnancies that miscarried had signs of TTTS. Twin pregnancies have an increased risk of congenital malformations and one out of four monochorionic pregnancies develops TTTS. Ultrasound screening to assess chorionicity and follow-up of monochorionic pregnancies to detect signs of TTTS, as well as malformation screening, are therefore essential in the antenatal care of twin pregnancies. Copyright (c) 2007 ISUOG.

  14. 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

    2018-04-01

    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.

  15. 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.

  16. 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.

  17. Impaired neural structure and function contributing to autonomic symptoms in congenital central hypoventilation syndrome.

    PubMed

    Harper, Ronald M; Kumar, Rajesh; Macey, Paul M; Harper, Rebecca K; Ogren, Jennifer A

    2015-01-01

    Congenital central hypoventilation syndrome (CCHS) patients show major autonomic alterations in addition to their better-known breathing deficiencies. The processes underlying CCHS, mutations in the PHOX2B gene, target autonomic neuronal development, with frame shift extent contributing to symptom severity. Many autonomic characteristics, such as impaired pupillary constriction and poor temperature regulation, reflect parasympathetic alterations, and can include disturbed alimentary processes, with malabsorption and intestinal motility dyscontrol. The sympathetic nervous system changes can exert life-threatening outcomes, with dysregulation of sympathetic outflow leading to high blood pressure, time-altered and dampened heart rate and breathing responses to challenges, cardiac arrhythmia, profuse sweating, and poor fluid regulation. The central mechanisms contributing to failed autonomic processes are readily apparent from structural and functional magnetic resonance imaging studies, which reveal substantial cortical thinning, tissue injury, and disrupted functional responses in hypothalamic, hippocampal, posterior thalamic, and basal ganglia sites and their descending projections, as well as insular, cingulate, and medial frontal cortices, which influence subcortical autonomic structures. Midbrain structures are also compromised, including the raphe system and its projections to cerebellar and medullary sites, the locus coeruleus, and medullary reflex integrating sites, including the dorsal and ventrolateral medullary nuclei. The damage to rostral autonomic sites overlaps metabolic, affective and cognitive regulatory regions, leading to hormonal disruption, anxiety, depression, behavioral control, and sudden death concerns. The injuries suggest that interventions for mitigating hypoxic exposure and nutrient loss may provide cellular protection, in the same fashion as interventions in other conditions with similar malabsorption, fluid turnover, or hypoxic exposure.

  18. Implications of Zika virus and congenital Zika syndrome for the number of live births in Brazil.

    PubMed

    Castro, Marcia C; Han, Qiuyi C; Carvalho, Lucas R; Victora, Cesar G; França, Giovanny V A

    2018-06-12

    An increase in microcephaly, associated with an epidemic of Zika virus (ZIKV) in Brazil, prompted the World Health Organization to declare a Public Health Emergency of International Concern in February 2016. While knowledge on biological and epidemiological aspects of ZIKV has advanced, demographic impacts remain poorly understood. This study uses time-series analysis to assess the impact of ZIKV on births. Data on births, fetal deaths, and hospitalizations due to abortion complications for Brazilian states, from 2010 to 2016, were used. Forecasts for September 2015 to December 2016 showed that 119,095 fewer births than expected were observed, particularly after April 2016 (a reduction significant at 0.05), demonstrating a link between publicity associated with the ZIKV epidemic and the decline in births. No significant changes were observed in fetal death rates. Although no significant increases in hospitalizations were forecasted, after the ZIKV outbreak hospitalizations happened earlier in the gestational period in most states. We argue that postponement of pregnancy and an increase in abortions may have contributed to the decline in births. Also, it is likely that an increase in safe abortions happened, albeit selective by socioeconomic status. Thus, the ZIKV epidemic resulted in a generation of congenital Zika syndrome (CZS) babies that reflect and exacerbate regional and social inequalities. Since ZIKV transmission has declined, it is unlikely that reductions in births will continue. However, the possibility of a new epidemic is real. There is a need to address gaps in reproductive health and rights, and to understand CZS risk to better inform conception decisions. Copyright © 2018 the Author(s). Published by PNAS.

  19. 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

  20. 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

  1. 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.

  2. Spectrum of Spinal Cord, Spinal Root, and Brain MRI Abnormalities in Congenital Zika Syndrome with and without Arthrogryposis.

    PubMed

    Aragao, M F V V; Brainer-Lima, A M; Holanda, A C; van der Linden, V; Vasco Aragão, L; Silva Júnior, M L M; Sarteschi, C; Petribu, N C L; Valença, M M

    2017-05-01

    Arthrogryposis is among the malformations of congenital Zika syndrome. Similar to the brain, there might exist a spectrum of spinal cord abnormalities. The purpose of this study was to explore and describe in detail the MR imaging features found in the spinal cords, nerve roots, and brains of children with congenital Zika syndrome with and without arthrogryposis. Twelve infants with congenital Zika syndrome (4 with arthrogryposis and 8 without) who had undergone brain and spinal cord MR imaging were retrospectively selected. Qualitative and quantitative analyses were performed and compared between groups. At visual inspection, both groups showed reduced thoracic spinal cord thickness: 75% (6/8) of the group without arthrogryposis and 100% (4/4) of the arthrogryposis group. However, the latter had the entire spinal cord reduced and more severely reduced conus medullaris anterior roots (respectively, P = .002 and .007). Quantitative differences were found for conus medullaris base and cervical and lumbar intumescences diameters (respectively, P = .008, .048, .008), with more prominent reduction in arthrogryposis. Periventricular calcifications were more frequent in infants with arthrogryposis ( P = .018). Most infants had some degree of spinal cord thickness reduction, predominant in the thoracic segment (without arthrogryposis) or in the entire spinal cord (with arthrogryposis). The conus medullaris anterior roots were reduced in both groups (thinner in arthrogryposis). A prominent anterior median fissure of the spinal cord was absent in infants without arthrogryposis. Brain stem hypoplasia was present in all infants with arthrogryposis, periventricular calcifications, in the majority, and polymicrogyria was absent. © 2017 by American Journal of Neuroradiology.

  3. Placental Histopathology and Clinical Presentation of Severe Congenital Zika Syndrome in a Human Immunodeficiency Virus-Exposed Uninfected Infant.

    PubMed

    Rabelo, Kíssila; de Souza Campos Fernandes, Regina Célia; de Souza, Luiz José; Louvain de Souza, Thais; Dos Santos, Flávia Barreto; Guerra Nunes, Priscila Conrado; de Azeredo, Elzinandes Leal; Salomão, Natália Gedeão; Trindade, Gisela Freitas; Basílio-de-Oliveira, Carlos A; de Carvalho, Jorge José; Medina-Acosta, Enrique; Paes, Marciano Viana

    2017-01-01

    In the large Zika virus (ZIKV) epidemic that occurred in Brazil in 2015, the intrauterine fetal exposure to ZIKV was associated with a significant risk of developing microcephaly and neurological disorders in the infected infants. ZIKV-associated disease has since been reported in 24 countries in the Americas. At present, definitive evidence is lacking regarding the intrauterine co-exposure to ZIKV and other viral infections and whether the coinfection impacts the risk of acquiring either infection or disease severity. Here, we provide evidence of intrauterine exposure to both ZIKV and human immunodeficiency virus (HIV) infections, causing congenital Zika syndrome in an HIV-exposed uninfected infant. Clinical, imaging and laboratory examinations of the pregnant woman and the newborn were performed. Histopathology, ZIKV/HIV-specific immunoassays, and ultrastructural evaluation of the placenta were performed. The Zika-asymptomatic, HIV-positive pregnant woman underwent ultrasounds revealing fetal cerebral ventriculomegaly, microcephaly, and brain atrophy. Her baby girl was born small for gestational age and with the neurological sequelae of congenital Zika syndrome. The evaluation of the abnormally large term placenta revealed severe damage to the maternal decidua and chorionic villi, cells positive for ZIKV-specific antigens but not for HIV antigens, and intracellular membranous clusters of virus-like particles approximately 25 nm in diameter. The rapid progression and severity of the congenital Zika syndrome may be related to the uncontrolled HIV disease in the mother. The poor inflammatory response observed in the placenta may have reduced the inherent risk of mother-to-child transmission of HIV.

  4. Placental Histopathology and Clinical Presentation of Severe Congenital Zika Syndrome in a Human Immunodeficiency Virus-Exposed Uninfected Infant

    PubMed Central

    Rabelo, Kíssila; de Souza Campos Fernandes, Regina Célia; de Souza, Luiz José; Louvain de Souza, Thais; dos Santos, Flávia Barreto; Guerra Nunes, Priscila Conrado; de Azeredo, Elzinandes Leal; Salomão, Natália Gedeão; Trindade, Gisela Freitas; Basílio-de-Oliveira, Carlos A.; de Carvalho, Jorge José; Medina-Acosta, Enrique; Paes, Marciano Viana

    2017-01-01

    In the large Zika virus (ZIKV) epidemic that occurred in Brazil in 2015, the intrauterine fetal exposure to ZIKV was associated with a significant risk of developing microcephaly and neurological disorders in the infected infants. ZIKV-associated disease has since been reported in 24 countries in the Americas. At present, definitive evidence is lacking regarding the intrauterine co-exposure to ZIKV and other viral infections and whether the coinfection impacts the risk of acquiring either infection or disease severity. Here, we provide evidence of intrauterine exposure to both ZIKV and human immunodeficiency virus (HIV) infections, causing congenital Zika syndrome in an HIV-exposed uninfected infant. Clinical, imaging and laboratory examinations of the pregnant woman and the newborn were performed. Histopathology, ZIKV/HIV-specific immunoassays, and ultrastructural evaluation of the placenta were performed. The Zika-asymptomatic, HIV-positive pregnant woman underwent ultrasounds revealing fetal cerebral ventriculomegaly, microcephaly, and brain atrophy. Her baby girl was born small for gestational age and with the neurological sequelae of congenital Zika syndrome. The evaluation of the abnormally large term placenta revealed severe damage to the maternal decidua and chorionic villi, cells positive for ZIKV-specific antigens but not for HIV antigens, and intracellular membranous clusters of virus-like particles approximately 25 nm in diameter. The rapid progression and severity of the congenital Zika syndrome may be related to the uncontrolled HIV disease in the mother. The poor inflammatory response observed in the placenta may have reduced the inherent risk of mother-to-child transmission of HIV. PMID:29270171

  5. HDR syndrome with a novel mutation in GATA3 mimicking a congenital X-linked stapes gusher: a case report.

    PubMed

    Yang, Aram; Kim, Jinsup; Ki, Chang-Seok; Hong, Sung Hwa; Cho, Sung Yoon; Jin, Dong-Kyu

    2017-10-26

    Hypoparathyroidism, sensorineural hearing loss, and renal disease (HDR) syndrome, also known as Barakat syndrome, is a rare genetic disorder with high phenotypic heterogeneity caused by haploinsufficiency of the GATA3 gene on chromosome 10p14-p15. For these reasons, the diagnosis of HDR syndrome is challenging and requires a high index of suspicion as well as genetic analysis. A 14-month-old boy, with sensorineural hearing loss in both ears, showed typical radiological features of X-linked stapes gusher on preoperative temporal bone computed tomography (CT) for cochlear implantations. Then after his discharge from hospital, he suffered a hypocalcemic seizure and we discovered a renal cyst during investigation of hypocalcemia. He was finally diagnosed with HDR syndrome by clinical findings, which were confirmed by molecular genetic testing. Direct sequencing of the GATA3 gene showed a heterozygous 2-bp deletion (c.1201_1202delAT), which is predicted to cause a frameshift of the reading frame (p.Met401Valfs*106). To our knowledge, this is the first case of HDR syndrome with a novel de novo variant mimicking a congenital X-linked stapes gusher syndrome. Novel mutations and the diversity of clinical manifestations expand the genotypic and phenotypic spectrum of HDR syndrome. Diagnosis of HDR syndrome is still challenging, but clinicians should consider it in their differential diagnosis for children with a wide range of clinical manifestations including hypocalcemia induced seizures and deafness. We hope that this case will contribute to further understanding and studies of HDR-associated GATA3 mutations.

  6. 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.

  7. Physiological basis for the etiology, diagnosis, and treatment of adrenal disorders: Cushing's syndrome, adrenal insufficiency, and congenital adrenal hyperplasia.

    PubMed

    Raff, Hershel; Sharma, Susmeeta T; Nieman, Lynnette K

    2014-04-01

    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. © 2014 American Physiological Society.

  8. Molecular and clinical characterization of a patient with a chromosome 4p deletion, Wolf-Hirschhorn syndrome, and congenital glaucoma.

    PubMed

    Finzi, S; Pinto, C F; Wiggs, J L

    2001-03-01

    Wolf-Hirschhorn syndrome is a developmental disorder associated with hemizygous deletion of the distal short arm of chromosome 4. We have identified a patient affected with Wolf-Hirschhorn syndrome and early onset glaucoma. Five other patients with Wolf-Hirschhorn syndrome and early onset glaucoma or ocular anomalies associated with early onset glaucoma have been previously described, suggesting that the association with Wolf-Hirschhorn syndrome is not coincidental. The infrequent association of early onset glaucoma suggests that the chromosomal region commonly deleted in Wolf-Hirschhorn patients does not contain genes responsible for early onset glaucoma. In this study, we performed a molecular characterization of the deleted chromosome 4 to determine the extent of the deletion in an attempt to begin to identify the chromosomal region responsible for the associated glaucoma. Using microsatellite repeat markers located on 4p, we determined that the deletion spanned a 60-cM region including the minimal Wolf-Hirschhorn region. The proximal breakpoint occurred between markers D4S3045 and D4S2974. These results support the hypothesis that patients with Wolf-Hirschhorn syndrome and early onset glaucoma may have large deletions of 4p that include a gene(s) that may be responsible for a dominant form of congenital glaucoma.

  9. A PIGN Mutation Responsible for Multiple Congenital Anomalies–Hypotonia–Seizures Syndrome 1 (MCAHS1) in an Israeli–Arab Family

    PubMed Central

    Khayat, Morad; Tilghman, Joseph Mark; Chervinsky, Ilana; Zalman, Lucia; Chakravarti, Aravinda; Shalev, Stavit A.

    2017-01-01

    Mutations in the PIGN gene involved in the glycosylphoshatidylinositol (GPI) anchor biosynthesis pathway cause Multiple Congenital Anomalies–Hypotonia–Seizures syndrome 1 (MCAHS1). The syndrome manifests developmental delay, hypotonia, and epilepsy, combined with multiple congenital anomalies. We report on the identification of a homozygous novel c.755A>T (p.D252V) deleterious mutation in a patient with Israeli–Arab origin with MCAHS1. The mutated PIGN caused a significant decrease of the overall GPI-anchored proteins and CD24 expression. Our results, strongly support previously published data, that partial depletion of GPI-anchored proteins is sufficient to cause severe phenotypic expression. PMID:26364997

  10. Mosaic NRAS Q61R mutation in a child with giant congenital melanocytic naevus, epidermal naevus syndrome and hypophosphataemic rickets.

    PubMed

    Ramesh, R; Shaw, N; Miles, E K; Richard, B; Colmenero, I; Moss, C

    2017-01-01

    The association of hypophosphataemic rickets with verrucous epidermal naevus (EN) and elevated fibroblast growth factor 23 levels is known as cutaneous-skeletal hypophosphataemia syndrome (CSHS), and can be caused by somatic activating mutations in RAS genes. We report a unique patient with CSHS associated with giant congenital melanocytic naevus (CMN), neurocutaneous melanosis and EN syndrome, manifesting as facial linear sebaceous naevus, developmental delay and ocular dermoids. An activating mutation Q61R in the NRAS gene was found in affected skin and ocular tissue but not blood, implying that the disparate manifestations are due to a multilineage activating mutation (mosaic RASopathy). We speculate on the apparently rare association of CSHS with CMN compared with EN. We also report the favourable outcome of this patient at the age of 8 years after extensive neonatal curettage of the giant CMN and use of vitamin D and phosphate supplementation. © 2016 British Association of Dermatologists.

  11. 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.

  12. Nutritional intakes in children with Prader–Willi syndrome and non-congenital obesity

    PubMed Central

    Rubin, Daniela A.; Nowak, Jill; McLaren, Erin; Patiño, Monzeratt; Castner, Diobel M.; Dumont-Driscoll, Marilyn C.

    2015-01-01

    Background Individuals with Prader–Willi syndrome (PWS) have extremely regulated diets to prevent the development of morbid obesity. Objective This study evaluated potential deficiencies in macro and micronutrients in a cohort of youth with PWS and compared them to a group of children with non-congenital obesity and to US national recommendations. Design Participants were 32 youth with PWS (age=10.8±2.6 years, body fat=46.7±10.1%) and 48 children without PWS but classified as obese (age=9.7±1.2 years, body fat=43.4±5.7%). Participants’ parents completed a training session on food recording before completing a 3-day food record during a typical week including a weekend day and two weekdays, as well as a screening form indicating nutritional supplements use. Results Youth with PWS reported less calories (1,312±75 vs. 1,531±61 kcal, p=0.03), carbohydrate (175±10 vs. 203±8 g), and sugars (67±5 vs. 81±4 g; p=0.04 for both) than obese. Youth with PWS consumed more vegetables (1.1±0.1 vs. 0.6±0.1 cups) and more of them met the daily recommendation (p<0.01 for both). Likewise, youth with PWS consumed more calcium than obese (899±53 vs. 752±43 mg) and more of them met the recommended daily dose (p=0.04 for both). The majority of participants in this study did not meet the vitamin D recommendation. Conclusion Despite consuming less calories, youth with PWS had a similar proportion of macronutrients in their diet as children with obesity. Micronutrient deficiencies in calcium and vitamin D in youth with PWS were noted despite a third of youth with PWS consuming multivitamin supplements. Special attention must be paid to the diets of youth with PWS and with obesity to ensure they are meeting micronutrient needs during this period of growth and development. PMID:26652260

  13. Raine Syndrome (OMIM #259775), Caused By FAM20C Mutation, Is Congenital Sclerosing Osteomalacia With Cerebral Calcification (OMIM 259660).

    PubMed

    Whyte, Michael P; McAlister, William H; Fallon, Michael D; Pierpont, Mary Ella; Bijanki, Vinieth N; Duan, Shenghui; Otaify, Ghada A; Sly, William S; Mumm, Steven

    2017-04-01

    In 1985, we briefly reported infant sisters with a unique, lethal, autosomal recessive disorder designated congenital sclerosing osteomalacia with cerebral calcification. In 1986, this condition was entered into Mendelian Inheritance In Man (MIM) as osteomalacia, sclerosing, with cerebral calcification (MIM 259660). However, no attestations followed. Instead, in 1989 Raine and colleagues published an affected neonate considering unprecedented the striking clinical and radiographic features. In 1992, "Raine syndrome" entered MIM formally as osteosclerotic bone dysplasia, lethal (MIM #259775). In 2007, the etiology emerged as loss-of-function mutation of FAM20C that encodes family with sequence similarity 20, member C. FAM20C is highly expressed in embryonic calcified tissues and encodes a kinase (dentin matrix protein 4) for most of the secreted phosphoproteome including FGF23, osteopontin, and other regulators of skeletal mineralization. Herein, we detail the clinical, radiological, biochemical, histopathological, and FAM20C findings of our patients. Following premortem tetracycline labeling, the proposita's non-decalcified skeletal histopathology after autopsy indicated no rickets but documented severe osteomalacia. Archival DNA revealed the sisters were compound heterozygotes for a unique missense mutation and a novel deletion in FAM20C. Individuals heterozygous for the missense mutation seemed to prematurely fuse their metopic suture and develop a metopic ridge sometimes including trigonocephaly. Our findings clarify FAM20C's role in hard tissue formation and mineralization, and show that Raine syndrome is congenital sclerosing osteomalacia with cerebral calcification. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.

  14. Obstructive Sleep Apnea in Patients with Congenital Long QT Syndrome: Implications for Increased Risk of Sudden Cardiac Death.

    PubMed

    Shamsuzzaman, Abu S; Somers, Virend K; Knilans, Timothy K; Ackerman, Michael J; Wang, Yu; Amin, Raouf S

    2015-07-01

    Congenital long QT syndrome (LQTS) is a familial arrhythmogenic cardiac channelopathy characterized by prolonged ventricular repolarization and increased risk of torsades de pointes-mediated syncope, seizures, and sudden cardiac death (SCD). QT prolongation corrected for heart rate (QTc) is an important diagnostic and prognostic feature in LQTS. Obstructive sleep apnea (OSA) has been increasingly implicated in the pathogenesis of cardiovascular disease, including arrhythmias and SCD. We tested the hypothesis that the presence of concomitant OSA in patients with LQTS is associated with increased QT intervals, both during sleep and while awake. Polysomnography with simultaneous overnight 12-lead electrocardiography (ECG) was recorded in 54 patients with congenital LQTS and 67 control subjects. OSA was diagnosed as apnea-hypopnea index (AHI) ≥ 5 events/h for adults and AHI > 1 event/h for children. RR and QT intervals were measured from the 12-lead surface ECG. QTc was determined by the Bazett formula. Respiratory disturbance index, AHI, and arousal index were significantly increased in patients with LQTS and with OSA compared to those without OSA and control subjects. QTc during different sleep stages and while awake was also significantly increased in patients with LQTS and OSA compared to those without OSA. Severity of OSA in patients with LQTS was directly associated with the degree of QTc. The presence and severity of obstructive sleep apnea (OSA) in patients with congenital long QT syndrome (LQTS) is associated with increased QT prolongation corrected for heart rate, which is an important biomarker of sudden cardiac death (SCD). Treatment of OSA in LQTS patients may reduce QT prolongation, thus reducing the risk of LQT-triggered SCD. © 2015 Associated Professional Sleep Societies, LLC.

  15. 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.

  16. Activating mutations in STIM1 and ORAI1 cause overlapping syndromes of tubular myopathy and congenital miosis

    PubMed Central

    Nesin, Vasyl; Wiley, Graham; Kousi, Maria; Ong, E-Ching; Lehmann, Thomas; Nicholl, David J.; Suri, Mohnish; Shahrizaila, Nortina; Katsanis, Nicholas; Gaffney, Patrick M.; Wierenga, Klaas J.; Tsiokas, Leonidas

    2014-01-01

    Signaling through the store-operated Ca2+ release-activated Ca2+ (CRAC) channel regulates critical cellular functions, including gene expression, cell growth and differentiation, and Ca2+ homeostasis. Loss-of-function mutations in the CRAC channel pore-forming protein ORAI1 or the Ca2+ sensing protein stromal interaction molecule 1 (STIM1) result in severe immune dysfunction and nonprogressive myopathy. Here, we identify gain-of-function mutations in the cytoplasmic domain of STIM1 (p.R304W) associated with thrombocytopenia, bleeding diathesis, miosis, and tubular myopathy in patients with Stormorken syndrome, and in ORAI1 (p.P245L), associated with a Stormorken-like syndrome of congenital miosis and tubular aggregate myopathy but without hematological abnormalities. Heterologous expression of STIM1 p.R304W results in constitutive activation of the CRAC channel in vitro, and spontaneous bleeding accompanied by reduced numbers of thrombocytes in zebrafish embryos, recapitulating key aspects of Stormorken syndrome. p.P245L in ORAI1 does not make a constitutively active CRAC channel, but suppresses the slow Ca2+-dependent inactivation of the CRAC channel, thus also functioning as a gain-of-function mutation. These data expand our understanding of the phenotypic spectrum of dysregulated CRAC channel signaling, advance our knowledge of the molecular function of the CRAC channel, and suggest new therapies aiming at attenuating store-operated Ca2+ entry in the treatment of patients with Stormorken syndrome and related pathologic conditions. PMID:24591628

  17. Application of whole-exome sequencing to unravel the molecular basis of undiagnosed syndromic congenital neutropenia with intellectual disability.

    PubMed

    Gauthier-Vasserot, Alexandra; Thauvin-Robinet, Christel; Bruel, Ange-Line; Duffourd, Yannis; St-Onge, Judith; Jouan, Thibaud; Rivière, Jean-Baptiste; Heron, Delphine; Donadieu, Jean; Bellanné-Chantelot, Christine; Briandet, Claire; Huet, Frédéric; Kuentz, Paul; Lehalle, Daphné; Duplomb-Jego, Laurence; Gautier, Elodie; Maystadt, Isabelle; Pinson, Lucile; Amram, Daniel; El Chehadeh, Salima; Melki, Judith; Julia, Sophia; Faivre, Laurence; Thevenon, Julien

    2017-01-01

    Neutropenia can be qualified as congenital when of neonatal onset or when associated with extra-hematopoietic manifestations. Overall, 30% of patients with congenital neutropenia (CN) remain without a molecular diagnosis after a multidisciplinary consultation and tedious diagnostic strategy. In the rare situations when neutropenia is identified and associated with intellectual disability (ID), there are few diagnostic hypotheses to test. This retrospective multicenter study reports on a clinically heterogeneous cohort of 10 unrelated patients with CN associated with ID and no molecular diagnosis prior to whole-exome sequencing (WES). WES provided a diagnostic yield of 40% (4/10). The results suggested that in many cases neutropenia and syndromic manifestations could not be assigned to the same molecular alteration. Three sub-groups of patients were highlighted: (i) severe, symptomatic chronic neutropenia, detected early in life, and related to a known mutation in the CN spectrum (ELANE); (ii) mild to moderate benign intermittent neutropenia, detected later, and associated with mutations in genes implicated in neurodevelopmental disorders (CHD2, HUWE1); and (iii) moderate to severe intermittent neutropenia as a probably undiagnosed feature of a newly reported syndrome (KAT6A). Unlike KAT6A, which seems to be associated with a syndromic form of CN, the other reported mutations may not explain the entire clinical picture. Although targeted gene sequencing can be discussed for the primary diagnosis of severe CN, we suggest that performing WES for the diagnosis of disorders associating CN with ID will not only provide the etiological diagnosis but will also pave the way towards personalized care and follow-up. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. Controversies in Poland Syndrome: Alternative Diagnoses in Patients With Congenital Pectoral Muscle Deficiency.

    PubMed

    Baas, Martijn; Burger, Elise B; Sneiders, Dimitri; Galjaard, Robert-Jan H; Hovius, Steven E R; van Nieuwenhoven, Christianne A

    2018-02-01

    Poland syndrome was first described as a deficiency of the pectoral muscle with ipsilateral symbrachydactyly. Currently, numerous case reports describe variations of Poland syndrome in which pectoral muscle deficiency is often used as the only defining criterion. However, more syndromes can present with pectoral muscle deficiency. The aim of this review is to illustrate the diversity of the phenotypic spectrum of Poland syndrome and to create more awareness for alternative diagnoses in pectoral muscle deficiency. A systematic literature search was performed. Articles containing phenotypical descriptions of Poland syndrome were included. Data extraction included number of patients, sex, familial occurrence, and the definition of Poland syndrome used. In addition, hand deformities, thoracic deformities, and other deformities in each patient were recorded. Alternative syndrome diagnoses were identified in patients with a combination of hand, thorax, and other deformities. One hundred-and-thirty-six articles were included, describing 627 patients. Ten different definitions of Poland syndrome were utilized. In 58% of the cases, an upper extremity deformity was found and 43% of the cases had an associated deformity. Classic Poland syndrome was seen in 29%. Fifty-seven percent of the patients with a pectoral malformation, a hand malformation, and another deformity had at least 1feature that matched an alternative syndrome. Pectoral muscle hypoplasia is not distinctive for Poland syndrome alone but is also present in syndromes with other associated anomalies with a recognized genetic cause. Therefore, in patients with an atypical phenotype, we recommend considering other diagnoses and/or syndromes before diagnosing a patient with Poland syndrome. This can prevent diagnostic and prognostic errors. Differentiating Poland syndrome from the alternative diagnoses has serious consequences for the patient and their family in terms of inheritance and possible related anomalies

  19. Mutations in 3 genes (MKS3, CC2D2A and RPGRIP1L) cause COACH syndrome (Joubert syndrome with congenital hepatic fibrosis)

    PubMed Central

    Doherty, D; Parisi, M A; Finn, L S; Gunay-Aygun, M; Al-Mateen, M; Bates, D; Clericuzio, C; Demir, H; Dorschner, M; van Essen, A J; Gahl, W A; Gentile, M; Gorden, N T; Hikida, A; Knutzen, D; Özyurek, H; Phelps, I; Rosenthal, P; Verloes, A; Weigand, H; Chance, P F; Dobyns, W B; Glass, I A

    2011-01-01

    Objective To identify genetic causes of COACH syndrome Background COACH syndrome is a rare autosomal recessive disorder characterised by Cerebellar vermis hypoplasia, Oligophrenia (developmental delay/mental retardation), Ataxia, Coloboma, and Hepatic fibrosis. The vermis hypoplasia falls in a spectrum of mid-hindbrain malformation called the molar tooth sign (MTS), making COACH a Joubert syndrome related disorder (JSRD). Methods In a cohort of 251 families with JSRD, 26 subjects in 23 families met criteria for COACH syndrome, defined as JSRD plus clinically apparent liver disease. Diagnostic criteria for JSRD were clinical findings (intellectual impairment, hypotonia, ataxia) plus supportive brain imaging findings (MTS or cerebellar vermis hypoplasia). MKS3/TMEM67 was sequenced in all subjects for whom DNA was available. In COACH subjects without MKS3 mutations, CC2D2A, RPGRIP1L and CEP290 were also sequenced. Results 19/23 families (83%) with COACH syndrome carried MKS3 mutations, compared to 2/209 (1%) with JSRD but no liver disease. Two other families with COACH carried CC2D2A mutations, one family carried RPGRIP1L mutations, and one lacked mutations in MKS3, CC2D2A, RPGRIP1L and CEP290. Liver biopsies from three subjects, each with mutations in one of the three genes, revealed changes within the congenital hepatic fibrosis/ductal plate malformation spectrum. In JSRD with and without liver disease, MKS3 mutations account for 21/232 families (9%). Conclusions Mutations in MKS3 are responsible for the majority of COACH syndrome, with minor contributions from CC2D2A and RPGRIP1L; therefore, MKS3 should be the first gene tested in patients with JSRD plus liver disease and/or coloboma, followed by CC2D2A and RPGRIP1L. PMID:19574260

  20. [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.

