[Analysis of an ophthalmic pathology cohort of human fetal eyes with regard to interesting findings].

PubMed

Herwig, M C; Müller, A M; Holz, F G; Loeffler, K U

2010-11-01

Information on the evaluation of prenatal ocular findings is sparse. This article provides an overview of the morphology in a cohort of human fetal eyes, with particular emphasis on interesting findings. The study investigated 216 eyes from 115 human fetuses. The majority of fetal eyes presented with a regular phenotype. Rarely, unexpected findings were discovered in fetuses with or without systemic malformations. Routine evaluation of fetal eyes reveals-albeit rarely-new aspects providing further knowledge and occasionally enabling the exact classification of syndromes.

Viewing condition dependence of the gaze-evoked nystagmus in Arnold Chiari type 1 malformation.

PubMed

Ghasia, Fatema F; Gulati, Deepak; Westbrook, Edward L; Shaikh, Aasef G

2014-04-15

Saccadic eye movements rapidly shift gaze to the target of interest. Once the eyes reach a given target, the brainstem ocular motor integrator utilizes feedback from various sources to assure steady gaze. One of such sources is cerebellum whose lesion can impair neural integration leading to gaze-evoked nystagmus. The gaze evoked nystagmus is characterized by drifts moving the eyes away from the target and a null position where the drifts are absent. The extent of impairment in the neural integration for two opposite eccentricities might determine the location of the null position. Eye in the orbit position might also determine the location of the null. We report this phenomenon in a patient with Arnold Chiari type 1 malformation who had intermittent esotropia and horizontal gaze-evoked nystagmus with a shift in the null position. During binocular viewing, the null was shifted to the right. During monocular viewing, when the eye under cover drifted nasally (secondary to the esotropia), the null of the gaze-evoked nystagmus reorganized toward the center. We speculate that the output of the neural integrator is altered from the bilateral conflicting eye in the orbit position secondary to the strabismus. This could possibly explain the reorganization of the location of the null position. Copyright © 2014 Elsevier B.V. All rights reserved.

RADIATION MALFORMATIONS BELONGING TO THE CYCLOPIA-ARRHINENCEPHALIA- OTECEPHALIA GROUP IN THE MOUSE FETUS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marakami, U.; Kameyana, Y.; Majima, A.

1962-03-01

Pregnant mice on the 8.5th day of gestation were subjected to 200-r whole-body irradiation and the fetuses were examined on the l3th to l9th day of gestation. Incidence of fetal death (23.0%) was much higher than in the controls (8.2%1, and malformations of the nose, eyes, and ears cecurred in 32%. These malformations included alterations leading to a beaklike snout (19%), a univentricular telencephalon with cyclopia (6%), and forms transitional between these two (6%). These malformations were specific for irradiation on the 8.5th day of gestation; in previous studies they were not prominent when irradiation was carried out on themore » 8th, lOth, or llth day. During this most sensitive developmental stsge at 8.5 days, 3 to 5 brain vesicles are formed and the anterior neuropore is closed, which may account for the greater effect of teratogenic agents on the central nervous system at this time. Other abnormalities included exencephalia 12%), hydrocephalus (4%), microcephalia 10.7%), abnormally shaped head (5%), spinal cord anomalies (6%), eye anomalies (29%1, harelip and cleft palate (12%), tail abnormalities (6%), and thoraco- abdominal hernia (5%). (H.H.D.)« less

RADIATION MALFORMATIONS BELONGING TO THE CYCLOPIA-ARRHINECEPHALIA- OCTOCEPHALIA GROUP IN THE MOUSE FETUS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Murakami, U.; Kameyama, Y.; Majima, A.

1962-03-01

Pregnant mice on the 8 1/2th day of gestation were subjected to 200 r whole-body irradiation and the fetuses were examined on the l3th to l9th day of gestation. Incidence of fetal death (23.0%) was much higher than in the controls (8.2%), and malformations of the nose, eyes, and ears occurred in 32%. These malformations included alterations leading to a beaklike snout (19%), a univentricular telencephalon with cyclopia (6%), and fomas transitional between these two (6%). These malformations were specific for irradiation on the 8 1/2th day of gestation. In previous studies they were not prominent when irradiation was carriedmore » out on the 8th, l0th, or llth day. During this most sensitive developmental stage at 8 1/2 days, 3 to 5 brain vesicles are formed and the anterior neuropore is closed, which may account for the greater effect of teratogenic agents on the central nervous system at this time. Other abnormalities included exencephalia (2%), hydrocephalus (4%), microcephalia (0.7%), abnormally shaped head (5%), spinal cord anomalies (6%), eye anomalies (29%), harelip and cleft palate (l2%), tail abnormalities (6%), and thoraco- abdominal hennia (5%). (H.H.D.)« less

Fetal eye movements on magnetic resonance imaging.

PubMed

Woitek, Ramona; Kasprian, Gregor; Lindner, Christian; Stuhr, Fritz; Weber, Michael; Schöpf, Veronika; Brugger, Peter C; Asenbaum, Ulrika; Furtner, Julia; Bettelheim, Dieter; Seidl, Rainer; Prayer, Daniela

2013-01-01

Eye movements are the physical expression of upper fetal brainstem function. Our aim was to identify and differentiate specific types of fetal eye movement patterns using dynamic MRI sequences. Their occurrence as well as the presence of conjugated eyeball motion and consistently parallel eyeball position was systematically analyzed. Dynamic SSFP sequences were acquired in 72 singleton fetuses (17-40 GW, three age groups [17-23 GW, 24-32 GW, 33-40 GW]). Fetal eye movements were evaluated according to a modified classification originally published by Birnholz (1981): Type 0: no eye movements; Type I: single transient deviations; Type Ia: fast deviation, slower reposition; Type Ib: fast deviation, fast reposition; Type II: single prolonged eye movements; Type III: complex sequences; and Type IV: nystagmoid. In 95.8% of fetuses, the evaluation of eye movements was possible using MRI, with a mean acquisition time of 70 seconds. Due to head motion, 4.2% of the fetuses and 20.1% of all dynamic SSFP sequences were excluded. Eye movements were observed in 45 fetuses (65.2%). Significant differences between the age groups were found for Type I (p = 0.03), Type Ia (p = 0.031), and Type IV eye movements (p = 0.033). Consistently parallel bulbs were found in 27.3-45%. In human fetuses, different eye movement patterns can be identified and described by MRI in utero. In addition to the originally classified eye movement patterns, a novel subtype has been observed, which apparently characterizes an important step in fetal brainstem development. We evaluated, for the first time, eyeball position in fetuses. Ultimately, the assessment of fetal eye movements by MRI yields the potential to identify early signs of brainstem dysfunction, as encountered in brain malformations such as Chiari II or molar tooth malformations.

The Arnold-Chiari Malformation and Its Implications for Individuals with Spina Bifida and Hydrocephalus.

ERIC Educational Resources Information Center

Mittler, Joel E.

1986-01-01

The Arnold-Chiari malformation is present in most infants born with myelomeningocele (a form of spina bifida) and hydrocephalus. The syndrome is responsible for structural abnormalities in the brain, and peripheral nervous system. Etiology, symptoms, impact on central nervous system structures, surgical treatment, and implications for education…

The Cerebellar Dysplasia of Chiari II Malformation as Revealed by Eye Movements

PubMed Central

Salman, Michael S.; Dennis, Maureen; Sharpe, James A.

2011-01-01

Introduction Chiari type II malformation (CII) is a developmental deformity of the hindbrain. We have previously reported that many patients with CII have impaired smooth pursuit, while few make inaccurate saccades or have an abnormal vestibulo-ocular reflex. In contrast, saccadic adaptation and visual fixation are normal. In this report, we correlate results from several eye movement studies with neuroimaging in CII. We present a model for structural changes within the cerebellum in CII. Methods Saccades, smooth pursuit, the vestibulo-ocular reflex, and visual fixation were recorded in 21 patients with CII, aged 8–19 years and 39 age-matched controls, using an infrared eye tracker. Qualitative and quantitative MRI data were correlated with eye movements in 19 CII patients and 28 controls. Results Nine patients with CII had abnormal eye movements. Smooth pursuit gain was subnormal in eight, saccadic accuracy abnormal in four, and vestibulo-ocular reflex gain abnormal in three. None had fixation instability. Patients with CII had a significantly smaller cerebellar volume than controls, and those with normal eye motion had an expanded midsagittal vermis compared to controls. However, patients with abnormal eye movements had a smaller (non-expanded) midsagittal vermis area, posterior fossa area and medial cerebellar volumes than CII patients with normal eye movements. Conclusions The deformity of CII affects the structure and function of the cerebellum selectively and differently in those with abnormal eye movements. We propose that the vermis can expand when compressed within a small posterior fossa in some CII patients, thus sparing its ocular motor functions. PMID:19960749

Chiari Type I Malformations in Young Adults: Implications for the College Health Practitioner

ERIC Educational Resources Information Center

Elam, Mary Jane; Vaughn, John A.

2011-01-01

In this article, the authors describe 2 cases of Chiari type I malformation (CM-I) in students presenting to a college health center within a 6-month period. A review of CM-I, including epidemiology, typical presentation, evaluation, and management, is followed by a discussion of the clinical and functional implications of the disorder in an…

[Associated brachial cleft anomalies in the cat eye syndrome].

PubMed

Avior, Galit; Derowe, Ari; Fliss, Dan M; Leicear-Trejo, Leonor; Braverman, Itzhak

2007-02-01

The cat eye syndrome is a congenital malformation usually associated with anal atresia, ocular coloboma, downward slanting eyes, microphthalmia, hypertelorism, strabismus, preauricular tags or fistulas, congenital heart defect particularly septal defect, urinary tract abnormalities, skeletal anomalies and frequently mental and physical retardation. A small supernumerary chromosome (smaller than chromosome 21) is present, frequently has 2 centromeres, is bisatellited and represents an inv dup 22 (q11). A two years old female presented to our department with an association of cat eye syndrome with preauricular tags and a first branchial arch anomaly. This article discusses the surgical management and the association between the cat eye syndrome and first branchial cleft anomaly.

Deletion of a conserved regulatory element required for Hmx1 expression in craniofacial mesenchyme in the dumbo rat: a newly identified cause of congenital ear malformation

PubMed Central

Quina, Lely A.; Kuramoto, Takashi; Luquetti, Daniela V.; Cox, Timothy C.; Serikawa, Tadao; Turner, Eric E.

2012-01-01

SUMMARY Hmx1 is a homeodomain transcription factor expressed in the developing eye, peripheral ganglia, and branchial arches of avian and mammalian embryos. Recent studies have identified a loss-of-function allele at the HMX1 locus as the causative mutation in the oculo-auricular syndrome (OAS) in humans, characterized by ear and eye malformations. The mouse dumbo (dmbo) mutation, with similar effects on ear and eye development, also results from a loss-of-function mutation in the Hmx1 gene. A recessive dmbo mutation causing ear malformation in rats has been mapped to the chromosomal region containing the Hmx1 gene, but the nature of the causative allele is unknown. Here we show that dumbo rats and mice exhibit similar neonatal ear and eye phenotypes. In midgestation embryos, dumbo rats show a specific loss of Hmx1 expression in neural-crest-derived craniofacial mesenchyme (CM), whereas Hmx1 is expressed normally in retinal progenitors, sensory ganglia and in CM, which is derived from mesoderm. High-throughput resequencing of 1 Mb of rat chromosome 14 from dmbo/dmbo rats, encompassing the Hmx1 locus, reveals numerous divergences from the rat genomic reference sequence, but no coding changes in Hmx1. Fine genetic mapping narrows the dmbo critical region to an interval of ∼410 kb immediately downstream of the Hmx1 transcription unit. Further sequence analysis of this region reveals a 5777-bp deletion located ∼80 kb downstream in dmbo/dmbo rats that is not apparent in 137 other rat strains. The dmbo deletion region contains a highly conserved domain of ∼500 bp, which is a candidate distal enhancer and which exhibits a similar relationship to Hmx genes in all vertebrate species for which data are available. We conclude that the rat dumbo phenotype is likely to result from loss of function of an ultraconserved enhancer specifically regulating Hmx1 expression in neural-crest-derived CM. Dysregulation of Hmx1 expression is thus a candidate mechanism for congenital ear malformation, most cases of which remain unexplained. PMID:22736458

Genes relacionados con microftalmia y anoftalmia hereditarias.

PubMed

Matías-Pérez, Diana; García-Montalvo, Iván Antonio; Zenteno, Juan Carlos

2017-01-01

Congenital eye malformations are the second most common cause of childhood blindness and are originated by disruption of the normal process of eye development during embryonic stage. Their etiology is variable, although monogenic causes are of great importance as they have a high risk of familial recurrence. Included among the most severe congenital eye abnormalities are microphthalmia, defined by an abnormally small eye, and anophthalmia, characterized by congenital absence of ocular structures. The currrent knowledge of the genes involved in human microphthalmia and anophthalmia in humans is revised in this work. Copyright: © 2017 SecretarÍa de Salud.

Fetal Eye Movements on Magnetic Resonance Imaging

PubMed Central

Woitek, Ramona; Kasprian, Gregor; Lindner, Christian; Stuhr, Fritz; Weber, Michael; Schöpf, Veronika; Brugger, Peter C.; Asenbaum, Ulrika; Furtner, Julia; Bettelheim, Dieter; Seidl, Rainer; Prayer, Daniela

2013-01-01

Objectives Eye movements are the physical expression of upper fetal brainstem function. Our aim was to identify and differentiate specific types of fetal eye movement patterns using dynamic MRI sequences. Their occurrence as well as the presence of conjugated eyeball motion and consistently parallel eyeball position was systematically analyzed. Methods Dynamic SSFP sequences were acquired in 72 singleton fetuses (17–40 GW, three age groups [17–23 GW, 24–32 GW, 33–40 GW]). Fetal eye movements were evaluated according to a modified classification originally published by Birnholz (1981): Type 0: no eye movements; Type I: single transient deviations; Type Ia: fast deviation, slower reposition; Type Ib: fast deviation, fast reposition; Type II: single prolonged eye movements; Type III: complex sequences; and Type IV: nystagmoid. Results In 95.8% of fetuses, the evaluation of eye movements was possible using MRI, with a mean acquisition time of 70 seconds. Due to head motion, 4.2% of the fetuses and 20.1% of all dynamic SSFP sequences were excluded. Eye movements were observed in 45 fetuses (65.2%). Significant differences between the age groups were found for Type I (p = 0.03), Type Ia (p = 0.031), and Type IV eye movements (p = 0.033). Consistently parallel bulbs were found in 27.3–45%. Conclusions In human fetuses, different eye movement patterns can be identified and described by MRI in utero. In addition to the originally classified eye movement patterns, a novel subtype has been observed, which apparently characterizes an important step in fetal brainstem development. We evaluated, for the first time, eyeball position in fetuses. Ultimately, the assessment of fetal eye movements by MRI yields the potential to identify early signs of brainstem dysfunction, as encountered in brain malformations such as Chiari II or molar tooth malformations. PMID:24194885

PHACE syndrome misdiagnosed as a port-wine stain

PubMed Central

Thomson, Jason; Greig, Aina; Lloyd, Claire; Morrison, Danny; Flohr, Carsten

2015-01-01

We present the case of a boy born with a large macular, segmental vascular anomaly over the left face, initially diagnosed as a capillary malformation (port-wine stain) by the postnatal paediatric team. The vascular anomaly in the face then grew rapidly during the first few weeks of life and started to occlude the left eye, causing parental concerns about the infant's vision. A dermatological opinion established that the lesion was a segmental infantile haemangioma (IH). This, in combination with the posterior fossa malformation previously detected on antenatal scanning and confirmed by an MRI postnatally, satisfied the criteria for Posterior fossa abnormalities, Haemangiomas, Arterial abnormalities, Cardiac abnormalities and Eye abnormalities (PHACE) syndrome: a rare cutaneous neurovascular syndrome. This case highlights the diagnostic challenge posed by early phenotypes of haemangiomas as well as the importance of correctly diagnosing PHACE syndrome. PMID:26177999

In vitro storage of unfertilized eggs of the Eurasian perch and its effect on egg viability rates and the occurrence of larval malformations.

PubMed

Samarin, A M; Żarski, D; Palińska-Żarska, K; Krejszeff, S; Blecha, M; Kucharczyk, D; Policar, T

2017-01-01

Ova ageing is the most important factor affecting fish egg quality after ovulation. Long-term storage of fish ova, using cryopreservation and vitrification techniques, has been unsuccessful to date. Instead, short-term in vitro ova storage has been used successfully and optimized in some cultured fish species. In vitro ova storage can drastically improve mass production of larvae and juveniles in the hatcheries by providing the possibility of the synchronous artificial fertilization for different females. To study how long unfertilized eggs of Eurasian perch (Perca fluviatilis L.) can retain their fertilizing ability after stripping, eggs were stored at temperatures of 4°C, 8°C and 12°C for 72 h post-stripping (HPS). The stored eggs of four female perch were separately fertilized at 0 h (i.e. control eggs fertilized before storage) and at 6-hour intervals during the experimental period of 72 h. The embryos reaching the eyed-egg and hatched-larvae stages, eyed-egg mortality and larval malformation rates were recorded as indices of egg quality. The results indicated that the maximum eyed eggs and hatched larvae (86% and 63%, respectively) were observed for eggs fertilized immediately after stripping, whereas the storage of the eggs at 4°C for 48 HPS decreased the eyed-egg and hatched-larvae rates to 46% and 17%, respectively. The use of a higher storage temperature resulted in a more rapid decrease in egg viability: eyed-egg and hatched-larvae rates of 23% and 9%, respectively, were obtained after 48 HPS storage at 8°C and 2% and 1% for eggs stored at 12°C. Eyed-egg mortality and larval malformation rates were not significantly affected by post-stripping ova ageing for at least up to 36 h. Thereafter, both values increased significantly and were measured to be the highest in the most aged ova. The present study demonstrated that stripped Eurasian perch eggs can be stored for at least 12 h at 4°C to 12°C without a significant reduction in their quality.

Familial Aggregation of Chiari Malformation: Presentation, Pedigree, and Review of the Literature.

PubMed

Nagy, Laszlo; Mobley, James; Ray, Coby

2016-01-01

This article reports the largest familial aggregation of Chiari malformation in a single family to date as reported in the literature. This study is a retrospective case series of a family of whom five individuals have a confirmed case of Chiari malformation and three additional individuals have Chiari signs and symptoms. This contribution further supports the implication of genetics in the transmission of Chiari malformation. The family reported in this study also has a significant incidence of Ehlers-Danlos. Three sisters, including a set of twins, presented with confirmed cases of Chiari malformation and four of the five children of the twin sisters presented with confirmed or suspected Chiari malformation. Of note, the non-twin sister has three children who are unaffected. This report provides further evidence for a shared loci between the Chiari malformation and Ehlers-Danlos.

Highly variable penetrance of abnormal phenotypes in embryonic lethal knockout mice

PubMed Central

Wilson, Robert; Geyer, Stefan H.; Reissig, Lukas; Rose, Julia; Szumska, Dorota; Hardman, Emily; Prin, Fabrice; McGuire, Christina; Ramirez-Solis, Ramiro; White, Jacqui; Galli, Antonella; Tudor, Catherine; Tuck, Elizabeth; Mazzeo, Cecilia Icoresi; Smith, James C.; Robertson, Elizabeth; Adams, David J.; Mohun, Timothy; Weninger, Wolfgang J.

2017-01-01

Background: Identifying genes that are essential for mouse embryonic development and survival through term is a powerful and unbiased way to discover possible genetic determinants of human developmental disorders. Characterising the changes in mouse embryos that result from ablation of lethal genes is a necessary first step towards uncovering their role in normal embryonic development and establishing any correlates amongst human congenital abnormalities. Methods: Here we present results gathered to date in the Deciphering the Mechanisms of Developmental Disorders (DMDD) programme, cataloguing the morphological defects identified from comprehensive imaging of 220 homozygous mutant and 114 wild type embryos from 42 lethal and subviable lines, analysed at E14.5. Results: Virtually all mutant embryos show multiple abnormal phenotypes and amongst the 42 lines these affect most organ systems. Within each mutant line, the phenotypes of individual embryos form distinct but overlapping sets. Subcutaneous edema, malformations of the heart or great vessels, abnormalities in forebrain morphology and the musculature of the eyes are all prevalent phenotypes, as is loss or abnormal size of the hypoglossal nerve. Conclusions: Overall, the most striking finding is that no matter how profound the malformation, each phenotype shows highly variable penetrance within a mutant line. These findings have challenging implications for efforts to identify human disease correlates. PMID:27996060

PHACE syndrome misdiagnosed as a port-wine stain.

PubMed

Thomson, Jason; Greig, Aina; Lloyd, Claire; Morrison, Danny; Flohr, Carsten

2015-07-15

We present the case of a boy born with a large macular, segmental vascular anomaly over the left face, initially diagnosed as a capillary malformation (port-wine stain) by the postnatal paediatric team. The vascular anomaly in the face then grew rapidly during the first few weeks of life and started to occlude the left eye, causing parental concerns about the infant's vision. A dermatological opinion established that the lesion was a segmental infantile haemangioma (IH). This, in combination with the posterior fossa malformation previously detected on antenatal scanning and confirmed by an MRI postnatally, satisfied the criteria for Posterior fossa abnormalities, Haemangiomas, Arterial abnormalities, Cardiac abnormalities and Eye abnormalities (PHACE) syndrome: a rare cutaneous neurovascular syndrome. This case highlights the diagnostic challenge posed by early phenotypes of haemangiomas as well as the importance of correctly diagnosing PHACE syndrome. 2015 BMJ Publishing Group Ltd.

22.5 MB DELETION OF 13q31.1-q34 ASSOCIATED WITH HPE, DWM, AND HSCR: A CASE REPORT AND REDEFINING THE SMALLEST DELETED REGIONS.

PubMed

Alp, M Y; Çebi, A H; Seyhan, S; Cansu, A; Aydin, H; Ikbal, M

2016-01-01

Partial deletion of the long arm of the chromosome 13, 13q deletion syndrome is a rare chromosomal disorder characterized by severe growth and mental retardation, microcephaly, facial dysmorphism, brain malformations (holoprosencephaly, Dandy-Walker malformation), distal limb defects, eye anomalies, genitourinary and gastrointestinal tract malformations (Hirschsprung's disease). Approximately 1.2 Mb region in 13q32 was suggested as minimal critical region which is responsible for severe mental and growth retardation and brain anomalies. Here we described a male patient with de novo interstitial deletion of 13q31.1-q34 associated with short stature, microcephaly, facial dysmorphism, clinodactyly, cryptorchidism, micropenis, epilepsy, HPE, DWM, and HSCR. According to the literature review, present case indicated that smallest deleted region associated with DWM and HPE might be located at the 13q32.3, limb defects 13q34, anogenital malformations 13q33.3-34, and HSCR 13q31.1-32.1.

Field surveys of Midwestern and Northeastern Fish and Wildlife Service lands for the presence of abnormal frogs and toads

USGS Publications Warehouse

Converse, K.A.; Mattsson, J.; Eaton-Poole, L.

2000-01-01

The national distribution of information on the discovery of malformations in Minnesota frogs in 1995 stimulated collection and examination of newly metamorphosed frogs during 1996. By late summer and early fall of 1996, malformed frogs and toads were reported on U.S. Fish and Wildlife Service (USFWS) lands in Vermont (Northeast, Region 5) and Minnesota (Midwest, Region 3). In response to these reports, biologists in USFWS Regions 3 and 5 conducted a survey, during the summer of 1997 to determine the distribution and type of malformations in frogs and toads on selected federal lands. Region 3 personnel surveyed 38 field stations at National Wildlife Refuges (NWR's) and Wetland Management Districts. Malformed frogs and toads were collected at 23 (61%) of the Region 3 sites. External malformations were detected in 110 of 6632 individuals representing seven of 13 frog species and one of three toad species examined for an overall of 1.7% affected (percentages for affected species ranged from 0.4-5.2%). In Region 5, 17 NWR's and one National Park were surveyed. Malformed frogs were collected at 10 (56%) of the Region 5 sites. External malformations were detected in 58 of 2267 individuals representing six of 11 frog species and one of two toad species examined for an overall total of 2.6% affected (percentages for affected species ranged from 1.8-15.6%). The majority of malformations observed in frogs and toads collected in Regions 3 and 5 were partially or completely missing hind limbs and digits (50%)or malformed hind limbs and digits (14%). A few individuals had an extra limb or toe, missing or malformed front limb, missing eye, or malformation of the mandible. Despite small sample sizes at some sites, malformations were confirmed to be present in eight species of frogs and two species of toads on Federal lands in USFWS Regions 3 and 5. Further study is needed to determine the extent and distribution of amphibian malformations in these Regions. Data from this study were provided to the national database on distribution of malformed amphibians.

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.

Congenital malformations associated with assisted reproductive technology: a California statewide analysis.

PubMed

Kelley-Quon, Lorraine I; Tseng, Chi-Hong; Janzen, Carla; Shew, Stephen B

2013-06-01

Management of congenital malformations comprises a large part of pediatric surgical care. Despite increasing utilization of assisted reproductive technology (ART) and fertility-related services (FRS), associations with birth defects are poorly understood. Infants born after ART or FRS were identified from the California Linked Birth Cohort Dataset from 2006 to 2007 and compared to propensity matched infants conceived naturally. Factors associated with major congenital malformations were evaluated using Firth logistic regression. With a cohort of 4,795 infants born after ART and 46,025 naturally conceived matched controls, major congenital malformations were identified in 3,463 infants. Malformations were increased for ART infants (9.0% vs. 6.6%, p<0.001). After adjusting for infant and maternal factors, ART infants exhibited increased odds of major malformations overall (OR 1.25, 95% CI 1.12-1.39), specifically defects of the eye (OR 1.81, 95% CI 1.04-3.16), head and neck (OR 1.37, 95% CI 1.00-1.86), heart (OR 1.41, 95% CI 1.22-1.64), and genitourinary system (OR 1.40, 95% CI 1.09-1.82). The likelihood of birth defects was increased for multiples (OR 1.35, 95% CI 1.18-1.54) and not singletons. Odds of congenital malformation after FRS alone (n=1,749) were non-significant. ART contributes a significant risk of congenital malformation and may be more pronounced for multiples. Accurate counseling for parents considering ART and multidisciplinary coordination of care prior to delivery are warranted. Copyright © 2013 Elsevier Inc. All rights reserved.

Unilateral microphthalmia or anophthalmia in eight pythons (Pythonidae).

PubMed

Da Silva, Mari-Ann O; Bertelsen, Mads F; Wang, Tobias; Pedersen, Michael; Lauridsen, Henrik; Heegaard, Steffen

2015-01-01

To provide morphological descriptions of microphthalmia or anophthalmia in eight pythons using microcomputerized tomography (μCT), magnetic resonance imaging (MRI), and histopathology. Seven Burmese pythons (Python bivittatus) and one ball python (P. regius) with clinically normal right eyes and an abnormal or missing left eye. At the time of euthanasia, four of the eight snakes underwent necropsy. Hereafter, the heads of two Burmese pythons and one ball python were examined using μCT, and another Burmese python was subjected to MRI. Following these procedures, the heads of these four pythons along with the heads of an additional three Burmese pythons were prepared for histology. All eight snakes had left ocular openings seen as dermal invaginations between 0.2 and 2.0 mm in diameter. They also had varying degrees of malformations of the orbital bones and a limited presence of nervous, glandular, and muscle tissue in the posterior orbit. Two individuals had small but identifiable eyes. Furthermore, remnants of the pigmented embryonic framework of the hyaloid vessels were found in the anophthalmic snakes. Necropsies revealed no other macroscopic anomalies. Eight pythons with unilateral left-sided microphthalmia or anophthalmia had one normal eye and a left orbit with malformed or incompletely developed ocular structures along with remnants of fetal structures. These cases lend further information to a condition that is often seen in snakes, but infrequently described. © 2014 American College of Veterinary Ophthalmologists.

PROBABILISTIC RISK ASSESSMENT FOR THE EFFECTS OF SOLAR ULTRAVIOLET RADIATION ON AMPHIBIANS

EPA Science Inventory

Several studies have demonstrated that exposure to solar ultraviolet (UV) radiation can cause elevated mortality and an increased prevalence of eye and limb malformations in developing amphibian larvae. From these observations scientists have hypothesized that recent increases in...

The molecular genetics of holoprosencephaly

PubMed Central

Roessler, Erich; Muenke, Maximilian

2009-01-01

Holoprosencephaly (or HPE) has captivated the imagination of Man for millennia because its most extreme manifestation, the single-eyed cyclopic newborn infant, brings to mind the fantastical creature Cyclops from Greek mythology. Attempting to understand this common malformation of the forebrain in modern medical terms requires a systematic synthesis of genetic, cytogenetic and environmental information typical for studies of a complex disorder. However, even with the advances in our understanding of HPE in recent years, there are significant obstacles remaining to fully understand its heterogeneity and extensive variability in phenotype. General lessons learned from HPE will likely be applicable to other malformation syndromes. Here we outline the common, and rare, genetic and environmental influences on this conserved developmental program of forebrain development and illustrate the similarities and differences between these malformations in humans and those of animal models. PMID:20104595

The molecular genetics of holoprosencephaly.

PubMed

Roessler, Erich; Muenke, Maximilian

2010-02-15

Holoprosencephaly (HPE) has captivated the imagination of Man for millennia because its most extreme manifestation, the single-eyed cyclopic newborn infant, brings to mind the fantastical creature Cyclops from Greek mythology. Attempting to understand this common malformation of the forebrain in modern medical terms requires a systematic synthesis of genetic, cytogenetic, and environmental information typical for studies of a complex disorder. However, even with the advances in our understanding of HPE in recent years, there are significant obstacles remaining to fully understand its heterogeneity and extensive variability in phenotype. General lessons learned from HPE will likely be applicable to other malformation syndromes. Here we outline the common, and rare, genetic and environmental influences on this conserved developmental program of forebrain development and illustrate the similarities and differences between these malformations in humans and those of animal models. 2010 Wiley-Liss, Inc.

Chiari I malformation presenting as downbeat nystagmus: clinical presentation, diagnosis, and management.

PubMed

Goodwin, Denise; Halvorson, Ami R

2012-02-15

Chiari I malformation is a congenital, neurological condition that is characterized by defects of the skull base resulting in herniation of the cerebellum through the foramen magnum into the cervical spinal canal. Because the condition can result in visual symptoms, patients will often search for answers from their eye care providers; A 28-year-old Hispanic diabetic male with a 10-year history of nystagmus was referred to the neuro-ophthalmic disease clinic following the initiation of oscillopsia 1 year previous. Downbeat nystagmus, which worsened in right and down gaze, was evident. Cranial nerve testing was unremarkable, but the patient did report trouble with choking on food and drink. Neuroimaging revealed Chiari I malformation. The patient underwent a suboccipital craniectomy which resulted in lessened nystagmus and improved symptoms; The majority of patients with Chiari I malformation have an onset of symptoms in the second or third decade of life. Most commonly, a suboccipital headache that worsens with Valsalva maneuver is present. Visual symptoms include retro-orbital pain, flashing lights or floaters, blurred vision, photophobia, diplopia, transient vision loss, and peripheral vision loss. Objective evidence is often lacking in these patients; however, horizontal or vertical nystagmus is present in up to 45% of those with Chiari I malformation. Surgery has proven to be an effective and safe method to treat symptomatic Chiari I malformation. American Optometric Association.

Neurotransmitter signaling pathways required for normal development in Xenopus laevis embryos: a pharmacological survey screen

PubMed Central

Sullivan, Kelly G.; Levin, Michael

2016-01-01

Neurotransmitters are not only involved in brain function but are also important signaling molecules for many diverse cell types. Neurotransmitters are widely conserved, from evolutionarily ancient organisms lacking nervous systems through man. Here, we report results from a loss- and gain-of-function survey, using pharmacologic modulators of several neurotransmitter pathways to examine possible roles in normal embryogenesis. Applying reagents targeting the glutamatergic, adrenergic, and dopaminergic pathways to embryos of Xenopus laevis from gastrulation to organogenesis stages, we observed and quantified numerous malformations including craniofacial defects, hyperpigmentation, muscle mispatterning, and miscoiling of the gut. These data implicate several key neurotransmitters in new embryonic patterning roles, reveal novel earlier stages for processes involved in eye development, suggest new targets for subsequent molecular-genetic investigation, and highlight the necessity for in-depth toxicology studies of psychoactive compounds to which human embryos might be exposed during pregnancy. PMID:27060969

RISK ASSESSMENT FOR THE EFFECTS OF SOLAR RADIATION ON AMPHIBIANS

EPA Science Inventory

Recent studies have demonstrated that exposure to solar ultraviolet radiation (UVR) can cause mortality and increase the occurrence of eye and limb malformation in some species of amphibians. Based on these reports and various field observations, it has been hypothesized that UV...

Anophthalmia-plus syndrome with unusual findings. A clinical report and review of the literature.

PubMed

Cayir, A; Tasdemir, S; Eroz, R; Yuce, I; Orbak, Z; Tatar, A

2013-01-01

We present a male child at 3 years old with Anophthalmia-Plus Syndrome (APS). He has asymmetry of the face and head, left choanal atresia, a sunken facial appearance, microphthalmia in the right eye, severe microphthalmia in the left eye, bilateral low-set ears, scarring from cleft palate surgery. Magnetic resonance imaging (MRI) sections revealed decreased right globe volume, an undeveloped left globe, decreased left optical nerve thickness, Chiari type 2 malformation, left choanal atresia and cleft palate. Echocardiography and abdominal ultrasonography were normal. The patient has a 45 dB conductive hearing loss in the left ear. Repeated thyroid function tests were evaluated as compatible with central hypothyroidism. We report a Fryns Anophthalmia-Plus Syndrome in a child with unusual findings including central hypothyroidism, chiari type 2 malformation, conductive hearing loss and developmental regression. Summary of the features reported in the present case and all 14 previous cases that might be defined as APS.

Clinical and molecular features of Joubert syndrome and related disorders

PubMed Central

Parisi, Melissa A.

2009-01-01

Joubert syndrome (JBTS; OMIM 213300) is a rare, autosomal recessive disorder characterized by a specific congenital malformation of the hindbrain and a broad spectrum of other phenotypic findings that is now known to be caused by defects in the structure and/or function of the primary cilium. The complex hindbrain malformation that is characteristic of JBTS can be identified on axial magnetic resonance imaging and is known as the molar tooth sign (MTS); other diagnostic criteria include intellectual disability, hypotonia, and often, abnormal respiratory pattern and/or abnormal eye movements. In addition, a broad spectrum of other anomalies characterize Joubert syndrome and related disorders (JSRD), and may include retinal dystrophy, ocular coloboma, oral frenulae and tongue tumors, polydactyly, cystic renal disease (including cystic dysplasia or juvenile nephronophthisis), and congenital hepatic fibrosis. The clinical course can be variable, but most children with this condition survive infancy to reach adulthood. At least 8 genes cause JSRD, with some genotype-phenotype correlations emerging, including the association between mutations in the MKS3 gene and hepatic fibrosis characteristic of the JSRD subtype known as COACH syndrome. Several of the causative genes for JSRD are implicated in other ciliary disorders, such as juvenile nephronophthisis and Meckel syndrome, illustrating the close association between these conditions and their overlapping clinical features that reflect a shared etiology involving the primary cilium. PMID:19876931

Assessment of Diiodoacetic Effects on Eye Malformations in a Developmental Toxicity Screen with F344 Rats

EPA Science Inventory

Diiodoacetic acid (DIA) is an iodinated haloacetic acid and a drinking water disinfection by-product (DBP) formed in drinking water treated by chloramination (chlorine plus ammonia) to prevent microbial contamination and regrowth. Although disinfection of drinking water has prove...

Congenital Arteriovenous Malformation of the Scalp Involving the Orbit.

PubMed

Feletti, Alberto; Dimitriadis, Stavros; Vallone, Stefano; Pavesi, Giacomo

2018-06-15

 Arteriovenous malformations (AVMs) of the scalp are rare and infrequently encountered by the neurosurgeon.  We report a unique case of a 42-year-old patient who presented with a progressive worsening of visual acuity in the right eye (lower quadrantanopia) and palpebral ptosis. Physical examination revealed a right exophthalmos and a right frontoparietal scalp soft swelling when the patient was in the supine position. Neurologic work-up showed a scalp AVM extending into the orbit and connected to an intraorbital cavernous angioma. The patient was treated with a frontotemporal craniotomy and decompression of the orbit.  In the rare case of intraorbital extension of a scalp AVM, neurologic symptoms may appear when the size of the vascular malformation increases with age. The aims of surgery should be decompression of the orbit and aesthetic preservation, rather than complete excision. A review of the literature is also provided. Georg Thieme Verlag KG Stuttgart · New York.

Mimosa tenuiflora as a cause of malformations in ruminants in the northeastern Brazilian semiarid rangelands.

PubMed

Pimentel, L A; Correa, F Riet; Gardner, D; Panter, K E; Dantas, A F M; Medeiros, R M T; Mota, R A; Araújo, J A S

2007-11-01

Craniofacial anomalies, eye malformations, and permanent flexures of the forelimbs are common malformations seen in ruminants grazing semiarid rangelands of Northeastern Brazil. To investigate the cause of these malformations, we fed 2 suspected plants, Mimosa tenuiflora or Prosopis juliflora, to groups of 4 pregnant goats each. Fresh green M. tenuiflora was collected daily and fed ad libitum to 4 goats in group 1 throughout pregnancy. This treatment group also received a supplemental feed concentrate equivalent to 1% body weight. Four goats in group 2 received a ration with 70% of P. juliflora pods and 30% hay throughout pregnancy. Four control goats were fed supplemental feed concentrate (1% body weight) and hay ad libitum throughout pregnancy. Goats treated with P. juliflora pods and the control goats delivered 9 normal kids. The four goats that were fed M. tenuiflora during pregnancy delivered 4 kids, 3 of which had abnormalities similar to those observed in field cases, including cleft lip, unilateral corneal opacity, ocular bilateral dermoids, buphthalmos with a cloudy brownish appearance of the anterior chamber due to an iridal cyst, and segmental stenosis of the colon. Malformations induced experimentally by M. tenuiflora were similar to those observed in field cases, suggesting that M. tenuiflora is a cause of the field cases observed in the Brazilian semiarid rangelands.

Pregnancy loss and eye malformations in offspring of F344 rats following gestational exposure to mixtures of regulated trihalomethanes and haloacetic acids

EPA Science Inventory

Chlorination of drinking water results in the formation of hundreds of disinfection byproducts (DBPs), the most prevalent are trihalomethanes (THMs) and haloacetic acids (HAAs). Four THMs (chloroform, bromodichloromethane, chlorodibromomethane, bromoform) and five HAAs (chloroac...

Prenatal Diagnosis of a Case of Norrie Disease with Late Development of Bilateral Ocular Malformation.

PubMed

Wu, Li Hong; Chen, Li-Hong; Xie, Hongning; Xie, Ying-Jun

2017-06-01

We report a case of Norrie disease, diagnosed by prenatal ultrasound, confirmed by Sanger sequencing of the DNP gene from the aborted fetal cord blood and histologically. Prenatal ultrasound revealed no abnormality in either eye at 22 +1 and 31 +4 gestational weeks, but at 36 +5 gestational weeks both eyes had massive vitreous cavity opacities with complete retinal detachment. Norrie disease was initially suspected because of an older male sibling with the disease. To our knowledge, prenatal ultrasound diagnosis of Norrie disease has been previously described only one case in 1993 in a 34-week-old fetus. The normal eye development until after 31 + 4 gestational weeks provides insight into the first manifestation and then the rapid progression of the eye disease.

Achondroplasia and Macular Coloboma.

PubMed

Ahoor, M H; Amizadeh, Y; Sorkhabi, R

2015-01-01

Achondroplasia is an autosomal dominant congenital disorder of enchondral ossification. It is clinically characterized by low stature, craniofacial deformity, and vertebral malformation. Associated ophthalmic features include telecanthus, exotropia, angle anomalies, and cone-rod dystrophy. A 24-year-old male presented with decreased vision bilaterally and typical achondroplasia. The best corrected visual acuity was 20/70 in both eyes. Anterior segment examination was normal. Fundus examination revealed a well-demarcated circular paramacular lesion in both eyes. As macular coloboma and achondroplasia are developmental disorders, the funduscopic examination is required in patients with achondroplasia.

Achondroplasia and Macular Coloboma

PubMed Central

Ahoor, M. H.; Amizadeh, Y.; Sorkhabi, R.

2015-01-01

Achondroplasia is an autosomal dominant congenital disorder of enchondral ossification. It is clinically characterized by low stature, craniofacial deformity, and vertebral malformation. Associated ophthalmic features include telecanthus, exotropia, angle anomalies, and cone-rod dystrophy. A 24-year-old male presented with decreased vision bilaterally and typical achondroplasia. The best corrected visual acuity was 20/70 in both eyes. Anterior segment examination was normal. Fundus examination revealed a well-demarcated circular paramacular lesion in both eyes. As macular coloboma and achondroplasia are developmental disorders, the funduscopic examination is required in patients with achondroplasia. PMID:26692730

SOX2 anophthalmia syndrome: 12 new cases demonstrating broader phenotype and high frequency of large gene deletions.

PubMed

Bakrania, P; Robinson, D O; Bunyan, D J; Salt, A; Martin, A; Crolla, J A; Wyatt, A; Fielder, A; Ainsworth, J; Moore, A; Read, S; Uddin, J; Laws, D; Pascuel-Salcedo, D; Ayuso, C; Allen, L; Collin, J R O; Ragge, N K

2007-11-01

Developmental eye anomalies, which include anophthalmia (absent eye) or microphthalmia (small eye) are an important cause of severe visual impairment in infants and young children. Heterozygous mutations in SOX2, a SOX1B-HMG box transcription factor, have been found in up to 10% of individuals with severe microphthalmia or anophthalmia and such mutations could also be associated with a range of non-ocular abnormalities. We performed mutation analysis on a new cohort of 120 patients with congenital eye abnormalities, mainly anophthalmia, microphthalmia and coloboma. Multiplex ligation-dependent probe amplification (MLPA) and fluorescence in situ hybridisation (FISH) were used to detect whole gene deletion. We identified four novel intragenic SOX2 mutations (one single base deletion, one single base duplication and two point mutations generating premature translational termination codons) and two further cases with the previously reported c.70del20 mutation. Of 52 patients with severe microphthalmia or anophthalmia analysed by MLPA, 5 were found to be deleted for the whole SOX2 gene and 1 had a partial deletion. In two of these, FISH studies identified sub-microscopic deletions involving a minimum of 328 Kb and 550 Kb. The SOX2 phenotypes include a patient with anophthalmia, oesophageal abnormalities and horseshoe kidney, and a patient with a retinal dystrophy implicating SOX2 in retinal development. Our results provide further evidence that SOX2 haploinsufficiency is a common cause of severe developmental ocular malformations and that background genetic variation determines the varying phenotypes. Given the high incidence of whole gene deletion we recommend that all patients with severe microphthalmia or anophthalmia, including unilateral cases be screened by MLPA and FISH for SOX2 deletions.

Partial Tetrasomy of Chromosome 22q11.1 Resulting from a Supernumerary Isodicentric Marker Chromosome in a Boy with Cat-eye Syndrome

PubMed Central

Kim, Jun Bum; Pai, Ki Soo; Yun, Jun-No; Park, Sang-Jin

2010-01-01

The 22q11 region has been implicated in chromosomal rearrangements that result in altered gene dosage, leading to three different congenital malformation syndromes: DiGeorge syndrome, cat-eye syndrome (CES), and der(22) syndrome. Although DiGeorge syndrome is a common genomic disorder on 22q11, CES is quite rare, and there has been no report of Korean CES cases with molecular cytogenetic confirmation. In this study, we present the phenotypic and genetic characteristics of a 3-month-old boy with CES. Clinical findings included micropthalmia, multiple colobomata, and renal and genital anomalies. Cytogenetic analyses showed the presence of a supernumerary marker chromosome, which was identified as a bisatellited and isodicentric chromosome derived from an acrocentric chromosome. The results of array comparative genomic hybridization and fluorescence in situ hybridization studies confirmed the karyotype as 47,XY,+mar.ish idic(22)(q11.1) (D22S43+).arr 22q11.1(15,500,000-15,900,000)x4, resulting in a partial tetrasomy of 22q11.1. To the best of our knowledge, this is the first report in Korea of CES confirmed by cytogenetic and molecular cytogenetic analyses. PMID:21165297

Partial tetrasomy of chromosome 22q11.1 resulting from a supernumerary isodicentric marker chromosome in a boy with cat-eye syndrome.

PubMed

Ko, Jung Min; Kim, Jun Bum; Pai, Ki Soo; Yun, Jun-No; Park, Sang-Jin

2010-12-01

The 22q11 region has been implicated in chromosomal rearrangements that result in altered gene dosage, leading to three different congenital malformation syndromes: DiGeorge syndrome, cat-eye syndrome (CES), and der(22) syndrome. Although DiGeorge syndrome is a common genomic disorder on 22q11, CES is quite rare, and there has been no report of Korean CES cases with molecular cytogenetic confirmation. In this study, we present the phenotypic and genetic characteristics of a 3-month-old boy with CES. Clinical findings included micropthalmia, multiple colobomata, and renal and genital anomalies. Cytogenetic analyses showed the presence of a supernumerary marker chromosome, which was identified as a bisatellited and isodicentric chromosome derived from an acrocentric chromosome. The results of array comparative genomic hybridization and fluorescence in situ hybridization studies confirmed the karyotype as 47,XY,+mar.ish idic(22)(q11.1) (D22S43+).arr 22q11.1(15,500,000-15,900,000)x4, resulting in a partial tetrasomy of 22q11.1. To the best of our knowledge, this is the first report in Korea of CES confirmed by cytogenetic and molecular cytogenetic analyses.

PREVALENCE OF SKELETAL AND EYE MALFORMATIONS IN FROGS FROM THE NORTH-CENTRAL UNITED STATES: ESTIMATIONS BASED ON COLLECTIONS FROM RANDOMLY SELECTED SITES. (R825867)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Operative correction and follow-up of craniofacial duplication.

PubMed

Kotrikova, Bibiana; Hassfeld, Stefan; Steiner, Hans H; Hähnel, Stefan; Krempien, Robert; Mühling, Joachim

2007-03-01

Anterior craniofacial duplication (diprosopus) is an extremely rare form of conjoined twins. The children share a single trunk with normal extremities and varying degrees of facial malformation. Duplication of specific structures, such as the nose (diprosopus dirrhinus), eyes (diprosopus tetraophthalmus), and ears, is possible. The authors present a case of partial facial duplication (diprosopus dirrhinus) in a male infant. The clinical and radiographic findings and the surgical correction and follow-up are described. In a single surgical session, the authors were able to achieve not only a functionally but also an aesthetically acceptable result. In the postoperative course, the child showed nearly normal growth and satisfactory psychosocial and motor development. However, 40 months postoperatively, we noticed a tendency of the orbitae to diverge (i.e., toward hypertelorism). The surgical management of complex craniofacial malformations such as diprosopus needs a precise morphologic analysis of the patient's deformity followed by a clear treatment plan. A staged reconstructive approach is carried out to coincide with facial growth patterns and brain and eye function. If the interorbital distance in our patient increases progressively, a second operation for reduction of the interorbital distance may be necessary.