  1. Rare copy number variants and congenital heart defects in the 22q11.2 deletion syndrome.

    PubMed

    Mlynarski, Elisabeth E; Xie, Michael; Taylor, Deanne; Sheridan, Molly B; Guo, Tingwei; Racedo, Silvia E; McDonald-McGinn, Donna M; Chow, Eva W C; Vorstman, Jacob; Swillen, Ann; Devriendt, Koen; Breckpot, Jeroen; Digilio, Maria Cristina; Marino, Bruno; Dallapiccola, Bruno; Philip, Nicole; Simon, Tony J; Roberts, Amy E; Piotrowicz, Małgorzata; Bearden, Carrie E; Eliez, Stephan; Gothelf, Doron; Coleman, Karlene; Kates, Wendy R; Devoto, Marcella; Zackai, Elaine; Heine-Suñer, Damian; Goldmuntz, Elizabeth; Bassett, Anne S; Morrow, Bernice E; Emanuel, Beverly S

    2016-03-01

    The 22q11.2 deletion syndrome (22q11DS; velocardiofacial/DiGeorge syndrome; VCFS/DGS; MIM #192430; 188400) is the most common microdeletion syndrome. The phenotypic presentation of 22q11DS is highly variable; approximately 60-75 % of 22q11DS patients have been reported to have a congenital heart defect (CHD), mostly of the conotruncal type, and/or aortic arch defect. The etiology of the cardiac phenotypic variability is not currently known for the majority of patients. We hypothesized that rare copy number variants (CNVs) outside the 22q11.2 deleted region may modify the risk of being born with a CHD in this sensitized population. Rare CNV analysis was performed using Affymetrix SNP Array 6.0 data from 946 22q11DS subjects with CHDs (n = 607) or with normal cardiac anatomy (n = 339). Although there was no significant difference in the overall burden of rare CNVs, an overabundance of CNVs affecting cardiac-related genes was detected in 22q11DS individuals with CHDs. When the rare CNVs were examined with regard to gene interactions, specific cardiac networks, such as Wnt signaling, appear to be overrepresented in 22q11DS CHD cases but not 22q11DS controls with a normal heart. Collectively, these data suggest that CNVs outside the 22q11.2 region may contain genes that modify risk for CHDs in some 22q11DS patients.

  2. Studies of malformation syndromes in man XXXX: multiple congenital anomalies/mental retardation syndrome or variant familial developmental pattern; differential diagnosis and description of the McDonough syndrome (with XXY son from XY/XXY father).

    PubMed

    Neuhäuser, G; Opitz, J M

    1975-11-13

    The McDonough syndrome is a "new" MCA/MR syndrome which was found in 3 children (1 girl, 2 boys) of non-consanguineous parents. The affected children were mentally retarded (IQ 47--67) and had congenital heart defect, sternal deformity, kyphosis and craniofacila anomalies (anteverted auricles, upward slanted palpebral fissures, squint); cryptorchidism was present in the 2 boys. In addition a possible VFDP is postulated as the explanation for similar features in affected and unaffected siblings and parents. However, the McDonough syndrome may be an autosomal recessive trait with minor manifestations in heterozygotes. The klinefelter syndrome in one affected boy and a 46,XY/47,XXY chromosome constitution in the father was a coincidental finding.

  3. 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

  4. 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.

  5. A novel lymphocyte signaling defect: trk A mutation in the syndrome of congenital insensitivity to pain and anhidrosis (CIPA).

    PubMed

    Melamed, I; Levy, J; Parvari, R; Gelfand, E W

    2004-07-01

    Congenital insensitivity to pain with anhidrosis is a syndrome characterized by loss of pain and sensation. The condition frequently evolves into deep wounds and prolonged healing times. Anhidrosis is another prominent component of the disorder. Often associated with recurrent episodes of unexplained fever, it can result in patient mortality. Recent investigations point to Trk A, the high affinity receptor for nerve growth factor (NGF), as a candidate for the site of the mutation that causes the disorder. Functional NGF receptors, such as Trk A and the Trk family of tyrosine kinases, are essential for NGF signaling of human lymphocytes. In this study, we demonstrated that the presence of a trk A mutation in patient B cells results in a novel lymphocyte signaling defect. In these B cells, NGF failed to induce Trk A phosphorylation, cytoskeleton assembly, or MAP kinase activation. These abnormalities may explain some of the clinical features of the disease.

  6. Clinical and Genetic Features of Congenital Myasthenic Syndromes due to CHAT Mutations: Case Report and Literature Review.

    PubMed

    Arican, Pinar; Gencpinar, Pinar; Cavusoglu, Dilek; Olgac Dundar, Nihal

    2018-05-21

    Congenital myasthenic syndromes (CMS) are neuromuscular transmission disorders caused by mutations in genes encoding neuromuscular junction proteins. CMS due to choline acetyltransferase (CHAT) gene is characterized by episodic apnea. We report a case of a 12-month-old female patient presented with recurrent episodic apnea carrying a mutation in CHAT gene, p.I336T. Furthermore, we describe the genetic and clinical findings in 44 CMS patients due to CHAT mutations in the literature up to date. Episodes of apnea and respiratory insufficiency are the hallmarks of CHAT mutations. Clinical manifestations usually provoked by infections and fever. CMS due to CHAT mutations are rare, but it is important to diagnosis. Early diagnosis and appropriate treatment can improve morbidity and mortality. Georg Thieme Verlag KG Stuttgart · New York.

  7. Congenital platelet function defects

    MedlinePlus

    Platelet storage pool disorder; Glanzmann's thrombasthenia; Bernard-Soulier syndrome; Platelet function defects - congenital ... This disorder may also cause severe bleeding. Platelet storage pool disorder (also called platelet secretion disorder) occurs ...

  8. Successful Repair of Hypoplastic Left Heart Syndrome With Intact Atrial Septum, Congenital Diaphragm Hernia, and Anomalous Origin of Coronary Artery: Defying the Odds.

    PubMed

    Sathanandam, Shyam; Kumar, T K Susheel; Feliz, Alexander; Knott-Craig, Christopher J

    2016-07-01

    We report a case of an infant who was postnatally diagnosed with hypoplastic left heart syndrome and an intact atrial septum who underwent emergent atrial decompression followed by the Norwood operation. She was also found to have a congenital diaphragmatic hernia on the left side and a congenital eventration of the right diaphragm, both requiring surgical repair. She was later found to have an anomalous origin of the left circumflex coronary artery from the right pulmonary artery that was ligated at the time of the bilateral bidirectional Glenn operation. She is currently thriving at home, defying all odds. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  9. Nasopharyngeal teratoma, congenital diaphragmatic hernia and Dandy-Walker malformation - a yet uncharacterized syndrome.

    PubMed

    Gupta, N; Shastri, S; Singh, P K; Jana, M; Mridha, A; Verma, G; Kabra, M

    2016-11-01

    An association of congenital diaphragmatic hernia, dandy walker malformation and nasopharyngeal teratoma is very rare. Here, we report a fourth case with this association where chromosomal microarray and whole exome sequencing (WES) was performed to understand the underlying genetic basis. Findings of few variants especially a novel variation in HIRA provided some insights. An association of congenital diaphragmatic hernia, dandy walker malformation and nasopharyngeal teratoma is very rare. Here, we report a fourth case with this association where chromosomal microarray and whole exome sequencing (WES) was performed to understand the underlying genetic basis. Findings of few variants especially a novel variation in HIRA provided some insights. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Ductal paucity and Warkany syndrome in a patient with congenital extrahepatic portocaval shunt

    PubMed Central

    Sood, Vikrant; Khanna, Rajeev; Alam, Seema; Rawat, Dinesh; Bhatnagar, Shorav; Rastogi, Archana

    2014-01-01

    An eleven-year-old clinically dysmorphic and developmentally retarded male child presenting with complaints of 5 episodes of recurrent cholestatic jaundice since 3 years of age was evaluated. Imaging revealed features consistent with congenital extrahepatic portocaval shunt (Abernethy type 1b), multiple regenerative liver nodules and intrahepatic biliary radical dilatation. The presence of ductal paucity and trisomy 8 were confirmed on liver biopsy and karyotyping. The explanation for unusual and previously unreported features in the present case has been proposed. PMID:24868329

  11. Major Contribution of Genomic Copy Number Variation in Syndromic Congenital Heart Disease: The Use of MLPA as the First Genetic Test.

    PubMed

    Monteiro, Rejane A C; de Freitas, Mariana L; Vianna, Gabrielle S; de Oliveira, Valdirene T; Pietra, Rafaella X; Ferreira, Luana C A; Rocha, Patrícia P O; da S Gonçalves, Michele; da C César, Giovana; de S Lima, Joziele; Medeiros, Paula F V; Mazzeu, Juliana F; Jehee, Fernanda S

    2017-08-01

    Congenital heart disease (CHD) is the most common congenital disorder among live births. When associated with extracardiac abnormalities, it is characterized as a syndromic heart disease (syndromic CHD) and corresponds to 25% of all liveborn infants with a heart defect. The etiology in about 65% of the cases still remains unknown, and in about 35% of the patients, it is associated with genetic factors. In the present study, MLPA and SNP-array techniques were used to investigate a group of 47 patients with syndromic CHD. In total, 16 defects (34%) were identified, of which 12 (25.5%) were classified as pathogenic or probably pathogenic. The most frequent abnormalities were 22q11.2 deletion (22q11.2 deletion syndrome) and 7q11.23 deletion (Williams-Beuren syndrome). We also show that rarer malformations may be associated with syndromic CHD, such as 14q32.33 deletion as well as 17q25.3, 15q11.2 (BP1-BP2), 22q13.31, and 12p13.31 ( SLC2A3 ) duplications. The present study demonstrates that CNVs are important causal factors and should be studied in patients with syndromic CHD. Furthermore, the use of MLPA as a first screening test was appropriate, as this less expensive technology detected 11 of the 12 pathogenic abnormalities (91.6%).

  12. 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.

  13. Congenital band syndrome with pseudarthrosis of the radius and ulna and impending vascular compromise: a case report.

    PubMed

    Ho, Christine A; Richards, B Stephens; Ezaki, Marybeth

    2014-09-01

    Although amniotic band syndrome is relatively rare, reports of pseudarthrosis in conjunction with amniotic band syndrome are even rarer, as are reports of impending vascular compromise in the neonatal period. Careful serial examinations and timely surgical intervention can successfully avoid the catastrophic event of limb loss. We report on a case of upper extremity amniotic band syndrome with pseudarthrosis of the radius and ulna that was complicated by vascular compromise in a neonate. Chart and radiographic data for this single case were reviewed and reported retrospectively. A 1-day-old neonate born at 28 3/7 weeks of gestational age was transferred to our institution for increased swelling to the forearm distal to a congenital band associated with an underlying radius and ulna pseudarthrosis. Although the forearm and hand were soft and viable initially, severe edema and swelling occurred after fluid resuscitation, and on the fourth day of life, the patient underwent simple band releases at bedside with 2 longitudinal incisions over the radius and ulna. Circulation was restored, and the pseudarthrosis healed with no further surgical intervention. Successful delayed reconstruction of the band with Z-plasties was performed when the baby was 7 months of age. In this case, a relatively simple, straightforward procedure that is familiar to most pediatric orthopaedists salvaged a compromised neonatal limb with amniotic band syndrome and allowed healing of a pseudarthrosis, allowing more complex reconstruction to be performed in a delayed, elective manner. Careful observation is necessary in the neonatal period of the baby with a severe band; a viable, well-perfused, compressible extremity may still be at risk.

  14. 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

  15. 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

  16. [Congenital cardiopathy in a patient with Sotos syndrome. Description of a case].

    PubMed

    Di Marco, G; Levantesi, G; Parisi, G; Chiarelli, A

    1989-05-01

    The number of cases of Sotos syndrome or cerebral gigantism described in the literature total more than 200. For 6 of these, cardiac malformations were described. The authors report a case of Sotos syndrome in which malformative alterations of the aortic and mitral valves were simultaneously present.

  17. 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.

  18. IGF-I replacement therapy in children with congenital IGF-I deficiency (Laron syndrome) maintains heart dimension and function.

    PubMed

    Scheinowitz, Mickey; Feinberg, Micha S; Laron, Zvi

    2009-06-01

    Untreated patients with congenital growth hormone deficiency (GHD) and IGF-I deficiency are characterized not only by dwarfism but also by acromicria and organomicria, such as the heart. We assessed cardiac dimensions and function in very young patients with Laron syndrome (LS) undergoing IGF-I replacement therapy. Two to seven echocardiographic measurements were performed during IGF-I replacement therapy on male (n=4) and female (n=4) LS -patients, mean+/-SD age of 7.1+/-3.6 years (range 1.6-11.6 years), weight 16.1+/-9.7 kg, and height 89.9+/-18.5 cm. As aged- and gender-matched controls served 44 healthy children, age: 8.7+/-5.5 years, weight: 36.1+/-22.4 kg, and height: 129.7+/-33.1cm. Data of LS patients were normalized to body surface area and compared to the control group as well as nomograms of normal echocardiographic parameters for this age group. Left ventricular diastolic and systolic dimensions (LVDD/ LVSD, mm) and LV mass (gr) were significantly smaller in boys and girls with IGF-I treated LS compared with controls while the shortening fraction (%) and intraventricular septum thickness (mm) were similar. When compared with standard values for this age group, all treated LS patients were within 1 standard deviation of the mean. IGF-I therapy of young patients with Laron syndrome maintain LV dimensions and function within the normal range of aged-matched controls.

  19. 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

  20. 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.

  1. Identification of a Novel Mutation in BRD4 that Causes Autosomal Dominant Syndromic Congenital Cataracts Associated with Other Neuro-Skeletal Anomalies

    PubMed Central

    Jin, Hyun-Seok; Kim, Jeonhyun; Kwak, Woori; Jeong, Hyeonsoo; Lim, Gyu-Bin

    2017-01-01

    Congenital cataracts can occur as a non-syndromic isolated ocular disease or as a part of genetic syndromes accompanied by a multi-systemic disease. Approximately 50% of all congenital cataract cases have a heterogeneous genetic basis. Here, we describe three generations of a family with an autosomal dominant inheritance pattern and common complex phenotypes, including bilateral congenital cataracts, short stature, macrocephaly, and minor skeletal anomalies. We did not find any chromosomal aberrations or gene copy number abnormalities using conventional genetic tests; accordingly, we conducted whole-exome sequencing (WES) to identify disease-causing genetic alterations in this family. Based on family WES data, we identified a novel BRD4 missense mutation as a candidate causal variant and performed cell-based experiments by ablation of endogenous BRD4 expression in human lens epithelial cells. The protein expression levels of connexin 43, p62, LC3BII, and p53 differed significantly between control cells and cells in which endogenous BRD4 expression was inhibited. We inferred that a BRD4 missense mutation was the likely disease-causing mutation in this family. Our findings may improve the molecular diagnosis of congenital cataracts and support the use of WES to clarify the genetic basis of complex diseases. PMID:28076398

  2. Pathology of parainfluenza virus infection in patients with congenital immunodeficiency syndromes.

    PubMed

    Madden, John F; Burchette, James L; Hale, Laura P

    2004-05-01

    Infection with parainfluenza virus typically produces a mild, self-limited upper respiratory infection. However, parainfluenza infections have become increasingly recognized as a source of severe morbidity and mortality in immunocompromised patients. In this retrospective study we identified 6 patients with congenital immunodeficiency and positive respiratory cultures for parainfluenza virus who died and underwent complete autopsy. Tissues obtained at autopsy were studied using hematoxylin and eosin-stained sections, immunoperoxidase staining for parainfluenza virus, and in selected cases, electron microscopy. All 6 patients exhibited typical cytopathic effects of parainfluenza virus, including giant cell formation, in lung and/or bronchial tissues. Parainfluenza virus infection was also documented by giant cell formation and immunohistochemistry in the pancreas (in 3 of 6 patients) and the kidney or bladder (in 2 of 4 patients). Anti-parainfluenza antibody also specifically reacted with cells in the gastrointestinal tract (in 2 of 4), spleen (in 4 of 6), thymus and/or lymph nodes (in 4 of 4), and small blood vessels in various organs (in 4 of 6). Pancreatic, bladder, colon, and thymic epithelial cell lines were susceptible to experimental infections with clinical isolates of parainfluenza virus type 3 in vitro. Parainfluenza virus infection was serious in patients with congenital immunodeficiencies, contributing directly to death in 5 of the 6 patients studied. Because this virus is capable of infecting tissues in the gastrointestinal and urinary systems as well as in the respiratory tract, body secretions and fluids from each of these locations should be considered potentially infectious.

  3. Hyperammonemia and Systemic Inflammatory Response Syndrome Predicts Presence of Hepatic Encephalopathy in Dogs with Congenital Portosystemic Shunts

    PubMed Central

    Tivers, Mickey S.; Handel, Ian; Gow, Adam G.; Lipscomb, Vicky J.; Jalan, Rajiv; Mellanby, Richard J.

    2014-01-01

    Hepatic encephalopathy (HE) is an important cause of morbidity and mortality in patients with liver disease. The pathogenesis of he is incompletely understood although ammonia and inflammatory cytokines have been implicated as key mediators. To facilitate further mechanistic understanding of the pathogenesis of HE, a large number of animal models have been developed which often involve the surgical creation of an anastomosis between the hepatic portal vein and the caudal vena cava. One of the most common congenital abnormalities in dogs is a congenital portosystemic shunt (cpss), which closely mimics these surgical experimental models of HE. Dogs with a cPSS often have clinical signs which mimic clinical signs observed in humans with HE. Our hypothesis is that the pathogenesis of HE in dogs with a cPSS is similar to humans with HE. The aim of the study was to measure a range of clinical, haematological and biochemical parameters, which have been linked to the development of HE in humans, in dogs with a cPSS and a known HE grade. One hundred and twenty dogs with a cPSS were included in the study and multiple regression analysis of clinical, haematological and biochemical variables revealed that plasma ammonia concentrations and systemic inflammatory response syndrome scores predicted the presence of HE. Our findings further support the notion that the pathogenesis of canine and human HE share many similarities and indicate that dogs with cPSS may be an informative spontaneous model of human HE. Further investigations on dogs with cPSS may allow studies on HE to be undertaken without creating surgical models of HE thereby allowing the number of large animals used in animal experimentation to be reduced. PMID:24392080

  4. Hyperammonemia and systemic inflammatory response syndrome predicts presence of hepatic encephalopathy in dogs with congenital portosystemic shunts.

    PubMed

    Tivers, Mickey S; Handel, Ian; Gow, Adam G; Lipscomb, Vicky J; Jalan, Rajiv; Mellanby, Richard J

    2014-01-01

    Hepatic encephalopathy (HE) is an important cause of morbidity and mortality in patients with liver disease. The pathogenesis of he is incompletely understood although ammonia and inflammatory cytokines have been implicated as key mediators. To facilitate further mechanistic understanding of the pathogenesis of HE, a large number of animal models have been developed which often involve the surgical creation of an anastomosis between the hepatic portal vein and the caudal vena cava. One of the most common congenital abnormalities in dogs is a congenital portosystemic shunt (cpss), which closely mimics these surgical experimental models of HE. Dogs with a cPSS often have clinical signs which mimic clinical signs observed in humans with HE. Our hypothesis is that the pathogenesis of HE in dogs with a cPSS is similar to humans with HE. The aim of the study was to measure a range of clinical, haematological and biochemical parameters, which have been linked to the development of HE in humans, in dogs with a cPSS and a known HE grade. One hundred and twenty dogs with a cPSS were included in the study and multiple regression analysis of clinical, haematological and biochemical variables revealed that plasma ammonia concentrations and systemic inflammatory response syndrome scores predicted the presence of HE. Our findings further support the notion that the pathogenesis of canine and human HE share many similarities and indicate that dogs with cPSS may be an informative spontaneous model of human HE. Further investigations on dogs with cPSS may allow studies on HE to be undertaken without creating surgical models of HE thereby allowing the number of large animals used in animal experimentation to be reduced.

  5. How to Spot Congenital Myasthenic Syndromes Resembling the Lambert-Eaton Myasthenic Syndrome? A Brief Review of Clinical, Electrophysiological, and Genetics Features.

    PubMed

    Lorenzoni, Paulo José; Scola, Rosana Herminia; Kay, Claudia Suemi Kamoi; Werneck, Lineu Cesar; Horvath, Rita; Lochmüller, Hanns

    2018-06-01

    Congenital myasthenic syndromes (CMS) are heterogeneous genetic diseases in which neuromuscular transmission is compromised. CMS resembling the Lambert-Eaton myasthenic syndrome (CMS-LEMS) are emerging as a rare group of distinct presynaptic CMS that share the same electrophysiological features. They have low compound muscular action potential amplitude that increment after brief exercise (facilitation) or high-frequency repetitive nerve stimulation. Although clinical signs similar to LEMS can be present, the main hallmark is the electrophysiological findings, which are identical to autoimmune LEMS. CMS-LEMS occurs due to deficits in acetylcholine vesicle release caused by dysfunction of different components in its pathway. To date, the genes that have been associated with CMS-LEMS are AGRN, SYT2, MUNC13-1, VAMP1, and LAMA5. Clinicians should keep in mind these newest subtypes of CMS-LEMS to achieve the correct diagnosis and therapy. We believe that CMS-LEMS must be included as an important diagnostic clue to genetic investigation in the diagnostic algorithms to CMS. We briefly review the main features of CMS-LEMS.

  6. 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.

  7. SHOX gene is expressed in vertebral body growth plates in idiopathic and congenital scoliosis: implications for the etiology of scoliosis in Turner syndrome.

    PubMed

    Day, Gregory; Szvetko, Attila; Griffiths, Lyn; McPhee, I Bruce; Tuffley, John; LaBrom, Robert; Askin, Geoffrey; Woodland, Peter; McClosky, Eamonn; Torode, Ian; Tomlinson, Francis

    2009-06-01

    Reduced SHOX gene expression has been demonstrated to be associated with all skeletal abnormalities in Turner syndrome, other than scoliosis (and kyphosis). There is evidence to suggest that Turner syndrome scoliosis is clinically and radiologically similar to idiopathic scoliosis, although the phenotypes are dissimilar. This pilot gene expression study used relative quantitative real-time PCR (qRT-PCR) of the SHOX (short stature on X) gene to determine whether it is expressed in vertebral body growth plates in idiopathic and congenital scoliosis. After vertebral growth plate dissection, tissue was examined histologically and RNA was extracted and its integrity was assessed using a Bio-Spec Mini, NanoDrop ND-1000 spectrophotometer and standard denaturing gel electrophoresis. Following cDNA synthesis, gene-specific optimization in a Corbett RotorGene 6000 real-time cycler was followed by qRT-PCR of vertebral tissue. Histological examination of vertebral samples confirmed that only growth plate was analyzed for gene expression. Cycling and melt curves were resolved in triplicate for all samples. SHOX abundance was demonstrated in congenital and idiopathic scoliosis vertebral body growth plates. SHOX expression was 11-fold greater in idiopathic compared to congenital (n = 3) scoliosis (p = 0.027). This study confirmed that SHOX was expressed in vertebral body growth plates, which implies that its expression may also be associated with the scoliosis (and kyphosis) of Turner syndrome. SHOX expression is reduced in Turner syndrome (short stature). In this study, increased SHOX expression was demonstrated in idiopathic scoliosis (tall stature) and congenital scoliosis. Copyright 2008 Orthopaedic Research Society

  8. Diagnostic and surgical challenge: middle ear dermoid cyst in 12 month old with branchio-oto-renal syndrome and multiple middle-ear congenital anomalies.

    PubMed

    Johnston, D R; Whittemore, K; Poe, D; Robson, C D; Perez-Atayde, A R

    2011-10-01

    Described is the first case report, to our knowledge, of a middle-ear dermoid in a child with branchio-oto-renal (BOR) syndrome. Radiographic, pathologic, and intraoperative figures are shown. This was a diagnostic and surgical challenge as the presentation was similar to a congenital cholesteatoma and the child had numerous significant temporal bone abnormalities. After the intraoperative findings suggested a non-destructive process, the treatment strategy was altered. This case reiterates the need for a cautious, flexible operative approach in a syndromic child. Included is a relevant review of the literature and a detailed clinical analysis. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  9. [Coffin-Lowry syndrome. Its association with congenitally narrow cervical canal and myelomalacia].

    PubMed

    García-Suárez, Adrián; Dansac-Rivera, Arie Benoit

    2014-01-01

    Typical clinical features of the Coffin-Lowry syndrome include facies with hypertelorism, small nose, wide mouth, full and everted lips; short stature, mental retardation, pectus deformity, mitral valve dysfunction, hippocampal and cerebellar involvement, hearing loss and spinal disorders such as kyphosis and scoliosis. Due to its scarce incidence, it is difficult making an early diagnosis. The aim of this report was to document the anatomical peculiarities identified during the surgical treatment of a patient with this syndrome. Male patient with Coffin-Lowry syndrome who evolved with narrow cervical canal plus myelomalacia at short age, making decompression from C3 to C6 and instrumentation from C2 to C7 necessary. During the surgery, in addition to calcification of the yellow ligament, adhesions on the dura mater from C4 to C4, dark purplish color in this area and hourglass-shaped thinning were found; the ends at C3 and C6 were normal. The purpose of the surgery was to stop the myopathy. Post-operatively, the patient had pulmonary complications; at the sixth day he passed away due to ventilatory complications and inadequate secretion control. The Coffin-Lowry syndrome is a rare diagnosis in our country; neurological involvement at the spinal level is characterized by kyphosis or scoliosis; for its diagnosis, an adequate medical history and a karyotype are necessary.