Congenital Dandy Walker malformation associated with first trimester warfarin: a case report and literature review.

PubMed

Kaplan, L C

1985-12-01

While the warfarin embryopathy is well defined, central nervous system abnormalities associated with gestational warfarin exposure require further definition. Based on the timing of warfarin exposure in humans, it has been proposed that second- and third-trimester exposure predisposes to CNS abnormalities while first-trimester exposure more typically is associated with the warfarin embryopathy. A case is presented of a liveborn male with Dandy Walker malformation, agenesis of the corpus callosum, and Peter anomaly of the right eye who was exposed to warfarin between the 8th and 12th weeks of gestation who had none of the stigmata of the warfarin embryopathy. His is the first known case of exposure confined to the first trimester, and the fifth case of Dandy Walker malformation among a total of 15 CNS cases associated with this drug. This case offers evidence that Dandy Walker malformation may represent a distinct complication of in utero first-trimester exposure, and consideration of these particular abnormalities with exposure limited to a period prior to the known appearance of vitamin K-dependent clotting factors suggests that warfarin has a direct teratogenic effect on central nervous system morphogenesis.

FOXC1 is required for normal cerebellar development and is a major contributor to chromosome 6p25.3 Dandy-Walker malformation

PubMed Central

Aldinger, Kimberly A; Lehmann, Ordan J; Hudgins, Louanne; Chizhikov, Victor V; Bassuk, Alexander G; Ades, Lesley C; Krantz, Ian D; Dobyns, William B; Millen, Kathleen J

2010-01-01

Dandy-Walker malformation (DWM), the most common human cerebellar malformation, has only one characterized associated locus1,2. Here we characterize a second DWM-linked locus on 6p25.3, showing that deletions or duplications encompassing FOXC1 are associated with cerebellar and posterior fossa malformations including cerebellar vermis hypoplasia (CVH), mega-cisterna magna (MCM) and DWM. Foxc1-null mice have embryonic abnormalities of the rhombic lip due to loss of mesenchyme-secreted signaling molecules with subsequent loss of Atoh1 expression in vermis. Foxc1 homozygous hypomorphs have CVH with medial fusion and foliation defects. Human FOXC1 heterozygous mutations are known to affect eye development, causing a spectrum of glaucoma-associated anomalies (Axenfeld-Rieger syndrome, ARS; MIM no. 601631). We report the first brain imaging data from humans with FOXC1 mutations and show that these individuals also have CVH. We conclude that alteration of FOXC1 function alone causes CVH and contributes to MCM and DWM. Our results highlight a previously unrecognized role for mesenchyme-neuroepithelium interactions in the mid-hindbrain during early embryogenesis. PMID:19668217

Multiple pregnancies achieved with IVF/ICSI and risk of specific congenital malformations: a meta-analysis of cohort studies.

PubMed

Zheng, Zan; Chen, Letao; Yang, Tubao; Yu, Hong; Wang, Hua; Qin, Jiabi

2018-04-01

Studies comparing risk of specific congenital malformations (CM) between multiple pregnancies resulting from IVF/intracytoplasmic sperm injection (ICSI) and those conceived naturally report conflicting results; furthermore, there is a lack of a complete overview. This meta-analysis aimed to address which types of CM are increased in IVF/ICSI multiple pregnancies compared with those conceived naturally. All studies testing the association between IVF/ICSI multiple pregnancies and specific CM identified in various databases were considered. The literature search yielded 856 records, of which 21 cohort studies were included for analysis. Overall, multiple pregnancies achieved with IVF/ICSI experienced a significantly higher risk of chromosomal defects (relative risk [RR] = 1.36; 95% confidence interval [CI]: 1.04-1.77), urogenital (RR = 1.18; 95% CI: 1.03-1.36) and circulatory (RR = 1.22; 95% CI: 1.01-1.47) system malformations. However, the remaining specific CM, such as cleft lip and/or palate, eye, ear, face and neck, respiratory, musculoskeletal, nervous and digestive system malformations, were similar in the two groups. No substantial heterogeneity was observed for most outcomes except for digestive (P = 0.094; I 2 = 38.3%) and circulatory (P = 0.070; I 2 = 35.2%) system malformations. These findings provide additional information on risks of IVF/ICSI for use when counselling patients. Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Amphibian ocular malformation associated with frog virus 3.

PubMed

Burton, Elizabeth C; Miller, Debra L; Styer, Eloise L; Gray, Matthew J

2008-09-01

During an on-going amphibian ecology study, a free-ranging American bullfrog (Rana catesbeiana) metamorph was captured in a pitfall trap adjacent to a constructed farm pond at the Plateau Research and Education Center (PREC) on the Cumberland Plateau near Crossville, Tennessee, USA. Grossly, the right eye was approximately 50% the size of the left. Stereo and light microscopic examination revealed two granulomas within the orbit. Electron microscopic examination revealed virus particles scattered throughout one structure but mostly aggregated toward the center. Subsequent PCR and sequencing (GenBank accession Number EF175670) confirmed frog virus 3 (FV3). This represents the first report of a malformation in an anuran associated with FV3.

Loss of the BMP Antagonist, SMOC-1, Causes Ophthalmo-Acromelic (Waardenburg Anophthalmia) Syndrome in Humans and Mice

PubMed Central

Rainger, Joe; van Beusekom, Ellen; Ramsay, Jacqueline K.; McKie, Lisa; Al-Gazali, Lihadh; Pallotta, Rosanna; Saponari, Anita; Branney, Peter; Fisher, Malcolm; Morrison, Harris; Bicknell, Louise; Gautier, Philippe; Perry, Paul; Sokhi, Kishan; Sexton, David; Bardakjian, Tanya M.; Schneider, Adele S.; Elcioglu, Nursel; Ozkinay, Ferda; Koenig, Rainer; Mégarbané, Andre; Semerci, C. Nur; Khan, Ayesha; Zafar, Saemah; Hennekam, Raoul; Sousa, Sérgio B.; Ramos, Lina; Garavelli, Livia; Furga, Andrea Superti; Wischmeijer, Anita; Jackson, Ian J.; Gillessen-Kaesbach, Gabriele; Brunner, Han G.; Wieczorek, Dagmar; van Bokhoven, Hans; FitzPatrick, David R.

2011-01-01

Ophthalmo-acromelic syndrome (OAS), also known as Waardenburg Anophthalmia syndrome, is defined by the combination of eye malformations, most commonly bilateral anophthalmia, with post-axial oligosyndactyly. Homozygosity mapping and subsequent targeted mutation analysis of a locus on 14q24.2 identified homozygous mutations in SMOC1 (SPARC-related modular calcium binding 1) in eight unrelated families. Four of these mutations are nonsense, two frame-shift, and two missense. The missense mutations are both in the second Thyroglobulin Type-1 (Tg1) domain of the protein. The orthologous gene in the mouse, Smoc1, shows site- and stage-specific expression during eye, limb, craniofacial, and somite development. We also report a targeted pre-conditional gene-trap mutation of Smoc1 (Smoc1tm1a) that reduces mRNA to ∼10% of wild-type levels. This gene-trap results in highly penetrant hindlimb post-axial oligosyndactyly in homozygous mutant animals (Smoc1tm1a/tm1a). Eye malformations, most commonly coloboma, and cleft palate occur in a significant proportion of Smoc1tm1a/tm1a embryos and pups. Thus partial loss of Smoc-1 results in a convincing phenocopy of the human disease. SMOC-1 is one of the two mammalian paralogs of Drosophila Pentagone, an inhibitor of decapentaplegic. The orthologous gene in Xenopus laevis, Smoc-1, also functions as a Bone Morphogenic Protein (BMP) antagonist in early embryogenesis. Loss of BMP antagonism during mammalian development provides a plausible explanation for both the limb and eye phenotype in humans and mice. PMID:21750680

Loss of the BMP antagonist, SMOC-1, causes Ophthalmo-acromelic (Waardenburg Anophthalmia) syndrome in humans and mice.

PubMed

Rainger, Joe; van Beusekom, Ellen; Ramsay, Jacqueline K; McKie, Lisa; Al-Gazali, Lihadh; Pallotta, Rosanna; Saponari, Anita; Branney, Peter; Fisher, Malcolm; Morrison, Harris; Bicknell, Louise; Gautier, Philippe; Perry, Paul; Sokhi, Kishan; Sexton, David; Bardakjian, Tanya M; Schneider, Adele S; Elcioglu, Nursel; Ozkinay, Ferda; Koenig, Rainer; Mégarbané, Andre; Semerci, C Nur; Khan, Ayesha; Zafar, Saemah; Hennekam, Raoul; Sousa, Sérgio B; Ramos, Lina; Garavelli, Livia; Furga, Andrea Superti; Wischmeijer, Anita; Jackson, Ian J; Gillessen-Kaesbach, Gabriele; Brunner, Han G; Wieczorek, Dagmar; van Bokhoven, Hans; Fitzpatrick, David R

2011-07-01

Ophthalmo-acromelic syndrome (OAS), also known as Waardenburg Anophthalmia syndrome, is defined by the combination of eye malformations, most commonly bilateral anophthalmia, with post-axial oligosyndactyly. Homozygosity mapping and subsequent targeted mutation analysis of a locus on 14q24.2 identified homozygous mutations in SMOC1 (SPARC-related modular calcium binding 1) in eight unrelated families. Four of these mutations are nonsense, two frame-shift, and two missense. The missense mutations are both in the second Thyroglobulin Type-1 (Tg1) domain of the protein. The orthologous gene in the mouse, Smoc1, shows site- and stage-specific expression during eye, limb, craniofacial, and somite development. We also report a targeted pre-conditional gene-trap mutation of Smoc1 (Smoc1(tm1a)) that reduces mRNA to ∼10% of wild-type levels. This gene-trap results in highly penetrant hindlimb post-axial oligosyndactyly in homozygous mutant animals (Smoc1(tm1a/tm1a)). Eye malformations, most commonly coloboma, and cleft palate occur in a significant proportion of Smoc1(tm1a/tm1a) embryos and pups. Thus partial loss of Smoc-1 results in a convincing phenocopy of the human disease. SMOC-1 is one of the two mammalian paralogs of Drosophila Pentagone, an inhibitor of decapentaplegic. The orthologous gene in Xenopus laevis, Smoc-1, also functions as a Bone Morphogenic Protein (BMP) antagonist in early embryogenesis. Loss of BMP antagonism during mammalian development provides a plausible explanation for both the limb and eye phenotype in humans and mice.

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.

Frog decline, frog malformations, and a comparison of frog and human health.

PubMed

Cohen, M M

2001-11-22

The decline in frog populations and the increase in the frequency of frog malformations are discussed. Topics considered for analysis include chytridiomycosis, retinoids, UV-B radiation, chemical contaminants, environmental threats, introduced invasive species and predation, unsustainable use, and enigmatic decline. Care must be taken to distinguish between hypotheses, laboratory experiments, and the findings in feral frog populations. Clearly, the causes of population decline and malformations are heterogeneous. The subject of frogs and humans is addressed under three subheadings: the importance of frogs to human societies, medical implications of frog studies, and a comparison of frog and human disease factors. Copyright 2001 Wiley-Liss, Inc.

Adult diagnosed Dandy Walker malformation presenting as an acute brainstem event--a case report and review of the literature.

PubMed

Warwick, C Tanya; Reyes, Bernardo J; Ayoob, M Rose; Subit, Michael

2008-01-01

The Dandy Walker Malformation (DWM) is an infrequent condition seen in pediatric patients. Adult presentation of DWM is extremely rare. This condition usually presents in childhood with hydrocephalus and cerebellar signs and symptoms. This case describes a woman with an undiagnosed DWM who was asymptomatic until the age of 56 when she developed the acute onset of headache, nausea, vomiting, and diplopia. Her history and physical exam were consistent with an acute brainstem infarct. MRI revealed the underlying malformation. The clinical and radiological findings are discussed as well as their implications and possible etiologies.

The CHARGE Association: Implications for Teachers.

ERIC Educational Resources Information Center

Jones, Thomas W.; Dunne, Michele T.

1988-01-01

CHARGE association is described as a diagnostic label for a group of congenital malformations, including coloboma, heart defects, atresia choanae, retarded postnatal growth/central nervous system defects, genital hypoplasia, and ear deformities. Etiology and characteristics of the CHARGE association are discussed, along with implications for…

[Anophthalmia and microphthalmia requires multidisciplinary care. Many of the children also have other medical problems].

PubMed

Jugård, Ylva; Odersjö, Marie; Topa, Alexandra; Lindgren, Gun; Andersson Grönlund, Marita

2015-07-13

Anophthalmia/microphthalmia (A/M) are rare congenital eye malformations. Early intervention with ocular prosthesis can stimulate orbital growth and prevent facial asymmetry. We reviewed medical records from 18 individuals with A/M (0.8-31 years) treated with ocular prosthesis at Sahlgrenska University Hospital between 2000 and 2012. A majority had other ocular findings. Seven had subnormal visual acuity in the fellow eye, one third were in contact with vision support services and half of the group wore glasses. Eleven individuals had extra-ocular findings such as cardiac defect, hearing impairment and neuropsychiatric disorders, possibly indicating syndromic conditions. We suggest that investigation of A/M children should include ultrasound of the eye, optionally visual evoked potential and magnetic resonance imaging of the CNS. The ophthalmologist should initiate treatment with prosthesis, pediatric assessment, hearing tests and genetic counseling, but should also monitor visual development of the fellow eye.

Anterior segment dysgenesis (Peters' anomaly) in two snow leopard (Panthera uncia) cubs.

PubMed

Hamoudi, Hassan; Rudnick, Jens-Christian; Prause, Jan U; Tauscher, Kerstin; Breithaupt, Angele; Teifke, Jens P; Heegaard, Steffen

2013-07-01

Two sibling snow leopards, a male and a female, with bilateral anterior segment dysgenesis (ASD), are reported. Both snow leopards also had colobomas of both upper eyelids. All eyes exhibited a central corneal opacity associated with a defect in posterior corneal stroma, endothelium and Descemet's membrane. Iris strands were present attached to the termination of Descemet's membrane and to the periphery of the posterior corneal defect. The iris was hypoplastic, and cataract was present in all four eyes. The left eye of the female was microphthalmic, with no trabecular meshwork and with persistent remnant of the hyaloid artery. The male had hydrocephalus and thus some of the features of Peters' plus syndrome (Peters' anomaly in addition to systemic malformations). The histological findings in the eyes of these snow leopard siblings are identical with those described in humans with Peters' anomaly. © 2012 American College of Veterinary Ophthalmologists.

[Persistence of the primordial vitreous body and buphthalmos].

PubMed

Cernea, P; Simionescu, C; Bosun, I

1995-01-01

Persistence of the hyperplasic primordial vitreous body is determined by a deletion of embryonal development of the vitreous body and of the hyaloid vascular system. Infant aged 3.5 years presents persistence of primordial vitreous body with crystalline dislocation in the camera aquosa and secondary buphthalmos of the left eye and microphthalmos with dislocation of the crystalline in the vitreous body of the right eye. At the back of the right eye we noticed a whitish mass, richly vascularized with vestiges from the hyaloid artery, but the posterior half of the vitreous cavity is filled with microscopic blood; the fibrovascular membrane is made of conjunctive tissue set in parallel layers and vessels with macrolipophagic degeneration. Microscopic investigation of retina reveals glial hyperplasia zones in the neighbourhood of the vitreous body. In the present paper the authors show the persistence of the primordial vitreous body in the left eye and bilateral dislocation of the crystalline, revealing multiple ocular malformations.

Bisphenol A causes malformation of the head region in embryos of Xenopus laevis and decreases the expression of the ESR-1 gene mediated by Notch signaling.

PubMed

Imaoka, Susumu; Mori, Tomohiro; Kinoshita, Tsutomu

2007-02-01

Bisphenol A (BpA) is widely used in industry and dentistry. Its effects on the embryonic development of Xenopus laevis were investigated. Xenopus embryos at stage 10.5 were treated with BpA. Developmental abnormalities were observed at stage 35; malformation of the head region including eyes and scoliosis. The expression of several markers of embryonic development was investigated by reverse transcription-polymerase chain reaction (RT-PCR). The pan-neural marker SOX-2, the neural stem cell marker nrp-1, the mesodermal marker MyoD, and the endodermal marker sox17alpha, were used. Although the expression of marker genes was not changed by treatment with BpA, that of Pax-6, a key regulator of the morphogenesis of the eyes, was decreased by BpA. Pax-6 is a downstream factor of Notch signaling. So, the expression of a typical Notch-dependent factor, ESR-1, was investigated in the presence of BpA. The expression of ESR-1 was efficiently suppressed by BpA. In whole mount in situ hybridization (WISH), Pax-6 was expressed in the central nervous system and eyes. The expression was lost completely on treatment with BpA. The expression of ESR-1 in the central nervous system and eyes also disappeared with BpA treatment. Injection of the intracellular domain of Notch efficiently recovered ESR-1 expression in the presence of BpA although injection of a ligand for notch, Delta, did not. These results suggest that BpA decreased the expression of ESR-1 by disrupting the Notch signal.

Stage specific effects of soluble copper and copper oxide nanoparticles during sea urchin embryo development and their relation to intracellular copper uptake.

PubMed

Torres-Duarte, Cristina; Ramos-Torres, Karla M; Rahimoff, René; Cherr, Gary N

2017-08-01

The effects of exposure to either soluble copper (copper sulfate) or copper oxide nanoparticles (nano-CuO) during specific early developmental stages of sea urchin embryos were analyzed. Soluble copper caused significant malformations in embryos (skeletal malformations, delayed development or gut malformations) when present at any given stage, while cleavage stage was the most sensitive to nano-CuO exposure causing skeletal malformations and decreased total antioxidant capacity. The stage specificity was linked to higher endocytic activity during the first hours of development that leads to higher accumulation of copper in specific cells critical for development. Results indicate that nano-CuO results in higher accumulation of copper inside of embryos and this intracellular copper is more persistent as compared to soluble copper. The possible implications later in development are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Fallout from the Chernobyl nuclear disaster and congenital malformations in Europe.

PubMed

Hoffmann, W

2001-01-01

Investigators estimate that the population exposure that resulted from the Chernobyl fallout is in the range of natural background radiation for most European countries. Given current radiobiologic knowledge, health effects-if any-would not be measurable with epidemiologic tools. In several independent reports, however, researchers have described isolated peaks in the prevalence of congenital malformations in the cohort conceived immediately after onset of the fallout. The consistency of the time pattern and the specific types of malformation raise concern about their significance. In this study, the author summarizes findings from Turkey, Belarus, Croatia, Finland, Germany, and other countries, and implications for radiation protection and public health issues are discussed.

The epidemiology of anophthalmia and microphthalmia in Sweden.

PubMed

Källén, Bengt; Tornqvist, Kristina

2005-01-01

Infants with a clinical diagnosis of anophthalmia or microphthalmia were identified from four health registers in Sweden, covering different parts of the period 1965-2001. During the observation period, the rate of anophthalmia decreased from the early 1970s from 0.4 to 0.2 per 10,000 births. The registered rate of microphthalmia increased markedly during the observation period to reach a maximum in 1987 of about 1.5 per 10,000. About 10% of the 432 identified children had a chromosome anomaly. There was no geographical variation in prevalence and infants born in urban or rural districts had, if anything, a lower risk than infants born in cities (0.93 and 1.13 per 10,000, respectively). Non-eye malformations were more common at anophthalmia (63%) than at microphthalmia (30%). Sex ratio was normal and no statistically significant variation between sub-groups (anophthalmia, microphthalmia, isolated, associated with non-eye malformations) could be demonstrated. There was a marked risk increase with maternal age but no certain parity effect, no effect of maternal education, but a possible association with subfertility. Maternal smoking in early pregnancy seemed to increase the risk for anophthalmia or microphthalmia in the absence of a coloboma.

Vascular anomalies: classification, imaging characteristics and implications for interventional radiology treatment approaches

PubMed Central

Prajapati, H J S; Martin, L G; Patel, T H

2014-01-01

The term vascular anomaly represents a broad spectrum of vascular pathology, including proliferating vascular tumours and vascular malformations. While the treatment of most vascular anomalies is multifactorial, interventional radiology procedures, including embolic therapy, sclerotherapy and laser coagulation among others, are playing an increasingly important role in vascular anomaly management. This review discusses the diagnosis and treatment of common vascular malformations, with emphasis on the technique, efficacy and complications of different interventional radiology procedures. PMID:24588666

Mutation of the Diamond-Blackfan Anemia Gene Rps7 in Mouse Results in Morphological and Neuroanatomical Phenotypes

PubMed Central

Watkins-Chow, Dawn E.; Cooke, Joanna; Pidsley, Ruth; Edwards, Andrew; Slotkin, Rebecca; Leeds, Karen E.; Mullen, Raymond; Baxter, Laura L.; Campbell, Thomas G.; Salzer, Marion C.; Biondini, Laura; Gibney, Gretchen; Phan Dinh Tuy, Françoise; Chelly, Jamel; Morris, H. Douglas; Riegler, Johannes; Lythgoe, Mark F.; Arkell, Ruth M.; Loreni, Fabrizio; Flint, Jonathan

2013-01-01

The ribosome is an evolutionarily conserved organelle essential for cellular function. Ribosome construction requires assembly of approximately 80 different ribosomal proteins (RPs) and four different species of rRNA. As RPs co-assemble into one multi-subunit complex, mutation of the genes that encode RPs might be expected to give rise to phenocopies, in which the same phenotype is associated with loss-of-function of each individual gene. However, a more complex picture is emerging in which, in addition to a group of shared phenotypes, diverse RP gene-specific phenotypes are observed. Here we report the first two mouse mutations (Rps7Mtu and Rps7Zma) of ribosomal protein S7 (Rps7), a gene that has been implicated in Diamond-Blackfan anemia. Rps7 disruption results in decreased body size, abnormal skeletal morphology, mid-ventral white spotting, and eye malformations. These phenotypes are reported in other murine RP mutants and, as demonstrated for some other RP mutations, are ameliorated by Trp53 deficiency. Interestingly, Rps7 mutants have additional overt malformations of the developing central nervous system and deficits in working memory, phenotypes that are not reported in murine or human RP gene mutants. Conversely, Rps7 mouse mutants show no anemia or hyperpigmentation, phenotypes associated with mutation of human RPS7 and other murine RPs, respectively. We provide two novel RP mouse models and expand the repertoire of potential phenotypes that should be examined in RP mutants to further explore the concept of RP gene-specific phenotypes. PMID:23382688

Molecular links among the causative genes for ocular malformation: Otx2 and Sox2 coregulate Rax expression.

PubMed

Danno, Hiroki; Michiue, Tatsuo; Hitachi, Keisuke; Yukita, Akira; Ishiura, Shoichi; Asashima, Makoto

2008-04-08

The neural-related genes Sox2, Pax6, Otx2, and Rax have been associated with severe ocular malformations such as anophthalmia and microphthalmia, but it remains unclear as to how these genes are linked functionally. We analyzed the upstream signaling of Xenopus Rax (also known as Rx1) and identified the Otx2 and Sox2 proteins as direct upstream regulators of Rax. We revealed that endogenous Otx2 and Sox2 proteins bound to the conserved noncoding sequence (CNS1) located approximately 2 kb upstream of the Rax promoter. This sequence is conserved among vertebrates and is required for potent transcriptional activity. Reporter assays showed that Otx2 and Sox2 synergistically activated transcription via CNS1. Furthermore, the Otx2 and Sox2 proteins physically interacted with each other, and this interaction was affected by the Sox2-missense mutations identified in these ocular disorders. These results demonstrate that the direct interaction and interdependence between the Otx2 and Sox2 proteins coordinate Rax expression in eye development, providing molecular linkages among the genes responsible for ocular malformation.

Orbital exenteration after transarterial embolization in a patient with Wyburn-Mason syndrome: pathological findings.

PubMed

Matsuo, Toshihiko; Yanai, Hiroyuki; Sugiu, Kenji; Tominaga, Susumu; Kimata, Yoshihiro

2008-01-01

We present the pathological findings at orbital exenteration in a patient with Wyburn-Mason syndrome who underwent transarterial embolization. A 31-year-old man with a 10-year history of gradual exacerbation of left exophthalmos and left cheek swelling was found to have facial and orbital arteriovenous malformations on the left side. There was no vascular malformation in the brain. The feeding arteries derived from the left internal maxillary artery, facial artery, and ophthalmic artery. He underwent several courses of transarterial embolization of the feeding arteries from the left internal maxillary artery and then from the facial artery, resulting in no reduction of the arteriovenous malformation. He finally elected to undergo ophthalmic artery embolization in the expectation of a reduction and with the understanding that he would lose sight in his left eye. Two years later, he requested lid-sparing orbital exenteration and reconstruction with cutaneous flap transfer and prosthesis for cosmetic reasons. Pathologically, orbital vascular channels of varying sizes were filled with embolizing glue and had degenerating vascular wall cells surrounded by inflammatory cell infiltration. The central retinal artery in the optic nerve was also filled with the embolizing glue, and the retina lost the ganglion cell layer and inner nuclear layer but maintained the outer nuclear layer and outer segments. Marked anastomoses and hence incomplete embolization among the feeding arteries of facial and orbital vascular malformations in Wyburn-Mason syndrome do not respond well to attempts at feeding vessel embolization, which result in unsuccessful closure of the malformation.

Unusual leg malformations in screech owls from a South Carolina Superfund site

USGS Publications Warehouse

Albers, P.H.; Hoffman, D.J.; Brisbin, I.L.

2001-01-01

In 1995, the discovery of leg malformations in several screech owl (Otis asio) nestlings and in their female parent at a Department of Energy (DOE) Superfund site in South Carolina prompted an investigation into the nature of the observed abnormalities. Surviving nestlings and the female parent were transferred to a captive screech owl breeding colony at the USGS Patuxent Wildlife Research Center, Laurel, MD. The malformed female parent and her offspring were each mated with normal owls from the colony for 3 yr. Matings of the malformed female produced five malformed and six normal owls; all owls produced by matings of normal offspring were normal. Malformed offspring were euthanized when it became apparent that their physical distress precluded survival under normal conditions of colony care. Euthanized owls were necropsied and examined for skeletal development. Detailed descriptions of eight malformed owls are presented. Results of the matings indicated that the leg malformations were caused by a genetic trait in the female parent that was heterozygous dominant. The characteristic was lethal except in occasional mild manifestations and resembled an extreme form of a dominant abnormality previously described for domestic fowl called duplicate polydactyly. Other reports of skeletal abnormalities in wild birds and potential environmental causes of genetic mutations at the DOE Super-fund site are presented. Other studies performed at the DOE Superfund site do not implicate elevated (above background) ionizing radiation from '37Cs, the dominant radio-nuclide where the owls were captured, as the cause of the mutation. The cause of this genetic abnormality remains unknown.

Mutations at the PAX6 locus are found in heterogeneous anterior segment malformations including Peters' anomaly.

PubMed

Hanson, I M; Fletcher, J M; Jordan, T; Brown, A; Taylor, D; Adams, R J; Punnett, H H; van Heyningen, V

1994-02-01

Mutation or deletion of the PAX6 gene underlies many cases of aniridia. Three lines of evidence now converge to implicate PAX6 more widely in anterior segment malformations including Peters' anomaly. First, a child with Peters' anomaly is deleted for one copy of PAX6. Second, affected members of a family with dominantly inherited anterior segment malformations, including Peters' anomaly are heterozygous for an R26G mutation in the PAX6 paired box. Third, a proportion of Sey/+ Smalleye mice, heterozygous for a nonsense mutation in murine Pax-6, have an ocular phenotype resembling Peters' anomaly. We therefore propose that a variety of anterior segment anomalies may be associated with PAX6 mutations.

Chromosome 6p25 deletion syndrome: report of a case with optic disc coloboma and review of published ophthalmic findings.

PubMed

Beby, Francis; Des Portes, Vincent; Till, Marianne; Mottolese, Carmine; Denis, Philippe

2012-12-01

The 6p25 deletion syndrome is a rare disorder characterized by Dandy-Walker malformation, congenital heart defects, developmental delay, dysmorphic facial features, and malformations of the anterior segment of the eye with a risk for glaucoma. Here we report a child harboring a cryptic de novo 6p25 deletion, bilateral optic disc coloboma and characteristic anterior segment anomalies. We review reported ophthalmic findings in patients with this syndrome. Retrospective case review of a 4-day-old male with Dandy-Walker malformation and cardiac defects who was referred with a suspected diagnosis of iris coloboma. The ophthalmic examination showed bilateral corectopia associated with posterior embryotoxon. Fundus examination revealed bilateral optic disc excavation, which was diagnosed as colobomatous because of its configuration and stability over time. Because of the association of posterior embryotoxon with Dandy-Walker malformation, a terminal 6p deletion syndrome was clinically suspected. Array comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) studies revealed a 3.2 Mb deletion at 6p25.2p25.3 including the FOXC1 gene. Neither unaffected parent carried this deletion. Optic disc colobomas may be found in patients carrying a 6p25 deletion. This has the potential to confound assessment of affected children for glaucoma and intracranial hypertension.

The human brain and face: mechanisms of cranial, neurological and facial development revealed through malformations of holoprosencephaly, cyclopia and aberrations in chromosome 18

PubMed Central

Gondré-Lewis, Marjorie C; Gboluaje, Temitayo; Reid, Shaina N; Lin, Stephen; Wang, Paul; Green, William; Diogo, Rui; Fidélia-Lambert, Marie N; Herman, Mary M

2015-01-01

The study of inborn genetic errors can lend insight into mechanisms of normal human development and congenital malformations. Here, we present the first detailed comparison of cranial and neuro pathology in two exceedingly rare human individuals with cyclopia and alobar holoprosencephaly (HPE) in the presence and absence of aberrant chromosome 18 (aCh18). The aCh18 fetus contained one normal Ch18 and one with a pseudo-isodicentric duplication of chromosome 18q and partial deletion of 18p from 18p11.31 where the HPE gene, TGIF, resides, to the p terminus. In addition to synophthalmia, the aCh18 cyclopic malformations included a failure of induction of most of the telencephalon – closely approximating anencephaly, unchecked development of brain stem structures, near absence of the sphenoid bone and a malformed neurocranium and viscerocranium that constitute the median face. Although there was complete erasure of the olfactory and superior nasal structures, rudiments of nasal structures derived from the maxillary bone were evident, but with absent pharyngeal structures. The second non-aCh18 cyclopic fetus was initially classified as a true Cyclops, as it appeared to have a proboscis and one median eye with a single iris, but further analysis revealed two eye globes as expected for synophthalmic cyclopia. Furthermore, the proboscis was associated with the medial ethmoid ridge, consistent with an incomplete induction of these nasal structures, even as the nasal septum and paranasal sinuses were apparently developed. An important conclusion of this study is that it is the brain that predicts the overall configuration of the face, due to its influence on the development of surrounding skeletal structures. The present data using a combination of macroscopic, computed tomography (CT) and magnetic resonance imaging (MRI) techniques provide an unparalleled analysis on the extent of the effects of median defects, and insight into normal development and patterning of the brain, face and their skeletal support. PMID:26278930

The human brain and face: mechanisms of cranial, neurological and facial development revealed through malformations of holoprosencephaly, cyclopia and aberrations in chromosome 18.

PubMed

Gondré-Lewis, Marjorie C; Gboluaje, Temitayo; Reid, Shaina N; Lin, Stephen; Wang, Paul; Green, William; Diogo, Rui; Fidélia-Lambert, Marie N; Herman, Mary M

2015-09-01

The study of inborn genetic errors can lend insight into mechanisms of normal human development and congenital malformations. Here, we present the first detailed comparison of cranial and neuro pathology in two exceedingly rare human individuals with cyclopia and alobar holoprosencephaly (HPE) in the presence and absence of aberrant chromosome 18 (aCh18). The aCh18 fetus contained one normal Ch18 and one with a pseudo-isodicentric duplication of chromosome 18q and partial deletion of 18p from 18p11.31 where the HPE gene, TGIF, resides, to the p terminus. In addition to synophthalmia, the aCh18 cyclopic malformations included a failure of induction of most of the telencephalon - closely approximating anencephaly, unchecked development of brain stem structures, near absence of the sphenoid bone and a malformed neurocranium and viscerocranium that constitute the median face. Although there was complete erasure of the olfactory and superior nasal structures, rudiments of nasal structures derived from the maxillary bone were evident, but with absent pharyngeal structures. The second non-aCh18 cyclopic fetus was initially classified as a true Cyclops, as it appeared to have a proboscis and one median eye with a single iris, but further analysis revealed two eye globes as expected for synophthalmic cyclopia. Furthermore, the proboscis was associated with the medial ethmoid ridge, consistent with an incomplete induction of these nasal structures, even as the nasal septum and paranasal sinuses were apparently developed. An important conclusion of this study is that it is the brain that predicts the overall configuration of the face, due to its influence on the development of surrounding skeletal structures. The present data using a combination of macroscopic, computed tomography (CT) and magnetic resonance imaging (MRI) techniques provide an unparalleled analysis on the extent of the effects of median defects, and insight into normal development and patterning of the brain, face and their skeletal support. © 2015 Anatomical Society.

Mutations in STAMBP, encoding a deubiquitinating enzyme, cause Microcephaly-Capillary Malformation syndrome

PubMed Central

McDonell, Laura M.; Mirzaa, Ghayda M.; Alcantara, Diana; Schwartzentruber, Jeremy; Carter, Melissa T.; Lee, Leo J.; Clericuzio, Carol L.; Graham, John M.; Morris-Rosendahl, Deborah J.; Polster, Tilman; Acsadi, Gyula; Townshend, Sharron; Williams, Simon; Halbert, Anne; Isidor, Bertrand; Smyser, Christopher D.; Paciorkowski, Alex R.; Willing, Marcia; Woulfe, John; Das, Soma; Beaulieu, Chandree L.; Marcadier, Janet; Geraghty, Michael T.; Frey, Brendan J.; Majewski, Jacek; Bulman, Dennis E.; Dobyns, William B.; O’Driscoll, Mark; Boycott, Kym M.

2014-01-01

Microcephaly-capillary malformation (MIC-CAP) syndrome exhibits severe microcephaly with progressive cortical atrophy, intractable epilepsy, profound developmental delay and multiple small capillary malformations on the skin. We employed whole-exome sequencing of five patients with MIC-CAP syndrome and identified novel recessive mutations in STAMBP, a gene encoding the deubiquitinating (DUB) isopeptidase STAMBP (STAM-binding protein)/AMSH (Associated Molecule with the SH3 domain of STAM), that plays a key role in cell surface receptor-mediated endocytosis and sorting. Patient cell lines showed reduced STAMBP expression associated with accumulation of ubiquitin-conjugated protein aggregates, elevated apoptosis and insensitive activation of the RAS-MAPK and PI3K-AKT-mTOR pathways. The latter cellular phenotype is significant considering the established connection between these pathways and their association with vascular and capillary malformations. Furthermore, our findings of a congenital human disorder caused by a defective DUB protein that functions in endocytosis, implicates ubiquitin-conjugate aggregation and elevated apoptosis as factors potentially influencing the progressive neuronal loss underlying MIC-CAP. PMID:23542699

Ablation of Mrds1/Ofcc1 Induces Hyper-γ-Glutamyl Transpeptidasemia without Abnormal Head Development and Schizophrenia-Relevant Behaviors in Mice

PubMed Central

Ohnishi, Tetsuo; Yamada, Kazuo; Watanabe, Akiko; Ohba, Hisako; Sakaguchi, Toru; Honma, Yota; Iwayama, Yoshimi; Toyota, Tomoko; Maekawa, Motoko; Watanabe, Kazutada; Detera-Wadleigh, Sevilla D.; Wakana, Shigeharu; Yoshikawa, Takeo

2011-01-01

Mutations in the Opo gene result in eye malformation in medaka fish. The human ortholog of this gene, MRDS1/OFCC1, is a potentially causal gene for orofacial cleft, as well as a susceptibility gene for schizophrenia, a devastating mental illness. Based on this evidence, we hypothesized that this gene could perform crucial functions in the development of head and brain structures in vertebrates. To test this hypothesis, we created Mrds1/Ofcc1-null mice. Mice were examined thoroughly using an abnormality screening system referred to as “the Japan Mouse Clinic”. No malformations of the head structure, eye or other parts of the body were apparent in these knockout mice. However, the mutant mice showed a marked increase in serum γ-glutamyl transpeptidase (GGT), a marker for liver damage, but no abnormalities in other liver-related measurements. We also performed a family-based association study on the gene in schizophrenia samples of Japanese origin. We found five single nucleotide polymorphisms (SNPs) located across the gene that showed significant transmission distortion, supporting a prior report of association in a Caucasian cohort. However, the knockout mice showed no behavioral phenotypes relevant to schizophrenia. In conclusion, disruption of the Mrds1/Ofcc1 gene elicits asymptomatic hyper-γ-glutamyl-transpeptidasemia in mice. However, there were no phenotypes to support a role for the gene in the development of eye and craniofacial structures in vertebrates. These results prompt further examination of the gene, including its putative contribution to hyper-γ-glutamyl transpeptidasemia and schizophrenia. PMID:22242126

GPR56-Related Polymicrogyria: Clinicoradiologic Profile of 4 Patients.

PubMed

Desai, Neelu A; Udani, Vrajesh

2015-11-01

Bilateral frontoparietal polymicrogyria is an autosomal recessive cortical malformation associated with abnormalities of neuronal migration, white matter changes, and mild brainstem and cerebellar abnormalities. Affected patients present with delayed milestones, intellectual disability, epilepsy, ataxia, and eye movement abnormalities. The clinicoradiologic profile resembles congenital muscular dystrophy. However, no muscle disease or characteristic eye abnormalities of congenial muscular dystrophy are detected in these children. GPR56 is the only confirmed gene associated with bilateral frontoparietal polymicrogyria. Antenatal diagnosis is possible if the index case is genetically confirmed. Four patients from different Indian families with a distinct clinicoradiologic profile resembling congenital muscular dystrophy with mutations in the GPR56 gene are described. © The Author(s) 2015.

Arnold-Chiari malformation and nystagmus of skew

PubMed Central

Pieh, C.; Gottlob, I.

2000-01-01

The Arnold-Chiari malfomation is typically associated with downbeat nystagmus. Eye movement recordings in two patients with Arnold-Chiari malfomation type 1 showed, in addition to downbeat and gaze evoked nystagmus, intermittent nystagmus of skew. To date this finding has not been reported in association with Arnold-Chiari malfomation. Nystagmus of skew should raise the suspicion of Arnold-Chiari malfomation and prompt sagittal head MRI examination.

 PMID:10864619

Moyamoya Vasculopathy in PHACE Syndrome: Six New Cases and Review of the Literature.

PubMed

Tortora, Domenico; Severino, Mariasavina; Accogli, Andrea; Martinetti, Carola; Vercellino, Nadia; Capra, Valeria; Rossi, Andrea; Pavanello, Marco

2017-12-01

PHACE syndrome (Posterior fossa malformations, large cervicofacial infantile Hemangiomas, Arterial anomalies, aortic coarctation and Cardiac abnormalities, and Eye abnormalities) is a neurocutaneous disorder including posterior fossa malformations, hemangiomas, arterial lesions, cardiac defects, and eye abnormalities. PHACE arteriopathies may be progressive and recently have been categorized based on the risk of acute ischemic stroke, increasing attention to the potentially devastating consequences of cerebrovascular complications in this syndrome. In contrast, the natural history of arteriopathy in PHACE syndrome remains poorly understood. At the moment, there are no established surgical guidelines for high-risk vasculopathies, including quasi-moyamoya, in this syndrome. We described the clinicoradiologic features of a small series of 6 patients with PHACE syndrome and quasi-moyamoya (5 female, age range 4 months to 12 years), focusing on the clinical course and surgical outcome of 3 children who were treated with encephaloduroarteriosynangiosis and encephalomyosynangiosis. In addition, we reviewed the radiologic, clinical, and surgical aspects of moyamoya vasculopathy in PHACE syndrome, providing information on 15 additional published cases. Although the natural history of arteriopathy in PHACE syndrome is poorly understood, patients with high-risk vasculopathies, such as quasi-moyamoya disease, may benefit of revascularization by using encephaloduroarteriosynangiosis and encephalomyosynangiosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Persistent hyperplastic primary vitreous: congenital malformation of the eye.

PubMed

Shastry, Barkur S

2009-12-01

Persistent hyperplastic primary vitreous (PHPV), also known as persistent fetal vasculature, is a rare congenital developmental malformation of the eye, caused by the failure of regression of the primary vitreous. It is divided into anterior and posterior types and is characterized by the presence of a vascular membrane located behind the lens. The condition can be of an isolated type or can occur with other ocular disorders. Most cases of PHPV are sporadic, but it can be inherited as an autosomal dominant or recessive trait. Inherited PHPV also occurs in several breeds of dogs and cats. In a limited number of cases, Norrie disease and FZD4 genes are found to be mutated in unilateral and bilateral PHPV. These genes when mutated also cause Norrie disease pseudoglioma and familial exudative vitreoretinopathy that share some of the clinical features with PHPV. Mice lacking arf and p53 tumour suppressor genes as well as Norrie disease pseudoglioma and LRP5 genes suggest that these genes are needed for hyaloid vascular regression. These experiments also indicate that abnormalities in normal apoptosis and defects in Wnt signalling pathway may be responsible for the pathogenesis of PHPV. Identification of other candidate genes in the future may provide a better understanding of the pathogenesis of the condition that may lead to a better therapeutic approach and better management.

Refined localization of the Prieto-syndrome locus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martinez, F.; Prieto, F.; Gal, A.

PRS designates the locus for a syndromal form of X-linked mental retardation (Prieto syndrome) characterized by minor facial anomalies, ear malformation, abnormal growth of teeth, clinodactyly, sacral dimple, patellar luxation, malformation of lower limbs, abnormalities of the fundus of the eye, and subcortical cerebral atrophy. Linkage analysis localized the disease locus between DXS84 (Xp21.1) and DXS255. Here we present additional linkage data that provide further support and refinement of this localization. Individual III-18 gave birth to a male, currently aged 2 7/12 years, who clearly shows delayed psychomotor development. He began to walk at 23 months and his speech ismore » delayed. In addition, he shows the characteristic facial anomalies, {open_quotes}dysplastic{close_quotes} ears, sacral dimple, and clinodactyly, as do all other affected males in this family. 7 refs., 1 tab.« less

A de novo 1.38 Mb duplication of 1q31.1 in a boy with hemifacial microsomia, anophthalmia, anotia, macrostomia, and cleft lip and palate.

PubMed

Huang, Xue-shuang; Zhu, Bao; Jiang, Hai-ou; Wu, Su-fan; Zhang, Zai-qi; Xiao, Lin; Yi, Li-lan; Zhang, Jian-xiang

2013-04-01

We reported a 2-year-old boy with developmental delay, mild mental retardation, and severe craniofacial malformation, including facial asymmetry with hypoplasia of the left zygoma, maxilla, and mandible, and left anophthalmia and anotia. A genome-wide screen revealed a 1.38 Mb duplication on chromosome 1q31.1, which was absent in his parents and 27 healthy controls. The duplication region contains two Refseq genes, PLA2G4A and C1orf99, which have not been reported to be implicated in craniofacial malformation. Functional studies of these genes and additional clinical analysis are necessary to elucidate the pathogenesis of craniofacial malformation. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

A novel homozygous variant in the SMOC1 gene underlying Waardenburg anophthalmia syndrome.

PubMed

Ullah, Asmat; Umair, Muhammad; Ahmad, Farooq; Muhammad, Dost; Basit, Sulman; Ahmad, Wasim

2017-01-01

Waardenburg anophthalmia syndrome (WAS), also known as ophthalmo-acromelic syndrome or anophthalmia-syndactyly, is a rare congenital disorder that segregates in an autosomal recessive pattern. Clinical features of the syndrome include malformation of the eyes and the skeleton. Mostly, WAS is caused by mutations in the SMOC-1 gene. The present report describes a large consanguineous family of Pakistani origin segregating Waardenburg anophthalmia syndrome in an autosomal recessive pattern. Genotyping followed by Sanger sequencing was performed to search for a candidate gene. SNP genotyping using AffymetrixGeneChip Human Mapping 250K Nsp array established a single homozygous region among affected members on chromosome 14q23.1-q24.3 harboring the SMOC1 gene. Sequencing of the gene revealed a novel homozygous missense mutation (c.812G>A; p.Cys271Tyr) in the family. This is the first report of Waardenburg anophthalmia syndrome caused by a SMOC1 variant in a Pakistani population. The mutation identified in the present investigation extends the body of evidence implicating the gene SMOC-1 in causing WAS.

The Effects of Alcohol on the Fetus.

ERIC Educational Resources Information Center

Furey, Eileen M.

1982-01-01

The article explores recent findings on Fatal Alcohol Syndrome (FAS), patterns of malformation, alcohol and other drugs, the toxicity of ethanol, the incidence of FAS, and implications of the syndrome. (Author)

A chicken embryo model for the study of umbilical and supraumbilical body wall malformations.

PubMed

Ridderbusch, Ina; Bergholz, Robert; Fattouh, Miriam; Eschenburg, Georg; Roth, Beate; Appl, Birgit; Maenner, Joerg; Reinshagen, Konrad; Kluth, Dietrich

2015-06-01

BACKGROUND/PURPOSE; The embryology of ventral body wall malformations is only partially understood, although their incidence is relatively common. As only few experimental data exist on the development of those defects, the aim of our study was to compare the teratogenic effect of trypan blue (TB) and suramin (SA) in their capability to induce umbilical and supraumbilical abdominal wall malformations in a chicken egg model. A total of 255 fertilized chicken eggs were incubated at 38 °C and 75% relative humidity. Embryos were treated in ovo on incubation day 2.5 (Hamburger/Hamilton (HH) stage 13). The eggshell was windowed, and solutions of TB or SA were injected into the coelomic cavity at the region of the umbilicus. The window was closed and the embryos reincubated until examination on day 8 (HH 34). A total of 60 embryos survived in each group. The largest number of embryos presented with defects in the umbilical and supraumbilical region (25% in the SA group and 40% in the TB group). A combination of both defects (thoracoabdominoschisis) was seen in 20% of the TB and 8.3% of the SA groups, respectively. Associated anomalies found in both groups were head and eye defects, abnormal pelvic configurations, leg deformities, and mild forms of cloacal exstrophies. TB and SA have both a high potential to induce umbilical and supraumbilical ventral body wall malformations in chicken embryos. This novel animal model might help to establish a more profound understanding of the developmental steps in ventral body wall formation and the embryology for its malformations. Georg Thieme Verlag KG Stuttgart · New York.

Phenotypic variability of the cat eye syndrome. Case report and review of the literature.

PubMed

Rosias, P R; Sijstermans, J M; Theunissen, P M; Pulles-Heintzberger, C F; De Die-Smulders, C E; Engelen, J J; Van Der Meer, S B

2001-01-01

We present a male infant with preauricular skin tags and pits, downslanting palpebral fissures, hypertelorism, ectopic anus, hypospadias, and hypoplastic left heart syndrome. The clinical features in our patient show phenotypic overlap with the cat eye syndrome, as illustrated by the review of 105 reported cases. Cytogenetic analysis revealed a supernumerary marker chromosome, which was identified by microdissection and fluorescence in situ hybridization as an isodicentric chromosome 22(pter --> q11.2::q11.2 --> pter). It was proved with probes specific for the cat eye syndrome critical region that this region was present in quadruplicate in the propositus. We conclude that CES is characterized by large phenotypic variability, ranging from near normal to severe malformations, as reflected in the neurodevelopmental outcome. Preauricular skin tags and/or pits are the most consistent features, and suggest the presence of a supernumerary bisatellited marker chromosome 22 derived from duplication of the CES critical region.