  10. A syndrome of congenital microcephaly, intellectual disability and dysmorphism with a homozygous mutation in FRMD4A.

    PubMed

    Fine, Dina; Flusser, Hagit; Markus, Barak; Shorer, Zamir; Gradstein, Libe; Khateeb, Shareef; Langer, Yshia; Narkis, Ginat; Birk, Ruth; Galil, Aharon; Shelef, Ilan; Birk, Ohad S

    2015-12-01

    A consanguineous Bedouin Israeli kindred presented with a novel autosomal recessive intellectual disability syndrome of congenital microcephaly, low anterior hairline, bitemporal narrowing, low-set protruding ears, strabismus and tented thick eyebrows with sparse hair in their medial segment. Brain imaging demonstrated various degrees of agenesis of corpus callosum and hypoplasia of the vermis and cerebellum. Genome-wide linkage analysis followed by fine mapping defined a 7.67 Mb disease-associated locus (LOD score 4.99 at θ=0 for marker D10S1653). Sequencing of the 48 genes within the locus identified a single non-synonymous homozygous duplication frameshift mutation of 13 nucleotides (c.2134_2146dup13) within the coding region of FRMD4A, that was common to all affected individuals and not found in 180 non-related Bedouin controls. Three of 50 remotely related healthy controls of the same tribe were heterozygous for the mutation. FRMD4A, member of the FERM superfamily, is involved in cell structure, transport and signaling. It regulates cell polarity by playing an important role in the activation of ARF6, mediating the interaction between Par3 and the ARF6 guanine nucleotide exchange factor. ARF6 is known to modulate cell polarity in neurons, and regulates dendritic branching in hippocampal neurons and neurite outgrowth. The FRMD4 domain that is essential for determining cell polarity through interaction with Par3 is truncated by the c.2134_2146dup13 mutation. FRMD4A polymorphisms were recently suggested to be a risk factor for Alzheimer's disease. We now show a homozygous frameshift mutation of the same gene in a severe neurologic syndrome with unique dysmorphism.

  11. Prophylactic milrinone for the prevention of low cardiac output syndrome and mortality in children undergoing surgery for congenital heart disease.

    PubMed

    Burkhardt, Barbara E U; Rücker, Gerta; Stiller, Brigitte

    2015-03-25

    Children with congenital heart disease often undergo heart surgery at a young age. They are at risk for postoperative low cardiac output syndrome (LCOS) or death. Milrinone may be used to provide inotropic and vasodilatory support during the immediate postoperative period. This review examines the effectiveness of prophylactic postoperative use of milrinone to prevent LCOS or death in children having undergone surgery for congenital heart disease. Electronic and manual literature searches were performed to identify randomised controlled trials. We searched CENTRAL, MEDLINE, EMBASE and Web of Science in February 2014 and conducted a top-up search in September 2014 as well as clinical trial registries and reference lists of published studies. We did not apply any language restrictions. Only randomised controlled trials were selected for analysis. We considered studies with newborn infants, infants, toddlers, and children up to 12 years of age. Two review authors independently extracted data according to a pre-defined protocol. We obtained additional information from all study authors. Three of the five included studies compared milrinone versus levosimendan, one study compared milrinone with placebo, and one compared milrinone verus dobutamine, with 101, 242, and 50 participants, respectively. Three trials were at low risk of bias while two were at higher risk of bias. The number and definitions of outcomes were non-uniform as well. In one study comparing two doses of milrinone and placebo, there was some evidence in an overall comparison of milrinone versus placebo that milrinone lowered risk for LCOS (risk ratio (RR) 0.52, 95% confidence interval (CI) 0.28 to 0.96; 227 participants). The results from two small studies do not provide enough information to determine whether milrinone increases the risk of LCOS when compared to levosimendan (RR 1.22, 95% CI 0.32 to 4.65; 59 participants). Mortality rates in the studies were low, and there was insufficient evidence to

  12. Polyalanine expansion and frameshift mutations of the paired-like homeobox gene PHOX2B in congenital central hypoventilation syndrome.

    PubMed

    Amiel, Jeanne; Laudier, Béatrice; Attié-Bitach, Tania; Trang, Ha; de Pontual, Loïc; Gener, Blanca; Trochet, Delphine; Etchevers, Heather; Ray, Pierre; Simonneau, Michel; Vekemans, Michel; Munnich, Arnold; Gaultier, Claude; Lyonnet, Stanislas

    2003-04-01

    Congenital central hypoventilation syndrome (CCHS or Ondine's curse; OMIM 209880) is a life-threatening disorder involving an impaired ventilatory response to hypercarbia and hypoxemia. This core phenotype is associated with lower-penetrance anomalies of the autonomic nervous system (ANS) including Hirschsprung disease and tumors of neural-crest derivatives such as ganglioneuromas and neuroblastomas. In mice, the development of ANS reflex circuits is dependent on the paired-like homeobox gene Phox2b. Thus, we regarded its human ortholog, PHOX2B, as a candidate gene in CCHS. We found heterozygous de novo mutations in PHOX2B in 18 of 29 individuals with CCHS. Most mutations consisted of 5-9 alanine expansions within a 20-residue polyalanine tract probably resulting from non-homologous recombination. We show that PHOX2B is expressed in both the central and the peripheral ANS during human embryonic development. Our data support an essential role of PHOX2B in the normal patterning of the autonomous ventilation system and, more generally, of the ANS in humans.

  13. 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.

  14. Congenital hyperinsulinism as the presenting feature of Kabuki syndrome: clinical and molecular characterization of 10 affected individuals.

    PubMed

    Yap, Kai Lee; Johnson, Amy E Knight; Fischer, David; Kandikatla, Priscilla; Deml, Jacea; Nelakuditi, Viswateja; Halbach, Sara; Jeha, George S; Burrage, Lindsay C; Bodamer, Olaf; Benavides, Valeria C; Lewis, Andrea M; Ellard, Sian; Shah, Pratik; Cody, Declan; Diaz, Alejandro; Devarajan, Aishwarya; Truong, Lisa; Greeley, Siri Atma W; De Leó-Crutchlow, Diva D; Edmondson, Andrew C; Das, Soma; Thornton, Paul; Waggoner, Darrel; Del Gaudio, Daniela

    2018-06-15

    Describe the clinical and molecular findings of patients with Kabuki syndrome (KS) who present with hypoglycemia due to congenital hyperinsulinism (HI), and assess the incidence of KS in patients with HI. We documented the clinical features and molecular diagnoses of 10 infants with persistent HI and KS via a combination of sequencing and copy-number profiling methodologies. Subsequently, we retrospectively evaluated 100 infants with HI lacking a genetic diagnosis, for causative variants in KS genes. Molecular diagnoses of KS were established by identification of pathogenic variants in KMT2D (n = 5) and KDM6A (n = 5). Among the 100 infants with HI of unknown genetic etiology, a KS diagnosis was uncovered in one patient. The incidence of HI among patients with KS may be higher than previously reported, and KS may account for as much as 1% of patients diagnosed with HI. As the recognition of dysmorphic features associated with KS is challenging in the neonatal period, we propose KS should be considered in the differential diagnosis of HI. Since HI in patients with KS is well managed medically, a timely recognition of hyperinsulinemic episodes will improve outcomes, and prevent aggravation of the preexisting mild to moderate intellectual disability in KS.

  15. Rubella metapopulation dynamics and importance of spatial coupling to the risk of congenital rubella syndrome in Peru

    PubMed Central

    Metcalf, C. J. E.; Munayco, C. V.; Chowell, G.; Grenfell, B. T.; Bjørnstad, O. N.

    2011-01-01

    Rubella is generally a mild childhood disease, but infection during early pregnancy may cause spontaneous abortion or congenital rubella syndrome (CRS), which may entail a variety of birth defects. Consequently, understanding the age-structured dynamics of this infection has considerable public health value. Vaccination short of the threshold for local elimination of transmission will increase the average age of infection. Accordingly, the classic concern for this infection is the potential for vaccination to increase incidence in individuals of childbearing age. A neglected aspect of rubella dynamics is how age incidence patterns may be moulded by the spatial dynamics inherent to epidemic metapopulations. Here, we use a uniquely detailed dataset from Peru to explore the implications of this for the burden of CRS. Our results show that the risk of CRS may be particularly severe in small remote regions, a prediction at odds with expectations in the endemic situation, and with implications for the outcome of vaccination. This outcome results directly from the metapopulation context: specifically, extinction–re-colonization dynamics are crucial because they allow for significant leakage of susceptible individuals into the older age classes during inter-epidemic periods with the potential to increase CRS risk by as much as fivefold. PMID:20659931

  16. Alloimmunization in Congenital Deficiencies of Platelet Surface Glycoproteins: Focus on Glanzmann's Thrombasthenia and Bernard-Soulier's Syndrome.

    PubMed

    Poon, Man-Chiu; d'Oiron, Roseline

    2018-06-07

    Glanzmann's thrombasthenia (GT) and Bernard-Soulier's syndrome (BSS) are well-understood congenital bleeding disorders, showing defect/deficiency of platelet glycoprotein (GP) IIb/IIIa (integrin αIIbβ3) and GPIb-IX-V complexes respectively, with relevant clinical, laboratory, biochemical, and genetic features. Following platelet transfusion, affected patients may develop antiplatelet antibodies (to human leukocyte antigen [HLA], and/or αIIbβ3 in GT or GPIb-IX in BSS), which may render future platelet transfusion ineffective. Anti-αIIbβ3 and anti-GPIb-IX may also cross the placenta during pregnancy to cause thrombocytopenia and bleeding in the fetus/neonate. This review will focus particularly on the better studied GT to illustrate the natural history and complications of platelet alloimmunization. BSS will be more briefly discussed. Platelet transfusion, if unavoidable, should be given judiciously with good indications. Patients following platelet transfusion, and women during and after pregnancy, should be monitored for the development of platelet antibodies. There is now a collection of data suggesting the safety and effectiveness of recombinant activated factor VII in the management of affected patients with platelet antibodies. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  17. 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.

  18. 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.

  19. Upper limb congenital muscular hypertrophy and aberrant muscle syndrome in children.

    PubMed

    Dahan, Emmanuel; Chaves, Camilo; Bachy, Manon; Fitoussi, Frank

    2018-01-01

    Congenital muscle hypertrophy of the upper limb is a very rare condition with unknown aetiology. This descriptive observational and retrospective series included eight children followed by a multidisciplinary team from 2005 to 2017. The diagnosis was based on a cluster of clinical and radiological characteristics after elimination of differential diagnoses. Patients were categorized according to: anomalies of the wrist, anomalies of long fingers of intrinsic or extrinsic origin; and anomalies of the thumb with or without first web space contracture. Treatment begins in young children with hand orthoses to limit muscle contraction and joint malposition. The purpose of surgical treatment was to release contractures and to restore muscle balance through, in the main, finger intrinsic releases and first web releases. At the 2-year follow-up, we found that limited surgical procedures improved finger, thumb and wrist positions. We conclude that muscle hypertrophy is the main cause of deformity and that selective releases of contracted musculo-tendinous units and skin lengthening are effective. IV.

  20. 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

  1. 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.

  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. 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.

  4. 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 ...

  5. 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

  6. Germline mosaicism of PHOX2B mutation accounts for familial recurrence of congenital central hypoventilation syndrome (CCHS).

    PubMed

    Rand, Casey M; Yu, Min; Jennings, Lawrence J; Panesar, Kelvin; Berry-Kravis, Elizabeth M; Zhou, Lili; Weese-Mayer, Debra E

    2012-09-01

    Congenital central hypoventilation syndrome (CCHS), a rare disorder characterized by alveolar hypoventilation and autonomic dysregulation, is caused by mutations in the PHOX2B gene. Most mutations occur de novo, but recent evidence suggests that up to 25% are inherited from asymptomatic parents with somatic mosaicism for these mutations. However, to date, germline mosaicism has not been reported. This report describes a family with recurrence of PHOX2B mutation-confirmed CCHS due to germline mosaicism. The first occurrence was a baby girl, noted on day 2 of life to have multiple episodes of apnea, bradycardia, and cyanosis while breathing room air. PHOX2B gene testing confirmed the diagnosis of CCHS with a heterozygous polyalanine repeat expansion mutation (PARM); genotype 20/27 (normal 20/20). Both parents tested negative for this mutation using fragment analysis (limit of detection<1%). Upon subsequent pregnancy [paternity confirmed using short tandem repeat (STR) analysis], amniocentesis testing identified the PHOX2B 20/27 genotype, confirmed with repeat testing. Elective abortion was performed at 21.5 weeks gestation. Testing of abortus tissue confirmed amniocentesis testing. The PHOX2B 20/27 expansion was not observed in a paternal sperm sample. This case represents the first reported family with recurrence of PHOX2B mutation-confirmed CCHS without detection of a parental carrier state or mosaicism, confirming the previously hypothesized possibility of germline mosaicism for PHOX2B mutations. This is an important finding for genetic counseling of CCHS families, suggesting that even if somatic mosaicism is not detected in parental samples, there is still reason for careful genetic counseling and consideration of prenatal testing during subsequent pregnancies. Copyright © 2012 Wiley Periodicals, Inc.

  7. Quantitative investigations of different vaccination policies for the control of congenital rubella syndrome (CRS) in the United Kingdom.

    PubMed Central

    Anderson, R. M.; Grenfell, B. T.

    1986-01-01

    The paper examines predictions of the impact of various one-, two- and three-stage vaccination policies on the incidence of congenital rubella syndrome (CRS) in the United Kingdom with the aid of a mathematical model of the transmission dynamics of rubella virus. Parameter estimates for the model are derived from either serological data or case notifications, and special attention is given to the significance of age-related changes in the rate of exposure to rubella infection and heterogeneous mixing between age groups. Where possible, model predictions are compared with observed epidemiological trends. The principal conclusion of the analyses is that benefit is to be gained in the UK, both in the short and long term, by the introduction of a multiple-stage vaccination policy involving high levels of vaccination coverage of young male and female children (at around two years of age) and teenage girls (between the ages of 10-15 years), plus continued surveillance and vaccination of adult women in the child-bearing age classes. Model predictions suggest that to reduce the incidence of CRS in future years, below the level generated by a continuation of the current UK policy (the vaccination of teenage girls), would require high rates of vaccination (greater than 60%) of both boys and girls at around two years of age. Numerical studies also suggest that uniform vaccination coverage levels of greater than 80-85% of young male and female children could, in the long term (40 years or more), eradicate rubella virus from the population. The robustness of these conclusions with respect to the accuracy of parameter estimates and various assumptions concerning the pattern of age-related change in exposure to infections and 'who acquires infection from whom' is discussed. PMID:3701044

  8. 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

  9. 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.

  10. 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

    2018-05-01

    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.

  11. Analysis of Copy Number Variants on Chromosome 21 in Down Syndrome-Associated Congenital Heart Defects.

    PubMed

    Rambo-Martin, Benjamin L; Mulle, Jennifer G; Cutler, David J; Bean, Lora J H; Rosser, Tracie C; Dooley, Kenneth J; Cua, Clifford; Capone, George; Maslen, Cheryl L; Reeves, Roger H; Sherman, Stephanie L; Zwick, Michael E

    2018-01-04

    One in five people with Down syndrome (DS) are born with an atrioventricular septal defect (AVSD), an incidence 2000 times higher than in the euploid population. The genetic loci that contribute to this risk are poorly understood. In this study, we tested two hypotheses: (1) individuals with DS carrying chromosome 21 copy number variants (CNVs) that interrupt exons may be protected from AVSD, because these CNVs return AVSD susceptibility loci back to disomy, and (2) individuals with DS carrying chromosome 21 genes spanned by microduplications are at greater risk for AVSD because these microduplications boost the dosage of AVSD susceptibility loci beyond a tolerable threshold. We tested 198 case individuals with DS+AVSD, and 211 control individuals with DS and a normal heart, using a custom microarray with dense probes tiled on chromosome 21 for array CGH (aCGH). We found that neither an individual chromosome 21 CNV nor any individual gene intersected by a CNV was associated with AVSD in DS. Burden analyses revealed that African American controls had more bases covered by rare deletions than did African American cases. Inversely, we found that Caucasian cases had more genes intersected by rare duplications than did Caucasian controls. We also showed that previously DS+AVSD (DS and a complete AVSD)-associated common CNVs on chromosome 21 failed to replicate. This research adds to the swell of evidence indicating that DS-associated AVSD is similarly heterogeneous, as is AVSD in the euploid population. Copyright © 2018 Rambo-Martin et al.

  12. Surgically Induced Necrotizing Scleritis Following Strabismus Surgery Treated Successfully with Topical N-acetylcysteine in a Child with Congenital Fibrosis of Extraocular Muscles and Varadi Papp Syndrome.

    PubMed

    Rajamani, Muralidhar; Nagasubramanian, Vidhya; Ayyavoo, Ahila; Raghupathy, Palany; Dandapani, Ramamurthy

    2017-03-01

    Surgically induced necrotizing scleritis (SINS) is a rare but serious disorder that can develop many years after strabismus surgery. It is generally treated with high-dose steroids or immunosuppression. We describe a patient with Varadi Papp syndrome and congenital fibrosis of the extraocular muscles, who developed surgically induced necrotizing scleritis a month after strabismus surgery and was successfully managed by oral vitamin C and topical N-acetylcysteine 10%. While SINS is conventionally treated with steroids/immunosuppression, a conservative approach may be tried in milder cases. The role of topical N-acetylcysteine in managing this complication needs to be explored.

  13. Implantable cardioverter-defibrillator explantation for overdiagnosed or overtreated congenital long QT syndrome.

    PubMed

    Gaba, Prakriti; Bos, J Martijn; Cannon, Bryan C; Cha, Yong-Mei; Friedman, Paul A; Asirvatham, Samuel J; Ackerman, Michael J

    2016-04-01

    Primary treatment of long QT syndrome (LQTS) currently consists of beta-blocker therapy, although an implantable cardioverter-defibrillator (ICD) is considered for high-risk patients. However, both overdiagnosis and overtreatment must be avoided because their sequelae can be significant. The purpose of this study was to evaluate the prevalence and details of ICD explants in a cohort of patients from a tertiary genetic heart rhythm clinic for a previously rendered diagnosis of LQTS. Overall, 1227 consecutive patients were included in the study. All patients had been referred to the Mayo Clinic for evaluation of possible LQTS and subsequently were either diagnosed with LQTS or dismissed as normal. Further stratification of patients was conducted to assess how many patients had an ICD and how many had a subsequent ICD explant. In total, 170 patients (14%) had an ICD, including 157 of 670 patients (23%) with confirmed LQTS and 13 of 557 patients (2%) who did not have LQTS. Among these, 12 of 1227 (1%) had the ICD removed: 7 of 157 LQTS patients (4.5%) compared to 5 of 14 non-LQTS patients (36%). Before explant, 5 of 12 patients (42%) experienced inappropriate shocks, ranging from 2 to as many as 54 shocks. In addition, 4 had a device-related infection, and 9 had device malfunction (including lead dysfunction or fracture). None of these patients had a breakthrough cardiac event since removal of their ICD during 5.5 ± 3.5 years of follow-up. Implications of overdiagnosis and overtreatment are profound because unnecessary ICD placement can be associated with infection, malfunction, inappropriate shocks, and subsequent anxiety. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  14. 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

  15. 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

  16. Congenital absence of dermatoglyphs.

    PubMed

    Límová, M; Blacker, K L; LeBoit, P E

    1993-08-01

    Congenital absence or unusual patterns of human dermatoglyphs (fingerprints) occur in several syndromes that are rare and poorly understood. The abnormalities of dermatoglyphs fall into four categories: complete absence, ridge hypoplasia, ridge dissociation, and ridges-off-the-end. Complete congenital absence of ridges is an exceedingly rare syndrome that consists of neonatal blisters and milia, adult traumatic blistering and fissuring, absence of sweating, contracture of digits, and absence of dermatoglyphs on the hands and feet. The syndrome is inherited in an autosomal dominant pattern, and only two kindreds have been described in the literature. We describe a newly identified patient and kindred with findings similar to the previously reported cases and review the clinical and histopathologic findings of this syndrome.

  17. Homozygous disruption of PDZD7 by reciprocal translocation in a consanguineous family: a new member of the Usher syndrome protein interactome causing congenital hearing impairment.

    PubMed

    Schneider, Eberhard; Märker, Tina; Daser, Angelika; Frey-Mahn, Gabriele; Beyer, Vera; Farcas, Ruxandra; Schneider-Rätzke, Brigitte; Kohlschmidt, Nicolai; Grossmann, Bärbel; Bauss, Katharina; Napiontek, Ulrike; Keilmann, Annerose; Bartsch, Oliver; Zechner, Ulrich; Wolfrum, Uwe; Haaf, Thomas

    2009-02-15

    A homozygous reciprocal translocation, 46,XY,t(10;11),t(10;11), was detected in a boy with non-syndromic congenital sensorineural hearing impairment. Both parents and their four other children were heterozygous translocation carriers, 46,XX,t(10;11) and 46,XY,t(10;11), respectively. Fluorescence in situ hybridization of region-specific clones to patient chromosomes was used to localize the breakpoints within bacterial artificial chromosome (BAC) RP11-108L7 on chromosome 10q24.3 and within BAC CTD-2527F12 on chromosome 11q23.3. Junction fragments were cloned by vector ligation and sequenced. The chromosome 10 breakpoint was identified within the PDZ domain containing 7 (PDZD7) gene, disrupting the open reading frame of transcript PDZD7-C (without PDZ domain) and the 5'-untranslated region of transcript PDZD7-D (with one PDZ and two prolin-rich domains). The chromosome 11 breakpoint was localized in an intergenic segment. Reverse transcriptase-polymerase chain reaction analysis revealed PDZD7 expression in the human inner ear. A murine Pdzd7 transcript that is most similar in structure to human PDZD7-D is known to be expressed in the adult inner ear and retina. PDZD7 shares sequence homology with the PDZ domain-containing genes, USH1C (harmonin) and DFNB31 (whirlin). Allelic mutations in harmonin and whirlin can cause both Usher syndrome (USH1C and USH2D, respectively) and congenital hearing impairment (DFNB18 and DFNB31, respectively). Protein-protein interaction assays revealed the integration of PDZD7 in the protein network related to the human Usher syndrome. Collectively, our data provide strong evidence that PDZD7 is a new autosomal-recessive deafness-causing gene and also a prime candidate gene for Usher syndrome.

  18. De novo mutations in NALCN cause a syndrome characterized by congenital contractures of the limbs and face, hypotonia, and developmental delay.

    PubMed

    Chong, Jessica X; McMillin, Margaret J; Shively, Kathryn M; Beck, Anita E; Marvin, Colby T; Armenteros, Jose R; Buckingham, Kati J; Nkinsi, Naomi T; Boyle, Evan A; Berry, Margaret N; Bocian, Maureen; Foulds, Nicola; Uzielli, Maria Luisa Giovannucci; Haldeman-Englert, Chad; Hennekam, Raoul C M; Kaplan, Paige; Kline, Antonie D; Mercer, Catherine L; Nowaczyk, Malgorzata J M; Klein Wassink-Ruiter, Jolien S; McPherson, Elizabeth W; Moreno, Regina A; Scheuerle, Angela E; Shashi, Vandana; Stevens, Cathy A; Carey, John C; Monteil, Arnaud; Lory, Philippe; Tabor, Holly K; Smith, Joshua D; Shendure, Jay; Nickerson, Deborah A; Bamshad, Michael J

    2015-03-05

    Freeman-Sheldon syndrome, or distal arthrogryposis type 2A (DA2A), is an autosomal-dominant condition caused by mutations in MYH3 and characterized by multiple congenital contractures of the face and limbs and normal cognitive development. We identified a subset of five individuals who had been putatively diagnosed with "DA2A with severe neurological abnormalities" and for whom congenital contractures of the limbs and face, hypotonia, and global developmental delay had resulted in early death in three cases; this is a unique condition that we now refer to as CLIFAHDD syndrome. Exome sequencing identified missense mutations in the sodium leak channel, non-selective (NALCN) in four families affected by CLIFAHDD syndrome. We used molecular-inversion probes to screen for NALCN in a cohort of 202 distal arthrogryposis (DA)-affected individuals as well as concurrent exome sequencing of six other DA-affected individuals, thus revealing NALCN mutations in ten additional families with "atypical" forms of DA. All 14 mutations were missense variants predicted to alter amino acid residues in or near the S5 and S6 pore-forming segments of NALCN, highlighting the functional importance of these segments. In vitro functional studies demonstrated that NALCN alterations nearly abolished the expression of wild-type NALCN, suggesting that alterations that cause CLIFAHDD syndrome have a dominant-negative effect. In contrast, homozygosity for mutations in other regions of NALCN has been reported in three families affected by an autosomal-recessive condition characterized mainly by hypotonia and severe intellectual disability. Accordingly, mutations in NALCN can cause either a recessive or dominant condition characterized by varied though overlapping phenotypic features, perhaps based on the type of mutation and affected protein domain(s). Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  19. [Value of indoleamine 2,3-dioxygenase in diagnosis of systemic inflammatory response syndrome after cardiopulmonary bypass in children with congenital heart disease].

    PubMed

    Wang, Xin; Li, Zong-Xiao; Wen, Yu-Peng; Chang, Cheng

    2018-01-01

    To study the value of indoleamine 2,3-dioxygenase (IDO) in the early diagnosis of systemic inflammatory response syndrome (SIRS) after cardiopulmonary bypass in children with congenital heart disease. A total of 90 children with congenital heart disease who underwent cardiopumonary bypass surgery between May 2012 and January 2016 were enrolled. According to the prsence or absence of SIRS after surgery, they were divided into SIRS group (n=43) and control group (n=47). Peripheral blood samples were collected before surgery, during surgery, and after surgery. Serum levels of IDO, C-reactive protein (CRP), and interleukin-6 (IL-6) were measured and compared between the two groups. The receiver operating characteristic (ROC) curve was used to evaluate their diagnostic efficiency. Compared with the control group, the SIRS group had higher serum CRP levels at 72 hours after surgery, higher IL-6 levels during surgery and at 72 hours after surgery, and higher IDO levels at 24 and 72 hours after surgery. IDO had a certain value in the diagnosis of SIRS at 24 hours after surgery with an area under the ROC curve (AUC) of 0.793, a specificity of 100%, and a sensitivity of 58.14%. CRP, IL-6, and IDO had a certain value in the diagnosis of SIRS at 72 hours after surgery. IDO had the highest diagnostic efficiency with an AUC of 0.927, a specificity of 95.74%, and a sensitivity of 76.74% at 72 hours after surgery. IL-6, CRP, and IDO have a certain value in the diagnosis of SIRS after surgery for congenital heart disease, and IDO has a higher diagnostic efficiency. IDO can predict the development of SIRS in children after surgery for congenital heart disease earlier.

  20. X-Linked Congenital Hypertrichosis Syndrome Is Associated with Interchromosomal Insertions Mediated by a Human-Specific Palindrome near SOX3

    PubMed Central

    Zhu, Hongwen; Shang, Dandan; Sun, Miao; Choi, Sunju; Liu, Qing; Hao, Jiajie; Figuera, Luis E.; Zhang, Feng; Choy, Kwong Wai; Ao, Yang; Liu, Yang; Zhang, Xiao-Lin; Yue, Fengzhen; Wang, Ming-Rong; Jin, Li; Patel, Pragna I.; Jing, Tao; Zhang, Xue

    2011-01-01

    X-linked congenital generalized hypertrichosis (CGH), an extremely rare condition characterized by universal overgrowth of terminal hair, was first mapped to chromosome Xq24-q27.1 in a Mexican family. However, the underlying genetic defect remains unknown. We ascertained a large Chinese family with an X-linked congenital hypertrichosis syndrome combining CGH, scoliosis, and spina bifida and mapped the disease locus to a 5.6 Mb critical region within the interval defined by the previously reported Mexican family. Through the combination of a high-resolution copy-number variation (CNV) scan and targeted genomic sequencing, we identified an interchromosomal insertion at Xq27.1 of a 125,577 bp intragenic fragment of COL23A1 on 5q35.3, with one X breakpoint within and the other very close to a human-specific short palindromic sequence located 82 kb downstream of SOX3. In the Mexican family, we found an interchromosomal insertion at the same Xq27.1 site of a 300,036 bp genomic fragment on 4q31.2, encompassing PRMT10 and TMEM184C and involving parts of ARHGAP10 and EDNRA. Notably, both of the two X breakpoints were within the short palindrome. The two palindrome-mediated insertions fully segregate with the CGH phenotype in each of the families, and the CNV gains of the respective autosomal genomic segments are not present in the public database and were not found in 1274 control individuals. Analysis of control individuals revealed deletions ranging from 173 bp to 9104 bp at the site of the insertions with no phenotypic consequence. Taken together, our results strongly support the pathogenicity of the identified insertions and establish X-linked congenital hypertrichosis syndrome as a genomic disorder. PMID:21636067

  1. 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

  2. Accelerate Genomic Aging in Congenital Neutropenia

    DTIC Science & Technology

    2015-08-01

    for the markedly increased risk of transformation to myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) in patients with congenital...Hematopoietic stem cells Granulocyte colony-stimulating factor Granulocyte colony-stimulating factor receptor Acute myeloid leukemia Myelodysplastic... myeloid leukemia (AML) is perhaps the major clinical concern in patients with severe congenital neutropenia (SCN) and Shwachman-Diamond syndrome (SDS

  3. 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 ...

  4. Congenital toxoplasmosis

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/001360.htm Congenital toxoplasmosis To use the sharing features on this page, please enable JavaScript. Congenital toxoplasmosis is a group of symptoms that occur when ...

  5. Congenital Neutropenia Syndromes

    MedlinePlus

    ... Award Negotiation & Initial Award After Award Foreign Grants Management Getting Your Initial International Award Actions You Can Take as the Project Leader on a Foreign Grant Subawards for Foreign ...

  6. 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

    syndrome. We present a unique case of a female neonate with a medical history significant for seizure -like activity, a hyperplastic thryoid nodelue. aortic coarctaction, patent ductus arterlosus, and epidermal nevus syndrome.

  7. Heterogeneity in phenotype of usher-congenital hyperinsulinism syndrome: hearing loss, retinitis pigmentosa, and hyperinsulinemic hypoglycemia ranging from severe to mild with conversion to diabetes.

    PubMed

    Al Mutair, Angham N; Brusgaard, Klaus; Bin-Abbas, Bassam; Hussain, Khalid; Felimban, Naila; Al Shaikh, Adnan; Christesen, Henrik T

    2013-03-01

    To evaluate the phenotype of 15 children with congenital hyperinsulinism (CHI) and profound hearing loss, known as Homozygous 11p15-p14 Deletion syndrome (MIM #606528). Prospective clinical follow-up and genetic analysis by direct sequencing, multiplex ligation-dependent probe amplification, and microsatellite markers. Genetic testing identified the previous described homozygous deletion in 11p15, USH1C:c.(90+592)_ABCC8:c.(2694-528)del. Fourteen patients had severe CHI demanding near-total pancreatectomy. In one patient with mild, transient neonatal hypoglycemia and nonautoimmune diabetes at age 11 years, no additional mutations were found in HNF1A, HNF4A, GCK, INS, and INSR. Retinitis pigmentosa was found in two patients aged 9 and 13 years. No patients had enteropathy or renal tubular defects. Neuromotor development ranged from normal to severe delay with epilepsy. The phenotype of Homozygous 11p15-p14 Deletion syndrome, or Usher-CHI syndrome, includes any severity of neonatal-onset CHI and severe, sensorineural hearing loss. Retinitis pigmentosa and nonautoimmune diabetes may occur in adolescence.

  8. Mutations in SMG9, Encoding an Essential Component of Nonsense-Mediated Decay Machinery, Cause a Multiple Congenital Anomaly Syndrome in Humans and Mice

    PubMed Central

    Shaheen, Ranad; Anazi, Shams; Ben-Omran, Tawfeg; Seidahmed, Mohammed Zain; Caddle, L. Brianna; Palmer, Kristina; Ali, Rehab; Alshidi, Tarfa; Hagos, Samya; Goodwin, Leslie; Hashem, Mais; Wakil, Salma M.; Abouelhoda, Mohamed; Colak, Dilek; Murray, Stephen A.; Alkuraya, Fowzan S.

    2016-01-01

    Nonsense-mediated decay (NMD) is an important process that is best known for degrading transcripts that contain premature stop codons (PTCs) to mitigate their potentially harmful consequences, although its regulatory role encompasses other classes of transcripts as well. Despite the critical role of NMD at the cellular level, our knowledge about the consequences of deficiency of its components at the organismal level is largely limited to model organisms. In this study, we report two consanguineous families in which a similar pattern of congenital anomalies was found to be most likely caused by homozygous loss-of-function mutations in SMG9, encoding an essential component of the SURF complex that generates phospho-UPF1, the single most important step in NMD. By knocking out Smg9 in mice via CRISPR/Cas9, we were able to recapitulate the major features of the SMG9-related multiple congenital anomaly syndrome we observed in humans. Surprisingly, human cells devoid of SMG9 do not appear to have reduction of PTC-containing transcripts but do display global transcriptional dysregulation. We conclude that SMG9 is required for normal human and murine development, most likely through a transcriptional regulatory role, the precise nature of which remains to be determined. PMID:27018474

  9. Congenital high airway obstruction syndrome in the breech presentation managed by ex utero intrapartum treatment procedure after intraoperative external cephalic version.

    PubMed

    Miwa, Ichiro; Sase, Masakatsu; Nakamura, Yasuhiko; Hasegawa, Keiko; Kawasaki, Masahiro; Ueda, Kazuyuki

    2012-05-01

    Congenital high airway obstruction syndrome (CHAOS) caused by laryngeal atresia was diagnosed by prenatal ultrasound in a male fetus at 26 weeks of gestation. Findings included massive ascites, subcutaneous edema, enlarged hyperechogenic lungs with diaphragmatic inversion, dilated trachea, polyhydramnios, and breech presentation. Those findings of CHAOS spontaneously returned to normal by 33 weeks of gestation. However, the placenta was localized to the anterior uterine wall. In addition, the fetal position had been breech until delivery. At 36 weeks of gestation, a planned ex utero intrapartum treatment (EXIT) procedure was performed following intraoperative external cephalic version (ECV) in which the fetus was approached from the posterior wall of the uterus. Laryngoscopy revealed the predicted laryngeal obstruction, and tracheostomy was placed. Intraoperative ECV may be a useful technique in breech presentation before EXIT procedure. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

  10. [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.

  11. FBXL4 defects are common in patients with congenital lactic acidemia and encephalomyopathic mitochondrial DNA depletion syndrome.

    PubMed

    Dai, H; Zhang, V W; El-Hattab, A W; Ficicioglu, C; Shinawi, M; Lines, M; Schulze, A; McNutt, M; Gotway, G; Tian, X; Chen, S; Wang, J; Craigen, W J; Wong, L-J

    2017-04-01

    Mutations in FBXL4 have recently been recognized to cause a mitochondrial disorder, with clinical features including early onset lactic acidosis, hypotonia, and developmental delay. FBXL4 sequence analysis was performed in 808 subjects suspected to have a mitochondrial disorder. In addition, 28 samples from patients with early onset of lactic acidosis, but without identifiable mutations in 192 genes known to cause mitochondrial diseases, were examined for FBXL4 mutations. Definitive diagnosis was made in 10 new subjects with a total of 7 novel deleterious variants; 5 null and 2 missense substitutions. All patients exhibited congenital lactic acidemia, most of them with severe encephalopathic presentation, and global developmental delay. Overall, FBXL4 defects account for at least 0.7% (6 out of 808) of subjects suspected to have a mitochondrial disorder, and as high as 14.3% (4 out of 28) in young children with congenital lactic acidosis and clinical features of mitochondrial disease. Including FBLX4 in the mitochondrial diseases panel should be particularly important for patients with congenital lactic acidosis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. 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.

  13. 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.

  14. Congenital heart diseases and cardiovascular abnormalities in 22q11.2 deletion syndrome: From well-established knowledge to new frontiers.

    PubMed

    Unolt, Marta; Versacci, Paolo; Anaclerio, Silvia; Lambiase, Caterina; Calcagni, Giulio; Trezzi, Matteo; Carotti, Adriano; Crowley, Terrence Blaine; Zackai, Elaine H; Goldmuntz, Elizabeth; Gaynor, James William; Digilio, Maria Cristina; McDonald-McGinn, Donna M; Marino, Bruno

    2018-04-16

    Congenital heart diseases (CHDs) and cardiovascular abnormalities are one of the pillars of clinical diagnosis of 22q11.2 deletion syndrome (22q11.2DS) and still represent the main cause of mortality in the affected children. In the past 30 years, much progress has been made in describing the anatomical patterns of CHD, in improving their diagnosis, medical treatment, and surgical procedures for these conditions, as well as in understanding the underlying genetic and developmental mechanisms. However, further studies are still needed to better determine the true prevalence of CHDs in 22q11.2DS, including data from prenatal studies and on the adult population, to further clarify the genetic mechanisms behind the high variability of phenotypic expression of 22q11.2DS, and to fully understand the mechanism responsible for the increased postoperative morbidity and for the premature death of these patients. Moreover, the increased life expectancy of persons with 22q11.2DS allowed the expansion of the adult population that poses new challenges for clinicians such as acquired cardiovascular problems and complexity related to multisystemic comorbidity. In this review, we provide a comprehensive review of the existing literature about 22q11.2DS in order to summarize the knowledge gained in the past years of clinical experience and research, as well as to identify the remaining gaps in comprehension of this syndrome and the possible future research directions. © 2018 Wiley Periodicals, Inc.

  15. Congenital Hypothalamic "Hamartoblastoma" Versus "Hamartoma": Suggestions for Neuropathologic Terminology Emanating From a Mid-gestational Autopsy Case of Pallister-Hall Syndrome.

    PubMed

    Dunham, C; McFadden, D; Dahlgren, L; Butler, B; Hamilton, S; McKinnon, M

    2018-01-01

    Pallister-Hall syndrome (PHS) is a rare malformative disorder that is due to truncating functional repressor mutations in GLI3. Since the seminal publication in 1980, hypothalamic tumors have been recognized to be a cardinal feature of PHS. In their original description of the neuropathologic features of PHS, Clarren et al. coined the term "hamartoblastoma" to characterize what they deemed to be a dual malformative and neoplastic mass of the hypothalamus. In subsequent published cases/series of PHS, the term "hamartoma" was often substituted for hamartoblastoma given what appeared to be a benign natural history of this lesion. Additional confusion in the literature has ensued since most hypothalamic hamartomas (HH) encountered on the clinical neuropathology service are "isolated" in nature (ie, no other congenital malformations) and present in a very different and stereotypical fashion with gelastic seizures and/or precocious puberty. While genomic investigations of isolated HH have begun to uncover a mutational profile of these cases, GLI3 mutations have only been recognized in a small subset of isolated HH. Herein, we describe the autopsy findings from a 21-week gestational age fetus with features of PHS. Moreover, we provide a detailed description of the hypothalamic tumor affecting this fetus and propose a novel subclassification of HH, distinguishing syndromic from isolated forms based upon the presence or absence of neocortical-like areas.

  16. [Neonatal tumours and congenital malformations].

    PubMed

    Berbel Tornero, O; Ortega García, J A; Ferrís i Tortajada, J; García Castell, J; Donat i Colomer, J; Soldin, O P; Fuster Soler, J L

    2008-06-01

    The association between pediatric cancer and congenital abnormalities is well known but, there is no exclusive data on the neonatal period and the underlying etiopathogenic mechanisms are unknown. First, to analyze the frequency of neonatal tumours associated with congenital abnormalities; and second, to comment on the likely etiopathogenic hypotheses of a relationship between neonatal tumours and congenital abnormalities. Historical series of neonatal tumours from La Fe University Children's Hospital in Valencia (Spain), from January 1990 to December 1999. Histological varieties of neonatal tumours and associated congenital abnormalities were described. A systematic review of the last 25 years was carried out using Medline, Cancerlit, Index Citation Science and Embase. The search profile used was the combination of "neonatal/congenital-tumors/cancer/neoplasms" and "congenital malformations/birth defects". 72 neonatal tumours were identified (2.8% of all pediatric cancers diagnosed in our hospital) and in 15 cases (20.8%) there was some associated malformation, disease or syndrome. The association between congenital abnormalities and neonatal tumours were: a) angiomas in three patients: two patients with congenital heart disease with a choanal stenosis, laryngomalacia; b) neuroblastomas in two patients: horseshoe kidney with vertebral anomalies and other with congenital heart disease; c) teratomas in two patients: one with cleft palate with vertebral anomalies and other with metatarsal varus; d) one tumour of the central nervous system with Bochdaleck hernia; e) heart tumours in four patients with tuberous sclerosis; f) acute leukaemia in one patient with Down syndrome and congenital heart disease; g) kidney tumour in one case with triventricular hydrocephaly, and h) adrenocortical tumour: hemihypertrophy. The publications included the tumours diagnosed in different pediatric periods and without unified criteria to classify the congenital abnormalities. Little data

  17. Congenital Abnormalities

    MedlinePlus

    ... tube defects. However, there is also a genetic influence to this type of congenital anomaly. Unknown Causes The vast majority of congenital abnormalities have no known cause. This is particularly troubling for parents who plan to have more children, because there is no way to predict if ...

  18. Copy-Number Variation of the Glucose Transporter Gene SLC2A3 and Congenital Heart Defects in the 22q11.2 Deletion Syndrome.

    PubMed

    Mlynarski, Elisabeth E; Sheridan, Molly B; Xie, Michael; Guo, Tingwei; Racedo, Silvia E; McDonald-McGinn, Donna M; Gai, Xiaowu; Chow, Eva W C; Vorstman, Jacob; Swillen, Ann; Devriendt, Koen; Breckpot, Jeroen; Digilio, Maria Cristina; Marino, Bruno; Dallapiccola, Bruno; Philip, Nicole; Simon, Tony J; Roberts, Amy E; Piotrowicz, Małgorzata; Bearden, Carrie E; Eliez, Stephan; Gothelf, Doron; Coleman, Karlene; Kates, Wendy R; Devoto, Marcella; Zackai, Elaine; Heine-Suñer, Damian; Shaikh, Tamim H; Bassett, Anne S; Goldmuntz, Elizabeth; Morrow, Bernice E; Emanuel, Beverly S

    2015-05-07

    The 22q11.2 deletion syndrome (22q11DS; velocardiofacial/DiGeorge syndrome; VCFS/DGS) is the most common microdeletion syndrome and the phenotypic presentation is highly variable. Approximately 65% of individuals with 22q11DS have a congenital heart defect (CHD), mostly of the conotruncal type, and/or an aortic arch defect. The etiology of this phenotypic variability is not currently known. We hypothesized that copy-number variants (CNVs) outside the 22q11.2 deleted region might increase the risk of being born with a CHD in this sensitized population. Genotyping with Affymetrix SNP Array 6.0 was performed on two groups of subjects with 22q11DS separated by time of ascertainment and processing. CNV analysis was completed on a total of 949 subjects (cohort 1, n = 562; cohort 2, n = 387), 603 with CHDs (cohort 1, n = 363; cohort 2, n = 240) and 346 with normal cardiac anatomy (cohort 1, n = 199; cohort 2, n = 147). Our analysis revealed that a duplication of SLC2A3 was the most frequent CNV identified in the first cohort. It was present in 18 subjects with CHDs and 1 subject without (p = 3.12 × 10(-3), two-tailed Fisher's exact test). In the second cohort, the SLC2A3 duplication was also significantly enriched in subjects with CHDs (p = 3.30 × 10(-2), two-tailed Fisher's exact test). The SLC2A3 duplication was the most frequent CNV detected and the only significant finding in our combined analysis (p = 2.68 × 10(-4), two-tailed Fisher's exact test), indicating that the SLC2A3 duplication might serve as a genetic modifier of CHDs and/or aortic arch anomalies in individuals with 22q11DS. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  19. Mutations in zebrafish pitx2 model congenital malformations in Axenfeld-Rieger syndrome but do not disrupt left-right placement of visceral organs.

    PubMed

    Ji, Yongchang; Buel, Sharleen M; Amack, Jeffrey D

    2016-08-01

    Pitx2 is a conserved homeodomain transcription factor that has multiple functions during embryonic development. Mutations in human PITX2 cause autosomal dominant Axenfeld-Rieger syndrome (ARS), characterized by congenital eye and tooth malformations. Pitx2(-/-) knockout mouse models recapitulate aspects of ARS, but are embryonic lethal. To date, ARS treatments remain limited to managing individual symptoms due to an incomplete understanding of PITX2 function. In addition to regulating eye and tooth development, Pitx2 is a target of a conserved Nodal (TGFβ) signaling pathway that mediates left-right (LR) asymmetry of visceral organs. Based on its highly conserved asymmetric expression domain, the Nodal-Pitx2 axis has long been considered a common denominator of LR development in vertebrate embryos. However, functions of Pitx2 during asymmetric organ morphogenesis are not well understood. To gain new insight into Pitx2 function we used genome editing to create mutations in the zebrafish pitx2 gene. Mutations in the pitx2 homeodomain caused phenotypes reminiscent of ARS, including aberrant development of the cornea and anterior chamber of the eye and reduced or absent teeth. Intriguingly, LR asymmetric looping of the heart and gut was normal in pitx2 mutants. These results suggest conserved roles for Pitx2 in eye and tooth development and indicate Pitx2 is not required for asymmetric looping of zebrafish visceral organs. This work establishes zebrafish pitx2 mutants as a new animal model for investigating mechanisms underlying congenital malformations in ARS and high-throughput drug screening for ARS therapeutics. Additionally, pitx2 mutants present a unique opportunity to identify new genes involved in vertebrate LR patterning. We show Nodal signaling-independent of Pitx2-controls asymmetric expression of the fatty acid elongase elovl6 in zebrafish, pointing to a potential novel pathway during LR organogenesis. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Accelerate Genomic Aging in Congenital Neutropenia

    DTIC Science & Technology

    2016-08-01

    transformation to myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) in patients with congenital neutropenia. We hypothesize that...colony-stimulating factor; Acute myeloid leukemia; Myelodysplastic syndrome 16. SECURITY CLASSIFICATION OF: U 17. LIMITATION OF ABSTRACT 18. NUMBER OF...responsible for the markedly increased risk of transformation to myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) in patients with

  1. A comparison of quality of present-day heat flow obtained from BHTs, Horner Plots of Malay Basin

    SciTech Connect

    Waples, D.W.; Mahadir, R.

    1994-07-01

    Reconciling temperature data obtained from measurement of single BHT, multiple BHT at a single depth, RFTs, and DSTs, is very difficult. Quality of data varied widely, however DST data were assumed to be most reliable. Data from 87 wells was used in this study, but only 47 wells have DST data. BASINMOD program was used to calculate the present-day heat flow, using measured thermal conductivity and calibrated against the DST data. The heat flows obtained from the DST data were assumed to be correct and representative throughout the basin. Then, heat flows using (1) uncorrected RFT data, (2) multiple BHTmore » data corrected by the Horner plot method, and (3) single BHT values corrected upward by a standard 10% were calculated. All of these three heat-flow populations had identically standard deviations to that for the DST data, but with significantly lower mean values. Correction factors were calculated to give each of the three erroneous populations the same mean value as the DST population. Heat flows calculated from RFT data had to be corrected upward by a factor of 1.12 to be equivalent to DST data; Horner plot data corrected by a factor of 1.18, and single BHT data by a factor of 1.2. These results suggest that present-day subsurface temperatures using RFT, Horner plot, and BHT data are considerably lower than they should be. The authors suspect qualitatively similar results would be found in other areas. Hence, they recommend significant corrections be routinely made until local calibration factors are established.« less

  2. 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

  3. Identification of De Novo and Rare Inherited Copy Number Variants in Children with Syndromic Congenital Heart Defects.

    PubMed

    Hussein, Ibtessam R; Bader, Rima S; Chaudhary, Adeel G; Bassiouni, Randa; Alquaiti, Maha; Ashgan, Fai; Schulten, Hans-Juergen; Al Qahtani, Mohammad H

    2018-06-01

    Congenital heart defects (CHDs) are the most common birth defects in neonatal life. CHDs could be presented as isolated defects or associated with developmental delay (DD) and/or other congenital malformations. A small proportion of cardiac defects are caused by chromosomal abnormalities or single gene defects; however, in a large proportion of cases no genetic diagnosis could be achieved by clinical examination and conventional genetic analysis. The development of genome wide array-Comparative Genomic Hybridization technique (array-CGH) allowed for the detection of cryptic chromosomal imbalances and pathogenic copy number variants (CNVs) not detected by conventional techniques. We investigated 94 patients having CHDs associated with other malformations and/or DD. Clinical examination and Echocardiography was done to all patients to evaluate the type of CHD. To investigate for genome defects we applied high-density array-CGH 2 × 400K (41 patients) and CGH/SNP microarray 2 × 400K (Agilent) for 53 patients. Confirmation of results was done using Fluorescent in situ hybridization (FISH) or qPCR techniques in certain cases. Chromosomal abnormalities such as trisomy 18, 13, 21, microdeletions: del22q11.2, del7q11.23, del18 (p11.32; p11.21), tetrasomy 18p, trisomy 9p, del11q24-q25, add 15p, add(18)(q21.3), and der 9, 15 (q34.2; q11.2) were detected in 21/94 patients (22%) using both conventional cytogenetics methods and array-CGH technique. Cryptic chromosomal anomalies and pathogenic variants were detected in 15/73 (20.5%) cases. CNVs were observed in a large proportion of the studied samples (27/56) (48%). Clustering of variants was observed in chromosome 1p36, 1p21.1, 2q37, 3q29, 5p15, 7p22.3, 8p23, 11p15.5, 14q11.2, 15q11.2, 16p13.3, 16p11.2, 18p11, 21q22, and 22q11.2. CGH/SNP array could detect loss of heterozygosity (LOH) in different chromosomal loci in 10/25 patients. Array-CGH technique allowed for detection of cryptic chromosomal imbalances that

  4. Bilateral congenital corneal keloids and anterior segment mesenchymal dysgenesis in a case of Rubinstein-Taybi syndrome.

    PubMed

    Rao, Srinivas K; Fan, Dorothy S P; Pang, C P; Li, Winnie W Y; Ng, Joan S K; Good, William V; Lam, Dennis S C

    2002-01-01

    To report the unusual association of bilateral corneal keloids and anterior segment mesenchymal dysgenesis in a child with Rubinstein-Taybi syndrome. Case report of a 2-year-old boy. Excision of the epicorneal mass in the right eye was followed by recurrence of the lesion. Multiple penetrating keratoplasties were unsuccessful in reconstructing the anterior segment because of recurrent corneal epithelial breakdown, suggesting limbal stem cell insufficiency. Histopathology and electron microscopy of the excised mass lesion showed features typical of a corneal keloid: thickened keratinized epithelium, absent Bowman's layer, and fibrovascular hyperplasia, with haphazard orientation of the collagen lamellae. Ultrasound biomicroscopy and intraoperative findings suggested a diagnosis of Peter anomaly, but genetic analysis did not show a PAX6 mutation. The findings in our patient add to the spectrum of ocular changes described in Rubinstein-Taybi syndrome and confirm earlier reports of poor ocular prognosis in corneal keloids and Rubinstein-Taybi syndrome.

  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. [Congenital ectropion of the upper eyelids due to an anomaly of the eyelids in down's syndrome (author's transl)].

    PubMed

    Hennighausen, U; Schmidt-Martens, F W; Reim, M

    1978-05-01

    A 5-months-old female baby with Down's Syndrome developed an intermittent spastic ectropion of the upper eyelids. The reasons for this are thought to be the flaccidity of the connective tissue, which is typical in Down's Syndrome, and a little anomaly of the eyelids, the tarsus was too short horizontally and very weak and the upper eyelids were somewhat larger than normal and elongated. Suturing Bangerter's lid-sheets on the upper eyelids for 15 days resulted in a scarring of the tarsus with the lax connective tissue of the upper eyelids. The ectropion disappeared and did not recur.

  7. Short stature with congenital ichthyosis.

    PubMed

    Lakhani, Som J; Lakhani, Om J

    2015-12-09

    PIBIDS syndrome (photosensitivity, ichthyosis, brittle hair, intellectual impairment, decreased fertility and short stature) is a variant of trichothiodystrophy. It is a rare form of autosomal recessive congenital ichthyosis. Short stature is a vital component of PIBIDS syndrome. We present the cases of two siblings in whom we diagnosed PIBIDS syndrome. On evaluation for short stature, they were found to have severe vitamin D deficiency, which on correction led to the patients having considerable gain in stature. With this case, we would also like to propose that vitamin D deficiency could be one of the treatable causes of short stature in PIBIDS syndrome. 2015 BMJ Publishing Group Ltd.

  8. Congenital rubella

    MedlinePlus

    ... mother is infected with the virus that causes German measles. Congenital means the condition is present at ... Gershon AA. Rubella virus (German measles). In: Bennett JE, Dolin R, ... Principles and Practice of Infectious Diseases, Updated ...

  9. Dysphagia caused by a lateral medullary infarction syndrome (Wallenberg's syndrome)

    PubMed Central

    El Mekkaoui, Amine; Irhoudane, Hanane; Ibrahimi, Adil; El Yousfi, Mounia

    2012-01-01

    A 68-year-old man was referred to our hospital for a dysphagia evolving for 10 days. Clinical examination had found neurological signs as contralateral Horner's syndrome, ipsilateral palatal paresis, gait ataxia and hoarseness. Video-fluoroscopy showed a lack of passage of contrast medium to the distal esophagus. Esogastroduodenoscopy was normal. The cranial MRI had shown an acute ischemic stroke in the left lateral medullar region and the diagnosis of Wallenberg syndrome (WS) was established. WS remains an unknown cause of dysphagia in the clinical practice of the gastroenterologist. PMID:23077713

  10. Mutations in GFPT1-related congenital myasthenic syndromes are associated with synaptic morphological defects and underlie a tubular aggregate myopathy with synaptopathy.

    PubMed

    Bauché, Stéphanie; Vellieux, Geoffroy; Sternberg, Damien; Fontenille, Marie-Joséphine; De Bruyckere, Elodie; Davoine, Claire-Sophie; Brochier, Guy; Messéant, Julien; Wolf, Lucie; Fardeau, Michel; Lacène, Emmanuelle; Romero, Norma; Koenig, Jeanine; Fournier, Emmanuel; Hantaï, Daniel; Streichenberger, Nathalie; Manel, Veronique; Lacour, Arnaud; Nadaj-Pakleza, Aleksandra; Sukno, Sylvie; Bouhour, Françoise; Laforêt, Pascal; Fontaine, Bertrand; Strochlic, Laure; Eymard, Bruno; Chevessier, Frédéric; Stojkovic, Tanya; Nicole, Sophie

    2017-08-01

    Mutations in GFPT1 (glutamine-fructose-6-phosphate transaminase 1), a gene encoding an enzyme involved in glycosylation of ubiquitous proteins, cause a limb-girdle congenital myasthenic syndrome (LG-CMS) with tubular aggregates (TAs) characterized predominantly by affection of the proximal skeletal muscles and presence of highly organized and remodeled sarcoplasmic tubules in patients' muscle biopsies. We report here the first long-term clinical follow-up of 11 French individuals suffering from LG-CMS with TAs due to GFPT1 mutations, of which nine are new. Our retrospective clinical evaluation stresses an evolution toward a myopathic weakness that occurs concomitantly to ineffectiveness of usual CMS treatments. Analysis of neuromuscular biopsies from three unrelated individuals demonstrates that the maintenance of neuromuscular junctions (NMJs) is dramatically impaired with loss of post-synaptic junctional folds and evidence of denervation-reinnervation processes affecting the three main NMJ components. Moreover, molecular analyses of the human muscle biopsies confirm glycosylation defects of proteins with reduced O-glycosylation and show reduced sialylation of transmembrane proteins in extra-junctional area. Altogether, these results pave the way for understanding the etiology of this rare neuromuscular disorder that may be considered as a "tubular aggregates myopathy with synaptopathy".

  11. 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.

  12. Mutations in a novel gene, NHS, cause the pleiotropic effects of Nance-Horan syndrome, including severe congenital cataract, dental anomalies, and mental retardation.

    PubMed

    Burdon, Kathryn P; McKay, James D; Sale, Michèle M; Russell-Eggitt, Isabelle M; Mackey, David A; Wirth, M Gabriela; Elder, James E; Nicoll, Alan; Clarke, Michael P; FitzGerald, Liesel M; Stankovich, James M; Shaw, Marie A; Sharma, Shiwani; Gajovic, Srecko; Gruss, Peter; Ross, Shelley; Thomas, Paul; Voss, Anne K; Thomas, Tim; Gécz, Jozef; Craig, Jamie E

    2003-11-01

    Nance-Horan syndrome (NHS) is an X-linked disorder characterized by congenital cataracts, dental anomalies, dysmorphic features, and, in some cases, mental retardation. NHS has been mapped to a 1.3-Mb interval on Xp22.13. We have confirmed the same localization in the original, extended Australian family with NHS and have identified protein-truncating mutations in a novel gene, which we have called "NHS," in five families. The NHS gene encompasses approximately 650 kb of genomic DNA, coding for a 1,630-amino acid putative nuclear protein. NHS orthologs were found in other vertebrates, but no sequence similarity to known genes was identified. The murine developmental expression profile of the NHS gene was studied using in situ hybridization and a mouse line containing a lacZ reporter-gene insertion in the Nhs locus. We found a complex pattern of temporally and spatially regulated expression, which, together with the pleiotropic features of NHS, suggests that this gene has key functions in the regulation of eye, tooth, brain, and craniofacial development.