Assessment of the risk of solar ultraviolet radiation to amphibians. I. Dose-dependent induction of hindlimb malformations in the northern leopard frog (Rana pipiens).

PubMed

Ankley, Gerald T; Diamond, Stephen A; Tietge, Joseph E; Holcombe, Gary W; Jensen, Kathleen M; Defoe, David L; Peterson, Ryan

2002-07-01

A number of environmental stressors have been hypothesized as responsible for recent increases in limb malformations in several species of North American amphibians. The purpose of this study was to generate dose-response data suitable for assessing the potential role of solar ultraviolet (UV) radiation in causing limb malformations in a species in which this phenomenon seemingly is particularly prevalent, the northern leopard frog (Rana pipiens). Frogs were exposed from early embryonic stages through complete metamorphosis to varying natural sunlight regimes, including unaltered (100%) sunlight, sunlight subjected to neutral density filtration to achieve relative intensities of 85%, 75%, 65%, 50%, and 25% of unaltered sunlight, and sunlight filtered with glass or acrylamide to attenuate, respectively, the UVB (290-320 nm) and UVB plus UVA (290-380 nm) portions of the spectrum. The experiments were conducted in a controlled setting, with continual monitoring of UVB, UVA, and visible light to support a robust exposure assessment. Full sunlight caused approximately 50% mortality of the frogs during early larval development; no significant treatment-related mortality occurred under any of the other exposure regimes, including 100% sunlight with glass or acrylamide filtration. There was a dose-dependent (p < 0.0001) induction of hindlimb malformations in the frogs, with the percentage of affected animals ranging from about 97% under unaltered sunlight to 0% in the 25% neutral density treatment. Malformations were comprised mostly of missing or truncated digits, and generally were bilateral as well as symmetrical. Filtration of sunlight with either glass or acrylamide both significantly reduced the incidence of malformed limbs. The estimated sunlight dose resulting in a 50% limb malformation rate (ED50) was 63.5%. The limb ED50 values based on measured sunlight intensities corresponded to average daily doses of 4.5 and 100 Wh x m(-2) for UVB and UVA, respectively. Exposure to sunlight also resulted in increased eye malformations in R. pipiens, however, the dose-response relationship for this endpoint was not monotonic. The results of this study, in conjunction with measured or predicted exposure data from natural settings, provide a basis for quantitative prediction of the risk of solar UV radiation to amphibians.

Molecular links among the causative genes for ocular malformation: Otx2 and Sox2 coregulate Rax expression

PubMed Central

Danno, Hiroki; Michiue, Tatsuo; Hitachi, Keisuke; Yukita, Akira; Ishiura, Shoichi; Asashima, Makoto

2008-01-01

The neural-related genes Sox2, Pax6, Otx2, and Rax have been associated with severe ocular malformations such as anophthalmia and microphthalmia, but it remains unclear as to how these genes are linked functionally. We analyzed the upstream signaling of Xenopus Rax (also known as Rx1) and identified the Otx2 and Sox2 proteins as direct upstream regulators of Rax. We revealed that endogenous Otx2 and Sox2 proteins bound to the conserved noncoding sequence (CNS1) located ≈2 kb upstream of the Rax promoter. This sequence is conserved among vertebrates and is required for potent transcriptional activity. Reporter assays showed that Otx2 and Sox2 synergistically activated transcription via CNS1. Furthermore, the Otx2 and Sox2 proteins physically interacted with each other, and this interaction was affected by the Sox2-missense mutations identified in these ocular disorders. These results demonstrate that the direct interaction and interdependence between the Otx2 and Sox2 proteins coordinate Rax expression in eye development, providing molecular linkages among the genes responsible for ocular malformation. PMID:18385377

[PHACES syndrome].

PubMed

Morcillo Azcárate, J; Bernabeu-Wittel, J; Fernández-Pineda, I; Conejo-Mir, M D; Tuduri Limousin, I; Aspiazu Salinas, D A; de Agustín Asensio, J C

2010-04-01

PHACES syndrome associates a segmental facial hemangioma with cerebral malformations, aortic branches/cranial arteries anomalies, cardiac defects, eye anomalies or ventral wall defects. The aim of this study is to analyze our experience with this syndrome. Retrospective study of the cases seen at our unit in the last year. We treat 4 cases; 3 girls and 1 child. Besides the segmental hemangioma they presented: 3 vascular cerebral malformations; 2 structural cardiopathies; 2 cerebral malformations, 1 microftalmia. We did not find ventral wall defects. A case received treatment with two cycles of metilprednisolone i.v. and oral prednisone, with favourable course; two cases received initial treatment with oral prednisone continued of oral propanolol in rising pattern up to 2 mg/kg/day, Obtaining both the detention of the tumour growth and regression of the lesion, with very good tolerance. A 7-year-old patient has been treated with colouring pulse laser for her residual lesions. When we see a segmental facial hemangioma we must perform a wide diagnostic study in order to discard a PHACES syndrome. Multidisciplinar approach to the patient by a wide expert's group gets an earlier diagnose and improves the outcome. Propranolol is a promising therapeutic alternative.

Mutations in extracellular matrix genes NID1 and LAMC1 cause autosomal dominant Dandy-Walker malformation and occipital cephaloceles

PubMed Central

Darbro, Benjamin W.; Mahajan, Vinit B.; Gakhar, Lokesh; Skeie, Jessica M.; Campbell, Elizabeth; Wu, Shu; Bing, Xinyu; Millen, Kathleen J.; Dobyns, William B.; Kessler, John A.; Jalali, Ali; Cremer, James; Segre, Alberto; Manak, J. Robert; Aldinger, Kimerbly A.; Suzuki, Satoshi; Natsume, Nagato; Ono, Maya; Hai, Huynh Dai; Viet, Le Thi; Loddo, Sara; Valente, Enza M.; Bernardini, Laura; Ghonge, Nitin; Ferguson, Polly J.; Bassuk, Alexander G.

2013-01-01

We performed whole-exome sequencing of a family with autosomal dominant Dandy-Walker malformation and occipital cephaloceles (ADDWOC) and detected a mutation in the extracellular matrix protein encoding gene NID1. In a second family, protein interaction network analysis identified a mutation in LAMC1, which encodes a NID1 binding partner. Structural modeling the NID1-LAMC1 complex demonstrated that each mutation disrupts the interaction. These findings implicate the extracellular matrix in the pathogenesis of Dandy-Walker spectrum disorders. PMID:23674478

Proximity to pollution sources and risk of amphibian limb malformation.

PubMed

Taylor, Brynn; Skelly, David; Demarchis, Livia K; Slade, Martin D; Galusha, Deron; Rabinowitz, Peter M

2005-11-01

The cause of limb deformities in wild amphibian populations remains unclear, even though the apparent increase in prevalence of this condition may have implications for human health. Few studies have simultaneously assessed the effect of multiple exposures on the risk of limb deformities. In a cross-sectional survey of 5,264 hylid and ranid metamorphs in 42 Vermont wetlands, we assessed independent risk factors for nontraumatic limb malformation. The rate of nontraumatic limb malformation varied by location from 0 to 10.2%. Analysis of a subsample did not demonstrate any evidence of infection with the parasite Ribeiroia. We used geographic information system (GIS) land-use/land-cover data to validate field observations of land use in the proximity of study wetlands. In a multiple logistic regression model that included land use as well as developmental stage, genus, and water-quality measures, proximity to agricultural land use was associated with an increased risk of limb malformation (odds ratio = 2.26; 95% confidence interval, 1.42-3.58; p < 0.001). The overall discriminant power of the statistical model was high (C = 0.79). These findings from one of the largest systematic surveys to date provide support for the role of chemical toxicants in the development of amphibian limb malformation and demonstrate the value of an epidemiologic approach to this problem.

Investigation of an outbreak of craniofacial deformity in yellow-eyed penguin (Megadyptes antipodes) chicks.

PubMed

Buckle, K N; Young, M J; Alley, M R

2014-09-01

To investigate an outbreak of severe craniofacial deformity in yellow-eyed penguin (Megadyptes antipodes, hōiho) chicks at a single breeding site on the Otago Peninsula in the South Island of New Zealand. Morbidity and mortality of yellow-eyed penguins breeding on the coastal regions of Otago was monitored from November 2008 to March 2009. Dead chicks and unhatched eggs were recovered and examined. Between October and December 2008 32 eggs were recorded at 17 nests in the Okia Reserve. Eleven chicks survived to about 90 days of age, of which eight were found to have moderate to severe craniofacial deformity. The six most severe chicks were subject to euthanasia and examined in detail at necropsy, and the remaining two affected chicks were released to the wild after a period of care in a rehabilitation centre. Post-mortem samples were analysed for inorganic and organic toxins. The six deformed chicks all had severe shortening of the mandible and maxilla by 20-50 mm. The rostral and caudal regions of the skull were approximately 40 and 80% of normal length, respectively. Other, more variable lesions included cross bill deformity, malformed bill keratin, microphthalmia with misshapen scleral ossicles and oral soft tissue excess thought to be secondary to bony malformations. During the same year, mild sporadic bill deformities were also reported in 10 unrelated chicks from >167 chicks at other breeding sites on the southern Otago coast. Concentrations of organic toxins and heavy metals in body tissues from affected chicks were apparently similar to those in unaffected chicks on other beaches. No cause of this outbreak of craniofacial deformity could be established although the high prevalence at a single site suggests that it was due to an unidentified local teratogen.

Clinical, functional, and neurophysiologic assessment of dysplastic cortical networks: Implications for cortical functioning and surgical management.

PubMed

Duchowny, Michael

2009-10-01

Cortical malformations are highly epileptogenic lesions associated with complex, unanticipated, and often aberrant electrophysiologic and functional relationships. These relationships are inextricably linked to widespread cortical networks subserving eloquent functions, particularly language and motor ability. Cytomegalic neurons but not balloon cells in Palmini type 2 dysplastic cortex are intrinsically hyperexcitable and contribute to local epileptogenesis and functional responsiveness. However, there is much evidence that focal cortical dysplasia is rarely a localized or even regional process, and is a functionally, electrophysiologically, and ultimately clinically integrated neural network disorder. Not surprisingly, malformed cortex is implicated in cognitive dysfunction, particularly disturbances of linguistic processing. An understanding of these relationships is critical for successful epilepsy surgery. Gains in surgical prognosis rely on multiple diagnostic modalities to delineate complex anatomic, electrophysiologic, and functional relationships in magnetic resonance imaging (MRI)-negative patients with rates of seizure-freedom roughly comparable to lesional patients.

Histological observation on unique phenotypes of malformation induced in Xenopus tropicalis larvae by tributyltin.

PubMed

Liu, Junqi; Cao, Qinzhen; Yuan, Jing; Zhang, Xiaoli; Yu, Lin; Shi, Huahong

2012-01-01

Tributyltin (TBT), a biocide used in antifouling paints, has shown strong teratogenic effects on Xenopus tropicalis embryos at environmentally relevant concentrations. X. tropicalis embryos were exposed to 50, 100 and 200 ng/L tributyltin chloride for 72 hr. The histological changes were further observed on abnormal eyes, enlarged trunks, enlarged proctodaeums and absence of fins induced by TBT. The lens and the retinal layers of abnormal eyes were slightly or barely differentiated, and that the pigment epithelium was neither continuous nor smooth. The abdomens were full of undifferentiated gut tissue with yolk-rich inclusions in the tadpoles with enlarged trunks. The proctodaeums formed a bump-like or columnar structure. The mass of yolk-rich cells occupied the lumen, blocked the opening and even turned inside out of the proctodaeum. Both the ventral and dorsal fins in trunks and tails became narrow or even disappeared totally. Our results suggest that great changes of histology took place corresponding to the unique phenotypes. The gut tissue was poorly differentiated, which led to the failed elongation of the guts and subsequently the enlarged trunks. The enlarged proctodaeums were due to the undifferentiation of inner layer, the expansion of outer epidermal part and the absence of fins around them. In brief, the histological observations provided insights into the reason of the unique external malformations in some degree.

Mutations in extracellular matrix genes NID1 and LAMC1 cause autosomal dominant Dandy-Walker malformation and occipital cephaloceles.

PubMed

Darbro, Benjamin W; Mahajan, Vinit B; Gakhar, Lokesh; Skeie, Jessica M; Campbell, Elizabeth; Wu, Shu; Bing, Xinyu; Millen, Kathleen J; Dobyns, William B; Kessler, John A; Jalali, Ali; Cremer, James; Segre, Alberto; Manak, J Robert; Aldinger, Kimerbly A; Suzuki, Satoshi; Natsume, Nagato; Ono, Maya; Hai, Huynh Dai; Viet, Le Thi; Loddo, Sara; Valente, Enza M; Bernardini, Laura; Ghonge, Nitin; Ferguson, Polly J; Bassuk, Alexander G

2013-08-01

We performed whole-exome sequencing of a family with autosomal dominant Dandy-Walker malformation and occipital cephaloceles and detected a mutation in the extracellular matrix (ECM) protein-encoding gene NID1. In a second family, protein interaction network analysis identified a mutation in LAMC1, which encodes a NID1-binding partner. Structural modeling of the NID1-LAMC1 complex demonstrated that each mutation disrupts the interaction. These findings implicate the ECM in the pathogenesis of Dandy-Walker spectrum disorders. © 2013 WILEY PERIODICALS, INC.

Assessment of thyroid endocrine system impairment and oxidative stress mediated by cobalt ferrite (CoFe2 O4 ) nanoparticles in zebrafish larvae.

PubMed

Ahmad, Farooq; Liu, Xiaoyi; Zhou, Ying; Yao, Hongzhou; Zhao, Fangfang; Ling, Zhaoxing; Xu, Chao

2016-12-01

Fascinating super paramagnetic uniqueness of iron oxide particles at nano-scale level make them extremely useful in the state of the art therapies, equipments, and techniques. Cobalt ferrite (CoFe 2 O 4 ) magnetic nanoparticles (MNPs) are extensively used in nano-based medicine and electronics, results in extensive discharge and accumulation into the environment. However, very limited information is available for their endocrine disrupting potential in aquatic organisms. In this study, the thyroid endocrine disrupting ability of CoFe 2 O 4 NPs in Zebrafish larvae for 168-h post fertilization (hpf) was evaluated. The results showed the elevated amounts of T4 and T3 hormones by malformation of hypothalamus pituitary axis in zebrafish larvae. These elevated levels of whole body THs leads to delayed hatching, head and eye malformation, arrested development, and alterations in metabolism. The influence of THs disruption on ROS production and change in activities of catalase (CAT), mu-glutathione s-transferase (mu-GST), and acid phosphatase (AP) were also studied. The production of significantly higher amounts of in vivo generation of ROS leads to membrane damage and oxidative stress. Presences of NPs and NPs agglomerates/aggregates were also the contributing factors in mechanical damaging the membranes and physiological structure of thyroid axis. The increased activities of CAT, mu-GST, and AP confirmed the increased oxidative stress, possible DNA, and metabolic alterations, respectively. The excessive production of in vivo ROS leads to severe apoptosis in head, eye, and heart region confirming that malformation leads to malfunctioning of hypothalamus pituitary axis. ROS-induced oxidative DNA damage by formation of 8-OHdG DNA adducts elaborates the genotoxicity potential of CoFe 2 O 4 NPs. This study will help us to better understand the risk and assessment of endocrine disrupting potential of nanoparticles. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 2068-2080, 2016. © 2015 Wiley Periodicals, Inc.

Antidepressant use during pregnancy and the risk of major congenital malformations in a cohort of depressed pregnant women: an updated analysis of the Quebec Pregnancy Cohort

PubMed Central

Bérard, Anick; Zhao, Jin-Ping; Sheehy, Odile

2017-01-01

Objective Antidepressant use during gestation has been associated with risk of major congenital malformations but estimates can lack statistical power or be confounded by maternal depression. We aimed to determine the association between first-trimester exposure to antidepressants and the risk of major congenital malformations in a cohort of depressed/anxious women. Setting and participants Data were obtained from the Quebec Pregnancy Cohort (QPC). All pregnancies with a diagnosis of depression or anxiety, or exposed to antidepressants in the 12 months before pregnancy, and ending with a live-born singleton were included. Outcome measures Antidepressant classes (selective serotonin reuptake inhibitors (SSRI), serotonin–norepinephrine reuptake inhibitors (SNRI), tricyclic antidepressants (TCA) and other antidepressants) and types were individually compared with non-exposure during the first trimester (depressed untreated). Major congenital malformations overall and organ-specific malformations in the first year of life were identified. Results 18 487 pregnant women were included. When looking at the specific types of antidepressant used during the first trimester, only citalopram was increasing the risk of major congenital malformations (adjusted OR, (aOR) 1.36, 95% CI 1.08 to 1.73; 88 exposed cases), although there was a trend towards increased risk for the most frequently used antidepressants. Antidepressants with serotonin reuptake inhibition effect (SSRI, SNRI, amitriptyline (the most used TCA)) increased the risk of certain organ-specific defects: paroxetine increased the risk of cardiac defects (aOR 1.45, 95% CI 1.12 to 1.88), and ventricular/atrial septal defects (aOR 1.39, 95% CI 1.00 to 1.93); citalopram increased the risk of musculoskeletal defects (aOR 1.92, 95% CI 1.40 to 2.62), and craniosynostosis (aOR 3.95, 95% CI 2.08 to 7.52); TCA was associated with eye, ear, face and neck defects (aOR 2.45, 95% CI 1.05 to 5.72), and digestive defects (aOR 2.55, 95% CI 1.40 to 4.66); and venlafaxine was associated with respiratory defects (aOR 2.17, 95% CI 1.07 to 4.38). Conclusions Antidepressants with effects on serotonin reuptake during embryogenesis increased the risk of some organ-specific malformations in a cohort of pregnant women with depression. PMID:28082367

De Novo Mutations in SON Disrupt RNA Splicing of Genes Essential for Brain Development and Metabolism, Causing an Intellectual-Disability Syndrome.

PubMed

Kim, Jung-Hyun; Shinde, Deepali N; Reijnders, Margot R F; Hauser, Natalie S; Belmonte, Rebecca L; Wilson, Gregory R; Bosch, Daniëlle G M; Bubulya, Paula A; Shashi, Vandana; Petrovski, Slavé; Stone, Joshua K; Park, Eun Young; Veltman, Joris A; Sinnema, Margje; Stumpel, Connie T R M; Draaisma, Jos M; Nicolai, Joost; Yntema, Helger G; Lindstrom, Kristin; de Vries, Bert B A; Jewett, Tamison; Santoro, Stephanie L; Vogt, Julie; Bachman, Kristine K; Seeley, Andrea H; Krokosky, Alyson; Turner, Clesson; Rohena, Luis; Hempel, Maja; Kortüm, Fanny; Lessel, Davor; Neu, Axel; Strom, Tim M; Wieczorek, Dagmar; Bramswig, Nuria; Laccone, Franco A; Behunova, Jana; Rehder, Helga; Gordon, Christopher T; Rio, Marlène; Romana, Serge; Tang, Sha; El-Khechen, Dima; Cho, Megan T; McWalter, Kirsty; Douglas, Ganka; Baskin, Berivan; Begtrup, Amber; Funari, Tara; Schoch, Kelly; Stegmann, Alexander P A; Stevens, Servi J C; Zhang, Dong-Er; Traver, David; Yao, Xu; MacArthur, Daniel G; Brunner, Han G; Mancini, Grazia M; Myers, Richard M; Owen, Laurie B; Lim, Ssang-Taek; Stachura, David L; Vissers, Lisenka E L M; Ahn, Eun-Young Erin

2016-09-01

The overall understanding of the molecular etiologies of intellectual disability (ID) and developmental delay (DD) is increasing as next-generation sequencing technologies identify genetic variants in individuals with such disorders. However, detailed analyses conclusively confirming these variants, as well as the underlying molecular mechanisms explaining the diseases, are often lacking. Here, we report on an ID syndrome caused by de novo heterozygous loss-of-function (LoF) mutations in SON. The syndrome is characterized by ID and/or DD, malformations of the cerebral cortex, epilepsy, vision problems, musculoskeletal abnormalities, and congenital malformations. Knockdown of son in zebrafish resulted in severe malformation of the spine, brain, and eyes. Importantly, analyses of RNA from affected individuals revealed that genes critical for neuronal migration and cortex organization (TUBG1, FLNA, PNKP, WDR62, PSMD3, and HDAC6) and metabolism (PCK2, PFKL, IDH2, ACY1, and ADA) are significantly downregulated because of the accumulation of mis-spliced transcripts resulting from erroneous SON-mediated RNA splicing. Our data highlight SON as a master regulator governing neurodevelopment and demonstrate the importance of SON-mediated RNA splicing in human development. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Teratogenic effects of 4-nonylphenol on early embryonic and larval development of the catfish Heteropneustes fossilis.

PubMed

Chaube, Radha; Gautam, Geeta J; Joy, Keerikattil P

2013-05-01

Alkylphenol polyethoxylates (APEs), which are widely used in detergents, paints, herbicides, insecticides, and in many other formulations, have been widely detected in aquatic environments. 4-Nonylphenol (NP) is an important APE detected at microgram levels per litre (0.1-336 μg/L) in water. The objective of the present study was to evaluate NP's toxic effects at low and high sublethal concentrations (0.1 and 1 μg/L) on embryonic development of the catfish Heteropneustes fossilis at different time intervals. The data show that fertilization rate was decreased and cleavage and blastula were severely affected leading to complete mortality of embryos. NP exposure resulted in various body malformations in larvae, such as vertebral deformations, e.g., fin blistering/necrosis, axial deformities (lordosis, kyphosis, and scoliosis) of the spine in the abdominal and caudal region, tail curved completely backward, shortened body, severe spinal and yolk sac malformations, C-shaped severe spinal curvature, cranial malformation with undeveloped head, and failure of eye development. The level of body malformations increased with the concentration and exposure time. After 72 h of exposure, all larvae were dead at both concentrations. Scanning electron microscope study showed that epidermal cells (keratinocytes) were severely damaged in both low- and high-dose treatments throughout development, leading to development of numerous depressions representing sinking holes on the skin. Mucous glands increased significantly in treatment groups compared with control groups. The present study highlights the severe teratogenic effects of NP. The prevalence of the contaminant, if not checked, can lead to decreased population and ultimate disappearance of the species.

Proximity to Pollution Sources and Risk of Amphibian Limb Malformation

PubMed Central

Taylor, Brynn; Skelly, David; Demarchis, Livia K.; Slade, Martin D.; Galusha, Deron; Rabinowitz, Peter M.

2005-01-01

The cause of limb deformities in wild amphibian populations remains unclear, even though the apparent increase in prevalence of this condition may have implications for human health. Few studies have simultaneously assessed the effect of multiple exposures on the risk of limb deformities. In a cross-sectional survey of 5,264 hylid and ranid metamorphs in 42 Vermont wetlands, we assessed independent risk factors for nontraumatic limb malformation. The rate of nontraumatic limb malformation varied by location from 0 to 10.2%. Analysis of a subsample did not demonstrate any evidence of infection with the parasite Ribeiroia. We used geographic information system (GIS) land-use/land-cover data to validate field observations of land use in the proximity of study wetlands. In a multiple logistic regression model that included land use as well as developmental stage, genus, and water-quality measures, proximity to agricultural land use was associated with an increased risk of limb malformation (odds ratio = 2.26; 95% confidence interval, 1.42–3.58; p < 0.001). The overall discriminant power of the statistical model was high (C = 0.79). These findings from one of the largest systematic surveys to date provide support for the role of chemical toxicants in the development of amphibian limb malformation and demonstrate the value of an epidemiologic approach to this problem. PMID:16263502

Hemifacial Microsomia in a Cat.

PubMed

Song, R B; Kent, M; Glass, E N; Davis, G J; Castro, F A; de Lahunta, A

2017-10-01

A 7-month-old domestic medium hair cat presented with facial asymmetry affecting the bony and soft tissue structures of the right side of the head including the maxilla, nose, eye and pinna of the ear. Additionally, neurological dysfunction of the facial and vestibulocochlear nerves on the affected side was present. A congenital malformation affecting the first and second embryologic pharyngeal arches was suspected. This is the first case of hemifacial microsomia of likely congenital origin reported in a cat. © 2017 Blackwell Verlag GmbH.

CANCER MORTALITY AND BIRTH MALFORMATIONS IN FOUR WHEAT - PRODUCING U.S. STATES.

EPA Science Inventory

Newly emerging global patterns of disease have been observed. Environmental exposures, which are involuntary, widespread, and mostly low-dose in nature, have been implicated. Comparisons of populations rather than individuals are needed to identify health effects resulting fr...

Do the cerebellar tonsils move during flexion and extension of the neck in patients with Chiari I malformation? A radiological study with clinical implications.

PubMed

Tubbs, R Shane; Kirkpatrick, Christina M; Rizk, Elias; Chern, Joshua J; Oskouian, Rod J; Oakes, W Jerry

2016-03-01

In the past, diagnosis of the Chiari I malformation has primarily been made on midsagittal MRI. We hypothesized that based on the frequent presentation of opisthotonos in patients with hindbrain hernia (primarily Chiari II malformation but sometimes Chiari I malformation) that the hyperextension might be a compensatory technique used by such patients to bring the cerebellar tonsils up out of the cervical spine. This prospective study reviewed imaging of patients with Chiari I malformation who underwent flexion/extension MRI for evaluation of their hindbrain herniation. Age-matched controls were used for comparison. In general, there was elevation of the cerebellar tonsils with extension and increased descent with flexion of the cervical spine. In 72 % of patients, flexion of the neck resulted in descent of the cerebellar tonsils. In 64 % of patients, extension of the neck resulted in ascent of the cerebellar tonsils. In the 14 patients with an associated syrinx, 71 % were found to have caudal movement of the cerebellar tonsils with neck flexion, and only 43 % were observed to have any movement of the cerebellar tonsils in neck extension compared to patients without a syrinx where ascent of the tonsils was seen in only nine during neck extension. Two patients were observed to have the reverse finding of ascent of the cerebellar tonsils with neck flexion and descent of the cerebellar tonsils with neck extension. Five patients had no movement of the cerebellar tonsils in either flexion or extension of the neck, and one of these had a small syrinx. Although minimal and not in all patients, we observed elevation of the herniated cerebellar tonsils with extension of the cervical spine in patients with Chiari I malformation. This finding provides evidence as to why some patients with hindbrain herniation present with opisthotonos and supports earlier findings that CSF flow is reduced at the craniocervical junction in flexion in patients with Chiari I malformation.

Double trisomy 48,XXX,+18 with multiple dysmorphic features.

PubMed

Jiang, Zi-Yan; Wu, Xiao-Hui; Zou, Chao-Chun

2015-02-01

Chromosomal abnormality is a common cause of congenital anomalies, psychiatric disorders, and mental retardation. However, the double trisomy 48,XXX,+18 is a rare chromosome abnormality. Case report and literature review. A 7-hour-old girl presented to our unit because of poor response after birth. She presented with multiple dysmorphic features, including small for gestational age infant, flat nasal bridge, widely-spaced eyes, the left thumb deformities, flat facial profile, raised sternum, ventricular septal defect, the third lateral brain ventricle enlargement, and small liver. This case expands the spectrum of malformations reported in association with the double trisomy 48,XXX,+18. The literature on 16 fetuses or infants with the 48,XXX,+18 were also reviewed. These data suggested that in patients with clinical features similar to trisomy 18, especially with anomalies of the ears and/or reproductive malformations, double trisomy (48,XXX,+18) should be considered and karyotyping should be performed although it is a rare disease.

Teratogenic effects of external egg applications of methyl mercury in the mallard, Anas platyrhynchos

USGS Publications Warehouse

Hoffman, D.J.; Moore, Johnnie N.

1979-01-01

The embryotoxic potential of external applications of methyl mercury on mallard eggs was investigated to assess the possible impact of mercury transferred from the plumage of effluent-contaminated aquatic birds to their eggs. Eggs were treated on day 3 of development with microliter applications of methyl mercury that was dissolved with ethyl acetate into an aliphatic hydrocarbon vehicle. Mercury analysis by atomic absorption indicated that almost half of the mercury applied entered the eggs past the shell membranes within several days of treatment. Most mortality occurred within this period at doses of 9 microgram of mercury per egg or higher. Decreased embryonic growth resulted with similar doses. A significant incidence of malformations occurred at a dose of 1 microgram per egg. These malformations were mainly minor skeletal aberrations and incomplete ossification. With higher doses of mercury, defects included gross external ones such as micromella, gastroschisis, and eye and brain defects. Application of the aliphatic hydrocarbon vehicle did not result in any of these defects.

The presentation and management of complex female genital malformations.

PubMed

Acién, Pedro; Acién, Maribel

2016-01-01

Common uterine anomalies are important owing to their impact on fertility, and complex mesonephric anomalies and certain Müllerian malformations are particularly important because they cause serious clinical symptoms and affect woman's quality of life, in addition to creating fertility problems. In these cases of complex female genital tract malformations, a correct diagnosis is essential to avoid inappropriate and/or unnecessary surgery. Therefore, acquiring and applying the appropriate embryological knowledge, management and therapy is a challenge for gynaecologists. Here, we considered complex malformations to be obstructive anomalies and/or those associated with cloacal and urogenital sinus anomalies, urinary and/or extragenital anomalies, or other clinical implications or symptoms creating a difficult differential diagnosis. A diligent and comprehensive search of PubMed and Scopus was performed for all studies published from 1 January 2011 to 15 April 2015 (then updated up to September 2015) using the following search terms: 'management' in combination with either 'female genital malformations' or 'female genital tract anomalies' or 'Müllerian anomalies'. The MeSH terms 'renal agenesis', 'hydrocolpos', 'obstructed hemivagina' 'cervicovaginal agenesis or atresia', 'vaginal agenesis or atresia', 'Herlyn-Werner-Wunderlich syndrome', 'uterine duplication' and 'cloacal anomalies' were also used to compile a list of all publications containing these terms since 2011. The basic embryological considerations for understanding female genitourinary malformations were also revealed. Based on our experience and the updated literature review, we studied the definition and classification of the complex malformations, and we analysed the clinical presentation and different therapeutic strategies for each anomaly, including the embryological and clinical classification of female genitourinary malformations. From 755 search retrieved references, 230 articles were analysed and 120 studied in detail. They were added to those included in a previous systematic review. Here, we report the clinical presentation and management of: agenesis or hypoplasia of one urogenital ridge; unilateral renal agenesis and ipsilateral blind or obstructed hemivagina or unilateral cervicovaginal agenesis; cavitated and non-communicating uterine horns and Müllerian atresias or agenesis, including Rokitansky syndrome; anomalies of the cloaca and urogenital sinus, including congenital vagino-vesical fistulas and cloacal anomalies; malformative combinations and other complex malformations. The clinical symptoms and therapeutic strategies for each complex genitourinary malformation are discussed. In general, surgical techniques to correct genital malformations depend on the type of anomaly, its complexity, the patient's symptoms and the correct embryological interpretation of the anomaly. Most anomalies can typically be resolved vaginally or by hysteroscopy, but laparoscopy or laparotomy is often required as well. We also include additional discussion of the catalogue and classification systems for female genital malformations, the systematic association between renal agenesis and ipsilateral genital malformation, and accessory and cavitated uterine masses. Knowledge of the correct genitourinary embryology is essential for the understanding, study, diagnosis and subsequent treatment of genital malformations, especially complex ones and those that lead to gynaecological and reproductive problems, particularly in young patients. Some anomalies may require complex surgery involving multiple specialties, and patients should therefore be referred to centres that have experience in treating complex genital malformations. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Cyclopia: from Greek antiquity to medical genetics.

PubMed

Kalantzis, George C; Tsiamis, Costas B; Poulakou-Rebelakou, Effie L

2013-01-01

Cyclops are among the best-known monsters of Greek mythology, also mentioned in art and literature. According to the most recent scientific knowledge, the malformations caused by defective development of the anterior brain and midline mesodermal structures include cyclopia (synophthalmos), ethmocephaly, cebocephaly and arrhinencephaly. These severe forebrain lesions often are accompanied by severe systemic malformations, and affected infants rarely survive. Neither true cyclopia nor synophthalmos are compatible with life because an anomalous development of the brain is involved. Thus, it is difficult to assume that ancient Greeks drew their inspiration from an adult patient suffering from cyclopia. Cyclops appear for the first time in literature in Homer's Odyssey (8th-7th century BC) and one of them, Polyphemus, is blinded by the hero of the epic poem. The description of the creature is identical with patients suffering from cyclopia; eyes are fused and above the median eye there is a proboscis, which is the result of an abnormal development of the surface ectodermal structures covering the brain. The next literature appearance of Cyclops is at the end of 7th century BC in "Theogonia", written by Hesiodus. Another interesting description is made by Euripides in his satyr play entitled 'Cyclops' (5th century BC). In conclusion, though it is not certain whether Homer's description of Cyclops was based on his personal experience or the narration of his ancestors, there is no doubt that the ophthalmological disease, cyclopia, was named after this mythical creature.

Acute Respiratory Distress Syndrome after Onyx Embolization of Arteriovenous Malformation

PubMed Central

Tawil, Isaac; Carlson, Andrew P.; Taylor, Christopher L.

2011-01-01

Purpose. We report a case of a 60-year-old male who underwent sequential Onyx embolizations of a cerebral arteriovenous malformation (AVM) which we implicate as the most likely etiology of subsequent acute respiratory distress syndrome (ARDS). Methods. Case report and literature review. Results. Shortly after the second Onyx embolization procedure, the patient declined from respiratory failure secondary to pulmonary edema. Clinical entities typically responsible for pulmonary edema including cardiac failure, renal failure, iatrogenic volume overload, negative-pressure pulmonary edema, and infectious etiologies were evaluated and excluded. The patient required mechanical ventilatory support for several days, delaying operative resection. The patient met clinical and radiographic criteria for ARDS. After excluding other etiologies of ARDS, we postulate that ARDS developed as a result of Onyx administration. The Onyx copolymer is dissolved in dimethyl sulfoxide (DMSO), a solvent excreted through the lungs and has been implicated in transient pulmonary side effects. Additionally, a direct toxic effect of the Onyx copolymer is postulated. Conclusion. Onyx embolization and DMSO toxicity are implicated as the etiology of ARDS given the lack of other inciting factors and the close temporal relationship. A strong physiologic rationale provides further support. Clinicians should consider this uncommon but important complication. PMID:21687580

A novel OTX2 mutation in a patient with combined pituitary hormone deficiency, pituitary malformation, and an underdeveloped left optic nerve.

PubMed

Gorbenko Del Blanco, Darya; Romero, Christopher J; Diaczok, Daniel; de Graaff, Laura C G; Radovick, Sally; Hokken-Koelega, Anita C S

2012-09-01

Orthodenticle homolog 2 (OTX2) is a homeobox family transcription factor required for brain and eye formation. Various genetic alterations in OTX2 have been described, mostly in patients with severe ocular malformations. In order to expand the knowledge of the spectrum of OTX2 mutation, we performed OTX2 mutation screening in 92 patients with combined pituitary hormone deficiency (CPHD). We directly sequenced the coding regions and exon-intron boundaries of OTX2 in 92 CPHD patients from the Dutch HYPOPIT study in whom mutations in the classical CPHD genes PROP1, POU1F1, HESX1, LHX3, and LHX4 had been ruled out. Among 92 CPHD patients, we identified a novel heterozygous missense mutation c.401C>G (p.Pro134Arg) in a patient with CPHD, pituitary malformation, and an underdeveloped left optic nerve. Binding of both the wild-type and mutant OTX2 proteins to bicoid binding sites was equivalent; however, the mutant OTX2 exhibited decreased transactivation. We describe a novel missense heterozygous OTX2 mutation that acts as a dominant negative inhibitor of target gene expression in a patient with CPHD, pituitary malformation, and optic nerve hypoplasia. We provide an overview of all OTX2 mutations described till date, which show that OTX2 is a promising candidate gene for genetic screening of patients with CPHD or isolated GH deficiency (IGHD). As the majority of the OTX2 mutations found in patients with CPHD, IGHD, or short stature have been found in exon 5, we recommend starting mutational screening in those patients in exon 5 of the gene.

PHACE syndrome: new views on diagnostic criteria.

PubMed

Poetke, M; Frommeld, T; Berlien, H P

2002-12-01

The association of large facial hemangiomas with posterior fossa malformations and vascular anomalies has been termed the PHACE syndrome. It is characterized by the association of posterior fossa malformations, hemangiomas, arterial anomalies, coarctation of the aorta and other cardiac defects, and eye abnormalities. Since most articles focus on isolated case reports, an extended retrospective literature review of all reports of large hemangiomas with associated abnormalities of the central nervous system and other malformations was performed to examine the clinical features, and other not as yet reported associated anomalies. Reports were found on 59 patients with PHACE syndrome, to which we added ten cases of our own. The Dandy-Walker syndrome is the most common CNS abnormality reported in association with PHACE syndrome and was seen in 48 (81 %) patients. Arterial malformations were found in 13 (22 %) cases; only 11 patients (19 %) had structural arterial abnormalities without associated Dandy-Walker complex. As published, about one third of patients (31 %) had further ophthalmologic abnormalities, and cardiac anomalies, including coarctation of the aorta. Subglottic hemangiomas were seen in 4 (7 %) patients and ventral developmental defects also in 3 cases. In seven of 59 patients (12 %) with PHACE syndrome, intracranial hemangiomas were present. This study demonstrates that among other CNS abnormalities, special attention should be given to intracranial hemangiomas which seems to be a peculiar phenotype of PHACE syndrome. We therefore suggest that a sixth criterion should be added to the five minimal inclusion criteria for PHACE syndrome. The inclusion criteria would then be: arterial abnormalities or/and intracranial hemangiomas. On the basis of our experience with our patients and with those previously reported, we stress the importance of using contrast-enhanced imaging to detect intracranial lesions.

Teratology in cultural documents and today.

PubMed

Schumacher, Gert-Horst

2004-12-01

Teratology is the science of congenital malformations. The incidence of birth defects amounts to 2-3%, but it doubles postnatal owing to the fact that many dysfunctions are not discernible at birth. Congenital malformations were already known in ancient cultures, records from Assyrian and Babylonian astrologists as well as from physicians and philosophers of the Hippocratic era are testifying it. In medieval times they were recognized as supernatural phenomenons, terata, from what the term TERATOLOGY derived. In the eyes of the superstitious people affected stillborns were regarded as monster, symbol of devil or miracle. The foundation of anatomy as a science by Vesalius marked the beginning of a reorientation. In the 17th century, when the age of enlightenment began, ideas concerning the origin of birth defects became more objective. Original studies dealing with congenital malformations became common in the 18th century. Fundamental discoveries made by microscopy placed Teratology on a truly scientific basis. Significant impetus was grown to teratological research with the discovery of Gregg (1941) that German measles (rubella virus) of pregnant women caused birth defects in the embryo and the contergan disaster (1959--1962). Congenital malformations originate from genetic factors (single gene defects and chromosomal aberrations) and environmental factors, such as radiation, drugs, chemicals, and infectious agents. The susceptibility of teratogen depends on the period of embryonal development, which is classified into gametogenesis, blastogenesis, embryogenesis and fetogenesis. The Food and Drug Administration of the USA published guidelines for teratogenetic testing (1966). There are in-vivo and in-vitro-test programmes, the latter became of increasing importance owing to the large number of chemicals to be tested and the activities of opponents against animal experiments. Although great advances were made, the problem remained to transfer results from in-vivo and in-vitro tests to the constitution of man without risk.

Posterior reversible encephalopathy syndrome in a patient with a Chiari I malformation

PubMed Central

Hansberry, David R.; Agarwal, Nitin; Tomei, Krystal L.; Goldstein, Ira M.

2013-01-01

Background: The authors describe a unique case of a patient who developed posterior reversible encephalopathy syndrome (PRES) following postoperative treatment of a Chiari I malformation. Case Decsription: A 25-year-old female presented with complaints of left upper and lower extremity paresthesias and gait disturbances. A magnetic resonance imaging (MRI) of the brain and cervical spine showed a Chiari I malformation with tonsillar descent beyond the level of the C1 lamina. She underwent a suboccipital craniectomy and C1 laminectomy with cerebellar tonsillar cauterization and duraplasty. Postoperatively, an MRI showed bilateral acute infarcts of the cerebellar vermis. She was initially treated for cerebellar ischemia with hypertensive therapy with a subsequent decline in her neurologic status and generalized tonic–clonic seizure. Further workup showed evidence of PRES. After weaning pressors, the patient had a significant progressive improvement in her mental status. Conclusion: Although the mechanism of PRES remains controversial given its diverse clinical presentation, several theories implicate hypertension and steroid use as causative agents. PMID:24232171

Frontonasal malformation with tetralogy of Fallot associated with a submicroscopic deletion of 22q11

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stratton, R.F.; Payne, R.M.

We report on a 14-month-old girl with bifid nasal tip and tetralogy of Fallot. Several similar patients have been described with CNS or eye abnormalities. Chromosome analysis with FISH, using Oncor DiGeorge probes, confirmed a submicroscopic deletion of 22q11. Many patients with Shprintzen (velo-cardio-facial) syndrome have a similar deletion with conotruncal cardiac defects and an abnormal nasal shape, suggesting that a gene in this area, possibly affecting neural crest cells, influences facial and other midline development. 13 refs., 1 fig.

[Partial trisomy 2p due to a familial translocation 2/6. Cytogenetic and clinical case with special reference to ophthalmologic changes].

PubMed

Mayer, U; Schwanitz, G; Grosse, K P; Etzold, R

1978-09-01

A translocation 2/6 inherited for 3 generations is described. The propositus, carrier of a partial trisomy 2p, showed multiple morphological anomalies of which microphtalmus and persistance of primary vitreous body were of particular interest. Based on a comparison of this with seven other patients in the literature, the most characteristic clinical symptoms of partial trisomy 2p are concluded to be the following: abundant lanugo at birth, glabella prominence, anteverted nares, dermatoglyphic anomalies, and malformations of the eyes.

Developmental toxicity of p,p'-dichlorodiphenyltrichloroethane, 2,4,6-trinitrotoluene, their metabolites, and benzo[a]pyrene in Xenopus laevis embryos.

PubMed

Saka, Masahiro

2004-04-01

Since 1995, high incidences of deformed frogs have been documented in Kitakyushu, Japan. In this area, relatively high concentrations of DDT, trinitrotoluene (TNT), their metabolites (p,p'-dichlorodiphenyldichloroethylene [DDE], p,p'-dichlorodiphenyldichloroethane [DDD], 2-amino-4,6-dinitrotoluene [2ADNT], and 4-amino-2,6-dinitrotoluene [4ADNT]), and benzo[a]pyrene [BaP]) have been identified from field samples. I used a standardized assay with Xenopus laevis embryos (frog embryo teratogenesis assay--Xenopus, FETAX) to examine the developmental toxicity of these compounds. Both DDE and BaP were considered nearly nontoxic in embryonic development because they induced low (< 10%) mortality and malformation incidence even at the highest concentrations tested (DDE, 393 microM; BaP, 13.2 microM). The DDD (96-h median lethal concentration [LC50] = 44.1 microM, 96-h median effective concentration [EC50] for malformation = 14.9 microM) was more lethal and teratogenic than its parent compound, DDT (96-h LC50 = 101 microM, 96-h EC50 = 41.5 microM). Predominant symptoms observed were axial malformations (DDT and DDD) and irregular gut coiling (DDT). However, DDT and DDD should not act as major lethal or teratogenic toxicants in the aquatic environment within a short-term exposure via water because their 96-h LC50 and 96-h EC50 values were extremely high, considering their low solubility in water. The TNT (96-h LC50 = 16.7 microM) was more lethal than 2ADNT (96-h LC50 = 166 microM) or 4ADNT (96-h LC50 = 115 microM). Although 4ADNT (96-h EC50 = 85.8 microM) induced various tadpole malformations, it was a weak teratogen compared with TNT (96-h EC50 = 9.78 microM) and 2ADNT (96-h EC50 = 16.9 microM). The most typical malformations observed were axial malformations, eye abnormalities (TNT), edema, and irregular gut coiling (2ADNT and 4ADNT). The 96-h LC50 and 96-h EC50 values of TNT, 2ADNT, and 4ADNT were lower than their saturated concentrations in water. Therefore, these nitroaromatic compounds may show lethal or teratogenic effects on aquatic animals if their habitats are severely contaminated with TNT.

Early physical and motor development of mouse offspring exposed to valproic acid throughout intrauterine development.

PubMed

Podgorac, Jelena; Pešić, Vesna; Pavković, Željko; Martać, Ljiljana; Kanazir, Selma; Filipović, Ljupka; Sekulić, Slobodan

2016-09-15

Clinical research has identified developmental delay and physical malformations in children prenatally exposed to the antiepileptic drug (AED) valproic acid (VPA). However, the early signs of neurodevelopmental deficits, their evolution during postnatal development and growth, and the dose effects of VPA are not well understood. The present study aimed to examine the influence of maternal exposure to a wide dose range (50, 100, 200 and 400mg/kg/day) of VPA during breeding and gestation on early physical and neuromotor development in mice offspring. Body weight gain, eye opening, the surface righting reflex (SRR) and tail suspension test (TST) were examined in the offspring at postnatal days 5, 10 and 15. We observed that: (1) all tested doses of VPA reduced the body weight of the offspring and the timing of eye opening; (2) offspring exposed to VPA displayed immature forms of righting and required more time to complete the SRR; (3) latency for the first immobilization in the TST is shorter in offspring exposed to higher doses of VPA; however, mice in all groups exposed to VPA exhibited atypical changes in this parameter during the examined period of maturation; (4) irregularities in swinging and curling activities were observed in animals exposed to higher doses of VPA. This study points to delayed somatic development and postponed maturation of the motor system in all of the offspring prenatally exposed to VPA, with stronger effects observed at higher doses. The results implicate that the strategy of continuous monitoring of general health and achievements in motor milestones during the early postnatal development in prenatally VPA-exposed offspring, irrespectively of the dose applied, could help to recognize early developmental irregularities. Copyright © 2016 Elsevier B.V. All rights reserved.

Ocular phenotypes associated with two mutations (R121W, C126X) in the Norrie disease gene.

PubMed

Kellner, U; Fuchs, S; Bornfeld, N; Foerster, M H; Gal, A

1996-06-01

To describe the ocular phenotypes associated with 2 mutations in the Norrie disease gene including a manifesting carrier. Ophthalmological examinations were performed in 2 affected males and one manifesting carrier. Genomic DNA was analyzed by direct sequencing of the Norrie disease gene. Family I: A 29-year-old male had the right eye enucleated at the age of 3 years. His left eye showed severe temporal dragging of the retina and central scars. Visual acuity was 20/300. DNA analysis revealed a C-to-T transition of the first nucleotide in codon 121 predicting the replacement of arginine-121 by tryptophan (R121W). Both the mother and maternal grandmother carry the same mutation in heterozygous form. Family 2: A 3-month-old boy presented with severe temporal dragging of the retina on both eyes and subsequently developed retinal detachment. Visual acuity was limited to light perception. His mother's left eye was amaurotic and phthitic. Her right eye showed severe retinal dragging, visual acuity was reduced to 20/60. DNA analysis revealed a T-to-A transversion of the third nucleotide in codon 126 creating a stop codon (C126X). The mother and maternal grandmother were carriers. Mutations in the Norrie disease gene can lead to retinal malformations of variable severity both in hemizygous males and manifesting carriers.

Maternal Inheritance of a Recessive RBP4 Defect in Canine Congenital Eye Disease.

PubMed

Kaukonen, Maria; Woods, Sean; Ahonen, Saija; Lemberg, Seppo; Hellman, Maarit; Hytönen, Marjo K; Permi, Perttu; Glaser, Tom; Lohi, Hannes

2018-05-29

Maternally skewed transmission of traits has been associated with genomic imprinting and oocyte-derived mRNA. We report canine congenital eye malformations, caused by an amino acid deletion (K12del) near the N terminus of retinol-binding protein (RBP4). The disease is only expressed when both dam and offspring are deletion homozygotes. RBP carries vitamin A (retinol) from hepatic stores to peripheral tissues, including the placenta and developing eye, where it is required to synthesize retinoic acid. Gestational vitamin A deficiency is a known risk factor for ocular birth defects. The K12del mutation disrupts RBP folding in vivo, decreasing its secretion from hepatocytes to serum. The maternal penetrance effect arises from an impairment in the sequential transfer of retinol across the placenta, via RBP encoded by maternal and fetal genomes. Our results demonstrate a mode of recessive maternal inheritance, with a physiological basis, and they extend previous observations on dominant-negative RBP4 alleles in humans. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Anophthalmia-plus syndrome: a clinical report and review of the literature.

PubMed

Makhoul, Imad R; Soudack, Michalle; Kochavi, Orna; Guilburd, Joseph N; Maimon, Shimon; Gershoni-Baruch, Ruth

2007-01-01

We describe a term male infant of healthy non-consanguineous parents, born with congenital malformations, including bilateral cleft palate and lip, mild microphthalmia with iris coloboma and glaucoma of the right eye, and blepharophimosis with severe microphthalmia of the left eye. Spine radiograph and MRI showed first sacral hemivertebra with spina bifida, and agenesis of the 2nd, 3rd, 4th, and 5th sacral vertebrae and coccyx. Spine MRI showed caudal tethering of spinal cord at L(3) level, filum terminalis lipoma and a syringomyelia. Brain ultrasound and MRI showed hypoplasia of corpus callosum with mild dilatation of the lateral ventricles. Orbital MRI showed bilateral microphthalmia-distorted small left eyeball with posteriorly located lens, and a split vitreous body in the right eye, suggestive of primary hyperplastic vitreous. The karyotype was normal. Summary of the findings in nine cases (our case and eight published cases) support the notion that anophthalmia-plus syndrome (APS) is a distinct syndrome. Gene locus of APS is yet to be identified. (c) 2006 Wiley-Liss, Inc.

Social Implications of Spina Bifida.

ERIC Educational Resources Information Center

Woodburn, Margaret

Investigated in Southeast Scotland were the social and practical problems faced by the parents of 86 children (ages 18 months to 38 years) with spina bifida, 74 of whom were classified as myelomeningoceles (a more serious condition involving malformation of the spinal cord). Questionnaires and interviews were used to gather information in the…

Strategies for assessing the implications of malformed frogs for environmental health.

PubMed Central

Burkhart, J G; Ankley, G; Bell, H; Carpenter, H; Fort, D; Gardiner, D; Gardner, H; Hale, R; Helgen, J C; Jepson, P; Johnson, D; Lannoo, M; Lee, D; Lary, J; Levey, R; Magner, J; Meteyer, C; Shelby, M D; Lucier, G

2000-01-01

The recent increase in the incidence of deformities among natural frog populations has raised concern about the state of the environment and the possible impact of unidentified causative agents on the health of wildlife and human populations. An open workshop on Strategies for Assessing the Implications of Malformed Frogs for Environmental Health was convened on 4-5 December 1997 at the National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina. The purpose of the workshop was to share information among a multidisciplinary group with scientific interest and responsibility for human and environmental health at the federal and state level. Discussions highlighted possible causes and recent findings directly related to frog deformities and provided insight into problems and strategies applicable to continuing investigation in several areas. Possible causes of the deformities were evaluated in terms of diagnostics performed on field amphibians, biologic mechanisms that can lead to the types of malformations observed, and parallel laboratory and field studies. Hydrogeochemistry must be more integrated into environmental toxicology because of the pivotal role of the aquatic environment and the importance of fates and transport relative to any potential exposure. There is no indication of whether there may be a human health factor associated with the deformities. However, the possibility that causal agents may be waterborne indicates a need to identify the relevant factors and establish the relationship between environmental and human health in terms of hazard assessment. PMID:10620528

Sturge-Weber syndrome type II treated with PDL 595 nm laser.

PubMed

Kowalska-Brocka, Joanna; Brocki, Maciej; Uczniak, Sebastian; Uczniak, Kamila; Kaszuba, Andrzej; Jurowski, Piotr

2015-02-01

Sturge-Weber syndrome (SWS) is rare congenital disorder presenting facial port-wine stains (PWS) eye abnormalities and cerebrovascular malformations. The frequency of SWS is estimated at 1 in 50 000. Cerebrovascular abnormalities can be responsible for seizures, hemiparesis, mental retardation and ophthalmologic abnormalities cause intraocular pressure, glaucoma. Etiopathogenesis of SWS remains elusive. We present a case of a 7-year-old girl with SWS type II. A port-wine stain involves the upper right part of half face and has been associated with glaucoma of both eyes. In the Department of Dermatology in 2009-2012 we performed 23 procedures within 2 months. We have been using PDL laser at wavelength 595 nm and very good cosmetic results were achieved. Given positive treatment effects, the laser therapy of port-wine stains is a method of selection. Port-wine stains in the course of SWS requires a large number of laser treatment.

Sturge-Weber syndrome type II treated with PDL 595 nm laser

PubMed Central

Brocki, Maciej; Uczniak, Sebastian; Uczniak, Kamila; Kaszuba, Andrzej; Jurowski, Piotr

2015-01-01

Sturge-Weber syndrome (SWS) is rare congenital disorder presenting facial port-wine stains (PWS) eye abnormalities and cerebrovascular malformations. The frequency of SWS is estimated at 1 in 50 000. Cerebrovascular abnormalities can be responsible for seizures, hemiparesis, mental retardation and ophthalmologic abnormalities cause intraocular pressure, glaucoma. Etiopathogenesis of SWS remains elusive. We present a case of a 7-year-old girl with SWS type II. A port-wine stain involves the upper right part of half face and has been associated with glaucoma of both eyes. In the Department of Dermatology in 2009–2012 we performed 23 procedures within 2 months. We have been using PDL laser at wavelength 595 nm and very good cosmetic results were achieved. Given positive treatment effects, the laser therapy of port-wine stains is a method of selection. Port-wine stains in the course of SWS requires a large number of laser treatment. PMID:25821431

SELECTIVE VULNERABILITY OF EMBRYONIC CELL POPULATIONS TO ETHANOL-INDUCED APOPTOSIS: IMPLICATIONS FOR ALCOHOL RELATED BIRTH DEFECTS AND NEURODEVELOPMENTAL DISORDER

EPA Science Inventory

The locations of cell death and resulting malformations in embryos following teratogen exposure vary depending on the teratogen used, the genotype of the conceptus, and the developmental stage of the embryo at time of exposure. To date, ethanol-induced cell death has been charac...

H-type tracheoesophageal fistula with type III laryngotracheoesophageal cleft.

PubMed

Antao, Brice; Soccorso, Giampiero; Bateman, Neil; Shawis, Rang

2007-11-01

H-type tracheoesophageal fistula and laryngotracheoesophageal cleft are both rare anomalies. Laryngotracheoesophageal clefts are identified as a part of Opitz-Frias syndrome. We report a neonate with this combination of rare congenital anomalies. These associated malformations can have major implications in terms of resuscitation, diagnosis and surgical management, which are discussed.

SPATIAL AND TEMPORAL VARIABILITY IN THE AMOUNT AND SOURCE OF DISSOLVED ORGANIC CARBON: IMPLICATIONS FOR UV EXPOSURE IN AMPHIBIAN HABITS

EPA Science Inventory

Ultraviolet radiation (UVR) has been suggested as a potential cause of population declines and increases in malformations in amphibians. This study indicates that the present distributions of amphibians in four western U.S. National Parks are not related to UVR exposure and sugge...

Anomalies of the systemic venous return: a review.

PubMed

Mazzucco, A; Bortolotti, U; Stellin, G; Gallucci, V

1990-06-01

Congenital anomalies of the systemic venous connection to the heart represent a rather wide and heterogeneous group of malformations, whose physiological consequences may vary from nil to the most severe form of systemic arterial desaturation. The malformations may be summarized as follows: (1) Left superior vena cava connected to the coronary sinus, interrupted inferior vena cava and absent right superior vena cava that do not indicate surgical repair 'per se', but require some technical attention during open heart surgery performed for other anomalies; (2) Left superior vena cava connected to the left atrium, due to incorporation of the coronary sinus into the left atrial cavity, resulting in a right-to-left-shunt; (3) Right superior vena cava or inferior vena cava draining into the left atrium, both are extremely rare and require treatment for the ensuing right-to-left shunt; (4) Total anomalous systemic venous connection to the left atrium, usually combined with atrial isomerism and other very complex heart malformations; (5) Cor triatriatum dexter, which has been frequently diagnosed as an anomalous venous connection for its similar hemodynamic consequences. Such anomalies are reviewed with particular respect to their surgical implications.

A series of parapharyngeal glial heterotopia mimicking lymphatic malformation.

PubMed

Haloob, Nora; Pepper, Christopher; Hartley, Benjamin

2015-12-01

Otolaryngologists will most frequently encounter extra-cranial glial tissue within the nasal cavity, where it is known as a 'nasal glioma', and may communicate with the dura. However, glial tissue can also present extra-nasally in the form of a neck mass with no intracranial connection. In these rare cases, they can present soon after birth as an enlarging neck mass, causing compressive symptoms with airway obstruction and feeding difficulties. In this way, it is often initially misdiagnosed as a more common lesion such as a lymphatic malformation, teratoma, branchial anomaly or vascular malformation. As with many congenital head and neck masses, offering the most the appropriate management relies heavily on radiological imaging and, where possible, histopathology from a diagnostic biopsy. Once the diagnosis of extra-nasal glial heterotopia has been confirmed, the gold standard management is complete surgical excision. We review three cases of extra-nasal glial heterotopia presenting to our institution over an eleven year period as a large neck mass, which mimicked other congenital neck lumps, and discuss them in the context of those in the literature. We highlight how their clinical and radiological features can easily be confused with lymphatic malformations, and the potential implications of misdiagnosis. Raising awareness of this diagnostic confusion will highlight the need for management of these cases within an appropriate paediatric multidisciplinary setting. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Cerebellar hematoma in a patient with Marfan syndrome.

PubMed

Passalacqua, Marcello; Grasso, Giovanni; Alafaci, Concetta; Collufio, Domenicantonio; Morabito, Antonio; Salpietro, Francesco M; Tomasello, Francesco

2003-08-01

Marfan syndrome is a connective tissue disorder affecting many structures, including the skeleton, lungs, eyes, heart and blood vessels. It is an autosomal dominant inherited disorder due to a mutation of a gene encoding fibrillin-1, which affects connective tissue. Few case reports have associated Marfan syndrome with vascular malformations of the brain and spinal cord. In this regard, association with intracranial aneurysm has been vaguely proposed. We report here a patient with Marfan syndrome who was admitted because of a sudden loss of consciousness. The patient underwent computed tomography (CT) examination, which disclosed a right intracerebellar hematoma. Cerebral angiogram did not demonstrate aneurysm or arteriovenous malformation (AVM), or evidence of any other vascular lesions or neoplasms in the posterior fossa. Conservative treatment was undertaken. The clinical course was uneventful and after 6 weeks the patient was discharged free of symptoms. Although patients with Marfan syndrome are at high risk of vascular abnormalities, a clear association with cerebral aneurysm has not yet been established. Our experience and the contrasting reports available in the medical literature strongly warrant further studies in order to better clarify this controversial association.

Use of intracranial and ocular thermography before and after arteriovenous malformation excision

NASA Astrophysics Data System (ADS)

Hwang, Peter Y. K.; Lewis, Philip M.; Maller, Jerome J.

2014-11-01

Excision of arteriovenous malformations (AVMs) is known to carry a risk of postoperative hemorrhage, postulated to be the result of normal perfusion pressure breakthrough. It is also possible that AVMs may cause a steal effect, reducing perfusion in nearby vessels. There is currently no simple method of visualizing the presence or absence of steal effect intraoperatively. We hypothesized that the infrared thermographic (heat sensitive) imaging of perilesional brain may be useful for detecting reduced perfusion due to steal. Moreover, we hypothesized that if steal effect was present, it could impact on ocular perfusion and thereby temperature. Our objective was, therefore, to investigate whether perilesional cortical and ocular temperature (OT) may be a marker of steal effect. We intraoperatively acquired conventional and thermal images of the surgical field and eyes bilaterally, pre- and post-excisions of a large left hemisphere AVM. We found OT asymmetry preoperatively, which was absent after the AVM was excised. Intraoperative thermal images showed an increase of perilesional temperature, although this could be confounded by generalized changes in cortical perfusion due to anesthetics or surgery.

Congenital Limb Deficiency Associated with Intellectual Disability: Unusual Presentation in Two Subjects.

PubMed

Raza, Muhammad Ummear; Ullah, Waheed; Malik, Sajid

2016-09-01

Congenital constriction ring (CCR) and symbrachydactyly are two distinct, rare, and heterogeneous limb deficiency conditions which affect the digits. Here, we report on two different individuals with an unusual presentation of limb deficiency accompanying intellectual disability (ID) and certain other malformations. In the first index female, CCR occurred with mild ID, squint eyes, obesity, and metatarsus adductus. The second index male was presented with symbrachydactyly, profound ID, and speech/hearing impairments. The association of limb deficiency conditions with these anomalies is very rare. Differential diagnosis and literature survey have been offered to establish the rarity of these entities.

Determination of metals and pharmaceutical compounds released in hospital wastewater from Toluca, Mexico, and evaluation of their toxic impact.

PubMed

Pérez-Alvarez, Itzayana; Islas-Flores, Hariz; Gómez-Oliván, Leobardo Manuel; Barceló, Damià; López De Alda, Miren; Pérez Solsona, Sandra; Sánchez-Aceves, Livier; SanJuan-Reyes, Nely; Galar-Martínez, Marcela

2018-05-08

Due to the activities inherent to medical care units, the hospital effluent released contains diverse contaminants such as tensoactives, disinfectants, metals, pharmaceutical products and chemical reagents, which are potentially toxic to the environment since they receive no treatment or are not effectively removed by such treatment before entering the drain. They are incorporated into municipal wastewater, eventually entering water bodies where they can have harmful effects on organisms and can result in ecological damage. To determine the toxicological risk induced by this type of eflluents, eight metals and 11 pharmaceuticals were quantified, in effluent from a hospital. Developmental effects, teratogenesis and oxidative stress induction were evaluated in two bioindicator species: Xenopus laevis and Lithobates catesbeianus. FETAX (frog embryo teratogenesis assay-Xenopus) was used to obtain the median lethal concentration (LC 50 ), effective concentration inducing 50% malformation (EC 50 ), teratogenic index (TI), minimum concentration to inhibit growth (MCIG), and the types of malformation induced. Twenty oocytes in midblastula transition were exposed to six concentrations of effluent (0.1, 0.3, 0.5, 0.7, 0.9, 1%) and negative and positive (6-aminonicotinamide) controls. After 96 h of exposure, diverse biomarkers of oxidative damage were evaluated: hydroperoxide content, lipid peroxidation, protein carbonyl content, and the antioxidant enzymes superoxide dismutase and catalase. TI was 3.8 in X. laevis and 4.0 in L. catesbeianus, both exceed the value in the FETAX protocol (1.2), indicating that this effluent is teratogenic to both species. Growth inhibition was induced as well as diverse malformation including microcephaly, cardiac and facial edema, eye malformations, and notochord, tail, fin and gut damage. Significant differences relative to the control group were observed in both species with all biomarkers. This hospital effluent contains contaminants which represents a toxic risk, since these substances are teratogenic to the bioindicators used. The mechanism of damage induction may be associated with oxidative stress. Copyright © 2018 Elsevier Ltd. All rights reserved.

Atypical febrile seizures, mesial temporal lobe epilepsy, and dual pathology.

PubMed

Sanon, Nathalie T; Desgent, Sébastien; Carmant, Lionel

2012-01-01

Febrile seizures occurring in the neonatal period, especially when prolonged, are thought to be involved in the later development of mesial temporal lobe epilepsy (mTLE) in children. The presence of an often undetected, underlying cortical malformation has also been reported to be implicated in the epileptogenesis process following febrile seizures. This paper highlights some of the various animal models of febrile seizures and of cortical malformation and portrays a two-hit model that efficiently mimics these two insults and leads to spontaneous recurrent seizures in adult rats. Potential mechanisms are further proposed to explain how these two insults may each, or together, contribute to network hyperexcitability and epileptogenesis. Finally the clinical relevance of the two-hit model is briefly discussed in light of a therapeutic and preventive approach to mTLE.

Eye-movements and ongoing task processing.

PubMed

Burke, David T; Meleger, Alec; Schneider, Jeffrey C; Snyder, Jim; Dorvlo, Atsu S S; Al-Adawi, Samir

2003-06-01

This study tests the relation between eye-movements and thought processing. Subjects were given specific modality tasks (visual, gustatory, kinesthetic) and assessed on whether they responded with distinct eye-movements. Some subjects' eye-movements reflected ongoing thought processing. Instead of a universal pattern, as suggested by the neurolinguistic programming hypothesis, this study yielded subject-specific idiosyncratic eye-movements across all modalities. Included is a discussion of the neurolinguistic programming hypothesis regarding eye-movements and its implications for the eye-movement desensitization and reprocessing theory.

Disruption of Msx-1 and Msx-2 reveals roles for these genes in craniofacial, eye, and axial development.

PubMed

Foerst-Potts, L; Sadler, T W

1997-05-01

In mouse embryos, the muscle segment homeobox genes, Msx-1 and Msx-2 are expressed during critical stages of neural tube, neural crest, and craniofacial development, suggesting that these genes play important roles in organogenesis and cell differentiation. Although the patterns of expression are intriguing, little is known about the function of these genes in vertebrate embryonic development. Therefore, the expression of both genes, separately and together, was disrupted using antisense oligodeoxynucleotides and whole embryo culture techniques. Antisense attenuation of Msx-1 during early stages of neurulation produced hypoplasia of the maxillary, mandibular, and frontonasal prominences, eye anomalies, and somite and neural tube abnormalities. Eye defects consisted of enlarged optic vesicles, which may ultimately result in micropthalmia similar to that observed in Small eye mice homozygous for mutations in the Pax-6 gene. Histological sections and SEM analysis revealed a thinning of the neuroepithelium in the diencephalon and optic vesicle and mesenchymal deficiencies in the craniofacial region. Injections of Msx-2 antisense oligodeoxynucleotides produced similar malformations as those targeting Msx-1, with the exception that there was an increase in number and severity of neural tube and somite defects. Embryos injected with the combination of Msx-1 + Msx-2 antisense oligodeoxynucleotides showed no novel abnormalities, suggesting that the genes do not operate in a redundant manner.

CC2D2A Is Mutated in Joubert Syndrome and Interacts with the Ciliopathy-Associated Basal Body Protein CEP290

PubMed Central

Gorden, Nicholas T.; Arts, Heleen H.; Parisi, Melissa A.; Coene, Karlien L.M.; Letteboer, Stef J.F.; van Beersum, Sylvia E.C.; Mans, Dorus A.; Hikida, Abigail; Eckert, Melissa; Knutzen, Dana; Alswaid, Abdulrahman F.; Özyurek, Hamit; Dibooglu, Sel; Otto, Edgar A.; Liu, Yangfan; Davis, Erica E.; Hutter, Carolyn M.; Bammler, Theo K.; Farin, Frederico M.; Dorschner, Michael; Topçu, Meral; Zackai, Elaine H.; Rosenthal, Phillip; Owens, Kelly N.; Katsanis, Nicholas; Vincent, John B.; Hildebrandt, Friedhelm; Rubel, Edwin W.; Raible, David W.; Knoers, Nine V.A.M.; Chance, Phillip F.; Roepman, Ronald; Moens, Cecilia B.; Glass, Ian A.; Doherty, Dan

2008-01-01

Joubert syndrome and related disorders (JSRD) are primarily autosomal-recessive conditions characterized by hypotonia, ataxia, abnormal eye movements, and intellectual disability with a distinctive mid-hindbrain malformation. Variable features include retinal dystrophy, cystic kidney disease, and liver fibrosis. JSRD are included in the rapidly expanding group of disorders called ciliopathies, because all six gene products implicated in JSRD (NPHP1, AHI1, CEP290, RPGRIP1L, TMEM67, and ARL13B) function in the primary cilium/basal body organelle. By using homozygosity mapping in consanguineous families, we identify loss-of-function mutations in CC2D2A in JSRD patients with and without retinal, kidney, and liver disease. CC2D2A is expressed in all fetal and adult tissues tested. In ciliated cells, we observe localization of recombinant CC2D2A at the basal body and colocalization with CEP290, whose cognate gene is mutated in multiple hereditary ciliopathies. In addition, the proteins can physically interact in vitro, as shown by yeast two-hybrid and GST pull-down experiments. A nonsense mutation in the zebrafish CC2D2A ortholog (sentinel) results in pronephric cysts, a hallmark of ciliary dysfunction analogous to human cystic kidney disease. Knockdown of cep290 function in sentinel fish results in a synergistic pronephric cyst phenotype, revealing a genetic interaction between CC2D2A and CEP290 and implicating CC2D2A in cilium/basal body function. These observations extend the genetic spectrum of JSRD and provide a model system for studying extragenic modifiers in JSRD and other ciliopathies. PMID:18950740

[Clinical feature of chronic compressive optic neuropathy without optic atrophy].

PubMed

Jiang, Libin; Shi, Jitong; Liu, Wendong; Kang, Jun; Wang, Ningli

2014-12-01

To investigate the clinical feature of the chronic compressive optic neuropathy without optic atrophy. Retrospective cases series study. The clinical data of 25 patients (37 eyes) with chronic compressive optic neuropathy without optic atrophy, treated in Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, from October, 2005 to March, 2014, were collected. Those patients had been showing visual symptoms for 6 months or longer, but missed diagnosed or misdiagnosed as other eye diseases due to their normal or slightly changed fundi. The collected data including visual acuities, visual fields, neuroimaging and/or pathologic diagnosis were analyzed. Among the 25 patients, there were 5 males and 20 females, and their ages range from 9 to 74 years [average (47.5 ± 13.4) years]. All patients suffered progressive impaired vision in single eye or both eyes, without exophthalmos or abnormal eye movements. Except one patient had a headache, other patients did not show systemic symptoms. The corrected visual acuities were between HM to 1.0, and their appearances of optic discs and colors of fundi were normal. After neuroimaging and/or pathological examination, it was proven that 14 patients suffered tuberculum sellae meningiomas, 5 patients with hypophysoma, 3 patient with optic nerve sheath meningioma in orbital apex, 1 patient with cavernous hemangioma, 1 patient with vascular malformation in orbital apex and 1 patient with optic nerve glioma. Among the 19 patients whose suffered occupied lesions of saddle area, 14 patients underwent visual field examinations, and only 4 patients showed classic visual field defects caused by optic chiasmal lesions. Occult progressive visual loss was the most important clinical feature of the disease.

DEHP (DI-N-ETHYLHEXYL PHTHALATE), WHEN ADMINISTERED DURING SEXUAL DIFFERENTIATION, INDUCES DOSE DEPENDENT DECREASES IN FETAL TESTIS INSL3 GENE EXPRESSION AND STERIOD HORMONE SYNTHESIS

EPA Science Inventory

Cryptorchidism is a fairly common human malformation, being displayed in 1-3 males per 100 at birth. Since only a small percentage of these lesions can be linked to known genetic defects, developmental exposure to man-made chemicals has been implicated in the increase in thisrepr...

Comparison of environmental risk factors for esophageal atresia, anorectal malformations, and the combined phenotype in 263 German families.

PubMed

Zwink, N; Choinitzki, V; Baudisch, F; Hölscher, A; Boemers, T M; Turial, S; Kurz, R; Heydweiller, A; Keppler, K; Müller, A; Bagci, S; Pauly, M; Brokmeier, U; Leutner, A; Degenhardt, P; Schmiedeke, E; Märzheuser, S; Grasshoff-Derr, S; Holland-Cunz, S; Palta, M; Schäfer, M; Ure, B M; Lacher, M; Nöthen, M M; Schumacher, J; Jenetzky, E; Reutter, H

2016-11-01

Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) and anorectal malformations (ARM) represent the severe ends of the fore- and hindgut malformation spectra. Previous research suggests that environmental factors are implicated in their etiology. These risk factors might indicate the influence of specific etiological mechanisms on distinct developmental processes (e.g. fore- vs. hindgut malformation). The present study compared environmental factors in patients with isolated EA/TEF, isolated ARM, and the combined phenotype during the periconceptional period and the first trimester of pregnancy in order to investigate the hypothesis that fore- and hindgut malformations involve differing environmental factors. Patients with isolated EA/TEF (n = 98), isolated ARM (n = 123), and the combined phenotype (n = 42) were included. Families were recruited within the context of two German multicenter studies of the genetic and environmental causes of EA/TEF (great consortium) and ARM (CURE-Net). Exposures of interest were ascertained using an epidemiological questionnaire. Chi-square, Fisher's exact, and Mann-Whitney U-tests were used to assess differences between the three phenotypes. Newborns with isolated EA/TEF and the combined phenotype had significantly lower birth weights than newborns with isolated ARM (P = 0.001 and P < 0.0001, respectively). Mothers of isolated EA/TEF consumed more alcohol periconceptional (80%) than mothers of isolated ARM or the combined phenotype (each 67%). Parental smoking (P = 0.003) and artificial reproductive techniques (P = 0.03) were associated with isolated ARM. Unexpectedly, maternal periconceptional multivitamin supplementation was most frequent among patients with the most severe form of disorder, i.e. the combined phenotype (19%). Significant differences in birth weight were apparent between the three phenotype groups. This might be attributable to the limited ability of EA/TEF fetuses to swallow amniotic fluid, thus depriving them of its nutritive properties. Furthermore, the present data suggest that fore- and hindgut malformations involve differing environmental factors. Maternal periconceptional multivitamin supplementation was highest among patients with the combined phenotype. This latter finding is contrary to expectation, and warrants further analysis in large prospective epidemiological studies. © 2015 International Society for Diseases of the Esophagus.

Atypical Febrile Seizures, Mesial Temporal Lobe Epilepsy, and Dual Pathology

PubMed Central

Sanon, Nathalie T.; Desgent, Sébastien; Carmant, Lionel

2012-01-01

Febrile seizures occurring in the neonatal period, especially when prolonged, are thought to be involved in the later development of mesial temporal lobe epilepsy (mTLE) in children. The presence of an often undetected, underlying cortical malformation has also been reported to be implicated in the epileptogenesis process following febrile seizures. This paper highlights some of the various animal models of febrile seizures and of cortical malformation and portrays a two-hit model that efficiently mimics these two insults and leads to spontaneous recurrent seizures in adult rats. Potential mechanisms are further proposed to explain how these two insults may each, or together, contribute to network hyperexcitability and epileptogenesis. Finally the clinical relevance of the two-hit model is briefly discussed in light of a therapeutic and preventive approach to mTLE. PMID:22957226

Clinical Characteristics of Patients Who Underwent Surgery for Genital Tract Malformations at Peking Union Medical College Hospital across 31 Years.

PubMed

Wang, Guang-Han; Zhu, Lan; Liu, Ai-Ming; Xu, Tao; Lang, Jing-He

2016-10-20

Female genital malformations represent miscellaneous deviations from normal anatomy. This study aimed to explore the clinical characteristics of patients who underwent surgery for genital tract malformations at Peking Union Medical College Hospital (PUMCH) during a 31-year period. We retrospectively reviewed surgical cases of congenital malformation of the female genital tract at PUMCH for a 31-year period, analyzed the clinical characteristics of 1634 hospitalized patients, and investigated their general condition, diagnosis, and treatment process. The average patient age was 27.6 ± 9.9 years. The average ages of patients who underwent surgery for uterine malformation and vaginal malformation were 31.9 ± 8.8 years and 24.7 ± 9.0 years, respectively; these ages differed significantly (P < 0.01). Among patients with genital tract malformation, the percentages of vaginal malformation, uterine malformation, vulva malformation, cervical malformation, and other malformations were 43.9%, 43.5%, 7.4%, 2.3%, and 2.8%, respectively. Among patients with uterine malformation, 34.5% underwent surgery for the genital tract malformation, whereas in patients with vaginal malformation, the proportion is 70.6%; the difference between the two groups was statistically significant (P < 0.01). The percentage of complications of the urinary system in patients with vaginal malformations was 10.2%, which was statistically significantly higher than that (5.3%) in patients with uterine malformations (P < 0.01). Compared to patients with uterine malformations, patients with vaginal malformations displayed more severe clinical symptoms, a younger surgical age, and a greater need for attention, early diagnosis, and treatment. Patients with genital tract malformations, particularly vaginal malformations, tend to have more complications of the urinary system and other malformations than patients with uterine malformations.

Perspectives on the use of the baboon in embryology and teratology research.

PubMed

Hendrickx, A G; Peterson, P E

1997-01-01

This paper summarizes the developmental stages of the baboon during the period of organ formation and provides comparative information for other primates, including the human. Special attention is directed to the early development of the nervous system, eye, ear and nose/palate. The similarity in development of these structures with humans indicates that the baboon is a suitable model for studies of normal and abnormal neurological development. Spontaneous prenatal loss rates in the baboon (2.4-11.2%) are slightly lower than those reported in rhesus and cynomologus monkeys. The baboon, in addition to the cynomologus monkey and macaque, has been used as a model in teratology research to assess the potential risk of thalidomide, sex steroids, Bendectin and rubella virus, as well as to study the pathogenesis of malformations associated with the corticosteroid triamcinolone acetonide. The rate of spontaneous malformations (<1%) in baboons, similar to that reported for other commonly used primates, supports their continued use as a teratological model. In this regard, a sample protocol is provided for the safety evaluation of biotechnology products using nonhuman primates, which are the most appropriate model for those compounds which are bioactive in species closely related to humans.

Implications in dosimetry of the implementation of the revised dose limit to the lens of the eye.

PubMed

Broughton, J; Cantone, M C; Ginjaume, M; Shah, B; Czarwinski, R

2015-04-01

In 2012, International Radiation Protection Association (IRPA) established a Task Group to provide an assessment of the impact of the implementation of the ICRP-revised dose limit for the lens of the eye for occupational exposure. Associated Societies (ASs) of IRPA were asked to provide views and comments on the basis of a questionnaire addressing three principal topics: (i) implications for dosimetry, (ii) implications for methods of protection and (iii) wider implications of implementing the revised limits. A summary of the collated responses regarding dosimetry is presented and discussed. There is large agreement on the most critical aspects and difficulties in setting up an appropriate monitoring programme for the lens of the eyes. The recent international standards and technical documents provide guidance for some of the concerns but other challenges remain in terms of awareness, acceptance and practicalities. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Looking at Eye Gaze Processing and Its Neural Correlates in Infancy--Implications for Social Development and Autism Spectrum Disorder

ERIC Educational Resources Information Center

Hoehl, Stefanie; Reid, Vincent M.; Parise, Eugenio; Handl, Andrea; Palumbo, Letizia; Striano, Tricia

2009-01-01

The importance of eye gaze as a means of communication is indisputable. However, there is debate about whether there is a dedicated neural module, which functions as an eye gaze detector and when infants are able to use eye gaze cues in a referential way. The application of neuroscience methodologies to developmental psychology has provided new…

The anterior segment disorder autosomal dominant keratitis is linked to the Aniridia/PAX-6 gene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mirzayans, F.; Pearce, W.G.; Mah, T.S.

1994-09-01

Autosomal dominant keratitis (ADK) is an eye disease characterized by anterior stromal corneal opacification and vascularization in the peripheral cornea. Progression into the central cornea may compromise visual acuity. Other anterior segment features include minimal radial defects of the iris stroma. Posterior segment involvement is characterized by foveal hypoplasia with minimal effect on visual acuity. Aniridia is a second autosomal dominantly inherited ocular disorder defined by structural defects of the iris, frequently severe enough to cause an almost complete absence of iris. This may be accompanied by other anterior segment manifestations, including cataract and keratitis. Posterior segment involvement in aniridiamore » is characterized by foveal hypoplasia resulting in a highly variable impairment of visual acuity, often with nystagmus. Aniridia is usually inherited as an autosomal dominant disease and occurs in 1 in 50,000 to 100,000 people. Aniridia has been shown to result from mutations in PAX-6, a gene thought to regulate fetal eye development. The similar clinical findings in ADK and aniridia, with the similar patterns of inheritance, compelled us to investigate if these two ocular disorders are variants of the same genetic disorder. We have tested for linkage between PAX-6 and ADK within an ADK family with 33 members over four generations, including 11 affected individuals. Linkage studies reveal that D11S914 (located within 3 cM of PAX-6) does not recombine with ADK (LOD score 3.61; {theta} = 0.00), consistent with PAX-6 mutations being responsible for ADK. Direct sequencing of PAX-6 RT-PCR products from ADK patients is underway to identify the mutation within the PAX-6 gene that results in ADK. The linkage of PAX-6 with ADK, along with a recent report that mutations in PAX-6 also underlie Peter`s anomaly, implicates PAX-6 widely in anterior segment malformations.« less

Effect of bilateral eye movements on frontal interhemispheric gamma EEG coherence: implications for EMDR therapy.

PubMed

Propper, Ruth E; Pierce, Jenna; Geisler, Mark W; Christman, Stephen D; Bellorado, Nathan

2007-09-01

The use of bilateral eye movements (EMs) is an important component of Eye Movement Desensitization and Reprocessing (EMDR) therapy for posttraumatic stress disorder. The neural mechanisms underlying EMDR remain unclear. However, prior behavioral work looking at the effects of bilateral EMs on the retrieval of episodic memories suggests that the EMs enhance interhemispheric interaction. The present study examined the effects of the EMs used in EMDR on interhemispheric electroencephalogram coherence. Relative to noneye-movement controls, engaging in bilateral EMs led to decreased interhemispheric gamma electroencephalogram coherence. Implications for future work on EMDR and episodic memory are discussed.

Neural tube defects – recent advances, unsolved questions and controversies

PubMed Central

Copp, Andrew J.; Stanier, Philip; Greene, Nicholas D. E.

2014-01-01

Neural tube defects (NTDs) are severe congenital malformations affecting around 1 in every 1000 pregnancies. Here we review recent advances and currently unsolved issues in the NTD field. An innovation in clinical management has come from the demonstration that closure of open spina bifida lesions in utero can diminish neurological dysfunction in children. Primary prevention by folic acid has been enhanced through introduction of mandatory food fortification in some countries, although not yet in UK. Genetic predisposition comprises the majority of NTD risk, and genes that regulate folate one-carbon metabolism and planar cell polarity have been strongly implicated. The sequence of human neural tube closure events remains controversial, but study of mouse NTD models shows that anencephaly, open spina bifida and craniorachischisis result from failure of primary neurulation, while skin-covered spinal dysraphism results from defective secondary neurulation. Other ‘NTD’ malformations, such as encephalocele, are likely to be post-neurulation disorders. PMID:23790957

Congenital cardiac malformations in relation to central venous access.

PubMed

Thompson, Christine

During the third and seventh weeks of gestation, teratogenic exposure may lead to fetal abnormality such as congenital heart defects or intrauterine death. Congenital heart defects are present from birth, but may appear at any time, or only revealed postmortem. Often defects are present by degree. Some defects are life-threatening, while other, less severe conditions, may have minimal physiological impact. Left superior vena cava exists in early embryonic development, but the vessel degenerates as the cardiovascular system matures. When not associated with other malformations, an incidence of persistent left-sided superior vena cava (PLSVC) has no clinical signs or symptoms. However, it may not be as innocuous as it appears due to its association with the cyanotic defect, tetralogy of Fallot (TOF). Using a case history as an illustration it can be shown that all cases of defect or chromosomal suspicion should be documented as there may be implications for future interventions.

The increasing incidence of foetal echogenic congenital lung malformations: an observational study.

PubMed

Stocker, Linden J; Wellesley, Diana G; Stanton, Michael P; Parasuraman, Rajeswari; Howe, David T

2015-02-01

The aim of this study was to investigate the incidence of congenital lung malformations over the past 19 years. Congenital lung malformations (CLM) are a heterogeneous group of lung abnormalities. The antenatal diagnosis is important for foetal and neonatal management but there have been no studies examining whether the reported incidence of this abnormality is constant. A retrospective cross-sectional study of cases identified from the Wessex Antenatally Detected Anomalies (WANDA) register 1994-2012. One hundred and thirty-three cases of CLM in 524 372 live and stillbirths were identified. All but seven were identified on antenatal ultrasound. During the early registry (1994-1998) the average incidence of CLM was 1.27 per 10,000 births. By the last 4 years (2008-2012) this had risen to 4.15 per 10,000 births, with a progressive increase during the intervening years. There was over a three-fold increase in the antenatally detected CLM in the Wessex region 1994-2012. Comparison with the antenatal detection of diaphragmatic hernia suggests that this is a true rise in incidence rather than an artefactual increase due to increased antenatal recognition secondary to improved ultrasound resolution and operator experience. These results have clinical and cost implications for practitioners of foetal medicine, neonatology and paediatric surgery services. © 2014 John Wiley & Sons, Ltd.

Clinical characteristics of a sample of patients with cat eye syndrome.

PubMed

Rosa, Rafael Fabiano Machado; Mombach, Rômulo; Zen, Paulo Ricardo Gazzola; Graziadio, Carla; Paskulin, Giorgio Adriano

2010-01-01

Cat eye syndrome is considered a rare chromosome disease with a highly variable phenotype. The objective of this paper was to describe the clinical characteristics of a sample of patients with cat eye syndrome who were seen at our service. This is a retrospective analysis of a sample of six patients with diagnoses of cat eye syndrome. All of these patients’ karyotypes exhibited the presence of an additional marker chromosome, inv dup(22)(pter->q11.2::q11.2->pter). One patient also exhibited mosaicism with a lineage that had a normal chromosomal constitution. Clinical and follow-up data were collected from the patients’ medical records. Fisher’s exact test was used to compare the frequencies observed in our study with figures given in the literature (P<0.05). The main abnormalities observed were preauricular tags and/or pits and anal atresia (both observed in 83% of cases). Coloboma of the iris, an important finding with this syndrome, was observed in two cases (33%). Congenital heart disease was detected in four patients (67%) and the main defect found was interatrial communication (75%). Uncommon findings included hemifacial microsomia combined with unilateral microtia and biliary atresia. Just one of these patients died, from chylothorax and sepsis. The phenotype observed in cat eye syndrome is highly variable and may be superimposed on the phenotype of the oculo-auriculo-vertebral spectrum. Although these patients usually have good prognosis, including from a neurological point of view, we believe that all patients with the syndrome should be assessed very early on for the presence of cardiac, biliary and anorectal malformations, which may avoid possible complications in the future, including patient deaths.

Magnetic resonance imaging features of complex Chiari malformation variant of Chiari 1 malformation.

PubMed

Moore, Hannah E; Moore, Kevin R

2014-11-01

Complex Chiari malformation is a subgroup of Chiari 1 malformation with distinct imaging features. Children with complex Chiari malformation are reported to have a more severe clinical phenotype and sometimes require more extensive surgical treatment than those with uncomplicated Chiari 1 malformation. We describe reported MR imaging features of complex Chiari malformation and evaluate the utility of craniometric parameters and qualitative anatomical observations for distinguishing complex Chiari malformation from uncomplicated Chiari 1 malformation. We conducted a retrospective search of the institutional imaging database using the keywords "Chiari" and "Chiari 1" to identify children imaged during the 2006-2011 time period. Children with Chiari 2 malformation were excluded after imaging review. We used the first available diagnostic brain or cervical spine MR study for data measurement. Standard measurements and observations were made of obex level (mm), cerebellar tonsillar descent (mm), perpendicular distance to basion-C2 line (pB-C2, mm), craniocervical angle (degrees), clivus length, and presence or absence of syringohydromyelia, basilar invagination and congenital craniovertebral junction osseous anomalies. After imaging review, we accessed the institutional health care clinical database to determine whether each subject clinically met criteria for Chiari 1 malformation or complex Chiari malformation. Obex level and craniocervical angle measurements showed statistically significant differences between the populations with complex Chiari malformation and uncomplicated Chiari 1 malformation. Cerebellar tonsillar descent and perpendicular distance to basion-C2 line measurements trended toward but did not meet statistical significance. Odontoid retroflexion, craniovertebral junction osseous anomalies, and syringohydromyelia were all observed proportionally more often in children with complex Chiari malformation than in those with Chiari 1 malformation. Characteristic imaging features of complex Chiari malformation, especially obex level, permit its distinction from the more common uncomplicated Chiari 1 malformation.

Knowledge and attitude of guardians towards eye health of primary school pupils in Ilorin, Nigeria.

PubMed

Ayanniyi, A A; Olatunji, F O; Mahmoud, A O; Ayanniyi, R O

2010-03-01

To determine guardians' knowledge and attitude towards pupils' eye health and draw implication for designing children-oriented ocular health messages. A survey of 1,393 guardians selected through multistage random sampling in Ilorin, Nigeria. Using structured questionnaire, information sought included guardians' demographic characteristics, relationship to pupils, occupation, awareness of eye specialists, perception of normal vision, pupils' eye complaints, and ways of treating children eye conditions. Data analysis was done with SPSS 12.0.1. The test of significance was performed using Chi square test and significance was taken at p < 0.05. Guardians comprised 689 (49.4%) males and 704 (50.6%) females, mean age 43.61 SD 11.45. Most (88.54%) were pupils' parents and (11.46%) were relations (n=1,318); (55.15%) were in low-paying occupations (n=1,311); (87.92%) were aware of eye specialists, (12.08%) unaware, (n=1192); (97.27%) adjudged normal vision at least important, (2.73%) not important (n=1,174). Pupils' eye complaints (n=914) included pain (26.04%), itching (24.73%), redness (21.12%), discharge (8.53%), blur vision (8.21%), photophobia (7.33%) and lacrimation (4.05%). Guardians (n=1,069) managed pupils' eye diseases using hospital treatment (61.65%), neglect (21.33%), self medication (9.26%) and traditional medication (7.76%). There were no significant associations between guardians' ways of managing pupils' eye diseases and their views on normal vision (p = 0.940); awareness of eye care specialists (p = 0.952); and economic occupational grouping (p = 0.959). The negative implications of neglecting eye diseases and use of self and harmful traditional eye-medications by some of the guardians need to be discouraged by appropriate eye health education.

Missense-depleted regions in population exomes implicate ras superfamily nucleotide-binding protein alteration in patients with brain malformation

PubMed Central

Ge, Xiaoyan; Gong, Henry; Dumas, Kevin; Litwin, Jessica; Phillips, Joanna J; Waisfisz, Quinten; Weiss, Marjan M; Hendriks, Yvonne; Stuurman, Kyra E; Nelson, Stanley F; Grody, Wayne W; Lee, Hane; Kwok, Pui-Yan; Shieh, Joseph T C

2016-01-01

Genomic sequence interpretation can miss clinically relevant missense variants for several reasons. Rare missense variants are numerous in the exome and difficult to prioritise. Affected genes may also not have existing disease association. To improve variant prioritisation, we leverage population exome data to identify intragenic missense-depleted regions (MDRs) genome-wide that may be important in disease. We then use missense depletion analyses to help prioritise undiagnosed disease exome variants. We demonstrate application of this strategy to identify a novel gene association for human brain malformation. We identified de novo missense variants that affect the GDP/GTP-binding site of ARF1 in three unrelated patients. Corresponding functional analysis suggests ARF1 GDP/GTP-activation is affected by the specific missense mutations associated with heterotopia. These findings expand the genetic pathway underpinning neurologic disease that classically includes FLNA. ARF1 along with ARFGEF2 add further evidence implicating ARF/GEFs in the brain. Using functional ontology, top MDR-containing genes were highly enriched for nucleotide-binding function, suggesting these may be candidates for human disease. Routine consideration of MDR in the interpretation of exome data for rare diseases may help identify strong genetic factors for many severe conditions, infertility/reduction in reproductive capability, and embryonic conditions contributing to preterm loss. PMID:28868155

Wilms Tumor in a Child With Bilateral Polycystic Kidneys and PHACE Syndrome: Successful Treatment Outcome Using Partial Nephrectomy and Chemotherapy.

PubMed

Thankamony, Priyakumari; Sivarajan, Venugopal; Mony, Rari P; Muraleedharan, Venugopal

2016-01-01

Congenital anomalies may be associated with Wilms tumor either as isolated anomalies or as part of a congenital malformation syndrome. Nephroblastoma occurring in association with polycystic kidneys is very rare. The optimal surgical management of nephroblastoma in the setting of polycystic kidneys is not defined because of the rarity of this presentation. PHACE syndrome includes posterior fossa anomalies, hemangioma, arterial lesions, cardiac abnormalities/coarctation of aorta, and eye abnormalities. We report a 17-month-old baby with bilateral polycystic kidneys and PHACE syndrome who developed nephroblastoma in the right polycystic kidney which was treated successfully with nephron-sparing partial nephrectomy and chemotherapy.

Magnetic Resonance Imaging of Malformations of Midbrain-Hindbrain.

PubMed

Abdel Razek, Ahmed Abdel Khalek; Castillo, Mauricio

2016-01-01

We aim to review the magnetic resonance imaging appearance of malformations of midbrain and hindbrain. These can be classified as predominantly cerebellar malformations, combined cerebellar and brain stem malformations, and predominantly brain stem malformations. The diagnostic criteria for the majority of these morphological malformations are based on neuroimaging findings. The predominantly cerebellar malformations include predominantly vermian hypoplasia seen in Dandy-Walker malformation and rhombencephalosynapsis, global cerebellar hypoplasia reported in lissencephaly and microlissencephaly, and unilateral cerebellar hypoplasia seen in PHACES, vanishing cerebellum, and cerebellar cleft. Cerebellar dysplasias are seen in Chudley-McCullough syndrome, associated with LAMA1 mutations and GPR56 mutations; Lhermitte-Duclos disease; and focal cerebellar dysplasias. Cerebellar hyperplasias are seen in megalencephaly-related syndromes and hemimegalencephaly with ipsilateral cerebellomegaly. Cerebellar and brain stem malformations include tubulinopathies, Joubert syndrome, cobblestone malformations, pontocerebellar hypoplasias, and congenital disorders of glycosylation type Ia. Predominantly brain stem malformations include congenital innervation dysgenesis syndrome, pontine tegmental cap dysplasia, diencephalic-mesencephalic junction dysplasia, disconnection syndrome, and pontine clefts.

OUT-OF-FIELD DOSES IN CHILDREN TREATED FOR LARGE ARTERIOVENOUS MALFORMATIONS USING HYPOFRACTIONATED GAMMA KNIFE RADIOSURGERY AND INTENSITY-MODULATED RADIATION THERAPY.