  13. Mutations in a Novel Gene, NHS, Cause the Pleiotropic Effects of Nance-Horan Syndrome, Including Severe Congenital Cataract, Dental Anomalies, and Mental Retardation

    PubMed Central

    Burdon, Kathryn P.; McKay, James D.; Sale, Michèle M.; Russell-Eggitt, Isabelle M.; Mackey, David A.; Wirth, M. Gabriela; Elder, James E.; Nicoll, Alan; Clarke, Michael P.; FitzGerald, Liesel M.; Stankovich, James M.; Shaw, Marie A.; Sharma, Shiwani; Gajovic, Srecko; Gruss, Peter; Ross, Shelley; Thomas, Paul; Voss, Anne K.; Thomas, Tim; Gécz, Jozef; Craig, Jamie E.

    2003-01-01

    Nance-Horan syndrome (NHS) is an X-linked disorder characterized by congenital cataracts, dental anomalies, dysmorphic features, and, in some cases, mental retardation. NHS has been mapped to a 1.3-Mb interval on Xp22.13. We have confirmed the same localization in the original, extended Australian family with NHS and have identified protein-truncating mutations in a novel gene, which we have called “NHS,” in five families. The NHS gene encompasses ∼650 kb of genomic DNA, coding for a 1,630–amino acid putative nuclear protein. NHS orthologs were found in other vertebrates, but no sequence similarity to known genes was identified. The murine developmental expression profile of the NHS gene was studied using in situ hybridization and a mouse line containing a lacZ reporter-gene insertion in the Nhs locus. We found a complex pattern of temporally and spatially regulated expression, which, together with the pleiotropic features of NHS, suggests that this gene has key functions in the regulation of eye, tooth, brain, and craniofacial development. PMID:14564667

  14. 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.

  15. 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

  16. Successful haploidentical PBSCT with subsequent T-cell addbacks in a boy with HyperIgM syndrome presenting as severe congenital neutropenia.

    PubMed

    Jasinska, Aleksandra; Kalwak, Krzysztof; Trelinska, Joanna; Borowiec, Maciej; Piatosa, Barbara; Zeman, Krzysztof; Mlynarski, Wojciech

    2013-02-01

    HIGM syndrome is a group of primary immunodeficiency disorders characterized by recurrent bacterial and opportunistic infections; it is also associated with normal to elevated serum IgM levels and a concomitant deficiency of IgG, IgA, and IgE. In this report, we give account of a boy with X-linked HIGM and a novel Y172C mutation within his CD40LG gene. He presented with severe neutropenia as the dominating symptom. His bone marrow showed maturation arrest at the promyelocyte/myelocyte stage, typical of congenital neutropenia. This boy suffered from life-threatening infections and required high doses of rhG-CSF, and a haploidentical PBSCT was also successfully performed, thus leading to reconstitution of CD40L expression on activated CD4+ T cells (as assessed with flow cytometry six months after the procedure). Two low-dose T-cell addbacks were required to re-establish full donor chimerism and clear CMV reactivation. The report demonstrates that in select cases, alternative donor allogeneic HSCT supported by DLI may be effective in correcting the defect in X-linked HIGM, and HSCT in HIGM children is not necessarily limited to matched sibling donor transplantation. © 2012 John Wiley & Sons A/S.

  17. 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

  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. Prenatal diagnosis of Wolf-Hirschhorn syndrome (4p-) in association with congenital hypospadias and foot deformity.

    PubMed

    Aslan, Halil; Karaca, Nilay; Basaran, Seher; Ermis, Hayri; Ceylan, Yavuz

    2003-01-24

    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.

  20. Germline mutations in ABL1 cause an autosomal dominant syndrome characterized by congenital heart defects and skeletal malformations.

    PubMed

    Wang, Xia; Charng, Wu-Lin; Chen, Chun-An; Rosenfeld, Jill A; Al Shamsi, Aisha; 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

    2017-04-01

    ABL1 is a proto-oncogene well known as part of the fusion gene BCR-ABL1 in the Philadelphia chromosome of leukemia cancer cells. Inherited germline ABL1 changes have not been associated with genetic disorders. Here we report ABL1 germline variants cosegregating 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 to occur de novo or cosegregate with disease in five individuals (families 1-3). Additionally, a de novo c.1066G>A (p.Ala356Thr) variant was identified in a 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 the p.Tyr245Cys and p.Ala356Thr substitutions. Our clinical and experimental findings, together with previously reported teratogenic effects of selective BCR-ABL inhibitors in humans and developmental defects in Abl1 knockout mice, suggest that ABL1 has an important role during organismal development.

  1. [Congenital intestinal lymphangiectasia].

    PubMed

    Popović, Dugan D j; Spuran, Milan; Alempijević, Tamara; Krstić, Miodrag; Djuranović, Srdjan; Kovacević, Nada; Damnjanović, Svetozar; Micev, Marjan

    2011-03-01

    Congenital intestinal lymphangiectasia is a disease which leads to protein losing enteropathy. Tortuous, dilated lymphatic vessels in the intestinal wall and mesenterium are typical features of the disease. Clinical manifestations include malabsorption, diarrhea, steatorrhea, edema and effusions. Specific diet and medication are required for disease control. A 19-year old male patient was hospitalized due to diarrhea, abdominal swelling, weariness and fatigue. Physical examination revealed growth impairment, ascites, and lymphedema of the right hand and forearm. Laboratory assessment indicated iron deficiency anaemia, lymphopenia, malabsorption, inflammatory syndrome, and urinary infection. Enteroscopy and video capsule endoscopy demonstrated dilated lymphatic vessels in the small intestine. The diagnosis was confirmed by intestinal biopsy. The patient was put on high-protein diet containing medium-chain fatty acids, somatotropin and supportive therapy. Congenital intestinal lymphangiectasia is a rare disease, usually diagnosed in childhood. Early recognition of the disease and adequate treatment can prevent development of various complications.

  2. 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.…

  3. Organocatalytic sequential alpha-amination-Horner-Wadsworth-Emmons olefination of aldehydes: enantioselective synthesis of gamma-amino-alpha,beta-unsaturated esters.

    PubMed

    Kotkar, Shriram P; Chavan, Vilas B; Sudalai, Arumugam

    2007-03-15

    A novel and highly enantioselective method for the synthesis of gamma-amino-alpha,beta-unsaturated esters via tandem alpha-amination-Horner-Wadsworth-Emmons (HWE) olefination of aldehydes is described. The one-pot assembly has been demonstrated for the construction of functionalized chiral 2-pyrrolidones, subunits present in several alkaloids. [structure: see text

  4. Mutations in SRP54 gene cause severe congenital neutropenia as well as Shwachman-Diamond-like syndrome.

    PubMed

    Bellanné-Chantelot, Christine; Schmaltz-Panneau, Barbara; Marty, Caroline; Fenneteau, Odile; Callebaut, Isabelle; Clauin, Séverine; Docet, Aurélie; Damaj, Gandhi-Laurent; Leblanc, Thierry; Pellier, Isabelle; Stoven, Cécile; Souquere, Sylvie; Antony-Debré, Iléana; Beaupain, Blandine; Aladjidi, Nathalie; Barlogis, Vincent; Bauduer, Frédéric; Bensaid, Philippe; Boespflug-Tanguy, Odile; Berger, Claire; Bertrand, Yves; Carausu, Liana; Fieschi, Claire; Galambrun, Claire; Schmidt, Aline; Journel, Hubert; Mazingue, Françoise; Nelken, Brigitte; Quah, Thuan Chong; Oksenhendler, Eric; Ouachée, Marie; Pasquet, Marlène; Saada, Véronique; Suarez, Felipe; Pierron, Gérard; Vainchenker, William; Plo, Isabelle; Donadieu, Jean

    2018-06-18

    Congenital neutropenias (CN) are rare heterogeneous genetic disorders with about 25% of patients without known genetic defects. Using whole-exome sequencing, we identified a heterozygous mutation in the SRP54 gene, encoding the signal recognition particle (SRP) 54 GTPase protein, in 3 sporadic cases and one autosomal dominant family. We subsequently sequenced the SRP54 gene in 66 probands from the French CN registry. In total, we identified 23 mutated cases (16 sporadic, 7 familial) with seven distinct germline SRP54 mutations including a recurrent in-frame deletion (Thr117del) in 14 cases. In nearly all patients, neutropenia was chronic and profound with promyelocytic maturation arrest, occurring within the first months of life and required long-term G-CSF therapy with a poor response. Neutropenia was sometimes associated with a severe neurodevelopmental delay (n=5) and/or an exocrine pancreatic insufficiency requiring enzyme supplementation (n=3) The SRP54 protein is a key component of the ribonucleoprotein complex that mediates the co-translational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER). We showed that SRP54 was specifically upregulated during the in vitro granulocytic differentiation and that SRP54 mutations or knockdown led to a drastically reduced proliferation of granulocytic cells associated with an enhanced P53-dependent apoptosis. Bone marrow examination of SRP54 -mutated patients revealed a major dysgranulopoiesis and features of cellular ER stress and autophagy that were confirmed using SRP54 -mutated primary cells and SRP54 knockdown cells. In conclusion, we characterized a pathological pathway, which represents the second most common cause of CN with maturation arrest in the French CN registry. Copyright © 2018 American Society of Hematology.

  5. Congenital syphilis.

    PubMed

    Cooper, Joshua M; Sánchez, Pablo J

    2018-04-01

    Congenital syphilis remains a major public health problem worldwide, and its incidence is increasing in the United States. This review highlights the ongoing problem of this preventable infection, and discusses vertical transmission and clinical manifestations while providing a practical algorithm for the evaluation and management of infants born to mothers with reactive serologic tests for syphilis. Every case of congenital syphilis must be seen as a failure of our public health system to provide optimal prenatal care to pregnant women, as congenital syphilis can be prevented by early and repeated prenatal serologic screening of mothers and penicillin treatment of infected women, their sexual partners, and their newborn infants. Copyright © 2018. Published by Elsevier Inc.

  6. Using Seroprevalence and Immunisation Coverage Data to Estimate the Global Burden of Congenital Rubella Syndrome, 1996-2010: A Systematic Review

    PubMed Central

    Vynnycky, Emilia; Adams, Elisabeth J.; Cutts, Felicity T.; Reef, Susan E.; Navar, Ann Marie; Simons, Emily; Yoshida, Lay-Myint; Brown, David W. J.; Jackson, Charlotte; Strebel, Peter M.; Dabbagh, Alya J.

    2016-01-01

    Background The burden of Congenital Rubella Syndrome (CRS) is typically underestimated in routine surveillance. Updated estimates are needed following the recent WHO position paper on rubella and recent GAVI initiatives, funding rubella vaccination in eligible countries. Previous estimates considered the year 1996 and only 78 (developing) countries. Methods We reviewed the literature to identify rubella seroprevalence studies conducted before countries introduced rubella-containing vaccination (RCV). These data and the estimated vaccination coverage in the routine schedule and mass campaigns were incorporated in mathematical models to estimate the CRS incidence in 1996 and 2000–2010 for each country, region and globally. Results The estimated CRS decreased in the three regions (Americas, Europe and Eastern Mediterranean) which had introduced widespread RCV by 2010, reaching <2 per 100,000 live births (the Americas and Europe) and 25 (95% CI 4–61) per 100,000 live births (the Eastern Mediterranean). The estimated incidence in 2010 ranged from 90 (95% CI: 46–195) in the Western Pacific, excluding China, to 116 (95% CI: 56–235) and 121 (95% CI: 31–238) per 100,000 live births in Africa and SE Asia respectively. Highest numbers of cases were predicted in Africa (39,000, 95% CI: 18,000–80,000) and SE Asia (49,000, 95% CI: 11,000–97,000). In 2010, 105,000 (95% CI: 54,000–158,000) CRS cases were estimated globally, compared to 119,000 (95% CI: 72,000–169,000) in 1996. Conclusions Whilst falling dramatically in the Americas, Europe and the Eastern Mediterranean after vaccination, the estimated CRS incidence remains high elsewhere. Well-conducted seroprevalence studies can help to improve the reliability of these estimates and monitor the impact of rubella vaccination. PMID:26962867

  7. 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.

  8. 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.

  9. Congenital Myasthenic Syndrome Type 19 Is Caused by Mutations in COL13A1, Encoding the Atypical Non-fibrillar Collagen Type XIII α1 Chain.

    PubMed

    Logan, Clare V; Cossins, Judith; Rodríguez Cruz, Pedro M; Parry, David A; Maxwell, Susan; Martínez-Martínez, Pilar; Riepsaame, Joey; Abdelhamed, Zakia A; Lake, Alice V R; Moran, Maria; Robb, Stephanie; Chow, Gabriel; Sewry, Caroline; Hopkins, Philip M; Sheridan, Eamonn; Jayawant, Sandeep; Palace, Jacqueline; Johnson, Colin A; Beeson, David

    2015-12-03

    The neuromuscular junction (NMJ) consists of a tripartite synapse with a presynaptic nerve terminal, Schwann cells that ensheathe the terminal bouton, and a highly specialized postsynaptic membrane. Synaptic structural integrity is crucial for efficient signal transmission. Congenital myasthenic syndromes (CMSs) are a heterogeneous group of inherited disorders that result from impaired neuromuscular transmission, caused by mutations in genes encoding proteins that are involved in synaptic transmission and in forming and maintaining the structural integrity of NMJs. To identify further causes of CMSs, we performed whole-exome sequencing (WES) in families without an identified mutation in known CMS-associated genes. In two families affected by a previously undefined CMS, we identified homozygous loss-of-function mutations in COL13A1, which encodes the alpha chain of an atypical non-fibrillar collagen with a single transmembrane domain. COL13A1 localized to the human muscle motor endplate. Using CRISPR-Cas9 genome editing, modeling of the COL13A1 c.1171delG (p.Leu392Sfs(∗)71) frameshift mutation in the C2C12 cell line reduced acetylcholine receptor (AChR) clustering during myotube differentiation. This highlights the crucial role of collagen XIII in the formation and maintenance of the NMJ. Our results therefore delineate a myasthenic disorder that is caused by loss-of-function mutations in COL13A1, encoding a protein involved in organization of the NMJ, and emphasize the importance of appropriate symptomatic treatment for these individuals. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  10. The genetics of folate metabolism and maternal risk of birth of a child with Down syndrome and associated congenital heart defects

    PubMed Central

    Coppedè, Fabio

    2015-01-01

    Almost 15 years ago it was hypothesized that polymorphisms of genes encoding enzymes involved in folate metabolism could lead to aberrant methylation of peri-centromeric regions of chromosome 21, favoring its abnormal segregation during maternal meiosis. Subsequently, more than 50 small case-control studies investigated whether or not maternal polymorphisms of folate pathway genes could be risk factors for the birth of a child with Down syndrome (DS), yielding conflicting and inconclusive results. However, recent meta-analyses of those studies suggest that at least three of those polymorphisms, namely MTHFR 677C>T, MTRR 66A>G, and RFC1 80G>A, are likely to act as maternal risk factors for the birth of a child with trisomy 21, revealing also complex gene-nutrient interactions. A large-cohort study also revealed that lack of maternal folic acid supplementation at peri-conception resulted in increased risk for a DS birth due to errors occurred at maternal meiosis II in the aging oocyte, and it was shown that the methylation status of chromosome 21 peri-centromeric regions could favor recombination errors during meiosis leading to its malsegregation. In this regard, two recent case-control studies revealed association of maternal polymorphisms or haplotypes of the DNMT3B gene, coding for an enzyme required for the regulation of DNA methylation at centromeric and peri-centromeric regions of human chromosomes, with risk of having a birth with DS. Furthermore, congenital heart defects (CHD) are found in almost a half of DS births, and increasing evidence points to a possible contribution of lack of folic acid supplementation at peri-conception, maternal polymorphisms of folate pathway genes, and resulting epigenetic modifications of several genes, at the basis of their occurrence. This review summarizes available case-control studies and literature meta-analyses in order to provide a critical and up to date overview of what we currently know in this field. PMID:26161087

  11. 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.

  12. A nationwide cross-sectional study on congenital heart diseases and symptoms of sleep-disordered breathing among Japanese Down's syndrome people.

    PubMed

    Sawatari, Hiroyuki; Chishaki, Akiko; Nishizaka, Mari; Matsuoka, Fumio; Yoshimura, Chikara; Kuroda, Hiromi; Rahmawati, Anita; Hashiguchi, Nobuko; Miyazono, Mami; Ono, Junji; Ohkusa, Tomoko; Ando, Shin-Ichi

    2015-01-01

    It is well known that people with Down's syndrome (DS) frequently complicate with congenital heart diseases (CHDs). Patients with heart diseases often have sleep-disordered breathing as a co-morbidity (SDB) which worsens the heart diseases. However, the relationship between SDB and CHDs in DS people has not yet been fully elucidated. The aim of this study was to establish the association between SDB and CHDs in DS people using data from a large nationwide questionnaire survey in Japan. We conducted a cross-sectional questionnaire survey of a randomly selected sample of 2,000 DS people and their caregivers throughout Japan to examine the associations between observed signs of SDB and CHDs in DS people. The questionnaire included the presence of SDB symptoms (snoring, apnea, arousal, nocturia, and napping) and CHDs (the presence and types of CHDs). Of the 1,222 replies received from the caregivers, 650 reported complications of some type of CHDs. The observed apnea tended to be higher among DS people with CHDs than those without CHDs (OR=1.28, 95% CI=0.97-1.70, p=0.09). DS people with tetralogy of Fallot reported significantly more frequent apnea than those without CHDs (OR=3.10, 95% CI=1.36-7.05, p<0.01). SDB prevailed among DS people with severe CHDs, such as tetralogy of Fallot. Careful attention to the signs of SDB in such patients may lead to earlier clinical intervention removing the vicious cycle between SDB and CHDs.

  13. Beyond the Length and Look of Repolarization: Defining the Non-QTc Electrocardiographic Profiles of Patients with Congenital Long QT Syndrome.

    PubMed

    Lane, Conor M; Bos, J Martijn; Rohatgi, Ram K; Ackerman, Michael J

    2018-04-30

    Little is known about the spectrum and prevalence of ECG features beyond the length and morphology of repolarization in patients with congenital long QT syndrome (LQTS). To characterize the full ECG phenotype of LQTS patients and evaluate differences by age and LQTS genotype. Retrospective review of 943 patients with LQTS (57% female, median age 25 years; IQR 9 - 34 years) was performed. Comprehensive analysis of their initial evaluation ECG was performed using definitions outlined in Heart Rhythm Society guidelines. Bradycardia was common (n=320; 34%), regardless of beta-blocker use. Left axis deviation (n=33, 3.5%) and bundle branch block (n=5, 0.5%) were uncommon. T-wave inversion (TWI) involving leads V1 and V3 was more common in LQT2 compared to LQT1 or LQT3 [OR for V1: 2.67 (95% CI 1.8 - 3.9) and OR for V3: 1.76 (95% CI 1.2 - 2.6)], while TWI in lead III and aVF was most common in LQT3 [OR for III: 2.38 (95% CI 1.4 - 4.2) and OR for aVF: 3.14 (95% CI 1.6 - 6.4)]. Notched T-waves were most apparent at younger ages (48% in patients between ages 4-10 compared to 12% in over 40s, p <0.0001). Beyond the QT interval and bradycardia, ECG abnormalities are uncommon in LQTS patients and patients almost never have concomitant bundle branch block. Notably, 19% of LQTS patients overall and 27% of LQT2 patients exhibit anterior TWI that would satisfy a diagnostic criterion for arrhythmogenic right ventricular cardiomyopathy creating the potential for diagnostic miscues. Copyright © 2018. Published by Elsevier Inc.

  14. Evaluation of a commercial rubella IgM assay for use on oral fluid samples for diagnosis and surveillance of congenital rubella syndrome and postnatal rubella.

    PubMed

    Vijaylakshmi, P; Muthukkaruppan, V R; Rajasundari, A; Korukluoglu, G; Nigatu, W; L A Warrener; Samuel, D; Brown, D W G

    2006-12-01

    Clinical diagnosis (surveillance) of rubella is unreliable and laboratory confirmation is essential. Detection of virus specific IgM in serum is the most commonly used method. However, the use of serum necessitates the drawing of blood, either through venipuncture or finger/heel prick, which can be difficult in young babies. Oral fluid samples have proved useful as an alternative, less invasive sample for virus specific IgM detection however until recently no commercial rubella IgM tests were available, restricting the usefulness of this approach. To evaluate the performance of the Microimmune Rubella IgM capture EIA using oral fluid samples from outbreaks as well as in cases of suspected congenital rubella syndrome (CRS). Paired serum and oral fluids were collected from cases during a rubella outbreak in three provinces in Turkey. Matched serum and oral fluid samples were collected from children with suspected CRS in an active surveillance programme at the Aravind Eye Hospital in South India. Serum samples were collected as part of the measles surveillance programme in Ethiopia. On serum samples the sensitivity and specificity of the Microimmune Rubella IgM capture EIA compared to Behring Enzygnost rubella IgM test was 96.9% (62/64; 95% CI 94.2-100%) and 100% (53/53; 95% CI 93.2-100%). On oral fluids compared to matched Behring results on serum the sensitivity was 95.5% (42/44; 95% CI 84.5-99.4%). The sensitivity and specificity of Microimmune Rubella IgM capture EIA on oral fluids from suspected CRS cases compared to serum results using Behring Enzygnost IgM assay was 100% (95% CI 84.5-100%) and 100% (95% CI 95.8-100.0%) respectively. Microimmune Rubella IgM capture EIA has adequate performance for diagnosis and surveillance of rubella in outbreak using either serum or oral fluid specimens.

  15. Congenital myasthenic syndrome with episodic apnoea: clinical, neurophysiological and genetic features in the long-term follow-up of 19 patients.

    PubMed

    McMacken, Grace; Whittaker, Roger G; Evangelista, Teresinha; Abicht, Angela; Dusl, Marina; Lochmüller, Hanns

    2018-01-01

    Congenital myasthenic syndrome with episodic apnoea (CMS-EA) is a rare but potentially treatable cause of apparent life-threatening events in infancy. The underlying mechanisms for sudden and recurrent episodes of respiratory arrest in these patients are unclear. Whilst CMS-EA is most commonly caused by mutations in CHAT, the list of associated genotypes is expanding. We reviewed clinical information from 19 patients with CMS-EA, including patients with mutations in CHAT, SLC5A7 and RAPSN, and patients lacking a genetic diagnosis. Lack of genetic diagnosis was more common in CMS-EA than in CMS without EA (56% n = 18, compared to 7% n = 97). Most patients manifested intermittent apnoea in the first 4 months of life (74%, n = 14). A degree of clinical improvement with medication was observed in most patients (74%, n = 14), but the majority of cases also showed a tendency towards complete remission of apnoeic events with age (mean age of resolution 2 years 5 months). Signs of impaired neuromuscular transmission were detected on neurophysiology studies in 79% (n = 15) of cases, but in six cases, this was only apparent following specific neurophysiological testing protocols (prolonged high-frequency stimulation). A relatively large proportion of CMS-EA remains genetically undiagnosed, which suggests the existence of novel causative CMS genes which remain uncharacterised. In light of the potential for recurrent life-threatening apnoeas in early life and the positive response to therapy, early diagnostic consideration of CMS-EA is critical, but without specific neurophysiology tests, it may go overlooked.

  16. 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.

  17. 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…

  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. Autre cause de mort subite du nourrisson: à propos d'un cas clinique de syndrome du QT long congenital

    PubMed Central

    Seka, Zena; Mols, Pierre; Gobin, Eric; Ngatchou, William

    2014-01-01

    Le syndrome du QT long congénital est une maladie rythmique liée à une mutation génétique et caractérisée par un espace QT allongé sur l’électrocardiogramme, des arythmies malignes type torsade de pointe et fibrillation ventriculaire entraînant une mort subite. Les gènes impliqués dans ces mutations codent pour des sous unités des canaux ioniques responsables de l'activité électrique cardiaque. Le diagnostic est basé sur l’électrocardiogramme, une enquête familiale et l’étude génétique. Le traitement repose sur les bêtabloquants, la sympathectomie et le stimulateur cardiaque. Nous rapportons le cas d'un nourrisson de 2 ans retrouvé en état de mort apparente. Nous discutons de sa prise en charge initiale, de l'enquête familiale et de son suivi ultérieur. PMID:25667708

  20. Congenital portosystemic shunt: our experience.

    PubMed

    Timpanaro, Tiziana; Passanisi, Stefano; Sauna, Alessandra; Trombatore, Claudia; Pennisi, Monica; Petrillo, Giuseppe; Smilari, Pierluigi; Greco, Filippo

    2015-01-01

    Introduction. Congenital portosystemic venous malformations are rare abnormalities in which the portal blood drains into a systemic vein and which are characterized by extreme clinical variability. Case Presentations. The authors present two case reports of a congenital extrahepatic portosystemic shunt (Type II). In the first patient, apparently nonspecific symptoms, such as headache and fatigue, proved to be secondary to hypoglycemic episodes related to the presence of a portosystemic shunt, later confirmed on imaging. During portal vein angiography, endovascular embolization of the portocaval fistula achieved occlusion of the anomalous venous tract. In the second patient, affected by Down's syndrome, the diagnosis of a portosystemic malformation was made by routine ultrasonography, performed to rule out concurrent congenital anomalies. Because of the absence of symptoms, we chose to observe this patient. Conclusions. These two case reports demonstrate the clinical heterogeneity of this malformation and the need for a multidisciplinary approach. As part of a proper workup, clinical evaluation must always be followed by radiographic diagnosis.

  1. 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.

  2. Accelerate Genomic Aging in Congenital Neutropenia

    DTIC Science & Technology

    2017-10-01

    syndrome (MDS) or acute myeloid leukemia (AML) in patients with congenital neutropenia. We hypothesize that replicative stress and/or changes in the...neutropenia; Shwachman Diamond syndrome ; Cyclic neutropenia; Hematopoietic stem cells; Granulocyte colony-stimulating factor; Acute myeloid leukemia... syndrome (MDS) or acute myeloid leukemia (AML). The cumulative incidence of MDS/AML in patients with SCN treated with G-CSF is 22%. Likewise, the

  3. [Sex differences in congenital heart disease].

    PubMed

    Aubry, P; Demian, H

    2016-12-01

    Gender influences the clinical presentation and the management of some acquired cardiovascular diseases, such as coronary artery disease, resulting in different outcomes. Differences between women and men are also noticed in congenital heart disease. They are mainly related to the prevalence and severity of some congenital heart defects at birth, and in adulthood to the prognosis, incidence of Eisenmenger syndrome and risks of pregnancy. The role of gender on the risk of operative mortality of congenital heart surgery remains debated. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  4. Poland syndrome

    PubMed Central

    Sharma, Chandra Madhur; Kumar, Shrawan; Meghwani, Manoj K.; Agrawal, Ravi P.

    2014-01-01

    Poland's syndrome is a rare congenital condition, characterized by the absence of the sternal or breastbone portion of the pectoralis major muscle, which may be associated with the absence of nearby musculoskeletal structures. We hereby report an 8-year-old boy with typical features of Poland syndrome, the first documented case from Uttar Pradesh, India. PMID:24959021

  5. Poland syndrome.

    PubMed

    Sharma, Chandra Madhur; Kumar, Shrawan; Meghwani, Manoj K; Agrawal, Ravi P

    2014-01-01

    Poland's syndrome is a rare congenital condition, characterized by the absence of the sternal or breastbone portion of the pectoralis major muscle, which may be associated with the absence of nearby musculoskeletal structures. We hereby report an 8-year-old boy with typical features of Poland syndrome, the first documented case from Uttar Pradesh, India.

  6. 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.

  7. Congenital anomalies

    PubMed Central

    Kunisaki, Shaun M.