PubMed

De Saint-Hubert, Marijke; Majer, Marija; Hršak, Hrvoje; Heinrich, Zdravko; Kneževic, Željka; Miljanic, Saveta; Porwol, Paulina; Stolarczyk, Liliana; Vanhavere, Filip; Harrison, Roger M

2018-01-17

The purpose of this study was to measure out-of-field organ doses in two anthropomorphic child phantoms for the treatment of large brain arteriovenous malformations (AVMs) using hypofractionated gamma knife (GK) radiosurgery and to compare these with an alternative treatment using intensity-modulated radiation therapy (IMRT). Target volume was identical in size and shape in all cases. Radiophotoluminescent (RPL), thermoluminescent (TL) and optically stimulated luminescent (OSL) dosimeters were used for out-of-field dosimetry during GK treatment and a good agreement within 1-2% between results was shown. In addition, the use of multiple dosimetry systems strengthens the reliability of the findings. The number of GK isocentres was confirmed to be important for the magnitude of out-of-field doses. Measured GK doses for the same distance from the target, when expressed per target dose and isocentre, were comparable in both phantoms. GK out-of-field doses averaged for both phantoms were evaluated to be 120 mGy/Gy for eyes then sharply reduced to 20 mGy/Gy for mandible and slowly reduced up to 0.8 mGy/Gy for testes. Taking into account the fractionation regimen used to treat AVM patients, the total treatment organ doses to the out-of-field organs were calculated and compared with IMRT. The eyes were better spared with GK whilst for more distant organs doses were up to a factor of 2.8 and 4 times larger for GK compared to IMRT in 5-year and 10-year old phantoms, respectively. Presented out-of-field dose values are specific for the investigated AVM case, phantoms and treatment plans used for GK and IMRT, but provide useful information about out-of-field dose levels and emphasise their importance. © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

B3GALNT2-Related Dystroglycanopathy: Expansion of the Phenotype with Novel Mutation Associated with Muscle-Eye-Brain Disease, Walker-Warburg Syndrome, Epileptic Encephalopathy-West Syndrome, and Sensorineural Hearing Loss.

PubMed

Al Dhaibani, Muna A; El-Hattab, Ayman W; Ismayl, Omar; Suleiman, Jehan

2018-05-23

Mutations in B3GALNT2 , encoding a glycosyltransferase enzyme involved in α-dystroglycan glycosylation, have been recently associated with dystroglycanopathy, a well-recognized subtype of congenital muscular dystrophy (CMD). Only a few cases have been reported with B3GALNT2 -related dystroglycanopathy with variable severity ranging from mild CMD to severe muscle-eye-brain disease. Here, we describe a child with a novel homozygous nonsense mutation in B3GALNT2 . The affected child has severe neurological disease since birth, including muscle disease manifested as hypotonia, muscle weakness, and wasting with elevated creatine kinase, eye disease including microphthalmia and blindness, brain disease with extensive brain malformations including massive hydrocephalus, diffuse cobblestone-lissencephaly, deformed craniocervical junction, and pontocerebellar hypoplasia. The clinical and radiologic findings are compatible with a diagnosis of severe muscle-eye-brain disease and more specifically Walker-Warburg syndrome. A more distinct aspect of the clinical phenotype in this child is the presence of refractory epilepsy in the form of epileptic spasms, epileptic encephalopathy, and West syndrome, as well as sensorineural hearing loss. These findings could expand the phenotype of B3GALNT2 -related dystroglycanopathy. In this report, we also provide a detailed review of previously reported cases with B3GALNT2 -related dystroglycanopathy and compare them to our reported child. In addition, we study the genotype-phenotype correlation in these cases. Georg Thieme Verlag KG Stuttgart · New York.

CNV analysis in 169 patients with bladder exstrophy-epispadias complex.

PubMed

von Lowtzow, Catharina; Hofmann, Andrea; Zhang, Rong; Marsch, Florian; Ebert, Anne-Karoline; Rösch, Wolfgang; Stein, Raimund; Boemers, Thomas M; Hirsch, Karin; Marcelis, Carlo; Feitz, Wouter F J; Brusco, Alfredo; Migone, Nicola; Di Grazia, Massimo; Moebus, Susanne; Nöthen, Markus M; Reutter, Heiko; Ludwig, Michael; Draaken, Markus

2016-04-30

The bladder exstrophy-epispadias complex (BEEC) represents the severe end of the congenital uro-rectal malformation spectrum. Initial studies have implicated rare copy number variations (CNVs), including recurrent duplications of chromosomal region 22q11.21, in BEEC etiology. To detect further CNVs, array analysis was performed in 169 BEEC patients. Prior to inclusion, 22q11.21 duplications were excluded using multiplex ligation-dependent probe amplification. Following the application of stringent filter criteria, seven rare CNVs were identified: n = 4, not present in 1307 in-house controls; n = 3, frequency of <0.002 in controls. These CNVs ranged from 1 to 6.08 Mb in size. To identify smaller CNVs, relaxed filter criteria used in the detection of previously reported BEEC associated chromosomal regions were applied. This resulted in the identification of six additional rare CNVs: n = 4, not present in 1307 in-house controls; n = 2, frequency <0.0008 in controls. These CNVs ranged from 0.03-0.08 Mb in size. For 10 of these 13 CNVs, confirmation and segregation analyses were performed (5 of maternal origin; 5 of paternal origin). Interestingly, one female with classic bladder extrophy carried a 1.18 Mb duplication of 22q11.1, a chromosomal region that is associated with cat eye syndrome. A number of rare CNVs were identified in BEEC patients, and these represent candidates for further evaluation. Rare inherited CNVs may constitute modifiers of, or contributors to, multifactorial BEEC phenotypes.

An open-label study to evaluate sildenafil for the treatment of lymphatic malformations.

PubMed

Danial, Christina; Tichy, Andrea L; Tariq, Umar; Swetman, Glenda L; Khuu, Phuong; Leung, Thomas H; Benjamin, Latanya; Teng, Joyce; Vasanawala, Shreyas S; Lane, Alfred T

2014-06-01

Lymphatic malformations can be challenging to treat. Mainstay interventions including surgery and sclerotherapy are invasive and can result in local recurrence and complications. We sought to assess the effect of 20 weeks of oral sildenafil on reducing lymphatic malformation volume and symptoms in children. Seven children (4 boys, 3 girls; ages 13-85 months) with lymphatic malformations were given oral sildenafil for 20 weeks in this open-label study. The volume of the lymphatic malformation was calculated blindly using magnetic resonance imaging performed before and after 20 weeks of sildenafil. Lymphatic malformations were assessed clinically on weeks 4, 12, 20, and 32. Both the physician and parents evaluated the lymphatic malformation in comparison with baseline. Four subjects had a lymphatic malformation volume decrease (1.0%-31.7%). In 2 subjects, despite a lymphatic malformation volume increase (1.1%-3.7%), clinical improvement was noted while on sildenafil. One subject had a 29.6% increase in lymphatic malformation volume and no therapeutic response. Lymphatic malformations of all 6 subjects who experienced a therapeutic response on sildenafil softened and became easily compressible. Adverse events were minimal. A randomized controlled trial will be necessary to verify the effects of sildenafil on lymphatic malformations. Sildenafil can reduce lymphatic malformation volume and symptoms in some children. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Unusual Association: Cerebral Arteriovenous Malformation and Chiari Type I Malformation.

PubMed

Ogul, Hayri; Kantarci, Mecit

2017-06-01

Cerebral arteriovenous malformation (AVM) is a common type of cerebral vascular malformation. The imaging findings are enlarged vessels, thrombosed sinuses, and hemorrhage or gliosis on adjacent brain parenchyma. Magnetic resonance (MR) imaging can be used safely for diagnosis. Chiari type I malformation is characterized by a caudal descent of the cerebellar tonsil. Coincidence of cerebral AVM and Chiari type I malformation is very rare. In this paper, the authors report MR imaging findings of a patient with coincidence of cerebral AVM and Chiari type I malformation.

Spectrum of prenatally detected central nervous system malformations: Neural tube defects continue to be the leading foetal malformation.

PubMed

Siddesh, Anjurani; Gupta, Geetika; Sharan, Ram; Agarwal, Meenal; Phadke, Shubha R

2017-04-01

Prenatal diagnosis of malformations is an important method of prevention and control of congenital anomalies with poor prognosis. Central nervous system (CNS) malformations amongst these are the most common. The information about the prevalence and spectrum of prenatally detected malformations is crucial for genetic counselling and policymaking for population-based preventive programmes. The objective of this study was to study the spectrum of prenatally detected CNS malformations and their association with chromosomal abnormalities and autopsy findings. This retrospective study was conducted in a tertiary care hospital in north India from January 2007 to December 2013. The details of cases with prenatally detected CNS malformations were collected and were related with the foetal chromosomal analysis and autopsy findings. Amongst 6044 prenatal ultrasonographic examinations performed; 768 (12.7%) had structural malformations and 243 (31.6%) had CNS malformations. Neural tube defects (NTDs) accounted for 52.3 per cent of CNS malformations and 16.5 per cent of all malformations. The other major groups of prenatally detected CNS malformations were ventriculomegaly and midline anomalies. Chromosomal abnormalities were detected in 8.2 per cent of the 73 cases studied. Foetal autopsy findings were available for 48 foetuses. Foetal autopsy identified additional findings in eight foetuses and the aetiological diagnosis changed in two of them (4.2%). Amongst prenatally detected malformations, CNS malformations were common. NTD, which largely is a preventable anomaly, continued to be the most common group. Moreover, 60 per cent of malformations were diagnosed after 20 weeks, posing legal issues. Chromosomal analysis and foetal autopsy are essential for genetic counselling based on aetiological diagnosis.

The Matrix Metalloproteinase 9 Point-of-Care Test in Dry Eye.

PubMed

Lanza, Nicole L; Valenzuela, Felipe; Perez, Victor L; Galor, Anat

2016-04-01

Dry eye is a common, multifactorial disease currently diagnosed by a combination of symptoms and signs. However, the subjective symptoms of dry eye poorly correlate to the current gold standard for diagnostic tests, reflecting the need to develop better objective tests for the diagnosis of dry eye. This review considers the role of ocular surface matrix metalloproteinase 9 (MMP-9) in dry eye and the implications of a novel point-of-care test that measures MMP-9 levels, InflammaDry (RPS, Sarasota, FL) on choosing appropriate therapeutic treatments. Published by Elsevier Inc.

Teachers' Experiences of Using Eye Gaze-Controlled Computers for Pupils with Severe Motor Impairments and without Speech

ERIC Educational Resources Information Center

Rytterström, Patrik; Borgestig, Maria; Hemmingsson, Helena

2016-01-01

The purpose of this study is to explore teachers' experiences of using eye gaze-controlled computers with pupils with severe disabilities. Technology to control a computer with eye gaze is a fast growing field and has promising implications for people with severe disabilities. This is a new assistive technology and a new learning situation for…

Temporal lobe developmental malformations and epilepsy: dual pathology and bilateral hippocampal abnormalities.

PubMed

Ho, S S; Kuzniecky, R I; Gilliam, F; Faught, E; Morawetz, R

1998-03-01

Temporal lobe developmental malformations (TLDM) with focal cortical dysplasia and balloon cells may coexist with mesial temporal sclerosis. The true incidence of this dual pathology is unknown. Our aim was to assess the frequency of amygdala (AM)-hippocampal abnormality in a homogeneous population with this specific developmental malformation. MRI-based volumetry of the AM and hippocampal formation (HF) in 30 patients with unilateral TLDM and intractable partial epilepsy was performed. A volume normalization process defined a normal range of HF and AM volumes in control subjects, and enabled the detection of bilateral volume loss. Normalized volumes detected HF atrophy in 26 patients (nine unilateral and 17 bilateral) and AM atrophy in 18 patients (three unilateral and 15 bilateral). Visual analysis detected unilateral HF abnormality in 21 patients and bilateral abnormality in two. When compared with a group of patients with temporal lobe epilepsy and pure hippocampal sclerosis (N = 92), where volumetry revealed bilateral HF atrophy in 18%, a significant difference in the frequency of bilateral HF atrophy was found (p < 0.0001). Dual pathology is frequent in patients with TLDM (87%), and the AM-HF abnormality is often bilateral (57%). Our data suggest that more widespread and potentially epileptogenic lesions coexist with visibly detectable unilateral TLDM. This has implications for the selection of patients for temporal lobe surgery and may influence surgical strategies.

Focal dermal hypoplasia (Goltz-Gorlin syndrome): a new case with a novel variant in the PORCN gene (c.1250T>C:p.F417S) and unusual spinal anomaly.

PubMed

Garavelli, Livia; Simonte, Graziella; Rosato, Simonetta; Wischmeijer, Anita; Albertini, Enrico; Guareschi, Elisa; Longo, Caterina; Albertini, Giuseppe; Gelmini, Chiara; Greco, Chiara; Errico, Stefania; Savino, Gustavo; Pavanello, Marco; Happle, Rudolf; Unger, Sheila; Superti-Furga, Andrea; Grzeschik, Karl-Heinz

2013-07-01

Focal dermal hypoplasia (FDH; Goltz-Gorlin syndrome; OMIM 305600) is a disorder that features involvement of the skin, skeletal system, and eyes. It is caused by loss-of-function mutations in the PORCN gene. We report a young girl with FDH, microphthalmos associated with colobomatous orbital cyst, dural ectasia and cystic malformation of the spinal cord, and a de novo variant in PORCN. This association has not been previously reported, and based on these observations the phenotypic spectrum of FDH might be broader than previously appreciated. It would be prudent to alter the suggested surveillance for this rare disorder. Copyright © 2013 Wiley Periodicals, Inc.

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.

PHACES syndrome associated with carcinoid endobronchial tumor.

PubMed

Mama, Nadia; H'mida, Dorra; Lahmar, Imen; Yacoubi, Mohamed Tahar; Tlili-Graiess, Kalthoum

2014-05-01

PHACES syndrome consists of the constellation of manifestations including posterior fossa anomalies of the brain (most commonly Dandy-Walker malformations), hemangiomas of the face and scalp, arterial abnormalities, cardiac defects, eye anomalies and sternal defects. We present a case with a possible PHACES syndrome including sternal cleft and supraumbilical raphé, precordial skin tag, persistent left superior vena cava and subtle narrowing of the aorta with an endobronchial carcinoid tumor. All these anomalies were discovered on chest multi-detector CT. This is a unique case of PHACES syndrome associated with carcinoid tumor. Review of the literature revealed 3 cases of PHACES syndrome with glial tumor. The authors tried to find the relationship between PHACES syndrome and carcinoid tumors or gliomas, which all derive from the neural crest cells.

TBC1D24 mutation associated with focal epilepsy, cognitive impairment and a distinctive cerebro-cerebellar malformation.

PubMed

Afawi, Zaid; Mandelstam, Simone; Korczyn, Amos D; Kivity, Sara; Walid, Simri; Shalata, Adel; Oliver, Karen L; Corbett, Mark; Gecz, Jozef; Berkovic, Samuel F; Jackson, Graeme D

2013-07-01

We describe the clinical and radiological features of a family with a homozygous mutation in TBC1D24. The phenotype comprised onset of focal seizures at 2 months with prominent eye-blinking, facial and limb jerking with an oral sensory aura. These were controllable with medication but persisted into adult life. Associated features were mild to moderate intellectual disability and cerebellar features. MRI showed subtle cortical thickening with cerebellar atrophy and high signal confined to the ansiform lobule. The disorder is allelic with familial infantile myoclonic epilepsy, where intellect and neurologic examination are normal, highlighting the phenotypic variation with mutations of TBC1D24. Copyright © 2013 Elsevier B.V. All rights reserved.

Implications of the implementation of the revised dose limit to the lens of the eye: the view of IRPA professionals.

PubMed

Broughton, J; Cantone, M C; Ginjaume, M; Shah, B; Czarwinski, R

2015-06-01

In April 2011, the International Commission on Radiological Protection issued a statement on reduction of the equivalent dose limits for the lens of the eye, and strongly recommended its consideration in the revision of the International Atomic Energy Agency's International Basic Safety Standards on Radiation Protection. The reduced dose limit was incorporated in the final version of the Basic Safety Standards. As significant concern was expressed by radiation protection professionals worldwide, the International Radiation Protection Association (IRPA) established a task group to assess the impact of implementation of the revised dose limit for the lens of the eye for occupational exposure. IRPA Associate Societies (ASs) were asked for their views using a questionnaire addressing three topics: implications for dosimetry, implications for methods of protection, and wider implications. The responses received indicate various methods of approach and express different points of view, reflecting nuances of particular ASs or specific professional groups. Topic experts nominated by ASs were selected to assist with collation of responses, and a report was produced by the task group. Conclusions were drawn on the three issues, including potential cost implications. A number of recommendations were drawn from the responses received including: the request for more understanding about the relationship between exposure of the lens of the eye and cataract formation, and further guidance to assist implementation; the importance of economic and social considerations when introducing the limits into national regulations; the need to propose or define procedures related to employment of people with existing or pre-cataract conditions; and the practical aspects relating to dosimetry and protective equipment. © The International Society for Prosthetics and Orthotics Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

[Unicornuate uterus with cavitary non-communicating rudimentary horn: magnetic resonance characterization].

PubMed

Chamorro-Oscullo, Jenny Del Rocío; Sánchez-Cortázar, Julián Antonio; Gómez-Pérez, María de Guadalupe

2018-01-01

Mullerian duct or paramesonephric anomalies are a group of congenital malformations of the female genital tract that result from the alteration in one or more stages of embryonic development. The prevalence has increased, probably due to the progress of diagnostic imaging methods and the relevance that it has acquired in young women with infertility problems. Magnetic resonance imaging (MRI) is currently the method of choice for characterizing the different types of Mullerian anomalies, its complications and associated pathology. Unicornuate uterus correspond to class II of classification of Mullerian duct anomalies developed by the American Society for Reproductive Medicine. According to this, four subtypes have been identified, each with different clinical implications. A cavitated, non-communicating rudimentary horn in a unicornuate uterus is associated with an increased incidence of gynecological problems and obstetric complications that sometimes threaten the lives of patients, reason why its suspicion, diagnosis and treatment is necessary. We report the case of a patient with infertility in which this subtype of congenital malformation was discovered.

Study of placenta of children born with congenital malformations.

PubMed

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

2003-01-01

The malformations in this study were observed in a series of 279,642 consecutive births of known outcome registered in our Registry of congenital anomalies. For each case, more than 50 factors included in the registration forms were studied. One of the factors studied was the placenta. For each malformed child, a control was chosen. Cases with maternal known factors impairing placenta function, i.e. vasculopathy and diabetes, were excluded. In each category of malformations studied, the malformed children were divided into isolated and non-isolated (multiple malformed) cases. The weight of placenta of isolated cases was not lower than the weight of placenta of the controls. In contrast, the weight of placenta of the cases with non-isolated malformations was lower than the weight of placenta of the controls and of the isolated cases, for all categories of malformations but gastroschisis and omphalocele. The mean weights at birth of the cases with multiple malformations were also lower than those of the controls. The human placenta discounts a principal functional part, the maternal blood in the intervillous space. Congenital malformations may interact with this function.

Ultrasound-guided high-intensity focused ultrasound ablation for treating uterine arteriovenous malformation.

PubMed

Yan, X; Zhao, C; Tian, C; Wen, S; He, X; Zhou, Y

2017-08-01

To explore HIFU treatment for uterine arteriovenous malformation. A case report. Gynaecological department in a university teaching hospital of China. A patient with uterine arteriovenous malformation. The diagnosis of uterine arteriovenous malformation was made through MRI. Ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation was performed. HIFU is effective in treating uterine arteriovenous malformation. The patient had reduction of the lesion volume and obvious symptom relief, without significant adverse effects. HIFU can be used as a new treatment option for uterine arteriovenous malformation. Ultrasound-guided high-intensity focused ultrasound ablation is effective in treating uterine arteriovenous malformation. © 2017 Royal College of Obstetricians and Gynaecologists.

Hind limb malformations in free-living northern leopard frogs (Rana pipiens) from Maine, Minnesota, and Vermont suggest multiple etiologies

USGS Publications Warehouse

Meteyer, C.U.; Loeffler, I.K.; Fallon, J.F.; Converse, K.A.; Green, E.; Helgen, J.C.; Kersten, S.; Levey, R.; Eaton-Poole, L.; Burkhart, J.G.

2000-01-01

Background Reports of malformed frogs have increased throughout the North American continent in recent years. Most of the observed malformations have involved the hind limbs. The goal of this study was to accurately characterize the hind limb malformations in wild frogs as an important step toward understanding the possible etiologies. Methods During 1997 and 1998, 182 recently metamorphosed northern leopard frogs (Rana pipiens) were collected from Minnesota, Vermont, and Maine. Malformed hind limbs were present in 157 (86%) of these frogs, which underwent necropsy and radiographic evaluation at the National Wildlife Health Center. These malformations are described in detail and classified into four major categories: (1) no limb (amelia); (2) multiple limbs or limb elements (polymelia, polydactyly, polyphalangy); (3) reduced limb segments or elements (phocomelia, ectromelia, ectrodactyly, and brachydactyly; and (4) distally complete but malformed limb (bone rotations, bridging, skin webbing, and micromelia). Results Amelia and reduced segments and/or elements were the most common finding. Frogs with bilateral hind limb malformations were not common, and in only eight of these 22 frogs were the malformations symmetrical. Malformations of a given type tended to occur in frogs collected from the same site, but the types of malformations varied widely among all three states, and between study sites within Minnesota. Conclusions Clustering of malformation type suggests that developmental events may produce a variety of phenotypes depending on the timing, sequence, and severity of the environmental insult. Hind limb malformations in free-living frogs transcend current mechanistic explanations of tetrapod limb development.

Upward gaze and head deviation with frontal eye field stimulation.

PubMed

Kaiboriboon, Kitti; Lüders, Hans O; Miller, Jonathan P; Leigh, R John

2012-03-01

Using electrical stimulation to the deep, most caudal part of the right frontal eye field (FEF), we demonstrate a novel pattern of vertical (upward) eye movement that was previously only thought possible by stimulating both frontal eye fields simultaneously. If stimulation was started when the subject looked laterally, the initial eye movement was back to the midline, followed by upward deviation. Our finding challenges current view of topological organisation in the human FEF and may have general implications for concepts of topological organisation of the motor cortex, since sustained stimulation also induced upward head movements as a component of the vertical gaze shift. [Published with video sequences].

Safety and Efficacy Study of Sirolimus in Complicated Vascular Anomalies

ClinicalTrials.gov

2015-02-03

Kaposiform Hemangioendotheliomas; Tufted Angioma; Capillary Venous Lymphatic Malformation; Venous Lymphatic Malformation; Microcystic Lymphatic Malformation; Mucocutaneous Lymphangiomatosis and Thrombocytopenia; Capillary Lymphatic Arterial Venous Malformations; PTEN Overgrowth Syndrome With Vascular Anomaly; Lymphangiectasia Syndromes

Chiari Malformation

MedlinePlus

... Staying Safe Videos for Educators Search English Español Chiari Malformation KidsHealth / For Parents / Chiari Malformation What's in this ... balance problems, and other symptoms. What Is a Chiari Malformation? Normally, the cerebellum sits at the back of ...

Delayed Retroclival and Cervical Spinal Subdural Hematoma Complicated by Preexisting Chiari Malformation in Adult Trauma Patient.

PubMed

Nguyen, Ha Son; Choi, Hoon; Kurpad, Shekar; Soliman, Hesham

2017-09-01

Traumatic spinal subdural hematoma involving the retroclival region and upper cervical spine is a rare pathology. To our knowledge, there have only been 2 prior cases in an adult trauma patient. We describe a patient with preexisting Chiari 1 malformation, who recently sustained a unilateral type 1 occipital condyle fracture with associated disruption of the tectorial membrane and transverse ligament, which returned with a retroclival subdural hematoma extending down to C7, causing spinal cord compression and symptomatic obstructive hydrocephalus. A 30-year-old female sustained a motor vehicle collision. Computed tomography C spine revealed a type I occipital condyle fracture. Magnetic resonance imaging C spine demonstrated disruption of the tectorial membrane and avulsion of the transverse ligament at its attachment to the left C1 tubercle; moreover, there was a Chiari 1 malformation. The patient was neurologically intact. A halo was recommended, but the patient opted for an aspen collar with close management. She was discharged but returned 3 days later with apneic episodes, along with bradycardia and hypertension. She was promptly intubated. Computed tomography head showed interval ventricular enlargement. Magnetic resonance imaging C spine revealed a new ventral hematoma spanning the retroclival region to C7, most pronounced at C2-C3. On examination, she opened her eyes to pain, her pupils were equal and reactive, and she withdrew in all extremities. An external ventricular drain was emergently placed. She underwent a suboccipital craniectomy, C1-3 laminectomies, and occiput-C4 instrumented fusion. The dura was significantly tense, and no epidural hematoma was observed during lateral exploration. Postoperatively, she woke up well, exhibiting a nonfocal neurologic examination. A diagnostic angiogram was negative. She was extubated uneventfully, and the external ventricular drain was weaned off in 4 days. Traumatic spinal subdural hematoma involving both the retroclival region and upper cervical spine can lead to bulbar signs and symptomatic obstructive hydrocephalus. There should be vigilance for this pathology in patients with high-energy craniocervical trauma. Disruption of the tectorial membrane and therapeutic anticoagulation may be risk factors. The clinical scenario can be complicated in the setting of a preexisting Chiari 1 malformation. Copyright © 2017 Elsevier Inc. All rights reserved.

Color-coded perfusion analysis of CEUS for pre-interventional diagnosis of microvascularisation in cases of vascular malformations.

PubMed

Teusch, V I; Wohlgemuth, W A; Piehler, A P; Jung, E M

2014-01-01

Aim of our pilot study was the application of a contrast-enhanced color-coded ultrasound perfusion analysis in patients with vascular malformations to quantify microcirculatory alterations. 28 patients (16 female, 12 male, mean age 24.9 years) with high flow (n = 6) or slow-flow (n = 22) malformations were analyzed before intervention. An experienced examiner performed a color-coded Doppler sonography (CCDS) and a Power Doppler as well as a contrast-enhanced ultrasound after intravenous bolus injection of 1 - 2.4 ml of a second-generation ultrasound contrast medium (SonoVue®, Bracco, Milan). The contrast-enhanced examination was documented as a cine sequence over 60 s. The quantitative analysis based on color-coded contrast-enhanced ultrasound (CEUS) images included percentage peak enhancement (%peak), time to peak (TTP), area under the curve (AUC), and mean transit time (MTT). No side effects occurred after intravenous contrast injection. The mean %peak in arteriovenous malformations was almost twice as high as in slow-flow-malformations. The area under the curve was 4 times higher in arteriovenous malformations compared to the mean value of other malformations. The mean transit time was 1.4 times higher in high-flow-malformations compared to slow-flow-malformations. There was no difference regarding the time to peak between the different malformation types. The comparison between all vascular malformation and surrounding tissue showed statistically significant differences for all analyzed data (%peak, TTP, AUC, MTT; p < 0.01). High-flow and slow-flow vascular malformations had statistically significant differences in %peak (p < 0.01), AUC analysis (p < 0.01), and MTT (p < 0.05). Color-coded perfusion analysis of CEUS seems to be a promising technique for the dynamic assessment of microvasculature in vascular malformations.

cis-Regulatory Mutations Are a Genetic Cause of Human Limb Malformations

PubMed Central

VanderMeer, Julia E.; Ahituv, Nadav

2011-01-01

The underlying mutations that cause human limb malformations are often difficult to determine, particularly for limb malformations that occur as isolated traits. Evidence from a variety of studies shows that cis-regulatory mutations, specifically in enhancers, can lead to some of these isolated limb malformations. Here, we provide a review of human limb malformations that have been shown to be caused by enhancer mutations and propose that cis-regulatory mutations will continue to be identified as the cause of additional human malformations as our understanding of regulatory sequences improves. PMID:21509892

Dose limits to the lens of the eye: International Basic Safety Standards and related guidance.

PubMed

Boal, T J; Pinak, M

2015-06-01

The International Atomic Energy Agency (IAEA) safety requirements: 'General Safety Requirements Part 3--Radiation protection and safety of radiation sources: International Basic Safety Standards' (BSS) was approved by the IAEA Board of Governors at its meeting in September 2011, and was issued as General Safety Requirements Part 3 in July 2014. The equivalent dose limit for the lens of the eye for occupational exposure in planned exposure situations was reduced from 150 mSv year(-1) to 20 mSv year(-1), averaged over defined periods of 5 years, with no annual dose in a single year exceeding 50 mSv. This reduction in the dose limit for the lens of the eye followed the recommendation of the International Commission on Radiological Protection in its statement on tissue reactions of 21 April 2011. IAEA has developed guidance on the implications of the new dose limit for the lens of the eye. This paper summarises the process that led to the inclusion of the new dose limit for the lens of the eye in the BSS, and the implications of the new dose limit. © The International Society for Prosthetics and Orthotics Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Targeted deletion of RIC8A in mouse neural precursor cells interferes with the development of the brain, eyes, and muscles.

PubMed

Kask, Keiu; Tikker, Laura; Ruisu, Katrin; Lulla, Sirje; Oja, Eva-Maria; Meier, Riho; Raid, Raivo; Velling, Teet; Tõnissoo, Tambet; Pooga, Margus

2018-04-01

Autosomal recessive disorders such as Fukuyama congenital muscular dystrophy, Walker-Warburg syndrome, and the muscle-eye-brain disease are characterized by defects in the development of patient's brain, eyes, and skeletal muscles. These syndromes are accompanied by brain malformations like type II lissencephaly in the cerebral cortex with characteristic overmigrations of neurons through the breaches of the pial basement membrane. The signaling pathways activated by laminin receptors, dystroglycan and integrins, control the integrity of the basement membrane, and their malfunctioning may underlie the pathologies found in the rise of defects reminiscent of these syndromes. Similar defects in corticogenesis and neuromuscular disorders were found in mice when RIC8A was specifically removed from neural precursor cells. RIC8A regulates a subset of G-protein α subunits and in several model organisms, it has been reported to participate in the control of cell division, signaling, and migration. Here, we studied the role of RIC8A in the development of the brain, muscles, and eyes of the neural precursor-specific conditional Ric8a knockout mice. The absence of RIC8A severely affected the attachment and positioning of radial glial processes, Cajal-Retzius' cells, and the arachnoid trabeculae, and these mice displayed additional defects in the lens, skeletal muscles, and heart development. All the discovered defects might be linked to aberrancies in cell adhesion and migration, suggesting that RIC8A has a crucial role in the regulation of cell-extracellular matrix interactions and that its removal leads to the phenotype characteristic to type II lissencephaly-associated diseases. © 2018 Wiley Periodicals, Inc. Develop Neurobiol 78: 374-390, 2018. © 2018 Wiley Periodicals, Inc.

Field guide to malformations of frogs and toads: with radiographic interpretations

USGS Publications Warehouse

Meteyer, Carol U.

2000-01-01

In 1995, students found numerous malformed frogs on a field trip to a Minnesota pond. Since that time, reports of malformed frogs have increased dramatically. Malformed frogs have now been reported in 44 states in 38 species of frogs, and 19 species of toads. Estimates as high as 60% of the newly metamorphosed frog populations have had malformations at some ponds (NARCAM, ’99). The wide geographic distribution of malformed frogs and the variety of malformations are a concern to resource managers, research scientists and public health officials. The potential for malformations to serve as a signal of ecosystem disruption, and the affect this potential disruption might have on other organisms that share those ecosystems, has not been resolved. Malformations represent an error that occurred early in development. The event that caused the developmental error is temporally distant from the malformation we see in the fully developed animal. Knowledge of normal developmental principles is necessary to design thoughtful investigations that will define the events involved in abnormal development in wild frog populations.Development begins at the time an egg is fertilized and progresses by chemical communication between cells and cell layers. This communication is programmed through gene expression. Malformations represent primary errors in development, errors in chemical communication or translation of genetic information. Deformations arise later in development and usually result from the influence of mechanical factors (such as amputation) that alter shape or anatomy of a structure that has developed normally. The occurrence and the type of malformations are influenced by the type of error or insult as well as the timing of the error (the developmental stage at which the error occurred). The appearance of the malformation can therefore provide clues that suggest when the error may have occurred. If the malformation is an incomplete organ, such as an incomplete limb, the factor or insult acted during a susceptible period prior to organ completion. Although defining the anatomy of the malformed metamorphosed frog can give us an idea of the approximate window during which the developmental insult was initiated, and might even suggest the type of insult that may have occurred, the morphology of the malformation does not define the cause. To define causes and mechanisms of frog malformations we need to use well designed investigations that are different from traditional tests used in acute toxicity or disease pathogenicity studies. When investigating malformations in metamorphosed frogs, we are looking at the affect of exposure to an agent that occurred early in tadpole development. Therefore investigations to determine causes of malformations need to look at agents that are present in the tadpoles or their environments at these early developmental times. Laboratory experiments need to expose embryos and tadpoles to suspect agents at appropriate developmental stages and look at acute results, such as toxicity and death, as well as following the developmental process to completion to determine the impact of the agent on the developing tadpole and the fully developed frog. This means holding animals past metamorphic climax to assure that the anatomy and physiology of the adult have developed normally.As we look at field collections of abnormal frogs, we need to keep in mind that these collections reflect survivors only. We are looking at malformations that were not fatal to tadpoles. We cannot assume that because we do not collect other malformations, they did not exist. More work needs to be done on the developing tadpole, in the field and in the laboratory, to better elucidate the range, frequency, character and causes of anuran malformations.

Diprosopus (partially duplicated head) associated with anencephaly: a case report.

PubMed

al Muti Zaitoun, A; Chang, J; Booker, M

1999-01-01

Craniofacial duplication (diprosopus) is a rare form of conjoined twin. A 16 year old mother with a twin pregnancy delivered one normally formed baby boy and one diprosopus male. The malformed baby was 33 weeks of gestation with a single trunk, normal limbs and various degrees of facial duplication. Of the following structures there were two of each: noses, eyes, ears (and one dimple), mouths, tongues and, with bilateral central cleft lips and cleft palates. This was associated with holoprosencephaly and craniorachischisis. Internal organs showed no duplication. There were multiple congenital anomalies including diaphragmatic hernia, small lungs, two lobes of the right lung, ventricular septal defect, small adrenal gland and small left kidney with short ureter. The body also had a short neck, small chest cavities and kyphosis. X-ray revealed duplication of the vertebral column. The case presented here represents a type II of diprosopia of Rating (1933) and is the least common type reported. We also reviewed 22 recently reported cases of diprosopus. In addition to facial duplication, anencephaly, neural tube defect and cardiac malformations represent the more common congenital abnormalities associated with diprosopus. The pathogenesis of diprosopus is not well understood. Factors that play a role in diprosopus are probably similar to those factors (genetic, environmental and abnormal placental circulation) which affect monozoygotic twins as observed in this case report. Early ultrasonography diagnosis of diprosopus permits one to consider a vaginal therapeutic abortion.

77 FR 29668 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-18

... Study of Diseases Such as Cancer, Autoimmune Conditions, Dry Eye and Other Indications that Involve A 3..., such as rheumatoid arthritis, psoriasis, and dry eye disease, and other conditions. This molecular... the Gli family. Mutations in human GLIS3 have been implicated in a syndrome characterized by neonatal...

[Lymphatic malformations in the head and neck area].

PubMed

Wiegand, S; Werner, J A

2016-02-01

Lymphatic malformations are congenital malformations of the lymphatic system. They are mainly located in the head and neck area, and grow proportional to the patients' body growth. Depending on the morphology, it can be distinguished between macrocystic, microcystic and mixed lymphatic malformations. Due to their infiltrative growth, microcystic lymphatic malformations are particularly difficult to treat. Therapeutic approaches include conventional surgical resection, laser therapy, sclerotherapy and systemic drug therapies.

Recurrent Hyperammonemia After Abernethy Malformation Type 2 Closure: a Case Report.

PubMed

Li, Hui; Ma, Zhi; Xie, Ying; Tian, Feng

The Abernethy malformation is a rare congenital malformation defined by the presence of an extrahepatic portosystemic shunt. Although most patients are asymptomatic, clinical encephalopathy is present in 15% of cases. We present a patient with type 2 Abernethy malformation, hyperammonemia, and encephalopathy. Shunt closure was performed successfully using interventional angiography; however, hyperammonemia recurred 3 months later. The diagnosis of Abernethy malformation can be made easily, but the ideal patient management strategy has not yet been established. This is the first reported patient with recurrence of hyperammonemia after interventional treatment; we discuss the therapeutic options for Abernethy malformation.

Trematode infection causes malformations and population effects in a declining New Zealand fish.

PubMed

Kelly, David W; Thomas, Harriet; Thieltges, David W; Poulin, Robert; Tompkins, Daniel M

2010-03-01

1. Animal malformations engender wide public and scientific concern because of associated environmental health risks. This is highlighted by increased incidence of limb malformations in amphibians associated with trematode infections and disturbance. Malformations may signal new emerging disease threats, but whether the phenomenon is broadly applicable across taxa, or has population-scale impacts, is unknown. 2. Malformations are widely reported in fish and, until now, have been attributed mainly to contaminants. We tested whether the trematode Telogaster opisthorchis caused severe malformations, leading to population effects, in Galaxias anomalus, a threatened New Zealand freshwater fish. 3. Experimental infection of larval fish caused increasing spinal malformation and mortality with infection intensity that closely matched field patterns. Field malformation frequency peaked in January (65%), before declining sharply in February (25%) and remaining low thereafter. 4. The peak occurred during a 'critical window' of larval development, with the decline coincident with a population crash, indicating that malformation was causing mortality in the field. 5. The occurrence of such critical developmental windows may explain why this mechanism of population impact has been overlooked. With global environmental stressors predicted to enhance trematode infections, our results show that parasite-induced malformation, and its population-scale impacts, could be more widespread than previously considered.

Blind ethics: Closing one's eyes polarizes moral judgments and discourages dishonest behavior.

PubMed

Caruso, Eugene M; Gino, Francesca

2011-02-01

Four experiments demonstrate that closing one's eyes affects ethical judgment and behavior because it induces people to mentally simulate events more extensively. People who considered situations with their eyes closed rather than open judged immoral behaviors as more unethical and moral behaviors as more ethical. In addition, considering potential decisions with closed eyes decreased stated intentions to behave ethically and actual self-interested behavior. This relationship was mediated by the more extensive mental simulation that occurred with eyes closed rather than open, which, in turn, intensified emotional reactions to the ethical situation. We discuss the implications of these findings for moral psychology and ethical decision making. Copyright © 2010 Elsevier B.V. All rights reserved.

Amphibian malformations

USGS Publications Warehouse

,

1998-01-01

Frog malformations have been reported from 42 states. The broad geographic distribution of these malformations warrants national attention. Scientists at the USGS National Wildlife Health Center in Madison, Wisconsin are studying this problem in an effort to document its scope and to determine the causes of the observed malformations.

16q24.1 microdeletion in a premature newborn: usefulness of array-based comparative genomic hybridization in persistent pulmonary hypertension of the newborn.

PubMed

Zufferey, Flore; Martinet, Danielle; Osterheld, Maria-Chiara; Niel-Bütschi, Florence; Giannoni, Eric; Schmutz, Nathalie Besuchet; Xia, Zhilian; Beckmann, Jacques S; Shaw-Smith, Charles; Stankiewicz, Pawel; Langston, Claire; Fellmann, Florence

2011-11-01

Report of a 16q24.1 deletion in a premature newborn, demonstrating the usefulness of array-based comparative genomic hybridization in persistent pulmonary hypertension of the newborn and multiple congenital malformations. Descriptive case report. Genetic department and neonatal intensive care unit of a tertiary care children's hospital. None. We report the case of a preterm male infant, born at 26 wks of gestation. A cardiac malformation and bilateral hydronephrosis were diagnosed at 19 wks of gestation. Karyotype analysis was normal, and a 22q11.2 microdeletion was excluded by fluorescence in situ hybridization analysis. A cesarean section was performed due to fetal distress. The patient developed persistent pulmonary hypertension unresponsive to mechanical ventilation and nitric oxide treatment and expired at 16 hrs of life. An autopsy revealed partial atrioventricular canal malformation and showed bilateral dilation of the renal pelvocaliceal system with bilateral ureteral stenosis and annular pancreas. Array-based comparative genomic hybridization analysis (Agilent oligoNT 44K, Agilent Technologies, Santa Clara, CA) showed an interstitial microdeletion encompassing the forkhead box gene cluster in 16q24.1. Review of the pulmonary microscopic examination showed the characteristic features of alveolar capillary dysplasia with misalignment of pulmonary veins. Some features were less prominent due to the gestational age. Our review of the literature shows that alveolar capillary dysplasia with misalignment of pulmonary veins is rare but probably underreported. Prematurity is not a usual presentation, and histologic features are difficult to interpret. In our case, array-based comparative genomic hybridization revealed a 16q24.1 deletion, leading to the final diagnosis of alveolar capillary dysplasia with misalignment of pulmonary veins. It emphasizes the usefulness of array-based comparative genomic hybridization analysis as a diagnostic tool with implications for both prognosis and management decisions in newborns with refractory persistent pulmonary hypertension and multiple congenital malformations.

Headache in children with Chiari I malformation.

PubMed

Toldo, Irene; Tangari, Marta; Mardari, Rodica; Perissinotto, Egle; Sartori, Stefano; Gatta, Michela; Calderone, Milena; Battistella, Pier Antonio

2014-05-01

Headache is the most common symptom of Chiari 1 malformation, a condition characterized by the herniation of cerebellar tonsils through the foramen magnum. However, the headache pattern of cases with Chiari 1 malformations is not well defined in the literature, especially in children. The aim of this retrospective chart review was to evaluate the frequency and the characteristics of headache in children with Chiari 1 malformation at initial evaluation and during follow up. Forty-five cases with tonsillar ectopia were selected among 9947 cases under 18 years of age who underwent neuroimaging between 2002 and 2010. A semistructured clinical interview (mean follow-up: 5.2 years) was conducted. Headache was classified according to the second edition of the International Classification of Headache Disorders. Possible associations between clinical picture, in particular headache pattern, but also other signs and symptoms attributable to Chiari 1 malformation, and the extent of tonsillar ectopia were found for 3 different groups: those with borderline (<5 mm, N = 12), mild (5-9 mm, N = 27), and severe tonsillar ectopia (≥10 mm, N = 6), respectively. Twenty-four out of 33 (73%) cases with Chiari 1 malformation complained of headache, and 9/33 (27%) of those patients (5 with mild and 4 with severe tonsillar ectopia) reported headache attributed to Chiari 1 malformation. In our studied pediatric population, the most common symptom for cases diagnosed with Chiari 1 malformation was headache, and headache attributed to Chiari 1 malformation was the most common headache pattern in patients with Chiari 1 malformation. The presence of headache attributed to Chiari 1 malformation along with 3 other signs or symptoms of Chiari 1 malformation were highly predictive of severe tonsillar ectopia. © 2014 American Headache Society.

Anophthalmia: an uncommon manifestation of neurofibromatosis type 1.

PubMed

Chen, Sheng; Pu, Jia-Li; Zhang, Jian-Min; Hong, Yuan

2011-11-01

Neurofibromatosis type 1 (NF-1) is an autosomal dominant, multisystem disorder, affecting approximately 1 of 3500 people. Ocular disorders, such as Lisch nodules, optic gliomas, and anterior segment defects, are typical with clinical presentation. Anophthalmia, as a rare eye malformation, has never been reported in patients with NF-1. We report a 27-year-old patient in whom clinical manifestations of café au lait spots, neurofibromas, osseous orbital dysplasia, and anophthalmia were observed. The diagnosis of NF-1 was made, according to clinical course and brain computed tomography and magnetic resonance imaging. Because the patient refused aggressive management approaches, she was managed conservatively and is well on follow-up. We suggest that patients presenting with anophthalmia need serious evaluation and that NF-1 needs to be considered in the differential diagnosis.

RMND5 from Xenopus laevis is an E3 ubiquitin-ligase and functions in early embryonic forebrain development.

PubMed

Pfirrmann, Thorsten; Villavicencio-Lorini, Pablo; Subudhi, Abinash K; Menssen, Ruth; Wolf, Dieter H; Hollemann, Thomas

2015-01-01

In Saccharomyces cerevisiae the Gid-complex functions as an ubiquitin-ligase complex that regulates the metabolic switch between glycolysis and gluconeogenesis. In higher organisms six conserved Gid proteins form the CTLH protein-complex with unknown function. Here we show that Rmnd5, the Gid2 orthologue from Xenopus laevis, is an ubiquitin-ligase embedded in a high molecular weight complex. Expression of rmnd5 is strongest in neuronal ectoderm, prospective brain, eyes and ciliated cells of the skin and its suppression results in malformations of the fore- and midbrain. We therefore suggest that Xenopus laevis Rmnd5, as a subunit of the CTLH complex, is a ubiquitin-ligase targeting an unknown factor for polyubiquitination and subsequent proteasomal degradation for proper fore- and midbrain development.

SOX2 anophthalmia syndrome and dental anomalies.

PubMed

Chacon-Camacho, Oscar Francisco; Fuerte-Flores, Bertha Irene; Ricardez-Marcial, Edgar F; Zenteno, Juan Carlos

2015-11-01

SOX2 anophthalmia syndrome is an uncommon autosomal dominant syndrome caused by mutations in the SOX2 gene and clinically characterized by severe eye malformations (anophthalmia/microphthalmia) and extraocular anomalies mainly involving brain, esophagus, and genitalia. In this work, a patient with the SOX2 anophthalmia syndrome and exhibiting a novel dental anomaly is described. SOX2 genotyping in this patient revealed an apparently de novo c.70del20 deletion, a commonly reported SOX2 mutation. A review of the phenotypic variation observed in patients carrying the recurrent SOX2 c.70del20 mutation is presented. Although dental anomalies are uncommonly reported in the SOX2 anophthalmia syndrome, we suggest that a dental examination should be performed in patients with SOX2 mutations. © 2015 Wiley Periodicals, Inc.

A case of pancreatic AV malformation in an elderly man.

PubMed

Gupta, Vipin; Kedia, Saurabh; Sonika, Ujjwal; Madhusudhan, Kumble Seetharama; Pal, Sujoy; Garg, Pramod

2018-06-01

A 60-year-old man presented with recurrent abdominal pain and weight loss for 6 months. Abdominal imaging showed a large vascular lesion in the head and neck of pancreas suggestive of arteriovenous malformation (AV malformation). Endoscopic ultrasound was done which showed features of AV malformation with no evidence of pancreatic malignancy. Surgery was planned for definitive treatment of malformation. Digital subtraction angiography with angioembolization was done prior to surgery to reduce vascularity of the lesion. He recovered after a pylorus preserving pancreaticoduodenectomy. Histopathology of the resected specimen confirmed the pancreatic AV malformation. There has been no recurrence at 2 years of follow-up.

A developmental classification of malformations of the brainstem.

PubMed

Barkovich, A James; Millen, Kathleen J; Dobyns, William B

2007-12-01

With advances in imaging and genetics, malformations of the brainstem are being more commonly identified. We describe and classify brainstem anomalies in 138 patients ascertained over a period of 10 years Magnetic resonance imaging studies and, where available, clinical records of the patients were retrospectively reviewed. Malformations were segregated according to magnetic resonance findings and classified when possible by embryological mechanisms The most common location for anomalies was the pons, which was involved in 114 patients. The midbrain was involved in 45 patients, whereas the medulla was involved in 14. In 53 patients, more than 1 region was affected (all 3 regions in 6 patients, midbrain and pons in 39, and medulla and pons in 8). The malformations were divided into four groups: (1) malformations with abnormal brainstem segmentation, (2) malformations with segmental hypoplasia, (3) postsegmentation malformations, and (4) malformations associated with abnormal cortical organization The malformations of the brainstem identified in this study were diverse and complex. This proposed classification organizes them into groupings based on known genetics and embryological events. Use of this system will help clinicians and scientists to better understand these disorders and, ultimately, to better counsel families of affected patients.

Amphibian malformations and body condition across an agricultural landscape of northwest Argentina.

PubMed

Guerra, Cecilia; Aráoz, Ezequiel

2016-09-26

Agricultural landscapes support large amphibian populations because they provide habitat for many species, although agriculture affects amphibians through various mechanisms. Pollution with agrochemicals is the major threat to amphibian populations after habitat loss, as chemicals alter the ecophysiology of amphibians, putting their health and survival at risk. We aimed to assess the effect of different environments, sites, width of forest buffers and sampling years on the health of amphibians, which was estimated through the prevalence of malformations and body condition. During 3 yr of pitfall trapping, we captured 4491 amphibians. The prevalence of malformations was higher in the croplands than in the forests, while the body condition was better within forests. The prevalence of malformations was higher in the narrower forest site than in the wider forest site. The prevalence of malformations and the body condition were higher in the third year. The prevalence of malformations differed by species. We found 11 types of malformation, which mainly affected limbs and were unilateral or bilaterally asymmetrical. Our results showed that the prevalence of malformations and body condition reflect different aspects of the health of amphibians and that forest individuals are healthier than those from croplands. The results also highlight the importance of spatial configuration besides the conservation of natural habitats to preserve healthy amphibians in agricultural landscapes. The types of malformation that we found suggest that agrochemicals could be an important cause of malformations.

Associated malformations among infants with anophthalmia and microphthalmia.

PubMed

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

2012-03-01

Infants with anophthalmia and microphthalmia frequently have other associated congenital anomalies. The reported frequency and types of associated malformations vary among different studies. The purpose of this investigation was to assess the frequency and types of associated malformations among infants with anophthalmia and microphthalmia in a geographically well defined population from 1979 to 2004 of 346,831 consecutive births. Of the 87 infants with anophthalmia and microphthalmia born during this period (prevalence at birth, 2.5 per 10,000), 90% had associated malformations. Infants with associated malformation were divided into recognizable conditions (22 infants [25%] with chromosomal and 15 infants [17%] with nonchromosomal conditions), and nonrecognizable conditions (41 infants [47%] with multiple malformations). Trisomies 13 and 18 were the most frequent chromosomal abnormalities. Amniotic bands sequence, CHARGE syndrome, Meckel-Gruber syndrome, and VACTERL association were most often present in recognizable nonchromosomal conditions. Malformations in the musculoskeletal, cardiovascular, and central nervous systems were the most common other anomalies in infants with multiple malformations and nonrecognizable conditions. The frequency of associated malformations in infants with anophthalmia or microphthalmia emphasizes the need for a thorough investigation of these infants. Routine screening for other malformations-especially musculoskeletal, cardiac, and central nervous system anomalies-may need to be considered in infants with anophthalmia or microphthalmia, and referral of these infants for genetics evaluation and counseling seems warranted. Copyright © 2012 Wiley Periodicals, Inc.

Progesterone receptors identified in vascular malformations of the head and neck.

PubMed

Duyka, Landon J; Fan, Chun Y; Coviello-Malle, Jean M; Buckmiller, Lisa; Suen, James Y

2009-10-01

To identify hormone receptors within vascular malformations (arteriovenous malformations [AVMs], venous malformations [VMs], and lymphatic malformations [LMs]) of the head and neck. Immunohistochemical staining for estrogen receptor (ER) and progesterone receptor (PR) was performed on archival vascular malformation tissue collected from both pediatric and adult patients. Tertiary referral center from 2006 to 2008. Twelve AVM, 10 VM, and eight LM specimens were stained for both ER and PR. Ten breast carcinoma specimens were used as controls, with the carcinoma cells serving as positive controls, and the endothelium and smooth muscle cells of the blood vessels serving as negative controls. Five normal supraglottic mucosal samples served as head and neck controls. The Fisher exact test was used for statistical analysis. Ten of the 12 (83%) AVM specimens stained diffusely positive for PR within the nuclei of the endothelium and smooth muscle of the malformed vessels (P < 0.0001). Five of the 10 (50%) VM specimens stained positive for PR (2 [20%] focal, 3 [30%] diffuse) within the nuclei of the endothelium and smooth muscle of the malformed vessels (P = 0.0325). Four of the eight (50%) LM specimens stained focally positive for PR within the nuclei of the endothelium of the malformed vessels (P = 0.0229). None of the vascular malformation specimens stained positive for ER. Our data suggest that PR, but not ER, is expressed in AVMs, VMs, and LMs of the head and neck.

Head and neck vascular malformations: time-resolved MR projection angiography.

PubMed

Ziyeh, S; Schumacher, M; Strecker, R; Rössler, J; Hochmuth, A; Klisch, J

2003-10-01

Extracranial vascular anomalies can be divided into haemangiomas and vascular malformations. The latter can be subdivided on the basis of the predominant type of vascular channels. Separation of high- and low-flow vascular malformations is of clinical importance. We report preliminary observations on time-resolved magnetic resonance projection angiography (MRPA) of vascular malformations of the head and neck. We examined eight patients with vascular anomalies of the head and neck. On MRPA the time between the early arterial phase and enhancement of the malformation could be used to distinguish high- and low-flow lesions. High-flow arteriovenous malformations showed early, intense enhancement. Venous malformations were either not visible on MRPA or showed late enhancement of veins. One patient was examined after embolisation of an arteriovenous fistula of the mandible. Normal MRPA was taken to indicate absence of a residual lesion.

Ocular-Motor Function and Information Processing: Implications for the Reading Process.

ERIC Educational Resources Information Center

Leisman, Gerald; Schwartz, Joddy

This paper discusses the dichotomy between continually moving eyes and the lack of blurred visual experience. A discontinuous model of visual perception is proposed, with the discontinuities being phase and temporally related to saccadic eye movements. It is further proposed that deviant duration and angular velocity characteristics of saccades in…

A secreted WNT-ligand-binding domain of FZD5 generated by a frameshift mutation causes autosomal dominant coloboma

PubMed Central

Liu, Chunqiao; Widen, Sonya A.; Williamson, Kathleen A.; Ratnapriya, Rinki; Gerth-Kahlert, Christina; Rainger, Joe; Alur, Ramakrishna P.; Strachan, Erin; Manjunath, Souparnika H.; Balakrishnan, Archana; Floyd, James A.; Li, Tiansen; Waskiewicz, Andrew; Brooks, Brian P.; Lehmann, Ordan J.; FitzPatrick, David R.; Swaroop, Anand

2016-01-01

Ocular coloboma is a common eye malformation resulting from incomplete fusion of the optic fissure during development. Coloboma is often associated with microphthalmia and/or contralateral anophthalmia. Coloboma shows extensive locus heterogeneity associated with causative mutations identified in genes encoding developmental transcription factors or components of signaling pathways. We report an ultra-rare, heterozygous frameshift mutation in FZD5 (p.Ala219Glufs*49) that was identified independently in two branches of a large family with autosomal dominant non-syndromic coloboma. FZD5 has a single-coding exon and consequently a transcript with this frameshift variant is not a canonical substrate for nonsense-mediated decay. FZD5 encodes a transmembrane receptor with a conserved extracellular cysteine rich domain for ligand binding. The frameshift mutation results in the production of a truncated protein, which retains the Wingless-type MMTV integration site family member-ligand-binding domain, but lacks the transmembrane domain. The truncated protein was secreted from cells, and behaved as a dominant-negative FZD5 receptor, antagonizing both canonical and non-canonical WNT signaling. Expression of the resultant mutant protein caused coloboma and microphthalmia in zebrafish, and disruption of the apical junction of the retinal neural epithelium in mouse, mimicking the phenotype of Fz5/Fz8 compound conditional knockout mutants. Our studies have revealed a conserved role of Wnt–Frizzled (FZD) signaling in ocular development and directly implicate WNT–FZD signaling both in normal closure of the human optic fissure and pathogenesis of coloboma. PMID:26908622

The Chiari 3 Malformation and a Systemic Review of the Literature.

PubMed

Young, Richard M; Shafa, Justin S; Myseros, John S

2015-01-01

Chiari type 3 is a rare hindbrain malformation that has been reported in the literature primarily as case reports and case series. Radiological, pathophysiological and surgical definitions of the malformation are inconsistent in the literature and subsequently can be confusing, and outcomes have also been uniformly poor. The definition of this rare malformation will be clarified through a case presentation. A retrospective review of prior publications in the PubMed and MEDLINE databases was performed looking for reports of 'Chiari 3 +/- malformation' and 'occipital encephalocele'. Relevant papers were reviewed and compiled into table format with associated descriptions of a Chiari type 3 malformation. A case illustration is presented with radiological and intraoperative imaging to reinforce and clarify the definition. Upon review of the prior publications in the detail of the descriptions and imaging associated with each article, there is a wide range of variability in the description of what is considered a Chiari 3 malformation. Occipital, occipitocervical and high cervical defects have all been described as Chiari 3 malformation. Our case illustration presents a patient with an occipitocervical encephalocele with neural elements, which is the classic and accepted definition of the Chiari 3 malformation. Chiari type 3 is a rare congenital malformation, and prior publications describing this developmental disorder have not demonstrated a consensus in its definition. In addition, outcomes have traditionally been reported as poor. This case illustration of a Chiari type 3 enforces the definition of an occipitocervical encephalocele with hindbrain herniation, and with proper management not all Chiari 3 malformation patients have bad outcomes. © 2015 S. Karger AG, Basel.

Notch-1 Signalling Is Activated in Brain Arteriovenous Malformations in Humans

ERIC Educational Resources Information Center

ZhuGe, Qichuan; Zhong, Ming; Zheng, WeiMing; Yang, Guo-Yuan; Mao, XiaoOu; Xie, Lin; Chen, Gourong; Chen, Yongmei; Lawton, Michael T.; Young, William L.; Greenberg, David A.; Jin, Kunlin

2009-01-01

A role for the Notch signalling pathway in the formation of arteriovenous malformations during development has been suggested. However, whether Notch signalling is involved in brain arteriovenous malformations in humans remains unclear. Here, we performed immunohistochemistry on surgically resected brain arteriovenous malformations and found that,…

Anaesthetic management of a child with massive extracranial arteriovenous malformation

PubMed Central

Shamim, Faisal; Ullah, Hameed; Rehman, Azhar

2012-01-01

Vascular tumors affect the head and neck commonly but arteriovenous malformations are rare. Vascular malformations are often present at birth and grow with the patient, usually only becoming significant later in childhood. Embolization has been the mainstay of treatment in massive and complex arteriovenous malformations. We present a case of massive extracranial arteriovenous malformation in a 7-year-old boy causing significant workload on right heart and respiratory distress. The management of angioembolization under general anaesthesia and anaesthetic concerns are presented. PMID:22345959

[Polythelia and renal malformation].

PubMed

Jójárt, G; Seres, E

1992-07-12

The authors found 241 polythelia (5.86) among 4113 schoolchildren (aged 6-14 years). They investigated 236 of the 241 with ultrasound and found 10 renal malformations (4.24%). Among 280 controls with respiratory infection, accident or tonsillectomy they found 9 renal malformations (3.21%). With screening of 1635 neonates they found 66 with accessory nipples (4.05%). Two of the 66 had renal malformations (3.03%), while among the 1957 control neonates 37 had renal malformations (1.89%). In the hospital and ambulancy the authors found 106 polythelia, five of them had renal abnormalities (4.72%). The authors did not found association of polythelia and renal malformation with ultrasound investigation of 408 children with polythelia.

Development of profound Chiari I malformation and cerebellar tissue loss and resolution following shunting of posterior fossa extra-axial cyst. Case report.

PubMed

Khan, Rabia; Oakes, Peter; Tubbs, R Shane; Oakes, W Jerry

2017-01-01

Chiari I malformation can be due to a multitude of etiologies such as craniosynostosis or hydrocephalus. A posterior fossa extra-axial cyst (PFEAC) appears to be an extremely rare cause of this form of hindbrain herniation. Herein, we report a case of PFEAC that presented with no Chiari I malformation and then presented months later with a significant Chiari I malformation. Following shunt placement of a PFEAC, striking reversal of the Chiari malformation as well as reconstitution of the cerebellum was noted. Patients with PFEAC might develop a Chiari I malformation and this might be treated with shunting of the PFEAC alone.

A regional survey of malformed frogs in Minnesota (USA) (Minnesota malformed frogs).

PubMed

Vandenlangenberg, Susan M; Canfield, Jeffrey T; Magner, Joseph A

2003-02-01

In late 1995, school children discovered malformed frogs in a south central Minnesota pond. Press coverage resulted in numerous citizen reports of frog malformation across Minnesota in 1996. After some initial site investigation, 3 affected frog sites and 4 nearby reference sites were selected for more detailed evaluation. Field biologists made 89 visits to study sites beginning spring 1997 through fall 1999 to examine the number and type of frog malformations. Over 5,100 Leopard frogs (Rana pipiens) were captured and examined at all study sites. Water elevations and associated littoral inundation were recorded from 1997-2000. Results indicate that malformation occurred at all study sites above historical background levels. Rana pipiens malformation across all sites over three seasons averaged 7.9% and ranged from 0 to 7% at reference sites and 4 to 23% at affected sites. At one northern Minnesota site, mink frog (Rana septentrionalis) malformation was 75% in 1998. A site characteristic common to the most affected sites was an elastic zone of littoral inundation. Climate driven hydrologic variation likely influenced water depth and associated breeding locations.

Congenital heart defects and extracardiac malformations.

PubMed

Rosa, Rosana Cardoso M; Rosa, Rafael Fabiano M; Zen, Paulo Ricardo G; Paskulin, Giorgio Adriano

2013-06-01

To review the association between congenital heart defects and extracardiac malformations. Scientific articles were searched in the Medline, Lilacs, and SciELO databases, using the descriptors "congenital heart disease," "congenital heart defects," "congenital cardiac malformations," "extracardiac defects," and "extracardiac malformations." All case series that specifically explored the association between congenital heart defects and extracardiac malformations were included. Congenital heart diseases are responsible for about 40% of birth defects, being one of the most common and severe malformations. Extracardiac malformations are observed in 7 to 50% of the patients with congenital heart disease, bringing a greater risk of comorbidity and mortality and increasing the risks related to heart surgery. Different studies have attempted to assess the presence of extracardiac abnormalities in patients with congenital heart disease. Among the changes described, those of the urinary tract are more often reported. However, no study has evaluated all patients in the same way. Extracardiac abnormalities are frequent among patients with congenital heart disease, and patients with these alterations may present an increased risk of morbimortality. Therefore, some authors have been discussing the importance and cost-effectiveness of screening these children for other malformations by complementary exams.

Vascular malformations: an update.

PubMed

Gloviczki, Peter; Duncan, Audra; Kalra, Manju; Oderich, Gustavo; Ricotta, Joseph; Bower, Thomas; McKusick, Michael; Bjarnason, Haraldur; Driscoll, David

2009-06-01

Vascular malformations occur as a result of an arrest in the development of the vascular system. The modified Hamburg classification distinguishes arterial, venous, arteriovenous, capillary, lymphatic, and mixed vascular malformations. Each malformation is further subdivided based on anatomy and on the time when arrest in development of the embryogenesis occurred; malformations can be truncular or extratruncular. Progress in the last decade in management has been significant because of improvements in open surgical procedures and perfection of percutaneous and hybrid endovascular interventions and devices, such as balloons, stents, and stent-grafts. There has been increasing use of embolization for the treatment of malformations with coils, other particles, glue, or with endovascular placement of occlusive plugs. Absolute alcohol, detergent liquids, or foam have been used for sclerotherapy with improved efficacy. The agents are delivered percutaneously or through a catheter placed either into the feeding arteries or the draining veins. This review aims to aid vascular and endovascular specialists in staying familiar with vascular malformations. These specialists need to be able to evaluate the patients, perform treatment if appropriate, or refer complex cases to multidisciplinary vascular malformation clinics and vascular centers.

[Poland'syndrome and hand's malformations: about a clinic series of 37 patients].

PubMed

Foucras, L; Grolleau, J L; Chavoin, J P

2005-04-01

Poland's syndrome is a rare malformation which associates thoracic anomalies and anomalies of homolateral upper end. We wish to know the frequency of hand's malformations in this syndrome in our clinical experience. We have revised 37 patients who were seen initially for a thoracomammary anomaly. This clinical series from plastic surgery service of Toulouse has been revised to know the importance of hand's malformations. Hand's malformations in Poland's syndrome are rare in your study, they touch only 12% patients. We find only 4 malformations in 33 patients, four were lost. They were only females, we find three brachymesophalangies and a major form. Hand's malformations in Poland's syndrome are less frequent than classically. There is no parallelism between gravity of thoracic malformation and that one of upper end. In this series, we find only one case with syndactyly; originally, Poland's syndrome was named < Poland's syndactyly >. Finally, we think that we can talk about Poland's syndrome without anomaly of homolateral upper end, the major element is musculary agenesia of sternocostal pectoralis major. The search of homolateral upper end has to be systematic in front of suspicious of Poland's syndrome.

Effect of 60Co gamma radiation on Biomphalaria glabrata (Mollusca, Gastropoda) embryos: mortality, malformation and hatching.

PubMed

Okazaki, K; Andrade Júnior, H F; Kawano, T

1996-08-01

A study was carried out on the radiosensitivity of Biomphalaria glabrata embryos submitted to doses of 5, 10, 15, 20 and 25 Gy of 60Co during the cleavage, blastula, gastrula, young trochophore and trochophore stages. Mortality, malformation and hatching were the parameters used to evaluate the damage induced by ionizing radiation. Estimated LD50 values (15 days) showed that the cleavage stage (4.3 Gy) was approximately four times more radiosensitive than the trochophore stage (17.0 Gy). Susceptibility to malformation induction was higher in the blastula, gastrula and young trochophore stages. Several types of morphogenetic malformations were observed, such as head malformations, exogastrulas, shell malformations, and embryos with everted stomodeum, with nonspecific malformations being the most frequent. The types of malformation induced by radiation probably are not radiation-specific and do not depend on the dose applied. The dose of 15 Gy was sufficient to greatly reduce the number of hatching snails regardless of the embryonic stage irradiated. We conclude that the effect of 60Co gamma radiation on B. glabrata embryos presented a specific pattern.

Pros, cons, and current indications of open craniotomy versus gamma knife in the treatment of arteriovenous malformations and the role of endovascular embolization.

PubMed

Surdell, Daniel L; Bhattacharjee, Sumon; Loftus, Christopher M

2002-06-01

The successful treatment of an intracranial arteriovenous malformation poses both technical and conceptual problems to the neurosurgeon. Treatment decisions are made in light of current understanding of the natural history of these lesions. It is important to understand the pros, cons and current indication of open craniotomy vs. gamma knife in the treatment of arteriovenous malformations and the role of endovascular embolization. Surgical removal of an arteriovenous malformation is indicated when the operative risk is less than the morbidity and mortality associated with its natural history. The treatment goal of complete angiographic obliteration of arteriovenous malformations is achieved most effectively by microneurosurgery in low-grade lesions. Large lesions frequently require a combination of embolization and microsurgery. Although recent advances in technology and medical management have allowed previously inoperable arteriovenous malformations to be surgically excised, there is still a small group of arteriovenous malformations that cannot be excised safely due to their size and location. Stereotactic radiosurgery is clearly an important adjunct in the multimodality treatment approach for large arteriovenous malformations. Endovascular embolization can potentially increase safety and efficacy in the treatment of arteriovenous malformations when applied to selective cases with well-defined treatment goals.

Anger Can Help: A Transactional Model and Three Pathways of the Experience and Expression of Anger.

PubMed

Butler, Mark H; Meloy-Miller, Kierea C; Seedall, Ryan B; Dicus, J Logan

2017-07-23

Anger is a significant human emotion with far-reaching implications for individuals and relationships. We propose a transactional model of anger that highlights its relational relevance and potentially positive function, in addition to problematic malformations. By evolutionary design, physical, self-concept, or attachment threats all similarly trigger diffuse physiological arousal, psychologically experienced as anger-emotion. Anger is first a signaling and motivational system. Anger is then formed to affirming, productive use or malformed to destructive ends. A functional, prosocial approach to anger organizes it for protective and corrective personal and relational adaptation. In our model, threat perception interacts with a person's view of self in relation to other to produce helpful or harmful anger. Inflated or collapsed views of self in relation to other produce distinct manifestations of destructive anger that are harmful to self, other, and relationship. Conversely, a balanced view of self in relation to other promotes constructive anger and catalyzes self, other, and relationship healing. Clinical use of the model to shape healing personal and relational contact with anger is explored. © 2017 Family Process Institute.

The impact of congenital cardiovascular malformations on the assessment and surgical management of infants with cleft lip and/or palate.

PubMed

Harry, Brian L; TeBockhorst, Seth; Deleyiannis, Frederic W-B

2013-05-01

The purpose of this study was to assess the cardiac evaluation of cleft lip and/or palate patients, characterize their cardiovascular malformations, and determine the impact of cardiovascular malformations on surgical management. A single-institution retrospective study of 329 consecutive cleft patients was performed. Cardiovascular malformations were categorized according to involvement of cardiac septa, vasculature, and valves. Their impact on the need for cardiac surgery, timing of cleft repair, need for subacute bacterial endocarditis (SBE) prophylaxis, and the perioperative experience was evaluated. Ten percent (33/329) of cleft patients had a cardiovascular malformation, and 3% underwent cardiac surgery prior to cleft repair. Malformations of the septa, vasculature, and valves were present in 9%, 6%, and 2% of cleft infants, respectively. Murmur as a sign of structural cardiovascular disease was 79% sensitive and 97% specific. Cleft palate repair was delayed by 2 months in patients with a cardiovascular malformation (P = .001). Subacute bacterial endocarditis prophylaxis was recommended, not recommended, or not specified by cardiology in 18%, 33%, and 48% of cleft patients with a cardiovascular malformation, respectively. Postoperative stay and surgical complications were not associated with cardiovascular malformation. Even in the absence of a murmur, echocardiographic screening should be considered in infants with nonspecific signs of cardiovascular disease. Greater awareness of the guidelines for SBE prophylaxis is needed. Most cleft patients with a cardiovascular malformation do not require cardiac surgery and do not experience an increased rate of complications associated with cleft surgery.

The archipelago of Fernando de Noronha: an intriguing malformed toad hotspot in South America.

PubMed

Toledo, Luís Felipe; Ribeiro, Ricardo S

2009-09-01

Malformed anurans raise concern among scientists, because deformities may relate to the recent global crisis among amphibian populations, although declining populations also may be associated with other causes (e.g., diseases, over-exploitation, and land use/land cover change). We examined a sample of toads (Rhinella jimi, Bufonidae) from an introduced population in the Archipelago of Fernando de Noronha, Brazil where malformations of anurans were thought to be high. Our sample of 159 specimens from the site revealed that 44.6% of all specimens had one or more malformations. Incidence of malformed toads on the mainland sites was substantially lower: 10.5% at Itamaracá, and 3.7% at Propriá. We describe the malformations observed, including six undescribed types of malformation of anurans, and we pose possible hypotheses to explain this high incidence of malformed toads. In addition to existing hypotheses, we suggest for the first time the hypothesis that lack of predation pressures contributes to numbers of malformed toads. We indicate the need of specific studies to understand the causes of malformations in the R. jimi population of Fernando de Noronha, which is thought to be extreme foci of malformed amphibians in the world. Our results may improve local conservation action plans as this is an alien population that may be affecting endemic fauna, and may affect populations in other parts of the world, because toad species of the genus Rhinella are recognized as exceptional colonizers. More importantly, unknown variables in these toads' environment are evidently affecting toads during development, which should be a concern for all species that inhabit the area, perhaps even humans.

Effect of Gastrointestinal Malformations on the Outcomes of Patients With Congenital Heart Disease.

PubMed

Mery, Carlos M; De León, Luis E; Rodriguez, J Rubén; Nieto, R Michael; Zhang, Wei; Adachi, Iki; Heinle, Jeffrey S; Kane, Lauren C; McKenzie, E Dean; Fraser, Charles D

2017-11-01

The goal of this study was to assess the effect of associated gastrointestinal malformations (GI) on the outcomes of patients undergoing congenital heart operations. Neonates and infants with thoracic (esophageal atresia, tracheoesophageal fistula) and abdominal (duodenal stenosis/atresia, imperforate anus, Hirschsprung disease) GI malformations undergoing congenital heart operations between 1995 and 2015 were included. Two control groups were created, one for each group. Patients were matched by diagnosis, procedure, history of prematurity, presence of genetic syndrome, and a propensity score including weight and year of operation. The cohort included 383 patients: 52 (14%) with thoracic GI malformations and 98 (25%) thoracic GI controls, 80 (21%) with abdominal GI malformations and 153 (40%) abdominal GI controls. Median follow-up was 6 years (range, 16 days to 20 years). Patients with thoracic GI malformations had longer length of stay (p < 0.001), longer intubation times (p = 0.002), and higher perioperative death (p = 0.015) than controls. There was a tendency for worse overall survival than controls, mainly explained by the higher risk of early death (p = 0.06). No difference was found in outcomes between patients with abdominal GI malformations and controls. Patients with thoracic GI malformations have worse perioperative outcomes than controls, but their long-term survival does not seem to be significantly different. Abdominal GI malformations do not have a significant effect on outcomes. The presence of GI malformations should likely not preclude patients from undergoing congenital heart operations, but careful family counseling is necessary, especially for thoracic GI malformations. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Congenital malformations in offspring of women with a history of malignancy.

PubMed

Sabeti Rad, Zahra; Friberg, Britt; Henic, Emir; Rylander, Lars; Ståhl, Olof; Källén, Bengt; Lingman, Göran

2017-02-15

Survival after malignancy has increased and the question of risks, including risk for congenital malformations for the offspring of these women has become important. Data on congenital malformations in such offspring are limited. We compared congenital malformation in offspring, born 1994 to 2011 of women with a history of malignancy (at least 1 year before delivery) with all other offspring. Adjustment for confounders was mainly made by Mantel-Haenszel methodology. Data were obtained by linkage between Swedish national health registers. We identified 71,954 (4.1%) infants with congenital malformation, of which 47,081 (2.7%) were relatively severe (roughly corresponding to major malformation). Among 7284 infants to women with a history of malignancy 204 relatively severe malformations were found (2.8%; odds ratio [OR] = 1.04; 95% confidence interval [CI], 0.91-1.20). After in vitro fertilization, the risk of a relatively severe malformation was significantly increased in women without a history of malignancy (OR = 1.31; 95% CI, 1.24-1.38) and still more in women with such a history (risk ratio = 1.85; 95% CI, 1.08-2.97). However, there were no significant differences neither, for any malformations (OR = 1.04; 95% CI, 0.92-1.16) nor for relatively severe malformations (OR = 1.04; 95% CI, 0.91-1.20), when comparing offspring only after maternal history of malignancy. No general increase in malformation rate was found in infants born to women with a history of malignancy. A previously known increased risk after in vitro fertilization was verified and it is possible that this risk is further augmented among infants born of women with a history of malignancy. Birth Defects Research 109:224-233, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

CONGENITAL HEART MALFORMATIONS IN NEWBORN BABIES WITH LOW BIRTH WEIGHT.

PubMed

Luca, Alina-Costina; Holoc, Andreea-Simona; Iordache, C

2015-01-01

Congenital heart malformations represent a public health problem, holding a significant percentage of the total of heart diseases. Beside the elevated frequency of the malformations, we also notice their occurrence in newborn babies with low birth weight, increasing, thus, the risk of complications and late therapeutic approach. The goal of the study was to highlight the general and particular aspects of cardiovascular malformations epidemiology in newborn babies with low weight at birth, the correlation of the malformations with implied genetic and environmental factors, assessing the complications and their procedures on the therapeutic management. Our study was performed on a group of 271 patients, hospitalized in the Department of Pediatric Cardiology of "Sf. Maria" Emergency Clinical Hospital for Children of Iasi, during January 2011-December 2013. The patients were assessed based on anamnesis, clinical, biological and imagistic exam. The study lot was divided according to the type of the structural defect: 95% of the patients were diagnosed with non-cyanogenic congenital heart malformations and 5% with cyanogenic congenital heart malformations. Regarding the patient's origin background, we notice an elevated frequency of the rural environment (71%). The incidence of the malformations was high in premature low birth weight (48%), followed by premature very low birth weight (22%). In evolution, congenital heart malformations often get more complicated heart failure, arterial hypertension and respiratory infections being most often met. Mortality was maximum in the first year of life, a third of the cases being associated with chromosomal malformations. Congenital heart malformations in newborn patients with low weight at birth represented an elevated percentage of 44.13% of the total of the cases hospitalized for cardiovascular diseases from the Department of Pediatric Cardiology of Iasi. Many cases were associated with other congenital malformations or different complications, being necessary an interdisciplinary collaboration to adequately monitor the anatom5ical and functional parameters and to ensure a somatic and mental development as normal as possible.

Dandy-Walker Malformation Presenting with Psychological Manifestations.

PubMed

Rohanachandra, Yasodha Maheshi; Dahanayake, Dulangi Maneksha Amerasinghe; Wijetunge, Swarna

2016-01-01

Dandy-Walker malformation, which is a congenital malformation of the cerebellum, is documented in literature to be associated with psychotic symptoms, obsessive compulsive symptoms, mood symptoms, hyperactivity, and impulsive behavior. The pathogenesis of psychiatric symptoms in Dandy-Walker malformation is thought to be due to disruption of the corticocerebellar tracts, resulting in what is known as cerebellar cognitive affective syndrome. We present a case of Dandy-Walker malformation presenting with psychiatric symptoms. This case highlights the necessity to be aware of psychiatric manifestations of cerebellar disease as it has an impact on the diagnosis and treatment.

Chiari type I malformation, syncope, headache, hypoglycemia and hepatic steatosis in an 8-year old girl: a causal association?

PubMed Central

Tarani, Luigi; Del Balzo, Francesca; Costantino, Francesco; Properzi, Enrico; D’Eufemia, Patrizia; Liberati, Natascia; Spalice, Alberto

2010-01-01

Chiari type I malformation (CMI) is a congenital hindbrain anomaly characterized by downward displacement of the cerebellar tonsils through the foramen magnum. Chiari type I malformation often presents with a complex clinical picture and can be sporadic or linked to a variety of genetic conditions. We report on a girl in whom Chiari type I malformation was associated with hypoglycemia, headache, vertigo, syncope and hepatic steatosis. We hypothesize that these symptoms are primarily a consequence of Chiari type I malformation. PMID:21589844

A Review of Eye Movement Desensitization and Reprocessing (EMDR): Research Findings and Implications for Counsellors.

ERIC Educational Resources Information Center

MacCluskie, Kathryn C.

1998-01-01

States that within the last six years a new therapeutic technique for the treatment of posttraumatic stress disorder, Eye Movement Desensitization and Reprocessing (EMDR), has emerged. Examines the strengths and weaknesses of published studies concerning EMDR, describes the nature of the debate about the efficacy of EMDR, and reviews implications…

Personalized ophthalmology.

PubMed

Porter, L F; Black, G C M

2014-07-01

Ophthalmology has been an early adopter of personalized medicine. Drawing on genomic advances to improve molecular diagnosis, such as next-generation sequencing, and basic and translational research to develop novel therapies, application of genetic technologies in ophthalmology now heralds development of gene replacement therapies for some inherited monogenic eye diseases. It also promises to alter prediction, diagnosis and management of the complex disease age-related macular degeneration. Personalized ophthalmology is underpinned by an understanding of the molecular basis of eye disease. Two important areas of focus are required for adoption of personalized approaches: disease stratification and individualization. Disease stratification relies on phenotypic and genetic assessment leading to molecular diagnosis; individualization encompasses all aspects of patient management from optimized genetic counseling and conventional therapies to trials of novel DNA-based therapies. This review discusses the clinical implications of these twin strategies. Advantages and implications of genetic testing for patients with inherited eye diseases, choice of molecular diagnostic modality, drivers for adoption of personalized ophthalmology, service planning implications, ethical considerations and future challenges are considered. Indeed, whilst many difficulties remain, personalized ophthalmology truly has the potential to revolutionize the specialty. © 2014 The Authors. Clinical Genetics published by JohnWiley & Sons A/S. Published by John Wiley & Sons Ltd.

Contribution of Rare Copy Number Variants to Isolated Human Malformations

PubMed Central

Serra-Juhé, Clara; Rodríguez-Santiago, Benjamín; Cuscó, Ivon; Vendrell, Teresa; Camats, Núria; Torán, Núria; Pérez-Jurado, Luis A.

2012-01-01

Background Congenital malformations are present in approximately 2–3% of liveborn babies and 20% of stillborn fetuses. The mechanisms underlying the majority of sporadic and isolated congenital malformations are poorly understood, although it is hypothesized that the accumulation of rare genetic, genomic and epigenetic variants converge to deregulate developmental networks. Methodology/Principal Findings We selected samples from 95 fetuses with congenital malformations not ascribed to a specific syndrome (68 with isolated malformations, 27 with multiple malformations). Karyotyping and Multiplex Ligation-dependent Probe Amplification (MLPA) discarded recurrent genomic and cytogenetic rearrangements. DNA extracted from the affected tissue (46%) or from lung or liver (54%) was analyzed by molecular karyotyping. Validations and inheritance were obtained by MLPA. We identified 22 rare copy number variants (CNV) [>100 kb, either absent (n = 7) or very uncommon (n = 15, <1/2,000) in the control population] in 20/95 fetuses with congenital malformations (21%), including 11 deletions and 11 duplications. One of the 9 tested rearrangements was de novo while the remaining were inherited from a healthy parent. The highest frequency was observed in fetuses with heart hypoplasia (8/17, 62.5%), with two events previously related with the phenotype. Double events hitting candidate genes were detected in two samples with brain malformations. Globally, the burden of deletions was significantly higher in fetuses with malformations compared to controls. Conclusions/Significance Our data reveal a significant contribution of rare deletion-type CNV, mostly inherited but also de novo, to human congenital malformations, especially heart hypoplasia, and reinforce the hypothesis of a multifactorial etiology in most cases. PMID:23056206

In vitro fertilization (IVF) in Sweden: risk for congenital malformations after different IVF methods.

PubMed

Källén, Bengt; Finnström, Orvar; Nygren, Karl Gösta; Olausson, Petra Otterblad

2005-03-01

The possible excess of congenital malformations in infants born after in vitro fertilization (IVF) has been much discussed in the literature, with controversial conclusions. This population based study is aimed at analyzing the presence of congenital malformations in a large group of infants born after IVF and to compare malformation risk both with that of all infants born and according to IVF method used. Infants born after IVF during the period 1982-2001 were ascertained from all IVF clinics in Sweden. The presence of congenital malformations was identified from three national health registers: the Swedish Medical Birth Register, the Swedish Registry of Congenital Malformations, and the Swedish Hospital Discharge Register. The IVF children were compared with all children born in Sweden during the same period and recorded in the Swedish Medical Birth Register. Among 16,280 IVF children (30% conceived after intracytoplasmatic sperm injection [ICSI]) a 42% excess of any congenital malformation was found, explainable by parental characteristics and in some cases by the high rate of multiple births. Among these children, 8% had a congenital malformation, and 5% had a relatively severe condition. For neural tube defects, choanal atresia, and alimentary tract atresia, an additional risk increase was seen. There was no difference in malformation rate according to IVF method except for an excess of hypospadias after ICSI. An increased risk for congenital malformations occurs after IVF, similar for the different IVF techniques used, and mainly a consequence of parental characteristics. A few specific conditions show an extra increase in risk. Copyright 2005 Wiley-Liss, Inc.

First approximation to congenital malformation rates in embryos and hatchlings of sea turtles.

PubMed

Bárcenas-Ibarra, Annelisse; de la Cueva, Horacio; Rojas-Lleonart, Isaias; Abreu-Grobois, F Alberto; Lozano-Guzmán, Rogelio Iván; Cuevas, Eduardo; García-Gasca, Alejandra

2015-03-01

Congenital malformations in sea turtles have been considered sporadical. Research carried out in the Mexican Pacific revealed high levels of congenital malformations in the olive ridley, but little or no information is available for other species. We present results from analyses of external congenital malformations in olive ridley, green, and hawskbill sea turtles from Mexican rookeries on the Pacific coast and Gulf of Mexico. We examined 150 green and hawksbill nests and 209 olive ridley nests during the 2010 and 2012 nesting seasons, respectively. Olive ridley eggs were transferred to a hatchery and incubated in styrofoam boxes. Nests from the other two species were left in situ. Number of eggs, live and dead hatchlings, and eggs with or without embryonic development were registered. Malformation frequency was evaluated with indices of prevalence and severity. Mortality levels, prevalence and severity were higher in olive ridley than in hawksbill and green sea turtles. Sixty-three types of congenital malformations were observed in embryos, and dead or live hatchlings. Of these, 38 are new reports; 35 for wild sea turtles, three for vertebrates. Thirty-one types were found in hawksbill, 23 in green, and 59 in olive ridley. The head region showed a higher number of malformation types. Malformation levels in the olive ridley were higher than previously reported. Olive ridleys seem more prone to the occurrence of congenital malformations than the other two species. Whether the observed malformation levels are normal or represent a health problem cannot be currently ascertained without long-term assessments. © 2015 Wiley Periodicals, Inc.

Bendectin and human congenital malformations.

PubMed

Shiono, P H; Klebanoff, M A

1989-08-01

The relationship between Bendectin exposure during the first trimester of pregnancy and the occurrence of congenital malformations was prospectively studied in 31,564 newborns registered in the Northern California Kaiser Permanente Birth Defects Study. The odds ratio for any major malformation and Bendectin use was 1.0 (95% confidence interval 0.8-1.4). There were 58 categories of congenital malformations; three of them were statistically associated with Bendectin exposure (microcephaly--odds ratio = 5.3, 95% confidence interval = 1.8-15.6; congenital cataract--odds ratio = 5.3, 95% confidence interval = 1.2-24.3; lung malformations (ICD-8 codes 484.4-484.8)--odds ratio = 4.6, 95% confidence interval = 1.9-10.9). This is exactly the number of associations that would be expected by chance. An independent study (the Collaborative Perinatal Project) was used to determine whether vomiting during pregnancy in the absence of Bendectin use was associated with these three malformations. Two of the three (microcephaly and cataract) had strong positive associations with vomiting in the absence of Bendectin use. We conclude that there is no increase in the overall rate of major malformations after exposure to Bendectin and that the three associations found between Bendectin and individual malformations are unlikely to be causal.

Vascular anomalies of the head and neck: a review of genetics.

PubMed

Yadav, Prashant; De Castro, Dawn K; Waner, Milton; Meyer, Lutz; Fay, Aaron

2013-01-01

Vascular anomalies comprise malformations, hemangiomas, and rare tumors. The commonality among these lesions is their origin in vascular endothelia. Most occur sporadically, but occasional inheritance is observed and thus allows genetic research and insight into etiology. This review highlights those vascular anomalies in which genetic inheritance has been demonstrated. A comprehensive literature search was performed on PubMed. Fifty-five full-length articles were reviewed. Five categories of vascular anomalies with patterned inheritance were identified: arteriovenous malformation (AVM), capillary malformation (CM), lymphatic malformation (LM), venous malformation (VM), and infantile hemangioma (IH). Capillary and arteriovenous malformation subtypes are associated with a RASA-1 gene mutation and show autosomal dominant inheritance. VEGFR3 mutations have been associated with generalized forms of LM and lymphedema. Mutations in TIE2/TEK genes cause inherited forms of venous malformations also with autosomal dominant inheritance. Familial clustering and atopic disease are associated with infantile hemangioma, and gene expression varies with the developmental stage of these lesions. Most vascular anomalies occur sporadically, but several genes and genetic disorders have been associated with them. Specific forms of capillary malformation appear to be most convincingly associated with genomic errors. Further research promises new insights into the development of this diverse group of disorders.

Do predators cause frog deformities? The need for an eco-epidemiological approach.

PubMed

Johnson, Pieter T J; Bowerman, Jay

2010-11-15

Renewed controversy has emerged over the likely causes and consequences of deformed amphibians, particularly those with missing limbs. The results of a series of experiments by Ballengée and Sessions (2009) implicate aquatic predators (i.e. dragonfly larvae) in causing such abnormalities. Skelly and Benard (2010), however, argued that the small scale of these experiments and the absence of a correlation between predator abundance and deformity frequencies in natural amphibian populations undermine such a conclusion. Drawing upon our experiences with frog malformations, we suggest that the study of amphibian deformities has been hindered by two, interrelated problems. First, empirical studies often fail to critically define the expected baseline level of abnormalities and differentiate between "epidemic" and "endemic" frequencies of malformations. Second, recognizing the likelihood of multiple causes in driving amphibian malformations, continued research needs to embrace a "multiple lines of evidence" approach that allows for complex etiologies by integrating field surveys, diagnostic pathology, comparative modeling, and experiments across a range of ecological scales. We conclude by highlighting the results of a recent study that uses this approach to identify the role of aquatic predators (i.e., fishes and dragonflies) in causing high frequencies of deformed frogs in Oregon. By combining long-term data, comparative data and mechanistic experiments, this study provides compelling evidence that certain predators do cause deformities under ecologically relevant conditions. In light of continuing concerns about amphibian deformities and population declines, we emphasize the need to integrate ecological, epidemiological, and developmental tools in addressing such environmental enigmas. Copyright © 2010 Wiley-Liss, Inc., A Wiley Company.

Two females with mutations in USP9X highlight the variable expressivity of the intellectual disability syndrome.

PubMed

Au, P Y B; Huang, L; Broley, S; Gallagher, L; Creede, E; Lahey, D; Ordorica, S; Mina, K; Boycott, K M; Baynam, G; Dyment, D A

2017-07-01

The genetic causes of intellectual disability (ID) are heterogeneous and include both chromosomal and monogenic etiologies. The X-chromosome is known to contain many ID-related genes and males show a marked predominance for intellectual disability. Here we report two females with syndromic intellectual disability. The first individual was relatively mild in her presentation with mild-moderate intellectual disability, hydronephrosis and altered pigmentation along the lines of Blaschko without additional congenital anomalies. A second female presented shortly after birth with dysmorphic facial features, post-axial polydactyly and, on follow-up assessment, demonstrated moderate intellectual disability. Chromosomal studies for Individual 1 identified an X-chromosome deletion due to a de novo pericentric inversion; the inversion breakpoint was associated with deletion of the 5'UTR of the USP9X, a gene which has been implicated in a syndromic intellectual disability affecting females. The second individual had a de novo frameshift mutation detected by whole-exome sequencing that was predicted to be deleterious, NM_001039590.2 (USP9X): c.4104_4105del (p.(Arg1368Serfs*2)). Haploinsufficiency of USP9X in females has been associated with ID and congenital malformations that include heart defects, scoliosis, dental abnormalities, anal atresia, polydactyly, Dandy Walker malformation and hypoplastic corpus callosum. The extent of the congenital malformations observed in Individual 1 was less striking than Individual 2 and other individuals previously reported in the literature, and suggests that USP9X mutations in females can have a wider spectrum of presentation than previously appreciated. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Intracranial Hypertension in a Patient with a Chiari Malformation Accompanied by Hyperthyroidism.

PubMed

Pang, Chang Hwan; Lee, Soo Eon; Kim, Chi Heon; Chung, Chun Kee

2015-09-01

The Chiari malformation is an infrequently detected congenital anomaly characterized by the downward displacement of the cerebellum with a tonsillar herniation below the foramen magnum that may be accompanied by either syringomyelia or hydrocephalus. Surgery, such as foramen magnum decompression, is indicated for a symptomatic Chiari malformation, although an incidental lesion may be followed-up without further treatment. Infrequently, increased intracranial pressure emerges due to hyperthyroidism. A nineteen-year-old girl visited our outpatient clinic presented with a headache, nausea and vomiting. A brain and spinal magnetic resonance image study (MRI) indicated that the patient had a Chiari I malformation without syringomyelia or hydrocephalus. An enlarged thyroid gland was detected on a physical examination, and serum markers indicated Graves' disease. The patient started anti-hyperthyroid medical treatment. Subsequently, the headache disappeared after the medical treatment of hyperthyroidism without surgical intervention for the Chiari malformation. A symptomatic Chiari malformation is indicated for surgery, but a surgeon should investigate other potential causes of the symptoms of the Chiari malformation to avoid unnecessary surgery.

[Venous and arteriovenous malformations in the head and neck region. Therapeutic options and challenges].

PubMed

Eivazi, B; Werner, J A

2014-01-01

Venous malformations are the prototype low-flow malformations in the head and neck region. Arteriovenous malformations (AVM) represent the main high-flow malformations. In recent years it has been possible to significantly optimize the therapeutic options for venous malformations. In addition to conventional surgery, laser treatment and sclerotherapy have become established techniques and the importance of embolization with new alcohol-based materials is increasing. AVM are progressive and destructive diseases. Therapy of choice is usually a combined treatment comprising embolization and surgical removal of the arteriovenous nidus. This curative approach is usually possible if diagnosis is made at an early stage. Incomplete embolization or sole ligation of the arterial supply causes progression. There is a clear need for improved therapeutic methods and pharmacotherapeutic approaches.

Epidemiologic characteristics of anophthalmia and bilateral microphthalmia among 2.5 million births in California, 1989-1997.

PubMed

Shaw, Gary M; Carmichael, Suzan L; Yang, Wei; Harris, John A; Finnell, Richard H; Lammer, Edward J

2005-08-15

There is a paucity of epidemiologic information about the eye malformations anophthalmia and microphthalmia. Using data from a large population-based registry, we explored prevalences and maternal/infant characteristics associated with anophthalmia and bilateral microphthalmia. Data were derived from the California Birth Defects Monitoring Program, a population-based active surveillance system for collecting information on infants and fetuses with congenital malformations using multiple source ascertainment. Approximately 2.5 million births (liveborn and stillborn) occurred during the ascertainment period, 1989-1997. Information on maternal and infant/fetal characteristics was obtained from California birth certificate and fetal death files. The prevalence per 10,000 livebirths and stillbirths for anophthalmia was 0.18 and for bilateral microphthalmia was 0.22. These estimates reflect prevalences among births without chromosomal anomalies. Relative risks of anophthalmia were modestly higher among women aged 40 or more (relative risk = 2.0, 95% confidence interval 0.5-8.6). Risks were substantially lower for those mothers with >12 years of education, even after adjusting for other study factors, relative risk = 0.6 (0.2-1.7). The risk of anophthalmia was approximately twofold among multiple births compared to singletons. Similar to results for anophthalmia, decreased risks for bilateral microphthalmia were observed for maternal education of 12 years or more and increased risks observed for multiple births. These data show descriptive epidemiologic features of anophthalmia and bilateral microphthalmia. Copyright 2005 Wiley-Liss, Inc.

Clival Malformations in CHARGE Syndrome.