    2012-01-01

    Over the past decade, amniotic fluid-derived stem cells have emerged as a novel, experimental approach for the treatment of a wide variety of congenital anomalies diagnosed either in utero or postnatally. There are a number of unique properties of amniotic fluid stem cells that have allowed it to become a major research focus. These include the relative ease of accessing amniotic fluid cells in a minimally invasive fashion by amniocentesis as well as the relatively rich population of progenitor cells obtained from a small aliquot of fluid. Mesenchymal stem cells, c-kit positive stem cells, as well as induced pluripotent stem cells have all been derived from human amniotic fluid in recent years. This article gives a pediatric surgeon’s perspective on amniotic fluid stem cell therapy for the management of congenital anomalies. The current status in the use of amniotic fluid-derived stem cells, particularly as they relate as substrates in tissue engineering-based applications, is described in various animal models. A roadmap for further study and eventual clinical application is also proposed. PMID:22986340

  8. DNA methylation abnormalities in congenital heart disease.

    PubMed

    Serra-Juhé, Clara; Cuscó, Ivon; Homs, Aïda; Flores, Raquel; Torán, Núria; Pérez-Jurado, Luis A

    2015-01-01

    Congenital heart defects represent the most common malformation at birth, occurring also in ∼50% of individuals with Down syndrome. Congenital heart defects are thought to have multifactorial etiology, but the main causes are largely unknown. We have explored the global methylation profile of fetal heart DNA in comparison to blood DNA from control subjects: an absolute correlation with the type of tissue was detected. Pathway analysis revealed a significant enrichment of differential methylation at genes related to muscle contraction and cardiomyopathies in the developing heart DNA. We have also searched for abnormal methylation profiles on developing heart-tissue DNA of syndromic and non-syndromic congenital heart defects. On average, 3 regions with aberrant methylation were detected per sample and 18 regions were found differentially methylated between groups. Several epimutations were detected in candidate genes involved in growth regulation, apoptosis and folate pathway. A likely pathogenic hypermethylation of several intragenic sites at the MSX1 gene, involved in outflow tract morphogenesis, was found in a fetus with isolated heart malformation. In addition, hypermethylation of the GATA4 gene was present in fetuses with Down syndrome with or without congenital heart defects, as well as in fetuses with isolated heart malformations. Expression deregulation of the abnormally methylated genes was detected. Our data indicate that epigenetic alterations of relevant genes are present in developing heart DNA in fetuses with both isolated and syndromic heart malformations. These epimutations likely contribute to the pathogenesis of the malformation by cis-acting effects on gene expression.

  9. 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.

  10. Congenital dacryocystocele.

    PubMed

    Harris, G J; DiClementi, D

    1982-11-01

    Four cases of congenital lacrimal sac distention were managed in an initially conservative manner to further elucidate the natural history of the condition and to formulate a more systematic approach to its treatment. In three cases, the abnormality resolved without nasolacrimal duct probing, with no adverse sequelae. In one case, dacryocystitis caused by Serratia marcescens, corneal astigmatism, and severe canthal distortion prompted surgical intervention. The management of individual cases of dacryocystocele should be influenced by the presence of inflammation, the virulence of any infecting organisms, the induction of astigmatism and anisometropia, and the degree of canthal distortion. Dacryocystocele appears to be a more specific term for lacrimal sac distention than either amniotocele or mucocele, and is not restricted to only one source of its fluid contents.

  11. Genetics Home Reference: Wiskott-Aldrich syndrome

    MedlinePlus

    ... other disorders: X-linked thrombocytopenia and severe congenital neutropenia . These conditions have overlapping signs and symptoms and ... Aldrich syndrome , X-linked thrombocytopenia , and severe congenital neutropenia are sometimes collectively referred to as WAS-related ...

  12. 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

  13. [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.

  14. 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.

  15. Imaging of Cranial Nerves III, IV, VI in Congenital Cranial Dysinnervation Disorders

    PubMed Central

    Kim, Jae Hyoung

    2017-01-01

    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. PMID:28534340

  16. Two case reports of anophthalmia and congenital heart disease: Adding a new dimension to this association.

    PubMed

    Wang, Jenny; Steelman, Charlotte K; Vincent, Robert; Richburg, Delene; Chang, Tiffany S; Shehata, Bahig M

    2010-01-01

    Anophthalmia is the congenital absence of ocular tissue from the orbit. Many syndromes and malformations (e.g., anophthalmia-esophageal-genital syndrome, Matthew-Wood syndrome, CHARGE syndrome, oculo-facial-cardio-dental-syndome, heterotaxy, and Fraser syndrome) have been associated with anophthalmia. However, its relation with congenital heart disease has not been fully elucidated. In this article, we discuss two cases of patients with anophthalmia and congenital heart defects, and we compare these findings with other syndromes with which anophthalmia has been associated. One of our two patients showed complex congenital heart disease with heterotaxia, polysplenia, and normal lung lobation. These findings may reflect a new dimension of anophthalmia, heterotaxia, and congenital heart disease associations.

  17. Mapping X-linked ophthalmic diseases. IV. Provisional assignment of the locus for X-linked congenital cataracts and microcornea (the Nance-Horan syndrome) to Xp22.2-p22.3.

    PubMed

    Lewis, R A; Nussbaum, R L; Stambolian, D

    1990-01-01

    The Nance-Horan syndrome (NHS) is an infrequent X-linked disorder typified by dense congenital central cataracts, microcornea, anteverted and simplex pinnae, brachymetacarpalia, and numerous dental anomalies. The regional location of the genetic mutation causing NHS is unknown. The authors applied the modern molecular techniques of analysis of restriction fragment length polymorphisms to five multigenerational kindreds in which NHS segregated. Provisional linkage is established to two DNA markers--DXS143 at Xp22.3-p22.2 and DXS43 at Xp22.2. Regional localization of NHS will provide potential antenatal diagnosis in families at risk for the disease and will enhance understanding of the multifaceted genetic defects.

  18. 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

  19. Extra-cardiac manifestations of adult congenital heart disease.

    PubMed

    Gaeta, Stephen A; Ward, Cary; Krasuski, Richard A

    2016-10-01

    Advancement in correction or palliation of congenital cardiac lesions has greatly improved the lifespan of congenital heart disease patients, resulting in a rapidly growing adult congenital heart disease (ACHD) population. As this group has increased in number and age, emerging science has highlighted the systemic nature of ACHD. Providers caring for these patients are tasked with long-term management of multiple neurologic, pulmonary, hepatic, renal, and endocrine manifestations that arise as syndromic associations with congenital heart defects or as sequelae of primary structural or hemodynamic abnormalities. In this review, we outline the current understanding and recent research into these extra-cardiac manifestations. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Four novel ELANE mutations in patients with congenital neutropenia.

    PubMed

    Kurnikova, Maria; Maschan, Michael; Dinova, Evgeniya; Shagina, Irina; Finogenova, Natalia; Mamedova, Elena; Polovtseva, Tatyana; Shagin, Dmitry; Shcherbina, Anna

    2011-08-01

    Congenital neutropenia is a heterogeneous bone marrow failure syndrome characterized by a maturation arrest of myelopoesis at the promyelocyte/myelocyte stage. Cyclic neutropenia (CyN) and severe congenital neutropenia (SCN) are two main forms of congenital neutropenia. Genetic analysis has shown that heterozygous mutations in the ELANE gene encoding the neutrophil elastase are the major cause of these disorders. We investigated the prevalence of ELANE mutations in a group of 16 patients from 14 families with congenital neutropenia. Five patients had typical manifestations of CyN, and 11 patients had SCN. Seven different heterozygous ELANE mutations were found, including four novel mutations. Copyright © 2011 Wiley-Liss, Inc.

  1. Congenital heart disease

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/001114.htm Congenital heart disease To use the sharing features on this page, please enable JavaScript. Congenital heart disease (CHD) is a problem with the heart's structure ...

  2. 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 © ...

  3. WAGR(O?) syndrome and congenital ptosis caused by an unbalanced t(11;15)(p13;p11.2)dn demonstrating a 7 megabase deletion by FISH.

    PubMed

    Lennon, P A; Scott, D A; Lonsdorf, D; Wargowski, D S; Kirkpatrick, S; Patel, A; Cheung, S W

    2006-06-01

    Aniridia usually occurs in isolation, but may also occur as part of the WAGR contiguous gene deletion syndrome, which includes Wilms tumor, aniridia, genitourinary abnormalities, and mental retardation. The aniridia and predisposition for Wilms tumor seen in WAGR are caused by haploinsufficiency for PAX 6 and WT1, respectively. We present a female infant with aniridia, bilateral ptosis, bilateral posterior capsular cataracts, nystagmus, left-sided glaucoma, microcephaly, mild unilateral hydronephrosis, poor linear growth, and gross motor delay consistent with a clinical diagnosis of WAGR syndrome. In addition, weight-for-height ratio at 12 months is at the 94th centile, raising the possibility of a diagnosis of WAGRO (WAGR + Obesity). Chromosome analysis revealed a translocation (11;15)(p13;p11.2) which has not been previously associated with a diagnosis of WAGR. Subsequent clinical WAGR fluorescent in situ hybridization (FISH) analysis demonstrated a deletion of 11p13 including PAX6 and WT1. A complete FISH-mapping of the breakpoints on chromosome 11 revealed a 7 Mb deletion within 11p13-11p14. The patient is examined in light of other reported patients with deletions and/or translocations involving the regions between 11p12 --> 11p14 including patients with WAGR + obesity (WAGRO) as well as with other reported patients with aniridia and congenital ptosis. Copyright 2006 Wiley-Liss, Inc.

  4. Homozygosity and linkage-disequilibrium mapping of the syndrome of congenital hypoparathyroidism, growth and mental retardation, and dysmorphism to a 1-cM interval on chromosome 1q42-43.

    PubMed

    Parvari, R; Hershkovitz, E; Kanis, A; Gorodischer, R; Shalitin, S; Sheffield, V C; Carmi, R

    1998-07-01

    The syndrome of hypoparathyroidism associated with growth retardation, developmental delay, and dysmorphism (HRD) is a newly described, autosomal recessive, congenital disorder with severe, often fatal consequences. Since the syndrome is very rare, with all parents of affected individuals being consanguineous, it is presumed to be caused by homozygous inheritance of a single recessive mutation from a common ancestor. To localize the HRD gene, we performed a genomewide screen using DNA pooling and homozygosity mapping for apparently unlinked kindreds. Analysis of a panel of 359 highly polymorphic markers revealed linkage to D1S235. The maximum LOD score obtained was 4.11 at a recombination fraction of 0. Analysis of three additional markers-GGAA6F06, D1S2678, and D1S179-in a 2-cM interval around D1S235 resulted in LOD scores >3. Analysis of additional chromosome 1 markers revealed evidence of genetic linkage disequilibrium and place the HRD locus within an approximately 1-cM interval defined by D1S1540 and D1S2678 on chromosome 1q42-43.

  5. Homozygosity and linkage-disequilibrium mapping of the syndrome of congenital hypoparathyroidism, growth and mental retardation, and dysmorphism to a 1-cM interval on chromosome 1q42-43.

    PubMed Central

    Parvari, R; Hershkovitz, E; Kanis, A; Gorodischer, R; Shalitin, S; Sheffield, V C; Carmi, R

    1998-01-01

    The syndrome of hypoparathyroidism associated with growth retardation, developmental delay, and dysmorphism (HRD) is a newly described, autosomal recessive, congenital disorder with severe, often fatal consequences. Since the syndrome is very rare, with all parents of affected individuals being consanguineous, it is presumed to be caused by homozygous inheritance of a single recessive mutation from a common ancestor. To localize the HRD gene, we performed a genomewide screen using DNA pooling and homozygosity mapping for apparently unlinked kindreds. Analysis of a panel of 359 highly polymorphic markers revealed linkage to D1S235. The maximum LOD score obtained was 4.11 at a recombination fraction of 0. Analysis of three additional markers-GGAA6F06, D1S2678, and D1S179-in a 2-cM interval around D1S235 resulted in LOD scores >3. Analysis of additional chromosome 1 markers revealed evidence of genetic linkage disequilibrium and place the HRD locus within an approximately 1-cM interval defined by D1S1540 and D1S2678 on chromosome 1q42-43. PMID:9634513

  6. Congenital anomalies of the breast.

    PubMed

    Caouette-Laberge, Louise; Borsuk, Daniel

    2013-02-01

    Poland syndrome is a combination of chest wall deformity and absent or hypoplastic pectoralis muscle and breast associated with shortening and brachysyndactyly of the upper limb. Clinical presentation varies widely; therefore, reconstructive procedures have to be adapted to the deformity, ranging from chest wall stabilization or augmentation, dynamic muscle transfer, nipple and areola repositioning, and breast augmentation using prosthesis or autologous tissue transfer. Other congenital breast anomalies include supernumerary nipple and areola (polythelia) and breast (polymastia), which can generally be found on the embryonic mammary ridge. Absence of the nipple, areola (athelia), or the breast tissue (amastia) is less frequent.

  7. Congenital Anomalies of the Breast

    PubMed Central

    Caouette-Laberge, Louise; Borsuk, Daniel

    2013-01-01

    Poland syndrome is a combination of chest wall deformity and absent or hypoplastic pectoralis muscle and breast associated with shortening and brachysyndactyly of the upper limb. Clinical presentation varies widely; therefore, reconstructive procedures have to be adapted to the deformity, ranging from chest wall stabilization or augmentation, dynamic muscle transfer, nipple and areola repositioning, and breast augmentation using prosthesis or autologous tissue transfer. Other congenital breast anomalies include supernumerary nipple and areola (polythelia) and breast (polymastia), which can generally be found on the embryonic mammary ridge. Absence of the nipple, areola (athelia), or the breast tissue (amastia) is less frequent. PMID:24872738

  8. JS-X syndrome: A multiple congenital malformation with vocal cord paralysis, ear deformity, hearing loss, shoulder musculature underdevelopment, and X-linked recessive inheritance.

    PubMed

    Hoeve, Hans L J; Brooks, Alice S; Smit, Liesbeth S

    2015-07-01

    We report on a family with a not earlier described multiple congenital malformation. Several male family members suffer from laryngeal obstruction caused by bilateral vocal cord paralysis, outer and middle ear deformity with conductive and sensorineural hearing loss, facial dysmorphisms, and underdeveloped shoulder musculature. The affected female members only have middle ear deformity and hearing loss. The pedigree is suggestive of an X-linked recessive inheritance pattern. SNP-array revealed a deletion and duplication on Xq28 in the affected family members. A possible aetiology is a neurocristopathy with most symptoms expressed in structures derived from branchial arches. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. 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

  10. Waardenburg syndrome.

    PubMed

    Tagra, Sunita; Talwar, Amrita Kaur; Walia, Rattan Lal Singh; Sidhu, Puneet

    2006-01-01

    Waardenburg syndrome is a rare inherited and genetically heterogenous disorder of neural crest cell development. Four distinct subtypes showing marked interfamilial and intrafamilial variability have been described. We report a girl showing constellation of congenital hearing impairment with 110 dB and 105 dB loss in right and left ear respectively, hypoplastic blue iridis, white forelock, dystopia canthorum and broad nasal root. Other affected relatives of the family, with variable features of the syndrome, have been depicted in the pedigree.

  11. 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

  12. Congenital Minamata disease: warnings from Japan's experience.

    PubMed

    Kondo, K

    2000-07-01

    Minamata disease is alkylmercury poisoning causing Hunter-Russell syndrome due to ingestion of seafood polluted by industrial waste. Two epidemics occurred in Minamata (1956) and Niigata (1965), Japan. Many infants with "cerebral palsy" in villages where adult cases occurred were established as having congenital Minamata disease. Developing brains were affected by alkylmercury through transplacental exposure and even by breastfeeding. This report reviews the history, clinical features, pathology, epidemiology, metal analysis, experiments, and sociolegal aspects of congenital Minamata disease. Many victims are still alive and their present conditions are reviewed.

  13. Severe congenital cyclic neutropenia: A case report

    PubMed Central

    Patil, Vidyavathi H; Hugar, Shivayogi M; Balikai, Girish; Patil, Sudha

    2016-01-01

    Congenital cyclic neutropenia syndrome is a constitutional genetic disorder which is characterized by very low number of neutrophils (neutropenia). Patients suffering from this disorder clinically present with neutropenia at early age, history of recurrent fever, ulcerations in the oral cavity, gingivitis, and other recurrent infections. This paper describes a case report of a child with recurrent mouth ulcers, fever, and later diagnosed with severe congenital cyclic neutropenia. This also emphasizes the importance of identification of rare causes of immunosuppressive conditions in children presenting with recurrent oral ulcers and poor dental hygiene, to prevent long-term complications of oral cavity and also morbidity and mortality secondary to neutropenic sepsis. PMID:27857902

  14. Congenital Portosystemic Shunt: Our Experience

    PubMed Central

    Timpanaro, Tiziana; Passanisi, Stefano; Sauna, Alessandra; Trombatore, Claudia; Pennisi, Monica; Petrillo, Giuseppe; Smilari, Pierluigi; Greco, Filippo

    2015-01-01

    Introduction. Congenital portosystemic venous malformations are rare abnormalities in which the portal blood drains into a systemic vein and which are characterized by extreme clinical variability. Case Presentations. The authors present two case reports of a congenital extrahepatic portosystemic shunt (Type II). In the first patient, apparently nonspecific symptoms, such as headache and fatigue, proved to be secondary to hypoglycemic episodes related to the presence of a portosystemic shunt, later confirmed on imaging. During portal vein angiography, endovascular embolization of the portocaval fistula achieved occlusion of the anomalous venous tract. In the second patient, affected by Down's syndrome, the diagnosis of a portosystemic malformation was made by routine ultrasonography, performed to rule out concurrent congenital anomalies. Because of the absence of symptoms, we chose to observe this patient. Conclusions. These two case reports demonstrate the clinical heterogeneity of this malformation and the need for a multidisciplinary approach. As part of a proper workup, clinical evaluation must always be followed by radiographic diagnosis. PMID:25709849

  15. Turner Syndrome

    MedlinePlus

    ... skin. What health problems can occur with Turner syndrome? Girls and women with TS are at risk for congenital (present at birth) abnormalities of the heart and kidneys, high blood pressure, chronic or repeated middle ear infections, hearing loss, diabetes, underactive thyroid gland, bowel ...

  16. Congenital abnormalities of the osseous spine: a radiological approach.

    PubMed

    Vanhoenacker, F M; De Schepper, A M; Parizel, P M

    2005-01-01

    The spine may act as a useful window to the diagnosis of many congenital malformations syndromes and skeletal dysplasias. However, radiological identification of these syndromes remains a difficult task, because there are so many syndromes and dysplasias to remember. Moreover, many spinal abnormalities are non-specific and there is much overlap between different genetic and congenital disorders. Consequently, many radiologists cringe when these topics are discussed. The purpose of this short review is to provide the general radiologist a workable primer for systematic analysis of spinal abnormalities encountered in genetic disorders, which may be helpful in (differential) diagnosis.

  17. 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

  18. Landiolol suppression of electrical storm of torsades de pointes in patients with congenital long-QT syndrome type 2 and myocardial ischemia.

    PubMed

    Kitajima, Ryota; Aiba, Takeshi; Kamakura, Tsukasa; Ishibashi, Kohei; Wada, Mitsuru; Inoue, Yuko; Miyamoto, Koji; Okamura, Hideo; Noda, Takashi; Nagase, Satoshi; Kataoka, Yu; Asaumi, Yasuhide; Noguchi, Teruo; Yasuda, Satoshi; Kusano, Kengo

    2017-10-01

    A 76-year-old man who had been diagnosed with long-QT syndrome type 2 had frequent syncopal attacks. The electrocardiogram was monitored, and frequent torsades de pointes (TdP) was detected despite administration of conventional medications: oral propranolol, verapamil, intravenous magnesium sulfate, verapamil, and lidocaine. In contrast, 2 μg/kg/min landiolol could completely suppress TdP. Subsequently, an implantable cardioverter defibrillator was placed, and he was diagnosed with silent myocardial ischemia using myocardial perfusion scintigraphy and coronary angiography. This is the first case report wherein landiolol effectively suppressed TdP due to long-QT syndrome with silent myocardial ischemia.

  19. Rubella epidemic in Vietnam: characteristic of rubella virus genes from pregnant women and their fetuses/newborns with congenital rubella syndrome.

    PubMed

    Pham, Van Hung; Nguyen, Thong Van; Nguyen, Truc Thanh Thi; Dang, Linh Duy; Hoang, Ngoc Hieu; Nguyen, Truong Van; Abe, Kenji

    2013-06-01

    Rubella remains poorly controlled in Southeast Asia, including Vietnam. The aim of this study was to characterize rubella virus spread in Vietnam during 2011-2012. Amniotic fluid, throat swab and placenta samples were collected from 130 patients (110 cases from pregnant women with suspected rubella and 20 cases from fetuses/newborns). Viral RNA was obtained directly from clinical specimens, amplified by PCR, and then the E1 gene containing 739 nucleotides recommended by the WHO to identify the viral genotypes was sequenced. By screening with real-time PCR, viral RNA was detectable in amniotic fluids from 103 out of 110 (93.6%) pregnant women with suspected rubella and in the throat swabs from all of 20 (100%) fetuses/newborns. In addition, viral RNA was also detected in the placenta from all cases of fetuses/newborns. All of 20 fetuses/newborns presented with congenital cataract. Twenty-four strains with the E1 gene were obtained by PCR. Using phylogenetic analysis with rubella reference sequences, all of the strains were found to be genotype 2B. Interestingly, 94% (30/32) of Vietnamese strains, including 9 strains from the database, formed an independent cluster within the genotype 2B suggesting that indigenous viruses are prevalent in this region. Rubella virus identified in Vietnam belonged to the genotype 2B. Importantly, the infection rate of rubella virus in fetuses/newborns was 100% and all of them had congenital cataract. Our results indicate an establishment of rubella prevention in this area is an urgent task in order to improve maternal and child health. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. 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

  1. Noonan syndrome.

    PubMed

    Bhambhani, Vikas; Muenke, Maximilian

    2014-01-01

    Noonan syndrome is a common genetic disorder that causes multiple congenital abnormalities and a large number of potential health conditions. Most affected individuals have characteristic facial features that evolve with age; a broad, webbed neck; increased bleeding tendency; and a high incidence of congenital heart disease, failure to thrive, short stature, feeding difficulties, sternal deformity, renal malformation, pubertal delay, cryptorchidism, developmental or behavioral problems, vision problems, hearing loss, and lymphedema. Familial recurrence is consistent with an autosomal dominant mode of inheritance, but most cases are due to de novo mutations. Diagnosis can be made on the basis of clinical features, but may be missed in mildly affected patients. Molecular genetic testing can confirm diagnosis in 70% of cases and has important implications for genetic counseling and management. Most patients with Noonan syndrome are intellectually normal as adults, but some may require multidisciplinary evaluation and regular follow-up care. Age-based Noonan syndrome-specific growth charts and treatment guidelines are available.

  2. Measles, mumps, and rubella--vaccine use and strategies for elimination of measles, rubella, and congenital rubella syndrome and control of mumps: recommendations of the Advisory Committee on Immunization Practices (ACIP).

    PubMed

    Watson, J C; Hadler, S C; Dykewicz, C A; Reef, S; Phillips, L

    1998-05-22

    These revised recommendations of the Advisory Committee on Immunization Practices (ACIP) on measles, mumps, and rubella prevention supersede recommendations published in 1989 and 1990. This statement summarizes the goals and current strategies for measles, rubella, and congenital rubella syndrome (CRS) elimination and for mumps reduction in the United States. Changes from previous recommendations include: Emphasis on the use of combined MMR vaccine for most indications; A change in the recommended age for routine vaccination to 12-15 months for the first dose of MMR, and to 4-6 years for the second dose of MMR; A recommendation that all states take immediate steps to implement a two dose MMR requirement for school entry and any additional measures needed to ensure that all school-aged children are vaccinated with two doses of MMR by 2001; A clarification of the role of serologic screening to determine immunity; A change in the criteria for determining acceptable evidence of rubella immunity; A recommendation that all persons who work in health-care facilities have acceptable evidence of measles and rubella immunity; Changes in the recommended interval between administration of immune globulin and measles vaccination; and Updated information on adverse events and contraindications, particularly for persons with severe HIV infection, persons with a history of egg allergy or gelatin allergy, persons with a history of thrombocytopenia, and persons receiving steroid therapy.

  3. 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.

  4. 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 ...

  5. 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.

  6. 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

  7. Review Recent progress in identification and characterization of loci associated with sex-linked congenital cataract.

    PubMed

    Zhang, D D; Du, J Z; Topolewski, J; Wang, X M

    2016-07-29

    Congenital cataract is a common cause of blindness in children; however, its pathogenesis remains unclear. Genetic factors have been shown to play an important role in the pathogenesis of congenital cataract. The current genetic models of congenital cataract include autosomal dominant, autosomal recessive, and sex-linked inheritance. Sex-linked congenital cataract could be inherited through the X or Y chromosome. Congenital cataract is a symptom associated with several X-linked disorders, including Nance-Horan syndrome, Lowe syndrome, Conradi-Hünermann-Happle syndrome, oculo-facio-cardio-dental syndrome, and Alport syndrome. On the other hand, the mechanism and characteristics of Y-linked congenital cataract remains to be identified. Despite its rarity, sex-linked congenital cataract has been known to seriously affect the quality of life of patients. In this review, we present our current understanding of the genes and loci associated with sex-linked congenital cataract. This could help identify novel approaches for the prevention, early diagnosis, and comprehensive disease treatment.

  8. EDUCATIONAL SERIES IN CONGENITAL HEART DISEASE: Congenital left-sided heart obstruction

    PubMed Central

    Carr, Michelle; Curtis, Stephanie; Marek, Jan

    2018-01-01

    Congenital obstruction of the left ventricular outflow tract remains a significant problem and multilevel obstruction can often coexist. Obstruction can take several morphological forms and may involve the subvalvar, valvar or supravalvar portion of the aortic valve complex. Congenital valvar stenosis presenting in the neonatal period represents a spectrum of disorders ranging from the hypoplastic left heart syndrome to almost normal hearts. Treatment options vary dependent on the severity of the left ventricular outflow tract obstruction (LVOTO) and the variable degree of left ventricular hypoplasia as well as the associated lesions such as arch hypoplasia and coarctation. PMID:29681546

  9. Infarcts presenting with a combination of medial medullary and posterior inferior cerebellar artery syndromes.

    PubMed

    Lee, Hyung; Baik, Seung Kug

    2004-09-15

    Cerebellar and medial medullary infarctions are well-known vertebrobasilar stroke syndromes. However, their development in a patient with distal vertebral artery occlusion has not been previously reported. A 49-year-old man with longstanding hypertension suddenly developed vertigo, right-sided Horner syndrome, and left-sided weakness. An MRI of the brain showed acute infarcts in the right inferior cerebellum (posterior inferior cerebellar artery territory) and the right upper medial medulla (direct penetrating branches of vertebral artery). Magnetic resonance angiogram showed occlusion of the distal vertebral artery on the right side. Atherothrombotic occlusion of the distal vertebral artery may cause this unusual combination of vertebrobasilar stroke.

  10. Incidence of environmental and genetic factors causing congenital cataract in Children of Lahore.

    PubMed

    Naz, Shagufta; Sharif, Saima; Badar, Hafsa; Rashid, Farzana; Kaleem, Afshan; Iqtedar, Mehwish

    2016-07-01

    To check the incidence of environmental and genetic factors causing congenital cataract in infants. The descriptive study was conducted at Layton Rahmatullah Benevolent Trust, Lahore, Pakistan, from October 2013 to April 2014, and comprised children under 15 years of age who had rubella syndrome, herpes simplex, birth trauma, trisomy 21, Nance-Horan syndrome or Lowe's syndrome. Of the 38,000 cases examined, 120(0.3%) patients were diagnosed with congenital cataract. Of them, 52(43.33%)were aged between 2 and 5 years,22(18.33%) <11 years and 10(8.33%) ?15 years. Bilateral congenital cataract was observed in 91(75.83%) patients and unilateral congenital cataract in 29(24.17%). Environmental factors caused 72(62.07%) cases and genetic factors caused 44(37.93%).. Congenital cataract predominated in boys compared to girls. Early diagnosis and adequate therapy requires specific technology, as well as long-term and permanent care..

  11. Urinary Peptides in Rett Syndrome.

    ERIC Educational Resources Information Center

    Solaas, K. M.; Skjeldal, O.; Gardner, M. L. G.; Kase, B. F.; Reichelt, K. L.

    2002-01-01

    A study found a significantly higher level of peptides in the urine of 53 girls with Rett syndrome compared with controls. The elevation was similar to that in 35 girls with infantile autism. Levels of peptides were lower in girls with classic Rett syndrome than those with congenital Rett syndrome. (Contains references.) (Author/CR)

  12. 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…

  13. A previously undescribed autosomal recessive multiple congenital anomalies/mental retardation (MCA/MR) syndrome with fronto-nasal dysostosis, cleft lip/palate, limb hypoplasia, and postaxial poly-syndactyly: acro-fronto-facio-nasal dysostosis syndrome.

    PubMed

    Richieri-Costa, A; Colletto, G M; Gollop, T R; Masiero, D

    1985-04-01

    We describe two sibs born to a consanguineous couple. Among other clinical findings both have mental retardation, short stature, facial and skeletal abnormalities characterized by hypertelorism, broad notched nasal tip, cleft lip/palate, campto-brachy-poly-syndactyly, fibular hypoplasia, and marked anomalies of foot structures. Facial signs of the reported patients resemble those present in the fronto-nasal "dysplasia" syndrome; however, the whole clinical picture in the present patients suggests a true MCA/MR syndrome, most likely inherited as an autosomal recessive trait. Clinical and genetic aspects of the present family are discussed.

  14. Giant congenital melanocytic nevus*

    PubMed Central

    Viana, Ana Carolina Leite; Gontijo, Bernardo; Bittencourt, Flávia Vasques

    2013-01-01

    Giant congenital melanocytic nevus is usually defined as a melanocytic lesion present at birth that will reach a diameter ≥ 20 cm in adulthood. Its incidence is estimated in <1:20,000 newborns. Despite its rarity, this lesion is important because it may associate with severe complications such as malignant melanoma, affect the central nervous system (neurocutaneous melanosis), and have major psychosocial impact on the patient and his family due to its unsightly appearance. Giant congenital melanocytic nevus generally presents as a brown lesion, with flat or mammilated surface, well-demarcated borders and hypertrichosis. Congenital melanocytic nevus is primarily a clinical diagnosis. However, congenital nevi are histologically distinguished from acquired nevi mainly by their larger size, the spread of the nevus cells to the deep layers of the skin and by their more varied architecture and morphology. Although giant congenital melanocytic nevus is recognized as a risk factor for the development of melanoma, the precise magnitude of this risk is still controversial. The estimated lifetime risk of developing melanoma varies from 5 to 10%. On account of these uncertainties and the size of the lesions, the management of giant congenital melanocytic nevus needs individualization. Treatment may include surgical and non-surgical procedures, psychological intervention and/or clinical follow-up, with special attention to changes in color, texture or on the surface of the lesion. The only absolute indication for surgery in giant congenital melanocytic nevus is the development of a malignant neoplasm on the lesion. PMID:24474093

  15. Breeding experiments and genome-wide association analysis elucidate two genetically different forms of non-syndromic congenital cleft lip and jaw in Vorderwald × Montbéliarde cattle.

    PubMed

    Reinartz, S; Distl, O

    2017-10-01

    Non-syndromic congenital cleft lip and jaw (CLJ) is a condition reported in Vorderwald × Montbéliarde cattle. The objective of the present study was to perform a genome-wide association study (GWAS) for 10 CLJ-affected and 50 unaffected Vorderwald × Montbéliarde cattle using the bovine Illumina high density bead chip to identify loci for this condition. Phenotypic classification of CLJ was based on a detailed recording of orofacial structures using computed tomography. A breeding experiment among CLJ-affected Vorderwald × Montbéliarde cattle and CLJ-affected Vorderwald × Montbéliarde cattle with unaffected Holsteins confirmed recessive inheritance and different loci for bilateral or left-sided versus right-sided CLJ. The GWAS for the five cases with right-sided CLJ gave a genome-wide signal on bovine chromosome (BTA) 29 at 16 Mb. For the four left-sided and one bilateral CLJ case, a genome-wide significant association was identified on BTA4 at 32 Mb. Two different loci are very likely to be involved in CLJ in Vorderwald × Montbéliarde cattle because experimental matings among affected cows and bulls with different types of CLJ did not result in CLJ-affected progeny, and in addition, two different loci were also found through GWAS and mapped on two different bovine chromosomes. Validation in 346 Vorderwald × Montbéliarde cattle for the highly associated SNPs on BTA4 and 29 gave ratios of 33/346 (0.095, BTA4) and 6/346 (0.017, BTA29) homozygous mutant genotypes. Further studies should elucidate the responsible mutations underlying the different types of CLJ in Vorderwald × Montbéliarde cattle. © 2017 Stichting International Foundation for Animal Genetics.

  16. 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.

  17. Genetics Home Reference: Pendred syndrome

    MedlinePlus

    ... syndrome is unknown. However, researchers estimate that it accounts for 7 to 8 percent of all hearing loss that is present from birth (congenital hearing loss). Related Information What information about a genetic condition can statistics ...

  18. Hypoplastic left heart syndrome (image)

    MedlinePlus

    Hypoplastic left heart syndrome is a congenital heart condition that occurs during the development of the heart in the ... womb. During the heart's development, parts of the left side of the heart (mitral valve, left ventricle ...

  19. Enantioselective synthesis of syn/anti-1,3-amino alcohols via proline-catalyzed sequential alpha-aminoxylation/alpha-amination and Horner-Wadsworth-Emmons olefination of aldehydes.

    PubMed

    Jha, Vishwajeet; Kondekar, Nagendra B; Kumar, Pradeep

    2010-06-18

    A novel and general method for asymmetric synthesis of both syn/anti-1,3-amino alcohols is described. The method uses proline-catalyzed sequential alpha-aminoxylation/ alpha-amination and Horner-Wadsworth-Emmons (HWE) olefination of aldehydes as the key step. By using this method, a short synthesis of a bioactive molecule, (R)-1-((S)-1-methylpyrrolidin-2-yl)-5-phenylpentan-2-ol, is also accomplished.

  20. Congenital Heart Disease: Causes, Diagnosis, Symptoms, and Treatments.

    PubMed

    Sun, RongRong; Liu, Min; Lu, Lei; Zheng, Yi; Zhang, Peiying

    2015-07-01

    The congenital heart disease includes abnormalities in heart structure that occur before birth. Such defects occur in the fetus while it is developing in the uterus during pregnancy. About 500,000 adults have congenital heart disease in USA (WebMD, Congenital heart defects medications, www.WebMD.com/heart-disease/tc/congenital-heart-defects-medications , 2014). 1 in every 100 children has defects in their heart due to genetic or chromosomal abnormalities, such as Down syndrome. The excessive alcohol consumption during pregnancy and use of medications, maternal viral infection, such as Rubella virus, measles (German), in the first trimester of pregnancy, all these are risk factors for congenital heart disease in children, and the risk increases if parent or sibling has a congenital heart defect. These are heart valves defects, atrial and ventricular septa defects, stenosis, the heart muscle abnormalities, and a hole inside wall of the heart which causes defect in blood circulation, heart failure, and eventual death. There are no particular symptoms of congenital heart disease, but shortness of breath and limited ability to do exercise, fatigue, abnormal sound of heart as heart murmur, which is diagnosed by a physician while listening to the heart beats. The echocardiogram or transesophageal echocardiogram, electrocardiogram, chest X-ray, cardiac catheterization, and MRI methods are used to detect congenital heart disease. Several medications are given depending on the severity of this disease, and catheter method and surgery are required for serious cases to repair heart valves or heart transplantation as in endocarditis. For genetic study, first DNA is extracted from blood followed by DNA sequence analysis and any defect in nucleotide sequence of DNA is determined. For congenital heart disease, genes in chromosome 1 show some defects in nucleotide sequence. In this review the causes, diagnosis, symptoms, and treatments of congenital heart disease are described.

  1. Lemierre syndrome: two cases and a review.

    PubMed

    Syed, Mohammed Iqbal; Baring, David; Addidle, Michael; Murray, Craig; Adams, Calum

    2007-09-01

    Lemierre syndrome is usually caused by an acute oropharyngeal infection in previously healthy young adults, resulting in thrombophlebitis of the internal jugular vein, leading to metastatic septic embolization and bacteraemia. The usual organism is Fusobacterium necrophorum. Lemierre syndrome, not so long ago labeled as the "forgotten disease," is on the rise. Today with increasing antibiotic-resistant organisms, and decreasing awareness of the syndrome, subsequent re-emergence of this "forgotten disease" is becoming more common in clinical settings. Lemierre syndrome has significant morbidity. Cranial nerve complications associated with the condition have been increasingly diagnosed in the last few years. Looking back at literature on Lemierre syndrome, there have been review articles in medical and microbiology journals but rarely in otolaryngology journals. By presenting our cases we demonstrate the diverse presentations and severity of the illness. A review of the literature and a case report on two cases seen in our institution in the last year are presented. Each of these had varied presentations and neurologic complications-one developed 9th to 12th cranial nerve palsies and Horner syndrome, which have not been described in previous literature, and the other developed polyneuropathy and a frontal lobe infarct among other multisystem complications. Diagnosis of Lemierre syndrome is not always straightforward as clinical features are variable and blood cultures are often negative. Awareness of the syndrome and a high degree of suspicion are needed.

  2. Congenital orbital teratoma.

    PubMed

    Aiyub, Shereen; Chan, Wengonn; Szetu, John; Sullivan, Laurence J; Pater, John; Cooper, Peter; Selva, Dinesh

    2013-12-01

    We present a case of mature congenital orbital teratoma managed with lid-sparing exenteration and dermis fat graft. This is a case report on the management of congenital orbital teratoma. A full-term baby was born in Fiji with prolapsed right globe which was surrounded by a nonpulsatile, cystic mass. Clinical and imaging features were consistent with congenital orbital teratoma. Due to limited surgical expertise, the patient was transferred to Adelaide, Australia for further management. The patient underwent a lid-sparing exenteration with frozen section control of the apical margin. A dermis fat graft from the groin was placed beneath the lid skin to provide volume. Histopathology revealed mature tissues from each of the three germ cell layers which confirmed the diagnosis of mature teratoma. We describe the successful use of demis fat graft in socket reconstruction following lid-sparing exenteration for congenital orbital teratoma.

  3. Congenital orbital teratoma

    PubMed Central

    Aiyub, Shereen; Chan, Weng Onn; Szetu, John; Sullivan, Laurence J; Pater, John; Cooper, Peter; Selva, Dinesh

    2013-01-01

    We present a case of mature congenital orbital teratoma managed with lid-sparing exenteration and dermis fat graft. This is a case report on the management of congenital orbital teratoma. A full-term baby was born in Fiji with prolapsed right globe which was surrounded by a nonpulsatile, cystic mass. Clinical and imaging features were consistent with congenital orbital teratoma. Due to limited surgical expertise, the patient was transferred to Adelaide, Australia for further management. The patient underwent a lid-sparing exenteration with frozen section control of the apical margin. A dermis fat graft from the groin was placed beneath the lid skin to provide volume. Histopathology revealed mature tissues from each of the three germ cell layers which confirmed the diagnosis of mature teratoma. We describe the successful use of demis fat graft in socket reconstruction following lid-sparing exenteration for congenital orbital teratoma. PMID:23619505

  4. Congenital adrenal hyperplasia

    MedlinePlus

    ... body produces more androgen, a type of male sex hormone. This causes male characteristics to appear early (or inappropriately). Congenital adrenal hyperplasia can affect both boys and girls. About 1 in 10,000 to ...

  5. 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 ...

  6. Multifocal Congenital Hemangiopericytoma.

    PubMed

    Robl, Renata; Carvalho, Vânia Oliveira; Abagge, Kerstin Taniguchi; Uber, Marjorie; Lichtvan, Leniza Costa Lima; Werner, Betina; Mehrdad Nadji, Mehrdad

    2017-01-01

    Congenital hemangiopericytoma (HPC) is a rare mesenchymal tumor with less aggressive behavior and a more favorable prognosis than similar tumors in adults. Multifocal presentation is even less common than isolated HPC and hence its clinical and histologic recognition may be challenging. A newborn infant with multifocal congenital HPC causing severe deformity but with a favorable outcome after chemotherapy and surgical removal is reported. © 2016 Wiley Periodicals, Inc.

  7. 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.

  8. Rare association of anophthalmia, complex congenital heart disease and pulmonary hypertension: case report.

    PubMed

    Ríos-Méndez, Raúl Enrique; Lozano Chinga, Michell Marola

    2016-10-07

    Clinical congenital anophthalmia is described as the uni- or bilateral absence of the eyeball that might occur in isolation or as part of a syndrome. It has a very low prevalence and its etiology is heterogeneous. Complex congenital cardiac malformations are also rare. The association of congenital anophthalmia and congenital heart disease is rarer still, and the etiology of those associations is not well understood yet. We report the case of a patient who had the very rare association of bilateral anophthalmia, multiple cardiac malformations and severe pulmonary hypertension.

  9. Diagnosis and clinical characteristics of congenital anosmia: case series report.

    PubMed

    Qu, Qiuyi; Liu, Jianfeng; Ni, Daofeng; Zhang, Qiuhang; Yang, Dazhang; Wang, Naya; Wu, Xueyan; Han, Honglei

    2010-12-01

    congenital anosmia is extremely rare and tends to present late. We report on a series of patients with congenital anosmia to analyze its clinical characteristics and present illustrative cases. retrospective chart review. tertiary care centre. thirty-five patients with congenital anosmia were reviewed. A thorough medical history taking, physical examination, and nasal endoscopy were performed in all patients. T&T olfactory testing (n = 33), olfactory event-related potentials (OERPs) (n = 33), and sinonasal computed tomography (CT) (n = 35) were carried out. Magnetic resonance images (MRIs) of the olfactory pathway (n = 34) were available. Serum sex hormones were tested (n = 33). physical examination, olfactory testing, MRI of the olfactory pathway, and serum sex hormones. twenty cases were isolated congenital anosmia (ICA). Fifteen cases were congenital anosmia with other anomalies, including 12 cases with Kallmann syndrome (KS), two with CHARGE syndrome, and one with hypoplasia of the nasal cavity and nasal sinus. T&T olfactory testing indicated anosmia (n = 33). No OERP was obtained (n = 33). CT scans indicated three abnormal patients, including two with unilateral choanal atresia and one with hypoplasia of the nasal cavity and sinus. MRI demonstrated aplasia or hypoplasia of the olfactory bulbs, tracts, and olfactory sulci (n = 34). Serum sex hormones were low in 12 patients with KS. early diagnosis of congenital anosmia on the basis of olfactory symptoms is difficult. MRI of the olfactory pathway plays an important role in anatomic location. ICA is the most common congenital anosmia. KS is the primary presentation of congenital anosmia with other anomalies.

  10. 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.

  11. Sotos syndrome (cerebral gigantism): analysis of 8 cases.

    PubMed

    Melo, Débora Gusmão; Acosta, Angelina Xavier; Salles, Maria Aparecida de Almeida; Pina-Neto, João Monteiro de; Castro, José Daniel Vieira de; Santos, Antonio Carlos

    2002-06-01

    Sotos syndrome or cerebral gigantism is characterized by macrocephaly, overgrowth, mental retardation and central nervous system abnormalities. Congenital heart defects may be present. We report 8 patients with this syndrome and relate their clinical features, neuroimaging and echocardiographic findings.

  12. Congenital Malaria in China

    PubMed Central

    Liu, Xue; Culleton, Richard; Tao, Li; Xia, Hui; Gao, Qi

    2014-01-01

    Abstract Background Congenital malaria, in which infants are directly infected with malaria parasites from their mother prior to or during birth, is a potentially life-threatening condition that occurs at relatively low rates in malaria-endemic regions. It is recognized as a serious problem in Plasmodium falciparum–endemic sub-Saharan Africa, where recent data suggests that it is more common than previously believed. In such regions where malaria transmission is high, neonates may be protected from disease caused by congenital malaria through the transfer of maternal antibodies against the parasite. However, in low P. vivax–endemic regions, immunity to vivax malaria is low; thus, there is the likelihood that congenital vivax malaria poses a more significant threat to newborn health. Malaria had previously been a major parasitic disease in China, and congenital malaria case reports in Chinese offer valuable information for understanding the risks posed by congenital malaria to neonatal health. As most of the literature documenting congenital malaria cases in China are written in Chinese and therefore are not easily accessible to the global malaria research community, we have undertaken an extensive review of the Chinese literature on this subject. Methods/Principal Findings Here, we reviewed congenital malaria cases from three major searchable Chinese journal databases, concentrating on data from 1915 through 2011. Following extensive screening, a total of 104 cases of congenital malaria were identified. These cases were distributed mainly in the eastern, central, and southern regions of China, as well as in the low-lying region of southwest China. The dominant species was P. vivax (92.50%), reflecting the malaria parasite species distribution in China. The leading clinical presentation was fever, and other clinical presentations were anaemia, jaundice, paleness, diarrhoea, vomiting, and general weakness. With the exception of two cases, all patients were cured

  13. Congenital portosystemic venous shunt.

    PubMed

    Papamichail, M; Pizanias, M; Heaton, N

    2018-03-01

    Congenital portosystemic venous shunts are rare developmental anomalies resulting in diversion of portal flow to the systemic circulation and have been divided into extra- and intrahepatic shunts. They occur during liver and systemic venous vascular embryogenesis and are associated with other congenital abnormalities. They carry a higher risk of benign and malignant liver tumors and, if left untreated, can result in significant medical complications including systemic encephalopathy and pulmonary hypertension. This article reviews the various types of congenital portosystemic shunts and their anatomy, pathogenesis, symptomatology, and timing and options of treatment. What is Known: • The natural history and basic management of this rare congenital anomaly are presented. What is New: • This paper is a comprehensive review; highlights important topics in pathogenesis, clinical symptomatology, and treatment options; and proposes an algorithm in the management of congenital portosystemic shunt disease in order to provide a clear idea to a pediatrician. An effort has been made to emphasize the indications for treatment in the children population and link to the adult group by discussing the consequences of lack of treatment or delayed diagnosis.

  14. 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 significant (p=0.10). Differences in overall estimated seroprevalence by study site were observed indicating variation by geographical area (p⩽0.03 for all). Estimated seroprevalence was similar for women declaring residence in urban (84%) versus rural (83%) settings (p=0.67). In 2013 for DRC nationally, the estimated incidence of CRS was 69/100,000 live births (95% CI 0, 186), corresponding to 2886 infants (95% CI 342, 6395) born with CRS. In the 3 provinces, rubella virus transmission is endemic, and most viral exposure and seroconversion occurs before age 15years. However, approximately 10-20% of the women were susceptible to rubella virus infection and thus at risk for having an infant with CRS. This analysis can guide plans for introduction of RCV in DRC. Per World Health Organization recommendations, introduction of RCV should be accompanied by a campaign targeting all children 9months to 14years of age as well as

  15. Adults with Congenital Heart Defects

    MedlinePlus

    ... Peripheral Artery Disease Venous Thromboembolism Aortic Aneurysm More Web Booklet: Adults With Congenital Heart Defects Updated:Aug ... topic from the list below to learn more. Web Booklet: Adults With Congenital Heart Defects Introduction Introduction: ...

  16. Congenital lesions of epithelial origin.

    PubMed

    Hills, Susannah E; Maddalozzo, John

    2015-02-01

    Defects of embryologic development give rise to a variety of congenital lesions arising from the epithelium and are among the most common congenital lesions of the head and neck in the pediatric population. This article presents several congenital lesions of epithelial origin, including congenital midline cervical cleft, pilomatrixoma, dermoid, foregut duplication cysts, and preauricular sinuses and pits. In addition, the management of these lesions is reviewed. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Congenital Toxoplasmosis: A Review.

    PubMed

    Hampton, Marissa Martinez

    2015-01-01

    Acute infection of toxoplasmosis during pregnancy is detrimental to the developing fetus. In the United States, approximately 1 in 10,000 live births are affected by congenital toxoplasmosis. Although multifactorial in etiology, maternal infection is primarily attributed to the consumption of contaminated meat or water. Infection and transmission to the fetus may result in devastating neurologic impairment. Screening methods for all pregnant women should be implemented in routine prenatal care. This article will highlight the inherent dangers of congenital toxoplasmosis, while including general care of the fetus for prevention of transmission, medical management, and long-term outcomes.

  18. Congenital brain infections.

    PubMed

    Arbelaez, Andres; Restrepo, Feliza; Davila, Jorge; Castillo, Mauricio

    2014-06-01

    Pediatric congenital intracranial infections are a group of different and important entities that constitute a small percentage of all pediatric infections. The causal factors and clinical presentations are different in children compared with adults. They require early recognition because delay diagnosis and initiation of treatment may have catastrophic consequences. Despite improvements in prenatal screening, vaccine safety, and antibiotics, infections of the central nervous system remain an important cause of neurological disabilities worldwide. This article reviews the most common congenital infections and their imaging findings.

  19. West syndrome in a patient with Schinzel-Giedion syndrome.

    PubMed

    Miyake, Fuyu; Kuroda, Yukiko; Naruto, Takuya; Ohashi, Ikuko; Takano, Kyoko; Kurosawa, Kenji

    2015-06-01

    Schinzel-Giedion syndrome is a rare recognizable malformation syndrome defined by characteristic facial features, profound developmental delay, severe growth failure, and multiple congenital anomalies. The causative gene of Schinzel-Giedion syndrome, SETBP1, has been identified, but limited cases have been confirmed by molecular analysis. We present a 9-month-old girl affected by West syndrome with Schinzel-Giedion syndrome. Congenital severe hydronephrosis, typical facial features, and multiple anomalies suggested a clinical diagnosis of Schinzel-Giedion syndrome. Hypsarrhythmia occurred at 7 months of age and was temporarily controlled by adrenocorticotropic hormone (ACTH) therapy during 5 weeks. SETBP1 mutational analysis showed the presence of a recurrent mutation, p.Ile871Thr. The implications in management of Schinzel-Giedion syndrome are discussed. © The Author(s) 2014.

  20. Clinical, Genetic and Environmental Factors Associated with Congenital Vertebral Malformations

    PubMed Central

    Giampietro, P.F.; Raggio, C.L.; Blank, R.D.; McCarty, C.; Broeckel, U.; Pickart, M.A.

    2013-01-01

    Congenital vertebral malformations (CVM) pose a significant health problem because they can be associated with spinal deformities, such as congenital scoliosis and kyphosis, in addition to various syndromes and other congenital malformations. Additional information remains to be learned regarding the natural history of congenital scoliosis and related health problems. Although significant progress has been made in understanding the process of somite formation, which gives rise to vertebral bodies, there is a wide gap in our understanding of how genetic factors contribute to CVM development. Maternal diabetes during pregnancy most commonly contributes to the occurrence of CVM, followed by other factors such as hypoxia and anticonvulsant medications. This review highlights several emerging clinical issues related to CVM, including pulmonary and orthopedic outcome in congenital scoliosis. Recent breakthroughs in genetics related to gene and environment interactions associated with CVM development are discussed. The Klippel-Feil syndrome which is associated with cervical segmentation abnormalities is illustrated as an example in which animal models, such as the zebrafish, can be utilized to provide functional evidence of pathogenicity of identified mutations. PMID:23653580

  1. Unclassified congenital deformities of the external ear.

    PubMed

    Vathulya, Madhubari

    2018-01-01

    Congenital ear deformities are a common entity. They are found in isolation or as a part of syndrome in patients. They may involve the external, middle or inner ear or in any of these combinations. Three patients of different ages presented with deformities including mirror image duplication of the superior auricle, unclassified deformities of ear lobule (wavy lobule) and deformity of superior auricle with unclassified variety of lateral ear pit. This article highlights that there are further cases of ear deformities that are noticed in the general population who come for cosmetic correction, and hence, there is a need for further modifying the classification of ear deformities.

  2. Increasing mortality burden among adults with complex congenital heart disease.

    PubMed

    Greutmann, Matthias; Tobler, Daniel; Kovacs, Adrienne H; Greutmann-Yantiri, Mehtap; Haile, Sarah R; Held, Leonhard; Ivanov, Joan; Williams, William G; Oechslin, Erwin N; Silversides, Candice K; Colman, Jack M

    2015-01-01

    Progress in management of congenital heart disease has shifted mortality largely to adulthood. However, adult survivors with complex congenital heart disease are not cured and remain at risk of premature death as young adults. Thus, our aim was to describe the evolution and mortality risk of adult patient cohorts with complex congenital heart disease. Among 12,644 adults with congenital heart disease followed at a single center from 1980 to 2009, 176 had Eisenmenger syndrome, 76 had unrepaired cyanotic defects, 221 had atrial switch operations for transposition of the great arteries, 158 had congenitally corrected transposition of the great arteries, 227 had Fontan palliation, and 789 had repaired tetralogy of Fallot. We depict the 30-year evolution of these 6 patient cohorts, analyze survival probabilities in adulthood, and predict future number of deaths through 2029. Since 1980, there has been a steady increase in numbers of patients followed, except in cohorts with Eisenmenger syndrome and unrepaired cyanotic defects. Between 1980 and 2009, 308 patients in the study cohorts (19%) died. At the end of 2009, 85% of survivors were younger than 50 years. Survival estimates for all cohorts were markedly lower than for the general population, with important differences between cohorts. Over the upcoming two decades, we predict a substantial increase in numbers of deaths among young adults with subaortic right ventricles, Fontan palliation, and repaired tetralogy of Fallot. Anticipatory action is needed to prepare clinical services for increasing numbers of young adults at risk of dying from complex congenital heart disease. © 2014 The Authors. Congenital Heart Disease Published by Wiley Periodicals, Inc.

  3. Prevention of congenital abnormalities by periconceptional multivitamin supplementation.

    PubMed Central

    Czeizel, A E

    1993-01-01

    OBJECTIVE--To study the effect of periconceptional multivitamin supplementation on neural tube defects and other congenital abnormality entities. DESIGN--Randomised controlled trial of supplementation with multivitamins and trace elements. SETTING--Hungarian family planning programme. SUBJECTS--4156 pregnancies with known outcome and 3713 infants evaluated in the eighth month of life. INTERVENTIONS--A single tablet of a multivitamin including 0.8 mg of folic acid or trace elements supplement daily for at least one month before conception and at least two months after conception. MAIN OUTCOME MEASURES--Number of major and mild congenital abnormalities. RESULTS--The rate of all major congenital abnormalities was significantly lower in the group given vitamins than in the group given trace elements and this difference cannot be explained totally by the significant reduction of neural tube defects. The rate of major congenital abnormalities other than neural tube defects and genetic syndromes was 9.0/1000 in pregnancies with known outcome in the vitamin group and 16.6/1000 in the trace element group; relative risk 1.85 (95% confidence interval 1.02 to 3.38); difference, 7.6/1000. The rate of all major congenital abnormalities other than neural tube defects and genetic syndromes diagnosed up to the eighth month of life was 14.7/1000 informative pregnancies in the vitamin group and 28.3/1000 in the trace element group; relative risk 1.95 (1.23 to 3.09); difference, 13.6/1000. The rate of some congenital abnormalities was lower in the vitamin group than in the trace element group but the differences for each group of abnormalities were not significant. CONCLUSIONS--Periconceptional multivitamin supplementation can reduce not only the rate of neural tube defects but also the rate of other major non-genetic syndromatic congenital abnormalities. Further studies are needed to differentiate the chance effect and vitamin dependent effect. PMID:8324432

  4. Congenital heart disease and chromossomopathies detected by the karyotype

    PubMed Central

    Trevisan, Patrícia; Rosa, Rafael Fabiano M.; Koshiyama, Dayane Bohn; Zen, Tatiana Diehl; Paskulin, Giorgio Adriano; Zen, Paulo Ricardo G.