PubMed

Mahdi, E S; Whitehead, M T

2018-06-01

CHARGE syndrome is a multisystemic congenital disorder, most commonly including coloboma, heart malformations, choanal atresia, developmental delay, and genital and ear anomalies. The diagnostic criteria for CHARGE syndrome have been refined with time. However, limited reports describe skull base and craniocervical junction abnormalities. Recently, a coronal clival cleft has been identified in association with CHARGE syndrome. The aim of our study was to assess the prevalence of clival pathology in CHARGE syndrome. In this retrospective study, the CT/MR imaging data base at a single academic children's hospital was queried for the phrase "CHARGE syndrome" during a 17-year period (2001-2017). Electronic medical records were reviewed to confirm the diagnosis. Images were assessed for skull base anomalies, specifically clival hypoplasia and dysplasia. The search yielded 42 examinations (21 CTs and 21 MRIs) from 15 distinct patients (mean age, 4.1 ± 5.6 years; range, 2 days to 19 years). CHARGE syndrome diagnosis was confirmed either by clinical and genetic testing ( n = 6) or by clinical diagnosis only ( n = 9). A coronal clival cleft was identified in 87% of patients (37 examinations, n = 13 patients), either partial (53%) or complete (33%). Clival hypoplasia without clefting was present in all 5 examinations from the remaining 2 patients. Clival pathology is universal in CHARGE syndrome. Coronal clival clefts are extremely common, representing a useful additional diagnostic finding. Detection of a clival cleft should alert the radiologist to examine the palate, choana, eyes, ears, and olfactory centers for other signs of CHARGE syndrome. © 2018 by American Journal of Neuroradiology.

Neurorehabilitation of saccadic ocular movement in a patient with a homonymous hemianopia postgeniculate caused by an arteriovenous malformation

PubMed Central

Pineda-Ortíz, Mirna; Pacheco-López, Gustavo; Rubio-Osornio, Moisés; Rubio, Carmen; Valadez-Rodríguez, Juan

2018-01-01

Abstract Rationale: Visual therapy, which includes a restorative and compensatory approach, seems to be a viable treatment option for homonymous defects of the visual field in patients with postgeniculate injury of the visual pathway, due to occipital arteriovenous malformation (AVM). Until now, the Mexican population suffering from homonymous hemianopia did not have health services that provided any type of visual therapy for their condition. Patient concerns: A 31-year-old patient, who underwent a surgical procedure for resection of the AVM, was referred with posterior low vision on the left side. Diagnoses: The patient was diagnosed with left homonymous hemianopia. Interventions: Visual neurorehabilitation therapy (NRT), which integrated restorative and compensatory approaches, was administered for 3 hours each week. NRT included fixation, follow-up, search, peripheral vision, and reading. Outcomes: The NRT did not change visual field defects and, retinotopocally, the same campimetric defects remained. However, after training the tracking ocular movements improved to standard values on the ENG, further, the visual search became more organized. The reading reached a level without mistakes, with rhythm and goog intonation. The Beck test demostrated an improvement in depression symptoms. Regarding the daily life activities, the patient reported significant improvements. Lessons: Visual NRT can significantly improve eye movements, as well as the quality of life and independence of the patient. This integral approach could be an effective therapeutic option for homonymous defects of the visual field. PMID:29538218

Dandy-Walker syndrome with severe velopharyngeal dysfunction: a contraindication for Le Fort I surgery?

PubMed

Nelke, Kamil H; Pawlak, Wojciech; Gerber, Hanna

2015-01-01

Dandy-Walker syndrome is a rare congenital brain deformation. Most symptoms are related with fourth ventricle and skull base malformations. Quite often, symptoms develop from infancy or progress rapidly. Cerebellar dysfunction, lack of muscle coordination, and skull deformities involving eye movement might be present. There are several Dandy-Walker syndrome complex types. We present a 23-year-old patient who had a severe dentofacial deformity with mandibular prognathism and extremely undeveloped maxillary bone resulting in palatopharyngeal and velopharyngeal dysfunction with complete lack of soft palate function resulting in increased speech tone and volume. Performing Le Fort I osteotomy in this case is greatly controversial and might result in even greater loss of function or even its total lack. Velopharyngeal complex is very important, and every surgeon should consider its value while planning Le Fort I osteotomies.

A de novo Pericentric Inversion in Chromosome 4 Associated with Disruption of PITX2 and a Microdeletion in 4p15.2 in a Patient with Axenfeld-Rieger Syndrome and Developmental Delay.

PubMed

Maldžienė, Živilė; Preikšaitienė, Eglė; Ignotienė, Salomėja; Kapitanova, Natalija; Utkus, Algirdas; Kučinskas, Vaidutis

2017-01-01

Axenfeld-Rieger syndrome (ARS) is a clinically and genetically heterogeneous group of autosomal dominantly inherited malformations that predominantly affect the eye but are also associated with craniofacial dysmorphism and dental abnormalities. A broad spectrum of genetic alterations involving PITX2 and FOXC1 lead to ARS. We report on a 4-year-old girl with clinical features of ARS and developmental delay due to a de novo apparently balanced pericentric inversion in chromosome 4. This report emphasizes that complementary investigations are necessary to precisely characterize chromosomal rearrangements. Elucidation of the exact genetic cause of ARS is important for comprehensive genetic counseling of the family members and for better patient management. © 2017 S. Karger AG, Basel.

Acquired Uterine Arteriovenous Malformation and Retained Placenta Increta.

PubMed

Roach, Michelle K; Thomassee, May S

2015-09-01

Uterine arteriovenous malformations are rare and have been reported to occur after uterine trauma (eg, surgery, gestational trophoblastic disease, malignancy). A 33-year-old woman, gravida 3 para 3, presented 4 weeks post-cesarean delivery with episodic profuse vaginal bleeding. Pelvic ultrasonography and magnetic resonance imaging revealed a left uterine arteriovenous malformation. After consideration of all treatment options, total laparoscopic hysterectomy was performed. Acquired uterine arteriovenous malformations and placental ingrowth into the myometrium are increasingly reported after surgical uterine procedures. This case of a postpartum patient with both uterine arteriovenous malformation and retained placenta increta suggests a correlation between the two complications.

Dandy-Walker Malformation Presenting with Psychological Manifestations

PubMed Central

Dahanayake, Dulangi Maneksha Amerasinghe

2016-01-01

Dandy-Walker malformation, which is a congenital malformation of the cerebellum, is documented in literature to be associated with psychotic symptoms, obsessive compulsive symptoms, mood symptoms, hyperactivity, and impulsive behavior. The pathogenesis of psychiatric symptoms in Dandy-Walker malformation is thought to be due to disruption of the corticocerebellar tracts, resulting in what is known as cerebellar cognitive affective syndrome. We present a case of Dandy-Walker malformation presenting with psychiatric symptoms. This case highlights the necessity to be aware of psychiatric manifestations of cerebellar disease as it has an impact on the diagnosis and treatment. PMID:27493822

[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.

Distinct eye movement patterns enhance dynamic visual acuity.

PubMed

Palidis, Dimitrios J; Wyder-Hodge, Pearson A; Fooken, Jolande; Spering, Miriam

2017-01-01

Dynamic visual acuity (DVA) is the ability to resolve fine spatial detail in dynamic objects during head fixation, or in static objects during head or body rotation. This ability is important for many activities such as ball sports, and a close relation has been shown between DVA and sports expertise. DVA tasks involve eye movements, yet, it is unclear which aspects of eye movements contribute to successful performance. Here we examined the relation between DVA and the kinematics of smooth pursuit and saccadic eye movements in a cohort of 23 varsity baseball players. In a computerized dynamic-object DVA test, observers reported the location of the gap in a small Landolt-C ring moving at various speeds while eye movements were recorded. Smooth pursuit kinematics-eye latency, acceleration, velocity gain, position error-and the direction and amplitude of saccadic eye movements were linked to perceptual performance. Results reveal that distinct eye movement patterns-minimizing eye position error, tracking smoothly, and inhibiting reverse saccades-were related to dynamic visual acuity. The close link between eye movement quality and DVA performance has important implications for the development of perceptual training programs to improve DVA.

Distinct eye movement patterns enhance dynamic visual acuity

PubMed Central

Palidis, Dimitrios J.; Wyder-Hodge, Pearson A.; Fooken, Jolande; Spering, Miriam

2017-01-01

Dynamic visual acuity (DVA) is the ability to resolve fine spatial detail in dynamic objects during head fixation, or in static objects during head or body rotation. This ability is important for many activities such as ball sports, and a close relation has been shown between DVA and sports expertise. DVA tasks involve eye movements, yet, it is unclear which aspects of eye movements contribute to successful performance. Here we examined the relation between DVA and the kinematics of smooth pursuit and saccadic eye movements in a cohort of 23 varsity baseball players. In a computerized dynamic-object DVA test, observers reported the location of the gap in a small Landolt-C ring moving at various speeds while eye movements were recorded. Smooth pursuit kinematics—eye latency, acceleration, velocity gain, position error—and the direction and amplitude of saccadic eye movements were linked to perceptual performance. Results reveal that distinct eye movement patterns—minimizing eye position error, tracking smoothly, and inhibiting reverse saccades—were related to dynamic visual acuity. The close link between eye movement quality and DVA performance has important implications for the development of perceptual training programs to improve DVA. PMID:28187157

Pax2 regulates a fadd-dependent molecular switch that drives tissue fusion during eye development.

PubMed

Viringipurampeer, Ishaq A; Ferreira, Todd; DeMaria, Shannon; Yoon, Jookyung J; Shan, Xianghong; Moosajee, Mariya; Gregory-Evans, Kevin; Ngai, John; Gregory-Evans, Cheryl Y

2012-05-15

Tissue fusion is an essential morphogenetic mechanism in development, playing a fundamental role in developing neural tube, palate and the optic fissure. Disruption of genes associated with the tissue fusion can lead to congenital malformations, such as spina bifida, cleft lip/palate and ocular coloboma. For instance, the Pax2 transcription factor is required for optic fissure closure, although the mechanism of Pax2 action leading to tissue fusion remains elusive. This lack of information defining how transcription factors drive tissue morphogenesis at the cellular level is hampering new treatments options. Through loss- and gain-of-function analysis, we now establish that pax2 in combination with vax2 directly regulate the fas-associated death domain (fadd) gene. In the presence of fadd, cell proliferation is restricted in the developing eye through a caspase-dependent pathway. However, the loss of fadd results in a proliferation defect and concomitant activation of the necroptosis pathway through RIP1/RIP3 activity, leading to an abnormal open fissure. Inhibition of RIP1 with the small molecule drug necrostatin-1 rescues the pax2 eye fusion defect, thereby overcoming the underlying genetic defect. Thus, fadd has an essential physiological function in protecting the developing optic fissure neuroepithelium from RIP3-dependent necroptosis. This study demonstrates the molecular hierarchies that regulate a cellular switch between proliferation and the apoptotic and necroptotic cell death pathways, which in combination drive tissue morphogenesis. Furthermore, our data suggest that future therapeutic strategies may be based on small molecule drugs that can bypass the gene defects causing common congenital tissue fusion defects.

Application of radiosurgical techniques to produce a primate model of brain lesions

PubMed Central

Kunimatsu, Jun; Miyamoto, Naoki; Ishikawa, Masayori; Shirato, Hiroki; Tanaka, Masaki

2015-01-01

Behavioral analysis of subjects with discrete brain lesions provides important information about the mechanisms of various brain functions. However, it is generally difficult to experimentally produce discrete lesions in deep brain structures. Here we show that a radiosurgical technique, which is used as an alternative treatment for brain tumors and vascular malformations, is applicable to create non-invasive lesions in experimental animals for the research in systems neuroscience. We delivered highly focused radiation (130–150 Gy at ISO center) to the frontal eye field (FEF) of macaque monkeys using a clinical linear accelerator (LINAC). The effects of irradiation were assessed by analyzing oculomotor performance along with magnetic resonance (MR) images before and up to 8 months following irradiation. In parallel with tissue edema indicated by MR images, deficits in saccadic and smooth pursuit eye movements were observed during several days following irradiation. Although initial signs of oculomotor deficits disappeared within a month, damage to the tissue and impaired eye movements gradually developed during the course of the subsequent 6 months. Postmortem histological examinations showed necrosis and hemorrhages within a large area of the white matter and, to a lesser extent, in the adjacent gray matter, which was centered at the irradiated target. These results indicated that the LINAC system was useful for making brain lesions in experimental animals, while the suitable radiation parameters to generate more focused lesions need to be further explored. We propose the use of a radiosurgical technique for establishing animal models of brain lesions, and discuss the possible uses of this technique for functional neurosurgical treatments in humans. PMID:25964746

Cystic kidneys in fetal Walker-Warburg syndrome with POMT2 mutation: Intrafamilial phenotypic variability in four siblings and review of literature.

PubMed

Nabhan, Marwa M; ElKhateeb, Nour; Braun, Daniela A; Eun, Sungho; Saleem, Sahar N; YungGee, Heon; Hildebrandt, Friedhelm; Soliman, Neveen A

2017-10-01

Walker-Warburg syndrome (WWS) is a severe form of congenital muscular dystrophy secondary to α-dystroglycanopathy with muscle, brain, and eye abnormalities often leading to death in the first weeks of life. It is transmitted in an autosomal recessive pattern, and has been linked to at least 15 different genes; including protein O-mannosyltransferase 1 (POMT1), protein O-mannosyltransferase 2 (POMT2), protein O-mannose beta-1,2-N acetylglucosaminyltransferase (POMGNT1), fukutin (FKTN), isoprenoid synthase domain-containing protein (ISPD), and other genes. We report on a consanguineous family with four consecutive siblings affected by this condition with lethal outcome in three (still birth), and termination of the fourth pregnancy based on antenatal MRI identification of brain and kidney anomalies that heralded proper and deep clinical phenotyping. The diagnosis of WWS was suggested based on the unique collective phenotype comprising brain anomalies in the form of lissencephaly, subcortical/subependymal heterotopia, and cerebellar hypoplasia shared by all four siblings; microphthalmia in one sibling; and large cystic kidneys in the fetus and another sibling. Other unshared neurological abnormalities included hydrocephalus and Dandy-Walker malformation. Whole exome sequencing of the fetus revealed a highly conserved missense mutation in POMT2 that is known to cause WWS with brain and eye anomalies.In conclusion, the heterogeneous clinical presentation in the four affected conceptions with POMT2 mutation expands the current clinical spectrum of POMT2-associated WWS to include large cystic kidneys; and confirms intra-familial variability in terms of brain, kidney, and eye anomalies. © 2017 Wiley Periodicals, Inc.

Gaze toward Naturalistic Social Scenes by Individuals with Intellectual and Developmental Disabilities: Implications for Augmentative and Alternative Communication Designs

ERIC Educational Resources Information Center

Liang, Jiali; Wilkinson, Krista

2018-01-01

Purpose: A striking characteristic of the social communication deficits in individuals with autism is atypical patterns of eye contact during social interactions. We used eye-tracking technology to evaluate how the number of human figures depicted and the presence of sharing activity between the human figures in still photographs influenced visual…

Dry eye disease: an immune-mediated ocular surface disorder

PubMed Central

Stevenson, William; Chauhan, Sunil K.; Dana, Reza

2013-01-01

Dry eye disease is a multifactorial disorder of the tears and ocular surface characterized by symptoms of dryness and irritation. Although the pathogenesis of dry eye disease is not fully understood, it is recognized that inflammation has a prominent role in the development and propagation of this debilitating condition. Factors that adversely affect tear film stability and osmolarity can induce ocular surface damage and initiate an inflammatory cascade that generates innate and adaptive immune responses. These immunoinflammatory responses lead to further ocular surface damage and the development of a self-perpetuating inflammatory cycle. Herein, we review the fundamental links between inflammation and dry eye disease and discuss the clinical implications of inflammation in disease management. PMID:22232476

Cyclosporine ophthalmic emulsions for the treatment of dry eye: a review of the clinical evidence

PubMed Central

Ames, Philip; Galor, Anat

2015-01-01

Dry eye has gained recognition as a public health problem given its high prevalence, morbidity and cost implications. Although dry eye is common and affects patients’ quality of life, only one medication, cyclosporine 0.05% emulsion, has been approved by the US FDA for its treatment. In this review, we summarize the basic science and clinical data regarding the use of cyclosporine in the treatment of dry eye. Randomized controlled trials showed that cyclosporine emulsion outperformed vehicles in the majority of trials, consistently decreasing corneal staining and increasing Schirmer scores. Symptom improvement was more variable, however, with ocular dryness shown to be the most consistently improved symptom over vehicle. PMID:25960865

Angiotensin-Converting Enzyme Inhibitors and the Risk of Congenital Malformations

PubMed Central

Bateman, Brian T; Patorno, Elisabetta; Desai, Rishi J; Seely, Ellen W; Mogun, Helen; Dejene, Sara Z; Fischer, Michael A; Friedman, Alexander M; Hernandez-Diaz, Sonia; Huybrechts, Krista F

2016-01-01

Objective To examine the association between first-trimester angiotensin-converting enzyme (ACE) inhibitor exposure and the risk for overall major congenital, cardiac, and central nervous system (CNS) malformations. Methods We used a cohort of completed pregnancies linked to liveborn infants derived from Medicaid claims from 2000 to 2010. We examined the risk of malformations associated with first-trimester exposure to an ACE inhibitor. Propensity score based methods were used to control for potential confounders including maternal demographics, medical conditions, exposure to other medications, and measures of health care utilization. Results The cohort included 1,333,624 pregnancies, of which 4,107 (0.31%) were exposed to ACE inhibitors during the first trimester. The prevalence of overall malformations in the ACE inhibitor–exposed was 5.9% versus 3.3% in the unexposed (unadjusted relative risk (RR), 1.82; 95% confidence interval (CI) 1.61 to 2.06), of cardiac malformations was 3.4% versus 1.2% (RR 2.95; 95% CI 2.50 to 3.47), and of CNS malformations was 0.27% versus 0.18% (RR 1.46; 95% CI 0.81 to 2.64). After restricting the cohort to pregnancies complicated by chronic hypertension (both exposed and unexposed) and accounting for other confounding factors, there was no significant increase in the risk for any of the outcomes assessed. Relative risks associated with first-trimester ACE inhibitor exposure were 0.89 (95% CI 0.75 to 1.06) for overall malformations, 0.95 (95% CI 0.75 to 1.21) for cardiac malformations, and 0.54 (95% CI 0.26 to 1.11) for CNS malformations. Conclusions After accounting for confounders, among women with hypertension, exposure to ACE inhibitors during the first trimester was not associated with an increased risk of major congenital malformations. PMID:27926639

Slide tracheoplasty outcomes in children with congenital pulmonary malformations.

PubMed

DeMarcantonio, Michael A; Hart, Catherine K; Yang, Christina J; Tabangin, Meredith; Rutter, Michael J; Bryant, Roosevelt; Manning, Peter B; de Alarcón, Alessandro

2017-06-01

Evaluate and compare surgical outcomes of slide tracheoplasty for the treatment of congenital tracheal stenosis in children with and without pulmonary malformations. Retrospective chart review at a tertiary care pediatric medical center. We identified patients with tracheal stenosis who underwent slide tracheoplasty from 2001 to 2014, and a subset of these patients who were diagnosed with congenital pulmonary malformations. Hospital course and preoperative and postoperative complications were recorded. One hundred thirty patients (18 with pulmonary malformations, 112 with normal pulmonary anatomy) were included. Pulmonary malformations included unilateral pulmonary agenesis (61%) and hypoplasia (39%). Children with pulmonary malformations had a greater median age compared to their normal lung anatomy counterparts. Preoperatively, patients with pulmonary malformations more frequently required preoperative mechanical ventilation (55.6% vs. 21.3%, P = .007), extracorporeal membrane oxygenation (ECMO) (11% vs. 0.9%, P = .05), and tracheostomy (22.2% vs. 3.6%, P = .01). Postoperatively, patients with pulmonary malformations more frequently required mechanical ventilation >48 hours (78% vs. 37%, P =.005) and ECMO use (11% vs. 0.9%, P = .05). Pulmonary malformation patients and children with normal anatomy did not differ in terms of postoperative tracheostomy (16.7% vs. 4.4%, P > .05), dehiscence (6% vs. 0%, P > .05%), restenosis (11% vs. 6%, P > .05) or postoperative figure 8 deformity (6% vs. 3%, P > .05). Mortality, however, was significantly increased (22.2% vs. 3.6%, P = .01) in children with pulmonary malformations. Although slide tracheoplasty can be successfully performed in patients with abnormal pulmonary anatomy, surgeons and families should anticipate a more difficult postoperative course, with possible associated prolonged mechanical ventilation, ECMO use, and higher mortality than in children with tracheal stenosis alone. 4. Laryngoscope, 127:1283-1287, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

[Characteristics of pregnancy and delivery of fetuses affected by either central nervous system malformations or chromosomal abnormalities].

PubMed

Friedler, Jordana Mashiach; Mazor, Moshe; Shoham-Vardi, Ilana; Bashiri, Asher

2011-11-01

To determine whether fetuses affected by either chromosomal abnormalities or central nervous system (CNS) malformations are prone to complications during pregnancy and delivery. In this study, 320 singleton pregnancies with CNS malformations and 133 singleton pregnancies with chromosomal abnormaLities were compared with 149,112 singleton births without any known congenital anomalies. Exclusion criteria were: births with other congenital anomalies or malformations, pregnancies Lacking prenatal care and multiple pregnancies. Data was obtained using the computerized birth discharge records. The statistical analysis was performed with the SPSS package. There were no statistically significant differences in maternal age, ethnicity, uterine anomalies or parity. The ratio of general anesthesia was almost double in the study groups compared to the control group: 25% in the CNS malformation group (RR 2.617, CI 2.031-3.372) and 25.6% in the chromosomal abnormality group (RR 2.696, CI 1.825-3.982) and 11.3% in the control group (p < 0.001). There were nearly double cesarean sections (CS) rates in both study groups: 21.5% in the CNS malformation group, 20.3% in the chromosomal abnormaLity group and 12% in the control group. A logistic regression model that included previous CS, maLpresentation, non-reassuring fetal heart monitor (NRFHR) and presence of a malformation, concluded that the presence of a malformation was not an independent risk factor for CS. However, indirect causes, such as malpresentation (4.34 OR), were independently associated with the malformations. Fetuses affected by either CNS malformations or chromosomal abnormalities have a higher rate of pregnancy and delivery complications, including those which increase the risk of maternal morbidity and mortality.

Angiotensin-Converting Enzyme Inhibitors and the Risk of Congenital Malformations.

PubMed

Bateman, Brian T; Patorno, Elisabetta; Desai, Rishi J; Seely, Ellen W; Mogun, Helen; Dejene, Sara Z; Fischer, Michael A; Friedman, Alexander M; Hernandez-Diaz, Sonia; Huybrechts, Krista F

2017-01-01

To examine the association between first-trimester angiotensin-converting enzyme (ACE) inhibitor exposure and the risk of overall major congenital, cardiac, and central nervous system malformations. We used a cohort of completed pregnancies linked to liveborn neonates derived from Medicaid claims from 2000 to 2010. We examined the risk of malformations associated with first-trimester exposure to an ACE inhibitor. Propensity score-based methods were used to control for potential confounders including maternal demographics, medical conditions, exposure to other medications, and measures of health care utilization. The cohort included 1,333,624 pregnancies, of which 4,107 (0.31%) were exposed to ACE inhibitors during the first trimester. The prevalence of overall malformations in the ACE inhibitor-exposed pregnancies was 5.9% compared with 3.3% in the unexposed (unadjusted relative risk, 1.82; 95% confidence interval [CI] 1.61-2.06), of cardiac malformations was 3.4% compared with 1.2% (relative risk 2.95, 95% CI 2.50-3.47), and of central nervous system malformations was 0.27% compared with 0.18% (relative risk 1.46, 95% CI 0.81-2.64). After restricting the cohort to pregnancies complicated by chronic hypertension (both exposed and unexposed) and accounting for other confounding factors, there was no significant increase in the risk of any of the outcomes assessed. Relative risks associated with first-trimester ACE inhibitor exposure were 0.89 (95% CI 0.75-1.06) for overall malformations, 0.95 (95% CI 0.75-1.21) for cardiac malformations, and 0.54 (95% CI 0.26-1.11) for CNS malformations. After accounting for confounders, among women with hypertension, exposure to ACE inhibitors during the first trimester was not associated with an increased risk of major congenital malformations.

Surgical management of venous malformations.

PubMed

Loose, D A

2007-01-01

Among vascular malformations, the predominantly venous malformations represent the majority of cases. They form a clinical entity and therefore need clear concepts concerning diagnosis and treatment. This paper presents an overview of contemporary classification as well as tactics and techniques of treatment. According to the Hamburg Classification, predominantly venous malformations are categorized into truncular and extratruncular forms, with truncular forms distinguished as obstructions and dilations, and extratruncular forms as limited or infiltrating. The tactics of treatment represent surgical and non-surgical methods or combined techniques. Surgical approaches utilize different tactics and techniques that are adopted based on the pathologic form and type of the malformation: (I) operation to reduce the haemodynamic activity of the malformation; (II) operation to eliminate the malformation; and (III) reconstructive operation. As for (I), a type of a tactic is the operation to derive the venous flow. In (II), the total or partial removal of the venous malformation is demonstrated subdivided into three different techniques. In this way, the infiltrating as well as the limited forms can be treated. An additional technique is dedicated to the treatment of a marginal vein. Approach (III) involves the treatment of venous aneurysms, where a variety of techniques have been successful. Long-term follow-up demonstrates positive results in 91% of the cases. Congenital predominantly venous malformations should be treated according to the principles developed during the past decades in vascular surgery, interventional treatment and multidisciplinary treatment. The days of predominantly conservative treatment should be relegated to the past. Special skills and experiences are necessary to carry out appropriate surgical strategy, and the required operative techniques should be dictated by the location and type of malformation and associated findings.

Dynamic MRI for distinguishing high-flow from low-flow peripheral vascular malformations.

PubMed

Ohgiya, Yoshimitsu; Hashimoto, Toshi; Gokan, Takehiko; Watanabe, Shouji; Kuroda, Masayoshi; Hirose, Masanori; Matsui, Seishi; Nobusawa, Hiroshi; Kitanosono, Takashi; Munechika, Hirotsugu

2005-11-01

The purpose of our study was to assess the usefulness of dynamic MRI in distinguishing high-flow vascular malformations from low-flow vascular malformations, which do not need angiography for treatment. Between September 2001 and January 2003, 16 patients who underwent conventional and dynamic MRI had peripheral vascular malformations (six high- and 10 low-flow). The temporal resolution of dynamic MRI was 5 sec. Time intervals between beginning of enhancement of an arterial branch in the vicinity of a lesion in the same slice and the onset of enhancement in the lesion were calculated. We defined these time intervals as "artery-lesion enhancement time." Time intervals between the onset of enhancement in the lesion and the time of the maximal percentage of enhancement above baseline of the lesion within 120 sec were measured. We defined these time intervals as "contrast rise time" of the lesion. Diagnosis of the peripheral vascular malformations was based on angiographic or venographic findings. The mean artery-lesion enhancement time of the high-flow vascular malformations (3.3 sec [range, 0-5 sec]) was significantly shorter than that of the low-flow vascular malformations (8.8 sec [range, 0-20 sec]) (Mann-Whitney test, p < 0.05). The mean maximal lesion enhancement time of the high-flow vascular malformations (5.8 sec [range, 5-10 sec]) was significantly shorter than that of the low-flow vascular malformations (88.4 sec [range, 50-100 sec]) (Mann-Whitney test, p < 0.01). Dynamic MRI is useful for distinguishing high-flow from low-flow vascular malformations, especially when the contrast rise time of the lesion is measured.

Transverse sinus stenosis in adult patients with Chiari malformation type I.

PubMed

Saindane, Amit M; Bruce, Beau B; Desai, Nilesh K; Roller, Lauren A; Newman, Nancy J; Biousse, Valérie

2014-10-01

Transverse sinus stenosis is an imaging finding very highly associated with elevated intracranial pressure (ICP). Patients with the Chiari I malformation may potentially have elevated ICP due to impairment of CSF flow at the foramen magnum. This study evaluated whether patients with Chiari I malformation have transverse sinus stenosis and other imaging findings indicative of elevated ICP. Thirty patients with Chiari I malformation treated surgically and 76 control subjects were identified retrospectively. All control subjects and all patients with Chiari I malformation (preoperatively) underwent standardized contrast-enhanced brain MRI including a contrast-enhanced 3D T1-weighted sequence from which curved reformats of the transverse sinuses were generated. Two different readers blinded to the diagnosis then independently evaluated these curved reformats for severity of transverse sinus stenosis. Orbital and skull-base findings previously described in association with elevated ICP were also evaluated. Frequency of MRI findings between the two groups was compared. Patients with Chiari I malformation had significantly greater frequency of unilateral or bilateral transverse sinus stenosis than did control subjects (p < 0.001). There was complete interreader agreement on presence or absence of transverse sinus stenosis by patient (κ = 1.0 [95% CI, 0.89-1.0]). Logistic regression analysis controlling for age, sex, and body mass index found that transverse sinus stenosis significantly predicted Chiari I malformation versus control status (odds ratio, 11.2 [95% CI, 2.1-59.0]; p = 0.004) but that no other features were significantly associated with the Chiari I malformation. Patients with Chiari I malformation who had transverse sinus stenosis had significantly greater pituitary flattening than did those without transverse sinus stenosis (p = 0.02). Patients with Chiari I malformation have higher likelihood of transverse sinus stenosis, which may reflect associated elevated ICP.

Initial evaluation of developmental malformation as an end point in mixture toxicity hazard assessment for aquatic vertebrates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dawson, D.A.; Wilke, T.S.

1991-04-01

The joint toxic action of three binary mixtures was determined for the embryo malformation endpoint of the aquatic FETAX (frog embryo teratogenesis assay: Xenopus) test system. Osteolathyrogenic compounds and short-chain carboxylic acids, representing separate, distinct modes of action for induction of malformation, were selected for testing in 96-hr, static-renewal tests. Three mixtures were tested for each combination, with each combination being tested on three separate occasions. Using toxic unit analysis, the combination of osteolathyrogens and the combination of carboxylic acids produced strictly additive (concentration addition) rates of malformation, while the combination of an osteolathyrogen and a carboxylic acid was less-than-additivemore » (response addition) for induction of malformation. Therefore, developmental malformation may have value as an endpoint in mixture toxicity hazard assessment.« less

[Coexistence of female sexual organ malformation and urinary tract anomalies].

PubMed

Rzymski, P; Szpakowska-Rzymska, I; el Yubi, R; Wilczak, M; Sajdak, S; Opala, T

2001-02-01

The aim of the study was to estimate the correlation between sexual organs and urinary tract malformation. The retrospective analysis of clinical data obtained from 50 patients with sexual organs anomalies diagnosed in the Academic Gynaecological Centre between 1992-1999 was performed. Material included 24 patients with the Meyer-Rokitansky-Küster-Hauser syndrome and 26 with other sexual organs' malformations. Frequency of urinary tract anomalies was 42%, 11 patients with Meyer-Rokitansky-Küster-Hauser syndrome and 11 with other malformations. The gravity of urinary tract anomalies showed no statistical significant difference dependent on the type and symmetry of genital malformation. Urinary tract anomalies were more frequent in cases of asymmetric genital malformation and the difference was statistically significant. Intravenous urography proofed to be more sensitive than ultrasonography in diagnosing urinary tract anomalies.

Leaping lopsided: a review of the current hypotheses regarding etiologies of limb malformations in frogs.

PubMed

Loeffler, I K; Stocum, D L; Fallon, J F; Meteyer, C U

2001-10-15

Recent progress in the investigation of limb malformations in free-living frogs has underlined the wide range in the types of limb malformations and the apparent spatiotemporal clustering of their occurrence. Here, we review the current understanding of normal and abnormal vertebrate limb development and regeneration and discuss some of the molecular events that may bring about limb malformation. Consideration of the differences between limb development and regeneration in amphibians has led us to the hypothesis that some of the observed limb malformations come about through misdirected regeneration. We report the results of a pilot study that supports this hypothesis. In this study, the distal aspect of the right hindlimb buds of X. laevis tadpoles was amputated at the pre-foot paddle stage. The tadpoles were raised in water from a pond in Minnesota at which 7% of surveyed newly metamorphosed feral frogs had malformations. Six percent (6 of 100) of the right limbs of the tadpoles raised in pond water developed abnormally. One truncated right limb was the only malformation in the control group, which was raised in dechlorinated municipal water. All unamputated limbs developed normally in both groups. Three major factors under consideration for effecting the limb malformations are discussed. These factors include environmental chemicals (primarily agrichemicals), encysted larvae (metacercariae) of trematode parasites, and increased levels of ultraviolet light. Emphasis is placed on the necessary intersection of environmental stressors and developmental events to bring about the specific malformations that are observed in free-living frog populations.

Chronic hypertension in pregnancy and the risk of congenital malformations: a cohort study.

PubMed

Bateman, Brian T; Huybrechts, Krista F; Fischer, Michael A; Seely, Ellen W; Ecker, Jeffrey L; Oberg, Anna S; Franklin, Jessica M; Mogun, Helen; Hernandez-Diaz, Sonia

2015-03-01

Chronic hypertension is a common medical condition in pregnancy. The purpose of the study was to examine the association between maternal chronic hypertension and the risk of congenital malformations in the offspring. We defined a cohort of 878,126 completed pregnancies linked to infant medical records using the Medicaid Analytic Extract. The risk of congenital malformations was compared between normotensive controls and those with treated and untreated chronic hypertension. Confounding was addressed using propensity score matching. After matching, compared with normotensive controls, pregnancies complicated by treated chronic hypertension were at increased risk of congenital malformations (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.2-1.5), as were pregnancies with untreated chronic hypertension (OR 1.2; 95% CI, 1.1-1.3). In our analysis of organ-specific malformations, both treated and untreated chronic hypertension was associated with a significant increase in the risk of cardiac malformations (OR, 1.6; 95% CI, 1.4-1.9 and OR, 1.5; 95% CI, 1.3-1.7, respectively). These associations persisted across a range of sensitivity analyses. There is a similar increase in the risk of congenital malformations (particularly cardiac malformations) associated with treated and untreated chronic hypertension that is independent of measured confounders. Studies evaluating the teratogenic potential of antihypertensive medications must control for confounding by indication. Fetuses and neonates of mothers with chronic hypertension should be carefully evaluated for potential malformations, particularly cardiac defects. Copyright © 2015 Elsevier Inc. All rights reserved.

Leaping lopsided: a review of the current hypotheses regarding etiologies of limb malformations in frogs

USGS Publications Warehouse

Loeffler, I.K.; Stocum, D.L.; Fallon, J.F.; Meteyer, C.U.

2001-01-01

Recent progress in the investigation of limb malformations in free-living frogs has underlined the wide range in the types of limb malformations and the apparent spatiotemporal clustering of their occurrence. Here, we review the current understanding of normal and abnormal vertebrate limb development and regeneration and discuss some of the molecular events that may bring about limb malformation. Consideration of the differences between limb development and regeneration in amphibians has led us to the hypothesis that some of the observed limb malformations come about through misdirected regeneration. We report the results of a pilot study that supports this hypothesis. In this study, the distal aspect of the right hindlimb buds of X. laevis tadpoles was amputated at the pre-foot paddle stage. The tadpoles were raised in water from a pond in Minnesota at which 7% of surveyed newly metamorphosed feral frogs had malformations. Six percent (6 of 100) of the right limbs of the tadpoles raised in pond water developed abnormally. One truncated right limb was the only malformation in the control group, which was raised in dechlorinated municipal water. All unamputated limbs developed normally in both groups. Three major factors under consideration for effecting the limb malformations are discussed. These factors include environmental chemicals (primarily agrichemicals), encysted larvae (metacercariae) of trematode parasites, and increased levels of ultraviolet light. Emphasis is placed on the necessary intersection of environmental stressors and developmental events to bring about the specific malformations that are observed in free-living frog populations.

Cell-type-specific regulation of the retinoic acid receptor mediated by the orphan nuclear receptor TLX.

PubMed

Kobayashi, M; Yu, R T; Yasuda, K; Umesono, K

2000-12-01

Malformations in the eye can be caused by either an excess or deficiency of retinoids. An early target gene of the retinoid metabolite, retinoic acid (RA), is that encoding one of its own receptors, the retinoic acid receptor beta (RARbeta). To better understand the mechanisms underlying this autologous regulation, we characterized the chick RARbeta2 promoter. The region surrounding the transcription start site of the avian RARbeta2 promoter is over 90% conserved with the corresponding region in mammals and confers strong RA-dependent transactivation in primary cultured embryonic retina cells. This response is selective for RAR but not retinoid X receptor-specific agonists, demonstrating a principal role for RAR(s) in retina cells. Retina cells exhibit a far higher sensitivity to RA than do fibroblasts or osteoblasts, a property we found likely due to expression of the orphan nuclear receptor TLX. Ectopic expression of TLX in fibroblasts resulted in increased sensitivity to RA induction, an effect that is conserved between chick and mammals. We have identified a cis element, the silencing element relieved by TLX (SET), within the RARbeta2 promoter region which confers TLX- and RA-dependent transactivation. These results indicate an important role for TLX in autologous regulation of the RARbeta gene in the eye.

Cell-Type-Specific Regulation of the Retinoic Acid Receptor Mediated by the Orphan Nuclear Receptor TLX†

PubMed Central

Kobayashi, Mime; Yu, Ruth T.; Yasuda, Kunio; Umesono, Kazuhiko

2000-01-01

Malformations in the eye can be caused by either an excess or deficiency of retinoids. An early target gene of the retinoid metabolite, retinoic acid (RA), is that encoding one of its own receptors, the retinoic acid receptor β (RARβ). To better understand the mechanisms underlying this autologous regulation, we characterized the chick RARβ2 promoter. The region surrounding the transcription start site of the avian RARβ2 promoter is over 90% conserved with the corresponding region in mammals and confers strong RA-dependent transactivation in primary cultured embryonic retina cells. This response is selective for RAR but not retinoid X receptor-specific agonists, demonstrating a principal role for RAR(s) in retina cells. Retina cells exhibit a far higher sensitivity to RA than do fibroblasts or osteoblasts, a property we found likely due to expression of the orphan nuclear receptor TLX. Ectopic expression of TLX in fibroblasts resulted in increased sensitivity to RA induction, an effect that is conserved between chick and mammals. We have identified a cis element, the silencing element relieved by TLX (SET), within the RARβ2 promoter region which confers TLX- and RA-dependent transactivation. These results indicate an important role for TLX in autologous regulation of the RARβ gene in the eye. PMID:11073974

Eye lens membrane junctional microdomains: a comparison between healthy and pathological cases

NASA Astrophysics Data System (ADS)

Buzhynskyy, Nikolay; Sens, Pierre; Behar-Cohen, Francine; Scheuring, Simon

2011-08-01

The eye lens is a transparent tissue constituted of tightly packed fiber cells. To maintain homeostasis and transparency of the lens, the circulation of water, ions and metabolites is required. Junctional microdomains connect the lens cells and ensure both tight cell-to-cell adhesion and intercellular flow of fluids through a microcirculation system. Here, we overview membrane morphology and tissue functional requirements of the mammalian lens. Atomic force microscopy (AFM) has opened up the possibility of visualizing the junctional microdomains at unprecedented submolecular resolution, revealing the supramolecular assembly of lens-specific aquaporin-0 (AQP0) and connexins (Cx). We compare the membrane protein assembly in healthy lenses with senile and diabetes-II cataract cases and novel data of the lens membranes from a congenital cataract. In the healthy case, AQP0s form characteristic square arrays confined by connexons. In the cases of senile and diabetes-II cataract patients, connexons were degraded, leading to malformation of AQP0 arrays and breakdown of the microcirculation system. In the congenital cataract, connexons are present, indicating probable non-membranous grounds for lens opacification. Further, we discuss the energetic aspects of the membrane organization in junctional microdomains. The AFM hence becomes a biomedical nano-imaging tool for the analysis of single-membrane protein supramolecular association in healthy and pathological membranes.

Imaging of retinal and choroidal vascular tumours

PubMed Central

Heimann, H; Jmor, F; Damato, B

2013-01-01

The most common intraocular vascular tumours are choroidal haemangiomas, vasoproliferative tumours, and retinal haemangioblastomas. Rarer conditions include cavernous retinal angioma and arteriovenous malformations. Options for ablating the tumour include photodynamic therapy, argon laser photocoagulation, trans-scleral diathermy, cryotherapy, anti-angiogenic agents, plaque radiotherapy, and proton beam radiotherapy. Secondary effects are common and include retinal exudates, macular oedema, epiretinal membranes, retinal fibrosis, as well as serous and tractional retinal detachment, which are treated using standard methods (ie, intravitreal anti-angiogenic agents or steroids as well as vitreoretinal procedures, such as epiretinal membrane peeling and release of retinal traction). The detection, diagnosis, and monitoring of vascular tumours and their complications have improved considerably thanks to advances in imaging. These include spectral domain and enhanced depth imaging optical coherence tomography (SD-OCT and EDI-OCT, respectively), wide-angle photography and angiography as well as wide-angle fundus autofluorescence. Such novel imaging has provided new diagnostic clues and has profoundly influenced therapeutic strategies so that vascular tumours and secondary effects are now treated concurrently instead of sequentially, enhancing any opportunities for conserving vision and the eye. In this review, we describe how SD-OCT, EDI-OCT, autofluorescence, wide-angle photography and wide-angle angiography have facilitated the evaluation of eyes with the more common vascular tumours, that is, choroidal haemangioma, retinal vasoproliferative tumours, and retinal haemangioblastoma. PMID:23196648

A comprehensive newborn exam: part I. General, head and neck, cardiopulmonary.

PubMed

Lewis, Mary L

2014-09-01

A comprehensive newborn examination involves a systematic inspection. A Ballard score uses physical and neurologic characteristics to assess gestational age. Craniosynostosis is caused by premature fusion of the sutures, and 20% of children with this condition have a genetic mutation or syndrome. The red reflex assessment is normal if there is symmetry in both eyes, without opacities, white spots, or dark spots. If the red reflex findings are abnormal or the patient has a family history of pertinent eye disorders, consultation with an ophthalmologist is warranted. Newborns with low-set ears should be evaluated for a genetic condition. Renal ultrasonography should be performed only in patients with isolated ear anomalies, such as preauricular pits or cup ears, if they are accompanied by other malformations or significant family history. If ankyloglossia is detected, a frenotomy may be considered if it impacts breastfeeding. The neck should be examined for full range of motion because uncorrected torticollis can lead to plagiocephaly and ear misalignment. Proper auscultation is crucial for evaluation of the bronchopulmonary circulation with close observation for signs of respiratory distress, including tachypnea, nasal flaring, grunting, retractions, and cyanosis. Benign murmurs are often present in the first hours of life. Pulse oximetry should be performed in a systematic fashion before discharge.

A 600 kb triplication in the cat eye syndrome critical region causes anorectal, renal and preauricular anomalies in a three-generation family.

PubMed

Knijnenburg, Jeroen; van Bever, Yolande; Hulsman, Lorette O M; van Kempen, Chantal A P; Bolman, Galhana M; van Loon, Rosa Laura E; Beverloo, H Berna; van Zutven, Laura J C M

2012-09-01

Cat eye syndrome (CES) is caused by a gain of the proximal part of chromosome 22. Usually, a supernumerary marker chromosome is present, containing two extra copies of the chromosome 22q11.1q11.21 region. More sporadically, the gain is present intrachromosomally. The critical region for CES is currently estimated to be about 2.1 Mb and to contain at least 14 RefSeq genes. Gain of this region may cause ocular coloboma, preauricular, anorectal, urogenital and congenital heart malformations. We describe a family in which a 600 kb intrachromosomal triplication is present in at least three generations. The copy number alteration was detected using MLPA and further characterized with interphase and metaphase FISH and SNP-array. The amplified fragment is located in the distal part of the CES region. The family members show anal atresia and preauricular tags or pits, matching part of the phenotype of this syndrome. This finding suggests that amplification of the genes CECR2, SLC25A18 and ATP6V1E1, mapping within the critical region for CES, may be responsible for anorectal, renal and preauricular anomalies in patients with CES.

A developmental and genetic classification for midbrain-hindbrain malformations

PubMed Central

Millen, Kathleen J.; Dobyns, William B.

2009-01-01

Advances in neuroimaging, developmental biology and molecular genetics have increased the understanding of developmental disorders affecting the midbrain and hindbrain, both as isolated anomalies and as part of larger malformation syndromes. However, the understanding of these malformations and their relationships with other malformations, within the central nervous system and in the rest of the body, remains limited. A new classification system is proposed, based wherever possible, upon embryology and genetics. Proposed categories include: (i) malformations secondary to early anteroposterior and dorsoventral patterning defects, or to misspecification of mid-hindbrain germinal zones; (ii) malformations associated with later generalized developmental disorders that significantly affect the brainstem and cerebellum (and have a pathogenesis that is at least partly understood); (iii) localized brain malformations that significantly affect the brain stem and cerebellum (pathogenesis partly or largely understood, includes local proliferation, cell specification, migration and axonal guidance); and (iv) combined hypoplasia and atrophy of putative prenatal onset degenerative disorders. Pertinent embryology is discussed and the classification is justified. This classification will prove useful for both physicians who diagnose and treat patients with these disorders and for clinical scientists who wish to understand better the perturbations of developmental processes that produce them. Importantly, both the classification and its framework remain flexible enough to be easily modified when new embryologic processes are described or new malformations discovered. PMID:19933510

Histologic change of arteriovenous malformations of the face and scalp after free flap transfer.

PubMed

Tark, K C; Chung, S

2000-07-01

In three patients with long-standing vascular malformations of the face and scalp, radial forearm free flaps were transferred after a near-total excision of the lesion. All patients had typical high-flow malformations with thrill and bruit. The onset and progression of the malformations were analyzed through clinical and histologic studies. After free flap transfer, the vascular malformations were followed up grossly and histologically for between 4 and 9 years. There was no recurrence of arteriovenous malformation after free flap transfer. The portion of the residual lesion adjacent to the transferred free flap disappeared, and the remaining discoloration also vanished grossly. Histologic comparison of immediate postoperative and 4-month postoperative specimens from the margin and residual lesion using Victoria blue staining showed that the typical preoperative findings for arteriovenous malformation-an intermingling of thick-walled vessels with abundant elastic fibers and thin-walled vessels without elastic fibers-had undergone change, resulting in the disappearance of the thick-walled vessels and leaving only homogeneous, thin-walled vasculature. The highly vascularized free flap, which does not contain abnormal fistulas, impacted the histologic change of the arteriovenous malformation by blocking the vicious cycle of ischemia and anatomic replacement of disfigured skin and subcutaneous tissues.

Giant occipital meningocele in an 8-year-old child with Dandy-Walker malformation.