    2014-01-01

    OBJECTIVE: To review the relationship between congenital heart defects and chromosomal abnormalities detected by the karyotype. DATA SOURCES: Scientific articles were searched in MEDLINE database, using the descriptors "karyotype" OR "chromosomal" OR "chromosome" AND "heart defects, congenital". The research was limited to articles published in English from 1980 on. DATA SYNTHESIS: Congenital heart disease is characterized by an etiologically heterogeneous and not well understood group of lesions. Several researchers have evaluated the presence of chromosomal abnormalities detected by the karyotype in patients with congenital heart disease. However, most of the articles were retrospective studies developed in Europe and only some of the studied patients had a karyotype exam. In this review, only one study was conducted in Latin America, in Brazil. It is known that chromosomal abnormalities are frequent, being present in about one in every ten patients with congenital heart disease. Among the karyotype alterations in these patients, the most important is the trisomy 21 (Down syndrome). These patients often have associated extra-cardiac malformations, with a higher risk of morbidity and mortality, which makes heart surgery even more risky. CONCLUSIONS: Despite all the progress made in recent decades in the field of cytogenetic, the karyotype remains an essential tool in order to evaluate patients with congenital heart disease. The detailed dysmorphological physical examination is of great importance to indicate the need of a karyotype. PMID:25119760

  5. Whole-exome analysis to detect congenital hemolytic anemia mimicking congenital dyserythropoietic anemia.

    PubMed

    Hamada, Motoharu; Doisaki, Sayoko; Okuno, Yusuke; Muramatsu, Hideki; Hama, Asahito; Kawashima, Nozomu; Narita, Atsushi; Nishio, Nobuhiro; Yoshida, Kenichi; Kanno, Hitoshi; Manabe, Atsushi; Taga, Takashi; Takahashi, Yoshiyuki; Miyano, Satoru; Ogawa, Seishi; Kojima, Seiji

    2018-06-23

    Congenital dyserythropoietic anemia (CDA) is a heterogeneous group of rare congenital disorders characterized by ineffective erythropoiesis and dysplastic changes in erythroblasts. Diagnosis of CDA is based primarily on the morphology of bone marrow erythroblasts; however, genetic tests have recently become more important. Here, we performed genetic analysis of 10 Japanese patients who had been diagnosed with CDA based on laboratory findings and morphological characteristics. We examined 10 CDA patients via central review of bone marrow morphology and genetic analysis for congenital bone marrow failure syndromes. Sanger sequencing for CDAN1, SEC23B, and KLF1 was performed for all patients. We performed whole-exome sequencing in patients without mutation in these genes. Three patients carried pathogenic CDAN1 mutations, whereas no SEC23B mutations were identified in our cohort. WES unexpectedly identified gene mutations known to cause congenital hemolytic anemia in two patients: canonical G6PD p.Val394Leu mutation and SPTA1 p.Arg28His mutation. Comprehensive genetic analysis is warranted for more effective diagnosis of patients with suspected CDA.

  6. Congenital sensory neuropathy

    PubMed Central

    Barry, J. E.; Hopkins, I. J.; Neal, B. W.

    1974-01-01

    Two infants with sporadic congenital sensory neuropathy are described. The criteria of generalized lack of superficial sensory appreciation, hypotonia, areflexia, together with histological evidence of abnormalities of sensory neural structures in skin and peripheral nerves have been met. No abnormality of motor or autonomic nerves was shown. ImagesFIG. PMID:4131674

  7. Congenital neck masses.

    PubMed

    Rosa, Peter A; Hirsch, David L; Dierks, Eric J

    2008-08-01

    Congenital neck lesions reflect abnormal embryogenesis in head and neck development. A thorough knowledge of embryology and anatomy is critical in the diagnosis and treatment of these lesions. The appropriate diagnosis of these lesions is necessary to provide appropriate treatment and long-term follow up, because some of these lesions may undergo malignant transformation or be harbingers of malignant disease.

  8. Congenital Anomalies of the Hand--Principles of Management.

    PubMed

    Little, Kevin J; Cornwall, Roger

    2016-01-01

    Physicians who specialize in pediatric orthopedics and hand surgery frequently encounter congenital hand abnormalities, despite their relative rarity. The treating physician should be aware of the associated syndromes and malformations that may, in some cases, be fatal if not recognized and treated appropriately. Although these congenital disorders have a wide variability, their treatment principles are similar in that the physician should promote functional use and cosmesis for the hand. This article discusses syndactyly, preaxial polydactyly and post-axial polydactyly, and the hypoplastic thumb. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Congenital cataracts and other abnormalities in a female with 46.X, del(X)(q26q28)mat: A new locus for X-linked congenital cataract?

    SciTech Connect

    Babul, R.; Chitayat, D.; Teshima, I.

    1994-09-01

    Three forms of X-linked congenital cataracts have been delineated: congenital cataract with posterior Y-sutural opacities in heterozygotes, congenital cataract and microcornea or microphthalmia and congenital cataract-dental syndrome (Nance-Horan syndrome). Of these, only the Nance-Horan syndrome has been mapped to Xp22.3-p21.1. However, Warburg has suggested that these different forms of X-linked congenital cataracts are due to deletions of varying sizes, placing them in the vicinity of the Nance-Horan syndrome region. We report on a female patient born to a 29-year-old primigravida woman who at birth was found to have hypotonia, dysmorphic facial features, hydrocephalus and dense white congenital bilateral cataracts. Othermore » ophthalmological findings included bilateral nystagmus and shallow orbits. Chromosome analysis revealed 46,X,del(X)(q26q28)mat. The mother, however, is phenotypically normal. Brain CT scan on the female infant revealed communicating hydrocephalus and a muscle biopsy showed congenital muscle fiber disproportion. An EMG and NCV were normal. At 4 years of age, her height and weight were below -3SD and her OFC was +2SD. Molecular studies using DNA markers located in Xq26-qter have revealed that the proximal breakpoint in the patient and her mother is defined by the HPRT locus while the distal breakpoint is defined by the locus DXS1108. This indicates that the deletion is not terminal but rather interstitial, retaining sequences proximal to the telomeric region. Other molecular studies are in progress to determine the X-inactivation status of the deleted chromosome in our patient and her mother as a possible explanation for the variation in the phenotype. These clinical and molecular findings suggest that another locus for X-linked congenital cataract exists at Xq26-28.« less

  10. Seminar on Usher's Syndrome: Proceedings.

    ERIC Educational Resources Information Center

    Rochester School for the Deaf, NY.

    Summarized are the presentation of M. Vernon and the Comments of primary panelists from a seminar on Usher's Syndrome, a genetic disease involving congenital deafness and progressive loss of vision due to retinitis pigmentosa. The following topics are addressed: genetics today, nature of Usher's Syndrome, symptoms, prevalence, lay diagnosis for…

  11. Dissociative phenomena in congenital monocular elevation deficiency.

    PubMed

    Olson, R J; Scott, W E

    1998-04-01

    Monocular elevation deficiency is characterized by unilateral limitation of elevation in both adduction and abduction and is usually present at birth. Dissociative phenomena such as dissociated vertical deviation are well recognized in association with conditions such as congenital esotropia but much less so in association with conditions such as congenital monocular elevation deficiency. All 129 patients given the diagnosis of monocular elevation deficiency or double elevator palsy in the Pediatric Ophthalmology and Strabismus Clinic at the University of Iowa Hospitals and Clinics between 1971 and 1995 were reviewed. After those with history of trauma, myasthenia gravis, thyroid eye disease, orbital lesions, Brown syndrome, or monocular elevation deficiency with acquired onset were excluded, 31 patients with congenital monocular elevation deficiency remained for retrospective study. First diagnosed at median age 2.6 years (although all were noted by parents at less than 6 months of age) with mean follow-up of 5.0 years (up to 15.5 years), 9 of 31 (29%) developed dissociated vertical deviation in the eye with monocular elevation deficiency, all of whom had undergone strabismus surgery 0 to 9.7 years previously (mean 3.5 years). Those who developed dissociated vertical deviation were generally younger, were followed up longer, and had more accompanying horizontal strabismus than did those who did not develop dissociated vertical deviation. The results did not reach significance. The current study demonstrates that dissociated vertical deviation occurs in association with monocular elevation deficiency.

  12. Arsenic in drinking water and congenital heart anomalies in Hungary.

    PubMed

    Rudnai, Tamás; Sándor, János; Kádár, Mihály; Borsányi, Mátyás; Béres, Judit; Métneki, Júlia; Maráczi, Gabriella; Rudnai, Péter

    2014-11-01

    Inorganic arsenic can get easily through the placenta however there are very few human data on congenital anomalies related to arsenic exposure. Objective of our study was to explore the associations between arsenic content of drinking water and prevalence of some congenital anomalies. Four anomalies reported to the Hungarian Congenital Anomalies Registry between 1987 and 2003 were chosen to be analysed in relation to arsenic exposure: congenital anomalies of the circulatory system (n=9734) were considered as cases, while Down syndrome, club foot and multiple congenital malformations were used as controls (n=5880). Arsenic exposure of the mothers during pregnancy was estimated by using archive measurement data for each year and for each settlement where the mothers lived. Analysis of the associations between the prevalence of congenital heart anomalies and arsenic exposure during pregnancy was performed by logistic regression. The child's gender and age of the mother were adjusted for. The associations were evaluated by using the present EU health limit value of 10.0 μg/L arsenic concentration as a cut-off point. Regular consumption of drinking water with arsenic concentration above 10 μg/L during pregnancy was associated with an increased risk of congenital heart anomalies in general (adjusted OR=1.41; 95% C.I.: 1.28-1.56), and especially that of ductus Botalli persistens (adjusted OR=1.81, 95%C.I.: 1.54-2.11) and atrial septal defect (adjusted OR=1.79; 95%C.I.: 1.59-2.01). The presented results showed an increased risk of congenital heart anomalies among infants whose mothers were exposed to drinking water with arsenic content above 10 μg/L during pregnancy. Further studies of possible similar effects of concentrations below 10 μg/L are warranted. Copyright © 2014 Elsevier GmbH. All rights reserved.

  13. The Education of Learners with CHARGE Syndrome

    ERIC Educational Resources Information Center

    Deuce, Gail

    2017-01-01

    CHARGE syndrome, although a low incidence condition, is now recognised as a leading cause of congenital deafblindness among genetic conditions. Anecdotal reporting has suggested that learners with CHARGE syndrome are distinct from the wider deafblind population. This study investigates the education of learners with CHARGE syndrome, while also…

  14. The Usher's Syndrome Adolescent: Programming Implications for School Administrators, Teachers, and Residential Advisors.

    ERIC Educational Resources Information Center

    Hicks, Wanda M.; Hicks, Doin E.

    1981-01-01

    The article examines educational programing implications for adolescents with Usher's syndrome, a condition of congenital deafness accompanied by progressive loss of vision through retinitis pigmentosa. (DB)

  15. [Genetic aspects in congenital hypothyrodism].

    PubMed

    Perone, Denise; Teixeira, Silvânia S; Clara, Sueli A; Santos, Daniela C dos; Nogueira, Célia R

    2004-02-01

    Congenital hypothyroidism (CH) affects between 1:3,000 and 1:4,000 newborns. Many genes are essential for normal development of the hypothalamus-pituitary-thyroid axis and hormone production, and are associated with CH. About 85% of primary hypothyroidism is called thyroid digenesis and evidence suggests that mutations in transcription factors (TTF2, TTF1, and PAX-8) and TSH receptor gene could be responsible for the disease. Genetic defects of hormone synthesis could be caused by mutations in the following genes: NIS (natrium-iodide symporter), pendrine, thyreoglobulin (TG), peroxidase (TPO). Recently, mutations in the THOX-2 gene have also been related to organification defects. Central hypothyroidism affects about 1:20,000 newborns and has been associated with mutations in pituitary transcriptional factors (POUIF1, PROP1, LHX3, and HESX1). The syndrome of resistance to thyroid hormone is rare, implies a hypothyroidism state for some tissues and is frequently associated with dominant autosomal mutations in the beta-receptor (TRss).

  16. Shah-Waardenburg Syndrome

    PubMed Central

    Mahmoudi, Abdelhalim; Rami, Mohamed; Khattala, Khalid; Elmadi, Aziz; Afifi, My Abderrahmane; Youssef, Bouabdallah

    2013-01-01

    Shah-Waardenburg syndrome (SWS) is a neurocristopathy and is characterized by Hirschsprung's disease (HD), deafness, and depigmentation of hairs, skin, and iris. Is a very rare congenital disorder with variable clinical expression. This report describes a 4-day-old male newborn with Waardenburg's syndrome associated with aganglionosis of the colon and terminal ileum, and review the relevant literature for draws attention to the causal relationship between these two entities. PMID:23565307

  17. Shah-Waardenburg syndrome.

    PubMed

    Mahmoudi, Abdelhalim; Rami, Mohamed; Khattala, Khalid; Elmadi, Aziz; Afifi, My Abderrahmane; Youssef, Bouabdallah

    2013-01-01

    Shah-Waardenburg syndrome (SWS) is a neurocristopathy and is characterized by Hirschsprung's disease (HD), deafness, and depigmentation of hairs, skin, and iris. Is a very rare congenital disorder with variable clinical expression. This report describes a 4-day-old male newborn with Waardenburg's syndrome associated with aganglionosis of the colon and terminal ileum, and review the relevant literature for draws attention to the causal relationship between these two entities.

  18. Radiological features of late-onset lymphoedema in Noonan's syndrome.

    PubMed

    Ho, Wan-Ling; Wang, Jou-Kou; Li, Yiu-Wah

    2003-03-01

    Noonan's syndrome is a multiple congenital anomaly syndrome with diverse manifestations. Lymphatic abnormalities occur in less than 20% of patients. We report a 14-year-old boy who presented with swollen lower limbs and dysmorphic features characteristic of Noonan's syndrome. The radiological features of this unusual case of late-onset lymphoedema in association with Noonan's syndrome are presented.

  19. A Reply to the Commentaries on "School-wide PBIS: An Example of Applied Behavior Analysis Implemented at a Scale of Social Importance" by Horner and Sugai (2015): PBIS is Function over Form: The Clear Behavioral Roots and Opportunities the PBIS Framework presents to the Field of Behavior Analysis Moving Forward.

    PubMed

    Putnam, Robert F; Knoster, Tim

    2016-03-01

    In the previous issue of Behavior Analysis in Practice (May 2015), a special section of the journal was devoted to positive behavior intervention and support (PBIS). Horner and Sugai (2015) published a manuscript providing an overview of school-wide PBIS describing how PBIS is an example of applied behavior analysis at a scale of social importance. A number of manuscripts providing commentary on the Horner and Sugai manuscript were also published in this special section of the journal. This paper will review this PBIS manuscript along with the associated commentaries published in the May 2015 special section.

  20. [10 congenital trigger fingers. Apropos of a case report].

    PubMed

    Moutet, F; Lebrun, C; Sartorius, C

    1987-01-01

    Ten congenital triggers fingers have been treated on a 3 years old girl after correction of congenital bilateral club feet. Such a case, without any other congenital malformation seems to be unique in the French literature and only found twice in the English one. This child in spite of a normal growth and good psychomotor development, presents an unusual face, with a mouth a little bit too small, but her karyotype is normal. No trismus and no microstomia were found to enable this case to be classified in a specific syndrome. The right diagnosis may be a non evolutive arthrogryposis of the extremities. Dividing the ten proximal pulleys (A1) let 10 voluminous nodules pass through and allowed full range of motion in nine out of ten fingers. A remaining flexion deformity of the proximal interphalangeal joint needed an anterior arthrolysis, the final result was good.

  1. Management of pulmonary arterial hypertension associated with congenital heart disease.

    PubMed

    Togănel, Rodica; Benedek, I; Suteu, Carmen; Blesneac, Cristina

    2007-01-01

    Congenital heart diseases are the most common congenital malformations and account for about eight cases per 1000 births and are often associated with pulmonary arterial hypertension. Increased shear stress and the excess flow through the pulmonary vascular bed due to a systemic-to-pulmonary shunt lead to the development of pulmonary vascular disease and an increase in pulmonary vascular resistance. Without surgical repair approximately 30% of patients develop pulmonary vascular disease. Eisenmenger syndrome represents the extreme end of pulmonary arterial hypertension with congenital heart disease. We summarized the current therapeutic options for pulmonary arterial hypertension; conventional treatments including calcium channel blockers, anticoagulation, digitalis, diuretics, and new treatment: prostacyclin, bosentan, sildenafil, ambrisentan. Preliminary data of new therapies are encouraging with disease significantly improved natural history, but there is need for more evidence-based data.

  2. Congenital portosystemic vascular malformations.

    PubMed

    Guérin, Florent; Blanc, Thomas; Gauthier, Frédéric; Abella, Stephanie Franchi; Branchereau, Sophie

    2012-08-01

    Congenital portosystemic shunts are developmental abnormalities of the portal venous system resulting in the diversion of portal blood away from the liver to the systemic venous system. Such malformations are believed to come from an insult occurring between the fourth and eighth week of gestation during the development of hepatic and systemic venous systems, and could explain their frequent association with cardiac and other vascular anomalies. They are currently categorized into end-to-side shunts (type I) or side-to-side shunts (type II). This article aims to review the common symptoms and complications encountered in congenital portosystemic shunts, the surgical and endovascular treatment, and the role of liver transplantation in this disease. We will also focus on the current controversies and the areas where there is potential for future studies. Copyright © 2012. Published by Elsevier Inc.

  3. Adult Congenital Cardiac Care.

    PubMed

    Kogon, Brian E; Miller, Kati; Miller, Paula; Alsoufi, Bahaaldin; Rosenblum, Joshua M

    2017-03-01

    The Adult Congenital Heart Association (ACHA) is dedicated to supporting patients with congenital heart disease. To guide patients to qualified providers and programs, it maintains a publicly accessible directory of dedicated adult congenital cardiac programs. We analyzed the directory in 2006 and 2015, aiming to evaluate the growth of the directory as a whole and to evaluate the growth of individual programs within the directory. We also hope this raises awareness of the growing opportunities that exist in adult congenital cardiology and cardiac surgery. Data in the directory are self-reported. Only data from US programs were collected and analyzed. By the end of 2015, compared to 2006, there were more programs reporting to the directory in more states (107 programs across 42 states vs 57 programs across 33 states), with higher overall clinical volume (591 vs 164 half-day clinics per week, 96,611 vs 34,446 patient visits). On average, each program was busier (5 vs 2 half-day clinics per week per program). Over the time period, the number of reported annual operations performed nearly doubled (4,346 operations by 210 surgeons vs 2,461 operations by 125 surgeons). Access to ancillary services including specific clinical diagnostic and therapeutic services also expanded. Between 2006 and 2015, the clinical directory and the individual programs have grown. Current directory data may provide benchmarks for staffing and services for newly emerging and existing programs. Verifying the accuracy of the information and inclusion of all programs will be important in the future.

  4. [Congenital syphilis (author's transl)].

    PubMed

    Arrate, J K; García Rodrigo, S; Ugidos, M; Saitúa, G; Gárate, J

    1979-12-01

    Authors present a study on eleven patients affected with congenital syphillis treated during the last six years. All of them presented bone lesions in one or more locations. Familiar antecedents, mechanism of infection, clinical symptoms and radiological findings are analized, emphasizing the importance of prophylaxis and early treatment with procaine penicillin in a dosage of 50,000 U./Kg. day for at least ten days.

  5. Congenital hearing loss

    PubMed Central

    Korver, Anna M. H.; Smith, Richard J. H.; Van Camp, Guy; Schleiss, Mark R.; Bitner-Glindzicz, Maria A. K.; Lustig, Lawrence R.; Usami, Shin-ichi; Boudewyns, An N.

    2017-01-01

    Congenital hearing loss (hearing loss present at birth) is one of the most prevalent chronic conditions in children. In the majority of developed countries, neonatal hearing-screening programmes enable early detection; early intervention will prevent delays in speech and language development and have long-lasting beneficial effects on social and emotional development and quality of life. A hearing loss diagnosis is usually followed by a search for an underlying aetiology. Congenital hearing loss might be attributed to environmental and prenatal factors, which prevail in low-income settings; congenital infections, particularly cytomegalovirus, are also a common risk factor for hearing loss. Genetic causes probably account for the majority of cases in developed countries; mutations can affect any component of the hearing pathway, in particular inner ear homeostasis (endolymph production and maintenance) and mechano-electrical transduction (conversion of a mechanical stimulus into electrochemical activity). Once the underlying cause of hearing loss is established, it might direct therapeutic decision-making and guide prevention and (genetic) counseling. Management options include specific antimicrobial therapies, surgical treatment of cranio-facial abnormalities and hearing aids. An improved understanding of the pathophysiology and molecular mechanisms underlying hearing loss and increased awareness of recent advances in genetic testing will promote the development of new treatment and screening strategies. PMID:28079113

  6. [Clinical and MRI Findings in Patients with Congenital Anosmia].

    PubMed

    Ogawa, Takao; Kato, Tomohisa; Ono, Mayu; Shimizu, Takeshi

    2015-08-01

    The clinical characteristics of 16 patients with congenital anosmia were examined retrospectively. MRI (magnetic resonance imaging) was used to assess the morphological changes in the olfactory bulbs and olfactory sulci according to the method of P. Rombaux (2009). Congenital anosmia was divided into two forms: syndromic forms in association with a syndrome, and isolated forms without evidence of other defects. Only three patients (19%) in our series had syndromic forms of congenital anosmia, such as the Kallmann syndrome. Most cases (13 patients, 81%) had isolated congenital anosmia. Psychophysical testing of the olfactory function included T&T olfactometry and the intravenous Alinamin test, which are widely used in Japan. In T&T olfactometry, detection and recognition thresholds for the five odorants are used to assign a diagnostic category representing the level of olfactory function. Most cases (14 patients, 88%) showed off-scale results on T&T olfactometry, and the Alinamin test resulted in no response in all 11 patients who underwent the test. Abnormal MRI findings of the olfactory bulbs and sulci were detected in 15 of 16 patients (94%). Olfactory bulbs were bilaterally absent in nine patients (56%), and two patients (13%) had unilateral olfactory bulbs. Four patients (25%) had bilateral hypoplastic olfactory bulbs, and only one patient had normal olfactory bulbs (6%). The olfactory sulcus was unilaterally absent in one patient (6%), and nine patients (56%) had bilaterally hypoplastic olfactory sulci. Two patients (13%) had a unilateral normal olfactory sulcus and hypoplastic olfactory sulcus. Three patients (19%) had normal olfactory sulci. Quantitative analysis showed that the volume of olfactory bulbs varied from 0 mm3 to 63.5 mm3, with a mean volume of 10.20 ± 18 mm3, and the mean depth of the olfactory sulcus varied from 0 mm to 12.22 mm, with a mean length of 4.85 ± 4.1 mm. Currently, there is no effective treatment for congenital anosmia. However

  7. Early detection of congenital syphilis.

    PubMed

    Chowdhary, Nagalakshmi; Rani, Bs Kavya; Mukunda, K S; Kiran, N K

    2014-01-01

    Late congenital syphilis is a very rare clinical entity, and its early diagnosis and treatment is essential. Dental findings often provide valuable evidence for the diagnosis of late congenital syphilis. It occurs due to the transmission of the disease from an infected mother to her fetus through placenta. This long forgotten disease continues to effect pregnant women resulting in perinatal morbidity and mortality. Congenital syphilis is a preventable disease, and its presence reflects a failure of prenatal care delivery system, as well as syphilis control programs. We are reporting a case of late congenital syphilis with only Hutchinson's teeth.

  8. Genetics Home Reference: congenital hyperinsulinism

    MedlinePlus

    ... Hospital: Hyperinsulinism Center GeneReview: Familial Hyperinsulinism MedlinePlus Encyclopedia: Neonatal Hypoglycemia The Children's Hospital of Philadelphia: Congenital Hyperinsulinism Center ...

  9. Genetics Home Reference: congenital hepatic fibrosis

    MedlinePlus

    ... Home Health Conditions Congenital hepatic fibrosis Congenital hepatic fibrosis Printable PDF Open All Close All Enable Javascript ... view the expand/collapse boxes. Description Congenital hepatic fibrosis is a disease of the liver that is ...

  10. Neuroimaging findings of congenital Zika virus infection: a pictorial essay.

    PubMed

    Zare Mehrjardi, Mohammad; Poretti, Andrea; Huisman, Thierry A G M; Werner, Heron; Keshavarz, Elham; Araujo Júnior, Edward

    2017-03-01

    Zika virus (ZIKV) is a mosquito-borne arbovirus from the Flaviviridae family. It had caused several epidemics since its discovery in 1947, but there was no significant attention to this virus until the recent outbreak in Brazil in 2015. The main concern is the causal relationship between prenatal ZIKV infection and congenital microcephaly, which has been confirmed recently. Moreover, ZIKV may cause other central nervous system abnormalities such as brain parenchymal atrophy with secondary ventriculomegaly, intracranial calcification, malformations of cortical development (such as polymicrogyria, and lissencephaly-pachygyria), agenesis/hypoplasia of the corpus callosum, cerebellar and brainstem hypoplasia, sensorineural hearing-loss, and ocular abnormalities as well as arthrogryposis in the infected fetuses. Postnatal (acquired) ZIKV infection usually has an asymptomatic or mildly symptomatic course, while prenatal (congenital) ZIKV infection has a more severe course and may cause severe brain anomalies that are described as congenital Zika syndrome. In this pictorial essay, we aim to illustrate the prenatal and postnatal neuroimaging findings that may be seen in fetuses and neonates with congenital Zika syndrome, and will discuss possible radiological differential diagnoses. A detailed knowledge of these findings is paramount for an early correct diagnosis, prognosis determination, and counseling of the affected children and families.

  11. A new documentation system for congenital absent digits.

    PubMed

    Jones, Neil F; Kaplan, Jesse

    2012-12-01

    Congenital absent digits continue to be described by many confusing terms and are currently classified in categories I, V, and VI of the International Federation of Societies for Surgery of the Hand classification and seven subclassification systems. Very few classification systems provide any logical basis for surgical reconstruction. The purpose of this study was to develop a simple alphanumerical documentation system to reproducibly describe the morphological or radiographic appearance of congenital absent digits and facilitate communication of these childrens' hand anomalies from one hand surgeon to another. Dorsal and palmar photographs and PA radiographs of 235 hands in 204 children born with congenital absent digits over a 15-year period were analyzed to determine which digital rays were missing and their level of absence. Each hand can be described by three letters, R (radial), C (central), and U (ulnar), as well as numbers 1-5. The first letter and number designate which rays are missing and the second and third letters and numbers designate which rays remain present. There are 15 morphological phenotypes of congenital absent digits. The three most common phenotypes are U4R1 (a thumb but absence of all four fingers), R1U4 (absent thumb), and R5 (aplastic hand). This new documentation system allows hand surgeons to describe the simple morphological or radiographic appearance of congenital absent digits; incorporates all the previous subclassification systems that have attempted to describe congenital absent digits in radial, central, and ulnar deficiencies, symbrachydactyly, and congenital constriction ring syndrome; and has subsequently allowed the development of an algorithm which predicts whether conventional or microsurgical reconstruction is indicated for each specific phenotype.

  12. Clinical features and teratogenic mechanisms of congenital absence of digits.

    PubMed

    Ogino, Toshihiko

    2007-08-01

    To have a better understanding of classification of congenital hand anomalies, clinical features and teratogenic mechanisms of congenital absence of digits including ulnar and radial deficiencies, cleft hand, symbrachydactyly and constriction band were reviewed. There seemed to be four different teratogenic mechanisms of congenital absence of digits. Ulnar and radial deficiencies have the same clinical features and the cause of these deficiencies is closely related to a deficit of mesenchymal cells in the limb-bud due to impairment before the formation of the limb-bud. Cleft hand, central polydactyly and osseous syndactyly were induced by the same treatment at the same developmental stage in rats. Roentgenograms of the clinical cases and skeletal changes of the anomalies in rats appear to demonstrate that cleft hand formation proceeds from osseous syndactylies and central polydactylies. The teratogenic mechanism of a cleft hand seemed to be failure of induction of digital rays in the hand plate. The sequence of anomalies from brachysyndactyly, or the atypical cleft hand, to the congenital amputation, can be regarded as equivalent to the category of transverse deficiency that is bony dysplasia of the hand. Congenital constriction ring syndrome appears after the formation of the digital rays.

  13. [Advances in genetics of congenital malformation of external and middle ear].

    PubMed

    Wang, Dayong; Wang, Qiuju

    2013-05-01

    Congenital malformation of external and middle ear is a common disease in ENT department, and the incidence of this disease is second only to cleft lip and palate in the whole congenital malformations of the head and face. The external and middle ear malformations may occur separately, or as an important ear symptom of the systemic syndrome. We systematically review and analysis the genetic research progress of congenital malformation of external and middle ear, which would be helpful to understand the mechanism of external and middle ear development, and to provide clues for the further discovery of new virulence genes.

  14. Congenital Morgagni's hernia: a national multicenter study.

    PubMed

    Al-Salem, Ahmed H; Zamakhshary, Mohammed; Al Mohaidly, Mohammed; Al-Qahtani, Aayed; Abdulla, Mohamed Ramadan; Naga, Mohamed Ibrahim

    2014-04-01

    Congenital Morgagni'