PubMed

Talamonti, Giuseppe; Picano, Marco; Debernardi, Alberto; Bolzon, Moreno; Teruzzi, Mario; D'Aliberti, Giuseppe

2011-01-01

The possibility of an association between Dandy-Walker malformation and occipital meningocele is well-known. However, just an overall number of about 40 cases have been previously reported. Giant occipital meningocele has been described only in three newborns. Incidence, pathology, clinical presentation, and proper management of this association are still poorly defined. An 8-year-old boy with Dandy-Walker malformation and giant (25 cm in diameter) occipital meningocele is presented. This boy was born without any apparent occipital mass and harbored no other significant malformations including hydrocephalus. On admission, he was neurologically intact and the giant occipital mass presented partially calcified cyst walls. Treatment consisted of the excision of the occipital malformation, cranioplasty, and cysto-peritoneal shunt. Outcome was excellent. To the best of our knowledge, among the few reported patients with Dandy-Walker malformation associated to occipital meningocele, this is the oldest one and the one with the largest occipital meningocele; he is unique with calcified walls of the occipital meningocele and the only one who survived the repair of the giant malformation. In Dandy-Walker malformation, occipital meningocele may develop and grow regardless of hydrocephalus. Giant size may be reached and the cyst may become calcified. Surgical repair may warrant favorable outcome.

Patients with lymphatic malformations who receive the immunostimulant OK-432 experience excellent long-term outcomes.

PubMed

Ghaffarpour, N; Petrini, B; Svensson, L A; Boman, K; Wester, T; Claesson, G

2015-11-01

Sclerotherapy is the primary treatment for lymphatic malformations. The aim of this study was to evaluate the long-term outcome in patients with lymphatic malformations treated with the immunostimulant OK-432 as a sclerosant. Between 1998 and 2013, we enrolled 131 of 138 eligible patients treated with OK-432 for lymphatic malformations in a retrospective study. The malformations were categorised according to the International Society for the Study of Vascular Anomalies. The outcome was assessed with a clinical examination and a questionnaire. The lymphatic malformations were localised to the head/neck (60%), the trunk (20%) and the extremities (6%) or involved with more than one region (14%). Patients with microcystic (10%), macrocystic (21%) and mixed lymphatic malformations (69%) underwent a median number of three, two and two injection treatments, respectively. The median age at the first injection was 3.4 years. Good or excellent clinical outcomes were seen in 70% of the patients. The number of injections, previous treatment and lesion localisation, but not time to follow-up and cyst size, predicted the clinical outcome. OK-432 treatment resulted in a successful outcome in 70% of patients with lymphatic malformations. The long-term outcome was comparable to the short-term outcome. ©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Acquired Chiari I Malformation with Syringomyelia Secondary to Colloid Cyst with Hydrocephalus-Case Report and Review of Literature.

PubMed

Thotakura, Amit Kumar; Marabathina, Nageswara R

2017-12-01

Acquired Chiari malformation and associated syringomyelia have been previously described following lumbar puncture/drainage, lumboperitoneal shunts, and spontaneous cerebrospinal fluid leakage. In addition to these etiologies, space-occupying lesions such as meningiomas, epidermoid cysts, medulloblastomas, and arachnoid cysts are rare causes of acquired Chiari malformation and syringomyelia. We report a rare case of colloid cyst with hydrocephalus causing secondary Chiari malformation with syringomyelia. A 58-year-old lady presented with neck pain and difficulty in walking and numbness of all 4 limbs of 1-year duration. Diagnostics with magnetic resonance imaging of the head and the cervical spine were done in the referring hospital. The patients was then referred with the diagnosis of colloid cyst with hydrocephalus and Chiari malformation 1 with cervicodorsal syringomyelia. She underwent colloid cyst excision through the transcallosal approach. Postoperatively the patient showed improvement in her symptomatology. Magnetic resonance imaging of the brain and cervical spine at 6 months' follow-up showed resolved Chiari malformation and resolving syrinx. Colloid cyst with hydrocephalus is a rare cause of secondary Chiari malformation with syringomyelia. Surgical management of the underlying lesion improves acquired Chiari malformation and associated syringomyelia. Copyright © 2017 Elsevier Inc. All rights reserved.

[Hemangiomas and vascular malformations of the head and neck].

PubMed

Hassmann-Poznańska, Elibieta; Kurzyna, Agnieszka

2006-01-01

This paper presents the review of current knowledge regarding vascular lesions of the head and neck. For many years the term hemangioma was used to describe all vascular lesions. Mulliken and Glowacki classified congenital vascular lesions and recognized two distinct entities, hemangiomas-vascular tumors and vascular malformations. Hemangiomas are usually not present at birth, proliferate during first year of life and then involute. They are composed of proliferating endothelial cells. Vascular malformations are always present at birth although not always apparent, increase slowly in size throughout whole life and never involute. They enlarge by hypertrophy of malformed vessels. Vascular malformations can be further subdivided according to the type of involved vessels as arterial, arteriovenous, venous, capillary or lymphatic. Accurate diagnosis of hemangiomas and vascular malformations remains a challenge for physicians. Although majority of hemangiomas are self limiting lesions some of them may develop complications such as; ulceration, airway obstruction, ophthalmic complications, psychosocial consequences. Segmental hemangiomas are associated with the risk of structural anomalies such as those that occur in PHACE syndrome. Clinical presentation and forms of treatment of various forms of vascular malformations are presented. Vascular malformations have to be treated according to their histopathology and location, as well as their hemodynamic features shown by radiological examinations.

Exome-wide Association Study Identifies GREB1L Mutations in Congenital Kidney Malformations.

PubMed

Sanna-Cherchi, Simone; Khan, Kamal; Westland, Rik; Krithivasan, Priya; Fievet, Lorraine; Rasouly, Hila Milo; Ionita-Laza, Iuliana; Capone, Valentina P; Fasel, David A; Kiryluk, Krzysztof; Kamalakaran, Sitharthan; Bodria, Monica; Otto, Edgar A; Sampson, Matthew G; Gillies, Christopher E; Vega-Warner, Virginia; Vukojevic, Katarina; Pediaditakis, Igor; Makar, Gabriel S; Mitrotti, Adele; Verbitsky, Miguel; Martino, Jeremiah; Liu, Qingxue; Na, Young-Ji; Goj, Vinicio; Ardissino, Gianluigi; Gigante, Maddalena; Gesualdo, Loreto; Janezcko, Magdalena; Zaniew, Marcin; Mendelsohn, Cathy Lee; Shril, Shirlee; Hildebrandt, Friedhelm; van Wijk, Joanna A E; Arapovic, Adela; Saraga, Marijan; Allegri, Landino; Izzi, Claudia; Scolari, Francesco; Tasic, Velibor; Ghiggeri, Gian Marco; Latos-Bielenska, Anna; Materna-Kiryluk, Anna; Mane, Shrikant; Goldstein, David B; Lifton, Richard P; Katsanis, Nicholas; Davis, Erica E; Gharavi, Ali G

2017-11-02

Renal agenesis and hypodysplasia (RHD) are major causes of pediatric chronic kidney disease and are highly genetically heterogeneous. We conducted whole-exome sequencing in 202 case subjects with RHD and identified diagnostic mutations in genes known to be associated with RHD in 7/202 case subjects. In an additional affected individual with RHD and a congenital heart defect, we found a homozygous loss-of-function (LOF) variant in SLIT3, recapitulating phenotypes reported with Slit3 inactivation in the mouse. To identify genes associated with RHD, we performed an exome-wide association study with 195 unresolved case subjects and 6,905 control subjects. The top signal resided in GREB1L, a gene implicated previously in Hoxb1 and Shha signaling in zebrafish. The significance of the association, which was p = 2.0 × 10 -5 for novel LOF, increased to p = 4.1 × 10 -6 for LOF and deleterious missense variants combined, and augmented further after accounting for segregation and de novo inheritance of rare variants (joint p = 2.3 × 10 -7 ). Finally, CRISPR/Cas9 disruption or knockdown of greb1l in zebrafish caused specific pronephric defects, which were rescued by wild-type human GREB1L mRNA, but not mRNA containing alleles identified in case subjects. Together, our study provides insight into the genetic landscape of kidney malformations in humans, presents multiple candidates, and identifies SLIT3 and GREB1L as genes implicated in the pathogenesis of RHD. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Neural tube defects – disorders of neurulation and related embryonic processes

PubMed Central

Copp, Andrew J.; Greene, Nicholas D. E.

2014-01-01

Neural tube defects (NTDs) are severe congenital malformations affecting 1 in every 1000 pregnancies. ‘Open’ NTDs result from failure of primary neurulation as seen in anencephaly, myelomeningocele (open spina bifida) and craniorachischisis. Degeneration of the persistently open neural tube in utero leads to loss of neurological function below the lesion level. ‘Closed’ NTDs are skin-covered disorders of spinal cord structure, ranging from asymptomatic spina bifida occulta to severe spinal cord tethering, and usually traceable to disruption of secondary neurulation. ‘Herniation’ NTDs are those in which meninges, with or without brain or spinal cord tissue, become exteriorised through a pathological opening in the skull or vertebral column (e.g. encephalocele and meningocele). NTDs have multifactorial etiology, with genes and environmental factors interacting to determine individual risk of malformation. While over 200 mutant genes cause open NTDs in mice, much less is known about the genetic causation of human NTDs. Recent evidence has implicated genes of the planar cell polarity signalling pathway in a proportion of cases. The embryonic development of NTDs is complex, with diverse cellular and molecular mechanisms operating at different levels of the body axis. Molecular regulatory events include the BMP and Sonic hedgehog pathways which have been implicated in control of neural plate bending. Primary prevention of NTDs has been implemented clinically following the demonstration that folic acid, when taken as a peri-conceptional supplement, can prevent many cases. Not all NTDs respond to folic acid, however, and adjunct therapies are required for prevention of this folic acid-resistant category. PMID:24009034

The morphology of the coronary sinus in patients with congenitally corrected transposition: implications for cardiac catheterisation and re-synchronisation therapy.

PubMed

Aiello, Vera D; Ferreira, Flávia C N; Scanavacca, Mauricio I; Anderson, Robert H; D'Avila, André

2016-02-01

Patients with congenitally corrected transposition frequently benefit from re-synchronisation therapy or ablation procedures. This is likely to require catheterisation of the coronary sinus. Its anatomy, however, is not always appreciated, despite being well-described. With this caveat in mind, we have evaluated its location and structure in hearts with congenitally corrected transposition in order to reinforce the guidance needed by the cardiac interventionist. We dissected and inspected the coronary sinus, the oblique vein of the left atrium, and the left-sided-circumflex venous channel in eight heart specimens with corrected transposition and eight controls, measuring the orifice and length of the sinus and the atrioventricular valves. In two-thirds of the malformed hearts, the sinus deviated from its anticipated course in the atrioventricular groove, ascending obliquely on the left atrial inferior wall to meet the left oblique vein. The maximal deviation coincided in all hearts with the point where the left oblique vein joined the left-sided-circumflex vein to form the coronary sinus. We describe a circumflex vein, rather than the great cardiac vein, as the latter venous channel is right-sided in the setting of corrected transposition. The length of the sinus correlated positively with the diameter of the tricuspid valve (p=0.02). Compared with controls, the left oblique vein in the malformed hearts joined the circumflex venous channel significantly closer to the mouth of the sinus. The unexpected course of the coronary sinus in corrected transposition and the naming of the cardiac veins have important implications for venous cannulation and interpretation of images.

Micro-RNAs and their roles in eye disorders.

PubMed

Raghunath, Azhwar; Perumal, Ekambaram

2015-01-01

Micro-RNAs (miRNAs) are members of the family of noncoding RNA molecules that regulate gene expression by translational repression and mRNA degradation. Initial identification of miRNAs revealed them only as developmental regulators; later, their radiated roles in various cellular processes have been established. They regulate several pathways, including developmental timing, hematopoiesis, organogenesis, apoptosis, cell differentiation and proliferation. Their roles in eye disorders are being explored by biologists around the world. Eye physiology requires the perfect orchestration of all the regulatory networks; any defect in any of the networks leads to eye disorders. The dysregulation of miRNA expression has been reported in many eye disorders, which paves the way for new therapeutics. This review summarizes the biogenesis of miRNAs and their role in eye disorders. miRNA studies also have implications for the understanding of various complex metabolic pathways leading to disorders of the eye. The ultimate understanding leads to potential opportunities in evaluating miRNAs as molecular biomarkers, prognostic tools, diagnostic tools and therapeutic agents for eye disorders. © 2015 S. Karger AG, Basel.

Stratified Whole Genome Linkage Analysis of Chiari Type I Malformation Implicates Known Klippel-Feil Syndrome Genes as Putative Disease Candidates

PubMed Central

Markunas, Christina A.; Soldano, Karen; Dunlap, Kaitlyn; Cope, Heidi; Asiimwe, Edgar; Stajich, Jeffrey; Enterline, David; Grant, Gerald; Fuchs, Herbert

2013-01-01

Chiari Type I Malformation (CMI) is characterized by displacement of the cerebellar tonsils below the base of the skull, resulting in significant neurologic morbidity. Although multiple lines of evidence support a genetic contribution to disease, no genes have been identified. We therefore conducted the largest whole genome linkage screen to date using 367 individuals from 66 families with at least two individuals presenting with nonsyndromic CMI with or without syringomyelia. Initial findings across all 66 families showed minimal evidence for linkage due to suspected genetic heterogeneity. In order to improve power to localize susceptibility genes, stratified linkage analyses were performed using clinical criteria to differentiate families based on etiologic factors. Families were stratified on the presence or absence of clinical features associated with connective tissue disorders (CTDs) since CMI and CTDs frequently co-occur and it has been proposed that CMI patients with CTDs represent a distinct class of patients with a different underlying disease mechanism. Stratified linkage analyses resulted in a marked increase in evidence of linkage to multiple genomic regions consistent with reduced genetic heterogeneity. Of particular interest were two regions (Chr8, Max LOD = 3.04; Chr12, Max LOD = 2.09) identified within the subset of “CTD-negative” families, both of which harbor growth differentiation factors (GDF6, GDF3) implicated in the development of Klippel-Feil syndrome (KFS). Interestingly, roughly 3–5% of CMI patients are diagnosed with KFS. In order to investigate the possibility that CMI and KFS are allelic, GDF3 and GDF6 were sequenced leading to the identification of a previously known KFS missense mutation and potential regulatory variants in GDF6. This study has demonstrated the value of reducing genetic heterogeneity by clinical stratification implicating several convincing biological candidates and further supporting the hypothesis that multiple, distinct mechanisms are responsible for CMI. PMID:23620759

[The case of completed pregnancy of the patient with Dandy-Walker malformation].

PubMed

Beliaeva, E V; Lapshina, L V; Shaposhnikova, E V; Molgachev, A A

2018-01-01

Dandy-Walker malformation is a rare disease of the central nervous system pathology (congenital malformations of the fossa cranii posterior). The key features of this syndrome are an enlargement of the fourth ventricle; complete absence of the cerebellar vermis, the posterior midline area of cerebellar cortex responsible for coordination of the axial musculature; and cyst formation near the internal base of the skull. Pregnant patients with Dandy-Walker malformation are at high risk and are managed by multidisciplinary teams including neurologists and obstetricians. We present a case report of full-term pregnancy and uncomplicated delivery in a women with Dandy-Walker malformation.

Combining EEG and eye tracking: identification, characterization, and correction of eye movement artifacts in electroencephalographic data

PubMed Central

Plöchl, Michael; Ossandón, José P.; König, Peter

2012-01-01

Eye movements introduce large artifacts to electroencephalographic recordings (EEG) and thus render data analysis difficult or even impossible. Trials contaminated by eye movement and blink artifacts have to be discarded, hence in standard EEG-paradigms subjects are required to fixate on the screen. To overcome this restriction, several correction methods including regression and blind source separation have been proposed. Yet, there is no automated standard procedure established. By simultaneously recording eye movements and 64-channel-EEG during a guided eye movement paradigm, we investigate and review the properties of eye movement artifacts, including corneo-retinal dipole changes, saccadic spike potentials and eyelid artifacts, and study their interrelations during different types of eye- and eyelid movements. In concordance with earlier studies our results confirm that these artifacts arise from different independent sources and that depending on electrode site, gaze direction, and choice of reference these sources contribute differently to the measured signal. We assess the respective implications for artifact correction methods and therefore compare the performance of two prominent approaches, namely linear regression and independent component analysis (ICA). We show and discuss that due to the independence of eye artifact sources, regression-based correction methods inevitably over- or under-correct individual artifact components, while ICA is in principle suited to address such mixtures of different types of artifacts. Finally, we propose an algorithm, which uses eye tracker information to objectively identify eye-artifact related ICA-components (ICs) in an automated manner. In the data presented here, the algorithm performed very similar to human experts when those were given both, the topographies of the ICs and their respective activations in a large amount of trials. Moreover it performed more reliable and almost twice as effective than human experts when those had to base their decision on IC topographies only. Furthermore, a receiver operating characteristic (ROC) analysis demonstrated an optimal balance of false positive and false negative at an area under curve (AUC) of more than 0.99. Removing the automatically detected ICs from the data resulted in removal or substantial suppression of ocular artifacts including microsaccadic spike potentials, while the relevant neural signal remained unaffected. In conclusion the present work aims at a better understanding of individual eye movement artifacts, their interrelations and the respective implications for eye artifact correction. Additionally, the proposed ICA-procedure provides a tool for optimized detection and correction of eye movement-related artifact components. PMID:23087632

Genetics Home Reference: megalencephaly-capillary malformation syndrome

MedlinePlus

... the prognosis of a genetic condition? Genetic and Rare Diseases Information Center Frequency The prevalence of MCAP is ... Brain Malformations Health Topic: Vascular Diseases Genetic and Rare Diseases Information Center (1 link) Megalencephaly-capillary malformation syndrome ...

Linking Brain Arteriovenous Malformations With Anorectal Hemorrhoids: A Clinical and Anatomical Review

PubMed Central

Cuoco, Joshua A.; Hoehmann, Christopher L.; Hitscherich, Kyle; Zakhary, Sherry M.; Leheste, Joerg R.

2017-01-01

ABSTRACT Patients who harbor brain arteriovenous malformations are at risk for intracranial hemorrhage. These malformations are often seen in inherited vascular diseases such as hereditary hemorrhagic telangiectasia. However, malformations within the brain also sporadically occur without a hereditary‐coding component. Here, we review recent insights into the pathophysiology of arteriovenous malformations, in particular, certain signaling pathways that might underlie endothelial cell pathology. To better interpret the origins, determinants and consequences of brain arteriovenous malformations, we present a clinical case to illustrate the phenotypic landscape of the disease. We also propose that brain arteriovenous malformations might share certain signaling dimensions with those of anorectal hemorrhoids. This working hypothesis provides casual anchors from which to understand vascular diseases characterized by arteriovenous lesions with a hemorrhagic‐ or bleeding‐risk component. Anat Rec, 2017. © The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists. Anat Rec, 300:1973–1980, 2017. © 2017 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists. PMID:28696502

Incidence and impact of axial malformations in larval bullfrogs (Rana catesbeiana) developing in sites polluted by a coal-burning power plant

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hopkins, W.A.; Congdon, J.; Ray, J.K.

2000-04-01

Amphibian malformations have recently received much attention from the scientific community, but few studies have provided evidence linking environmental pollution to larval amphibian malformations in the field. The authors document an increased incidence of axial malformations in bullfrog larvae (Rana catesbeiana) inhabiting two sites contaminated with coal combustion wastes. In the polluted sites, 18 and 37% of larvae exhibited lateral curvatures of the spine, whereas zero and 4% of larvae from two reference sites had similar malformations. Larvae from the most heavily polluted site had significantly higher tissue concentrations of potentially toxic trace elements, including As, Cd, Se, Cu, Cr,more » and V, compared with conspecifics from the reference sites. In addition, malformed larvae from the cost contaminated site had decreased swimming speeds compared with those of normal larvae from the same site. The authors hypothesize that the complex mixture of contaminants produced by coal combustion is responsible for the high incidence of malformations and associated effects on swimming performance.« less

Patterns of anomalies of structures of the middle ear and the facial nerve as revealed in newborn temporal bones.

PubMed

Tóth, Miklós; Sirirattanapan, Jarinratn; Mann, Wolf

2013-08-01

The purpose of this study is to offer new data about facial nerve malformations in the tympanic cavity. Prospective anatomic study of newborns to demonstrate the submacroscopic anatomy of the intratympanic facial nerve and its surrounding structures by malformations. Step-by-step microdissection of 12 newborn temporal bones and histologic evaluation of 4 middle ears showing multiple malformations. Four of 12 temporal bones presented malformation in the middle ear. All 4 temporal bones showed developmental failures of the stapes, and 3 of them had malposition of the tympanic portion of the facial nerve. In 3 cases, there was an oval window atresia, and in 1 case, the rim of the oval window was not ossified and was positioned medial to the stapes. Malformation or displacement of the stapes can be an indirect sign for facial nerve malformation. The most common site for facial nerve malformation is the tympanic portion. The tympanic segment of the nerve is devoid of bony covering in association with these anomalies of the stapes.

Intracranial Hypertension in a Patient with a Chiari Malformation Accompanied by Hyperthyroidism

PubMed Central

Pang, Chang Hwan; Kim, Chi Heon; Chung, Chun Kee

2015-01-01

The Chiari malformation is an infrequently detected congenital anomaly characterized by the downward displacement of the cerebellum with a tonsillar herniation below the foramen magnum that may be accompanied by either syringomyelia or hydrocephalus. Surgery, such as foramen magnum decompression, is indicated for a symptomatic Chiari malformation, although an incidental lesion may be followed-up without further treatment. Infrequently, increased intracranial pressure emerges due to hyperthyroidism. A nineteen-year-old girl visited our outpatient clinic presented with a headache, nausea and vomiting. A brain and spinal magnetic resonance image study (MRI) indicated that the patient had a Chiari I malformation without syringomyelia or hydrocephalus. An enlarged thyroid gland was detected on a physical examination, and serum markers indicated Graves' disease. The patient started anti-hyperthyroid medical treatment. Subsequently, the headache disappeared after the medical treatment of hyperthyroidism without surgical intervention for the Chiari malformation. A symptomatic Chiari malformation is indicated for surgery, but a surgeon should investigate other potential causes of the symptoms of the Chiari malformation to avoid unnecessary surgery. PMID:26512271

Eye growth in the second decade of life: implications for the implantation of a multifocal intraocular lens.

PubMed

Wilson, M Edward; Trivedi, Rupal H; Burger, Berdine M

2009-12-01

There is a growing interest in multifocal intraocular lens (IOL) implantation in children because they lose accommodation when a cataract is removed. Many have assumed that very little, if any, eye growth occurs in the second decade of life. Multifocal IOL implantation requires precise biometry to arrive at the correct IOL power for spectacle independence. If the eye grows and the refraction becomes myopic, spectacle dependence may return. Therefore, knowing when the eye has completed its growth is critical to the decision of when to implant a multifocal IOL. Ninety-eight eyes were analyzed retrospectively. Each had at least two axial length (AL) measurements using immersion A-scan ultrasound in the second decade of life. Globe AL was 23.36 +/- 1.52 mm at initial measurement and 23.89 +/- 1.64 mm at last measurement. Measurement data show variable growth throughout the second decade of life. Based on our data, a theoretical patient was constructed with an AL at age 10 of 23.11 mm, who would need an IOL power of 21.5 for emmetropia. That same patient would have an AL of 23.76 mm (IOL power of 19.5) at age 15 and 24.41 mm (IOL power of 17.5) at age 20. That is a 4-diopter change in the IOL power need. Axial eye growth continues throughout the second decade of life, at least to age 20. These data have important implications for the use of multifocal IOLs in the preteen and teenage years.

Neuropathic ocular pain: an important yet underevaluated feature of dry eye

PubMed Central

Galor, A; Levitt, R C; Felix, E R; Martin, E R; Sarantopoulos, C D

2015-01-01

Dry eye has gained recognition as a public health problem given its prevalence, morbidity, and cost implications. Dry eye can have a variety of symptoms including blurred vision, irritation, and ocular pain. Within dry eye-associated ocular pain, some patients report transient pain whereas others complain of chronic pain. In this review, we will summarize the evidence that chronicity is more likely to occur in patients with dysfunction in their ocular sensory apparatus (ie, neuropathic ocular pain). Clinical evidence of dysfunction includes the presence of spontaneous dysesthesias, allodynia, hyperalgesia, and corneal nerve morphologic and functional abnormalities. Both peripheral and central sensitizations likely play a role in generating the noted clinical characteristics. We will further discuss how evaluating for neuropathic ocular pain may affect the treatment of dry eye-associated chronic pain. PMID:25376119

Life-threatening haemothorax: a rare presentation of pulmonary arteriovenous malformation.

PubMed

Kundu, Somenath; Mitra, Subhra; Mukherjee, Shubhasis; Chakravorty, Anushree

2010-11-01

Arteriovenous malformations of the lung are rare pulmonary vascular disorders which can suddenly lead to life threatening complications. Haemothorax due to rupture of a pulmonary arteriovenous malformation (PAVM) is very rare. We report here a case of a 39 year-old lady who presented with an acute onset of shortness of breath due to right-sided massive haemothorax and was subsequently detected to have pulmonary as well as cerebral arteriovenous malformation (CAVM).

Congenital malformations of the skull and meninges.

PubMed

Kanev, Paul M

2007-02-01

The surgery and management of children who have congenital malformations of the skull and meninges require multidisciplinary care and long-term follow-up by multiple specialists in birth defects. The high definition of three-dimensional CT and MRI allows precise surgery planning of reconstruction and management of associated malformations. The reconstruction of meningoencephaloceles and craniosynostosis are challenging procedures that transform the child's appearance. The embryology, clinical presentation, and surgical management of these malformations are reviewed.

Brainstem and cerebellar cavernous malformations.

PubMed

Atwal, Gursant S; Sarris, Christina E; Spetzler, Robert F

2017-01-01

Cavernous malformations are vascular lesions that occur throughout the central nervous system, most commonly in the supratentorial location, with brainstem and cerebellar cavernous malformations occurring more rarely. Cavernous malformations are associated with developmental venous anomalies that occur sporadically or in familial form. Patients with a cavernous malformation can present with headaches, seizures, sensorimotor disturbances, or focal neurologic deficits based on the anatomic location of the lesion. Patients with infratentorial lesions present more commonly with a focal neurologic deficit. Cavernous malformations are increasingly discovered incidentally due to the increasing use of magnetic resonance imaging. Understanding the natural history of these lesions is essential to their management. Observation and surgical resection are both reasonable options in the treatment of patients with these lesions. The clinical presentation of the patient, the location of the lesion, and the surgical risk assessment all play critical roles in management decision-making. © 2017 Elsevier B.V. All rights reserved.

A comparison of neural tube defects identified by two independent routine recording systems for congenital malformations in Northern Ireland.

PubMed

Nevin, N C; McDonald, J R; Walby, A L

1978-12-01

The efficiency of two systems for recording congenital malformations has been compared; one system, the Registrar General's Congenital Malformation Notification, is based on registering all malformed infants, and the other, the Child Health System, records all births. In Northern Ireland for three years [1974--1976], using multiple sources of ascertainment, a total of 686 infants with neural tube defects was identified among 79 783 live and stillbirths. The incidence for all neural tube defects in 8 60 per 1 000 births. The Registrar General's Congenital Malformation Notification System identified 83.6% whereas the Child Health System identified only 63.3% of all neural tube defects. Both systems together identified 86.2% of all neural tube defects. The two systems are suitable for monitoring of malformations and the addition of information from the Genetic Counselling Clinics would enhance the data for epidemiological studies.

Antipsychotic Use in Pregnancy and the Risk for Congenital Malformations.

PubMed

Huybrechts, Krista F; Hernández-Díaz, Sonia; Patorno, Elisabetta; Desai, Rishi J; Mogun, Helen; Dejene, Sara Z; Cohen, Jacqueline M; Panchaud, Alice; Cohen, Lee; Bateman, Brian T

2016-09-01

The frequency of antipsychotic (AP) use during pregnancy has approximately doubled during the last decade. However, little is known about their safety for the developing fetus, and concerns have been raised about a potential association with congenital malformations. To examine the risk for congenital malformations overall and cardiac malformations associated with first-trimester exposure to APs. This nationwide sample of 1 360 101 pregnant women enrolled in Medicaid with a live-born infant constituted the pregnancy cohort nested in the Medicaid Analytic Extract database, which included data from January 1, 2000, to December 31, 2010. Participants were enrolled in Medicaid from 3 months before their last menstrual period through at least 1 month after delivery. Relative risks (RRs) were estimated using generalized linear models with fine stratification on the propensity score to control for the underlying psychiatric disorders and other potential confounders. Data were analyzed during 2015. Use of APs during the first trimester, the etiologically relevant period for organogenesis. Major congenital malformations overall and cardiac malformations identified during the first 90 days after delivery. Of the 1 341 715 pregnancies that met inclusion criteria (mean [SD] age of women, 24.02 [5.77] years), 9258 (0.69%) filled at least 1 prescription for an atypical AP and 733 (0.05%) filled at least 1 prescription for a typical AP during the first trimester. Overall, 32.7 (95% CI, 32.4-33.0) per 1000 births not exposed to APs were diagnosed with congenital malformations compared with 44.5 (95% CI, 40.5-48.9) per 1000 births exposed to atypical and 38.2 (95% CI, 26.6-54.7) per 1000 births exposed to typical APs. Unadjusted analyses suggested an increased risk for malformations overall for atypical APs (RR, 1.36; 95% CI, 1.24-1.50) but not for typical APs (RR, 1.17; 95% CI, 0.81-1.68). After confounding adjustment, the RR was reduced to 1.05 (95% CI, 0.96-1.16) for atypical APs and 0.90 (95% CI, 0.62-1.31) for typical APs. The findings for cardiac malformations were similar. For the individual agents examined, a small increased risk in overall malformations (RR, 1.26; 95% CI, 1.02-1.56) and cardiac malformations (RR, 1.26; 95% CI, 0.88-1.81) was found for risperidone that was independent of measured confounders. Evidence from this large study suggests that use of APs early in pregnancy generally does not meaningfully increase the risk for congenital malformations overall or cardiac malformations in particular. The small increase in the risk for malformations observed with risperidone requires additional study.

Analysis of Maternal Risk Factors Associated With Congenital Vertebral Malformations

PubMed Central

Hesemann, Jennifer; Lauer, Emily; Ziska, Stephen; Noonan, Kenneth; Nemeth, Blaise; Scott-Schwoerer, Jessica; McCarty, Catherine; Rasmussen, Kristen; Goldberg, Jacob M.; Sund, Sarah; Eickhoff, Jens; Raggio, Cathleen L.; Giampietro, Philip F.

2014-01-01

Study Design A retrospective chart review of cases with congenital vertebral malformations (CVM) and controls with normal spine morphology. Objective To determine the relative contribution of maternal environmental factors (MEF) during pregnancy including maternal insulin dependent diabetes mellitus, valproic acid, alcohol, smoking, hyperthermia, twin gestation, assisted reproductive technology, in-vitro fertilization and maternal clomiphene usage to CVM development. Summary of Background Data Congenital vertebral malformations (CVM) represent defects in formation and segmentation of somites occurring with an estimated incidence of between 0.13–0.50 per 1000 live births. CVM may be associated with congenital scoliosis, Klippel-Feil syndrome, hemifacial microsomia and VACTERL syndromes, and represent significant morbidity due to pain and cosmetic disfigurement. Methods A multicenter retrospective chart review of 229 cases with CVM and 267 controls with normal spine morphology between the ages of 1–50 years was performed in order to obtain the odds ratio (OR) of MEF related to CVM among cases vs. controls. CVM due to an underlying syndrome associated with a known gene mutation or chromosome etiology were excluded. An imputation based analysis was performed in which subjects with no documentation of MEF history were treated as no maternal exposure.” Univariate and multivariate analysis was conducted to calculate the OR. Results Of the 229 total cases, 104 cases had single or multiple CVM without additional congenital malformations (CM) (Group 1) and 125 cases had single or multiple CVM and additional CM (Group 2). Nineteen percent of total cases had an identified MEF. The OR (95% CI, P-value) for MEF history for Group 1 was 6.0 (2.4–15.1, P<0.001) in the univariate analysis. The OR for MEF history in Group 2 was 9.1 (95%CI, P-value) (3.8–21.6, P<0.001) in the univariate analysis. The results were confirmed in the multivariate analysis, after adjusting for age, gender, and institution. Discussion These results support a hypothesis for an association between the above MEF during pregnancy and CVM and have implications for development of prevention strategies. Further prospective studies are needed to quantify association between CVM and specific MEF. PMID:23446706

An Analysis of Eye Movement and Cognitive Load about the Editorial Design in Elementary Science Textbook

ERIC Educational Resources Information Center

Kim, Seong-un; Lim, Sung-man; Kim, Eun-ae; Yang, Il-ho

2016-01-01

This study is for the implication of editorial design in science textbooks which are designed for student-centered instruction, when the elements of the editorial design are different, we focus on how the students' eye movement and cognitive load change. For this, we produced a new book for 5th grade students in elementary school that is modified…

Assessment of environmental stressors potentially responsible for malformations in North American anuran amphibians.

PubMed

Ankley, Gerald T; Degitz, S J; Diamond, S A; Tietge, J E

2004-05-01

Several species of anuran amphibians from different regions across North America have recently exhibited an increased occurrence of malformations, predominantly of the hindlimb. Research concerning the potential causes of these malformations has focused extensively on three stressors: chemical contaminants, ultraviolet (UV) radiation, and parasitic trematodes. In this overview of recent work with each of these stressors, we assess their plausibility as contributors to the malformations observed in field-collected amphibians. There is as yet little evidence that chemical contaminants are responsible for the limb malformations. This includes chemicals, such as the pesticide methoprene, that could affect retinoid-signaling pathways that are critical to limb development. Exposure to UV radiation also seems to be an unlikely explanation for hindlimb malformations in amphibians. Although solar UV can cause hindlimb deficiencies in amphibians, a probabilistic assessment based on empirical dose-response and exposure data indicates that UV exposures sufficient to induce limb defects would be uncommon in most wetlands. Results of controlled studies conducted with some affected species and field-monitoring work suggest infection by digenetic trematodes as a promising explanation for the malformations observed in anurans collected from many field sites. Controlled experimentation with additional species and monitoring across a broader range of affected sites are required to assess fully the role of trematodes in relation to other stressors in causing limb malformations. If trematode infestations are indeed related to the recent increases in malformed amphibians, then the question remains as to what alterations in the environment might be causing changes in the distribution and abundance of the parasites.

The history of female genital tract malformation classifications and proposal of an updated system.

PubMed

Acién, Pedro; Acién, Maribel I

2011-01-01

A correct classification of malformations of the female genital tract is essential to prevent unnecessary and inadequate surgical operations and to compare reproductive results. An ideal classification system should be based on aetiopathogenesis and should suggest the appropriate therapeutic strategy. We conducted a systematic review of relevant articles found in PubMed, Scopus, Scirus and ISI webknowledge, and analysis of historical collections of 'female genital malformations' and 'classifications'. Of 124 full-text articles assessed for eligibility, 64 were included because they contained original general, partial or modified classifications. All the existing classifications were analysed and grouped. The unification of terms and concepts was also analysed. Traditionally, malformations of the female genital tract have been catalogued and classified as Müllerian malformations due to agenesis, lack of fusion, the absence of resorption and lack of posterior development of the Müllerian ducts. The American Fertility Society classification of the late 1980s included seven basic groups of malformations also considering the Müllerian development and the relationship of the malformations to fertility. Other classifications are based on different aspects: functional, defects in vertical fusion, embryological or anatomical (Vagina, Cervix, Uterus, Adnex and Associated Malformation: VCUAM classification). However, an embryological-clinical classification system seems to be the most appropriate. Accepting the need for a new classification system of genitourinary malformations that considers the experience gained from the application of the current classification systems, the aetiopathogenesis and that also suggests the appropriate treatment, we proposed an update of our embryological-clinical classification as a new system with six groups of female genitourinary anomalies.

Personalized ophthalmology

PubMed Central

Porter, LF; Black, GCM

2014-01-01

Porter L.F., Black G.C.M. Personalized ophthalmology. Clin Genet 2014: 86: 1–11. © 2014 The Authors. Clinical Genetics published by John Wiley & Sons A/S. Published by John Wiley & Sons Ltd., 2014 Ophthalmology has been an early adopter of personalized medicine. Drawing on genomic advances to improve molecular diagnosis, such as next-generation sequencing, and basic and translational research to develop novel therapies, application of genetic technologies in ophthalmology now heralds development of gene replacement therapies for some inherited monogenic eye diseases. It also promises to alter prediction, diagnosis and management of the complex disease age-related macular degeneration. Personalized ophthalmology is underpinned by an understanding of the molecular basis of eye disease. Two important areas of focus are required for adoption of personalized approaches: disease stratification and individualization. Disease stratification relies on phenotypic and genetic assessment leading to molecular diagnosis; individualization encompasses all aspects of patient management from optimized genetic counseling and conventional therapies to trials of novel DNA-based therapies. This review discusses the clinical implications of these twin strategies. Advantages and implications of genetic testing for patients with inherited eye diseases, choice of molecular diagnostic modality, drivers for adoption of personalized ophthalmology, service planning implications, ethical considerations and future challenges are considered. Indeed, whilst many difficulties remain, personalized ophthalmology truly has the potential to revolutionize the specialty. PMID:24665880

Neurodevelopmental malformations of the cerebellar vermis in genetically engineered rats

EPA Science Inventory

The cerebellar vermis is particularly vulnerable to neurodevelopmental malformations in humans and rodents. Sprague-Dawley, and Long-Evans rats exhibit spontaneous cerebellar malformations consisting of heterotopic neurons and glia in the molecular layer of the vermis. Malformati...

Genetically induced abnormal cranial development in human trisomy 18 with holoprosencephaly: comparisons with the normal tempo of osteogenic-neural development.

PubMed

Reid, Shaina N; Ziermann, Janine M; Gondré-Lewis, Marjorie C

2015-07-01

Craniofacial malformations are common congenital defects caused by failed midline inductive signals. These midline defects are associated with exposure of the fetus to exogenous teratogens and with inborn genetic errors such as those found in Down, Patau, Edwards' and Smith-Lemli-Opitz syndromes. Yet, there are no studies that analyze contributions of synchronous neurocranial and neural development in these disorders. Here we present the first in-depth analysis of malformations of the basicranium of a holoprosencephalic (HPE) trisomy 18 (T18; Edwards' syndrome) fetus with synophthalmic cyclopia and alobar HPE. With a combination of traditional gross dissection and state-of-the-art computed tomography, we demonstrate the deleterious effects of T18 caused by a translocation at 18p11.31. Bony features included a single developmentally unseparated frontal bone, and complete dual absence of the anterior cranial fossa and ethmoid bone. From a superior view with the calvarium plates removed, there was direct visual access to the orbital foramen and hard palate. Both the eyes and the pituitary gland, normally protected by bony structures, were exposed in the cranial cavity and in direct contact with the brain. The middle cranial fossa was shifted anteriorly, and foramina were either missing or displaced to an abnormal location due to the absence or misplacement of its respective cranial nerve (CN). When CN development was conserved in its induction and placement, the respective foramen developed in its normal location albeit with abnormal gross anatomical features, as seen in the facial nerve (CNVII) and the internal acoustic meatus. More anteriorly localized CNs and their foramina were absent or heavily disrupted compared with posterior ones. The severe malformations exhibited in the cranial fossae, orbital region, pituitary gland and sella turcica highlight the crucial involvement of transcription factors such as TGIF, which is located on chromosome 18 and contributes to neural patterning, in the proper development of neural and cranial structures. Our study of a T18 specimen emphasizes the intricate interplay between bone and brain development in midline craniofacial abnormalities in general. © 2015 Anatomical Society.

Risk of major congenital malformations in relation to maternal overweight and obesity severity: cohort study of 1.2 million singletons

PubMed Central

Cnattingius, Sven; Villamor, Eduardo; Söderling, Jonas; Pasternak, Björn; Stephansson, Olof; Neovius, Martin

2017-01-01

Objective To estimate the risks of major congenital malformations in the offspring of mothers who are underweight (body mass index (BMI) <18.5), overweight (BMI 25 to <30), or in obesity classes I (BMI 30 to <35), II (35 to <40), or III (≥40) compared with offspring of normal weight mothers (BMI 18.5 to <25) in early pregnancy. Design Population based cohort study. Setting Nationwide Swedish registries. Participants 1 243 957 liveborn singleton infants from 2001 to 2014 in Sweden. Data on maternal and pregnancy characteristics were obtained by individual record linkages. Exposure Maternal BMI at the first prenatal visit. Main outcome measures Offspring with any major congenital malformation, and subgroups of organ specific malformations diagnosed during the first year of life. Risk ratios were estimated using generalised linear models adjusted for maternal factors, sex of offspring, and birth year. Results A total of 43 550 (3.5%) offspring had any major congenital malformation, and the most common subgroup was for congenital heart defects (n=20 074; 1.6%). Compared with offspring of normal weight mothers (risk of malformations 3.4%), the proportions and adjusted risk ratios of any major congenital malformation among the offspring of mothers with higher BMI were: overweight, 3.5% and 1.05 (95% confidence interval 1.02 to 1.07); obesity class I, 3.8% and 1.12 (1.08 to 1.15), obesity class II, 4.2% and 1.23 (1.17 to 1.30), and obesity class III, 4.7% and 1.37 (1.26 to 1.49). The risks of congenital heart defects, malformations of the nervous system, and limb defects also progressively increased with BMI from overweight to obesity class III. The largest organ specific relative risks related to maternal overweight and increasing obesity were observed for malformations of the nervous system. Malformations of the genital and digestive systems were also increased in offspring of obese mothers. Conclusions Risks of any major congenital malformation and several subgroups of organ specific malformations progressively increased with maternal overweight and increasing severity of obesity. For women who are planning pregnancy, efforts should be encouraged to reduce adiposity in those with a BMI above the normal range. PMID:28615173

Antenatal hemorrhage of a cervical lymphatic malformation presenting as a draining neck mass: An unusual presentation.

PubMed

Haricharan, R N; Nawaz, M; Bettolli, M; Ferretti, E

2014-01-01

Lymphatic malformations in the neck can present as large fetal neck masses causing airway obstructions with potential perinatal demise and can pose a therapeutic challenge. We present a rare case of prenatally diagnosed large fetal neck mass with features of lymphatic malformation with intralesional hemorrhage of uncertain origin. Postnatal evaluation showed a complex cystic-solid lesion eroding through the skin with an open wound that made it clinically hard to differentiate from a teratoma. Given that malignancy could not be completely ruled out, surgery was favored. Final pathology showed a complex lymphatic malformation with intralesional hemorrhage, despite having no associated capillary, venous or arterial malformations.

Chronic cerebral herniation in shunted Dandy-Walker malformation.

PubMed

Naidich, T P; Radkowski, M A; McLone, D G; Leestma, J

1986-02-01

A review of serial computed tomography (CT) scans of 25 patients with the Dandy-Walker malformation revealed six patients with chronic downward transincisural herniation of the cerebrum after shunt decompression of the posterior fossa cyst or malfunction of a lateral ventricular drainage catheter, or both. Chronic cerebral herniation was detected postmortem in a seventh patient with the Dandy-Walker malformation. The CT findings and autopsy appearance of this previously undescribed feature of shunted Dandy-Walker malformation are illustrated.

Congenital malformations according to etiology in newborns from the floricultural zone of Mexico state.

PubMed

Castillo-Cadena, Julieta; Mejia-Sanchez, Fernando; López-Arriaga, Jerónimo Amado

2017-03-01

Birth defects are the number one cause of child mortality worldwide and in 2010 it was the second cause in Mexico. Congenital malformations are a public health issue, because they cause infant mortality, chronic disease and disability. The origin can be genetic, environmental or unknown causes. Among environmental contaminants, pesticides stand out. In this study, we determine the frequency and etiology of congenital malformations in newborns (NBs) of a floricultural community and we compare it with that in the urban community. For 18 months, the NBs were monitored at the Tenancingo General Hospital and the Mother and Child Gynecology and Obstetrics Hospital (IMIEM) in Toluca. The identification of these malformations was carried out in accordance with the WHO. In Tenancingo, 1149 NBs were viewed, where 20% had some kind of congenital malformations. While in the IMIEM, 5069 were reviewed and 6% had some malformation. According to the etiology, in Tenancingo, 69% were multifactorial, 28% were monogenetic and 2% were chromosomal. In the IMIEM, 47% were multifactorial, then 18.3% were monogenetic and 2.8% were chromosomal. There was a significant difference between the global frequency of malformations and the multifactorial etiology of both institutions. Our results show that congenital malformations in the NBs occurred more frequently in the floricultural zone and that because the percentage of multifactorial etiology is higher, it is likely there is an association with exposure to pesticides.

Prospective long-term follow up of children with anorectal malformation: growth and development until 5years of age.

PubMed

van den Hondel, Desiree; Sloots, Cornelius E J; Gischler, Saskia J; Meeussen, Conny J H M; Wijnen, Rene M H; IJsselstijn, Hanneke

2013-04-01

To evaluate growth and development in children with anorectal malformations and to analyze effects of type of malformation and comorbidities. Non-syndromal children with anorectal malformations were prospectively evaluated at 0.5, 1, 2, and 5 years. Biometrics were obtained at all visits. Mental and psychomotor function development was determined. 108 children (59% male) were included. 49% had a high malformation, and 46% had ≥ 1 additional major comorbidity. All growth parameters were below the norm at all ages (p<0.01), irrespective of type of malformation. Children with ≥ 1 additional major anomaly had lower height at all ages; at 5 years, mean (95% CI) height was -1.83 (-2.7 to -1.1) and -0.70 (-1.3 to -0.1) in children with and without comorbidities, respectively (p=0.019). Mental development was normal, irrespective of the type of malformation or comorbidities. Motor development was delayed at all ages. At 5 years, motor development (n=30) was normal in 70%, borderline in 23%, and 7% had definitive motor problems (p=0.043). Non-syndromal children with anorectal malformations are at risk for growth impairment, especially those with additional major comorbidity. Mental development is normal. Motor development is slightly impaired. Supportive care should focus on growth, dietary management, and motor development besides defecation problems. Copyright © 2013 Elsevier Inc. All rights reserved.

Association of Chiari malformation and vitamin B12 deficit in a family.

PubMed

Welsch, Melanie; Antes, Sebastian; Kiefer, Michael; Meyer, Sascha; Eymann, Regina

2013-07-01

A clear etiology of Chiari malformation is still lacking. Some associations between this disorder and genetical variations have been reported. Documented cases of familial Chiari malformation in three consecutive generations are rare. Furthermore, an association of Chiari disorder and vitamin B12 deficit has rarely been described in literature. In this study, three generations of a family suffering from Chiari 1 or Chiari 0 malformation have been examined with MRI, clinically and laboratory (hemograms). Chiari malformation could be confirmed in all presented patients: While the F2 generation (children: 1 × ♀, 1 × ♂) and the female F1 generation (mother and sister of mother) suffered from Chiari type 1, the male F0 generation showed Chiari 0 malformation. F0 and F1 generation further presented with syringomyelia (F0: C4-D1; F1: C4-D2). All patients except the grandfather (F0) underwent surgical posterior fossa decompression to relive successfully cerebellar and hydrocephalus associated progressing clinical symptoms. The hemograms of generation 1 and 2 revealed familial vitamin B12 deficit. A hereditary component is discussed in Chiari malformation, yet proved etiology is still lacking. As folic acid plays an important role in the development of the neural tube, vitamin B12 deficit might have some impact on the development of Chiari malformations.

Analysis of the Ush2a gene in medaka fish (Oryzias latipes).

PubMed

Aller, Elena; Sánchez-Sánchez, Ana V; Chicote, Javier U; García-García, Gema; Udaondo, Patricia; Cavallé, Laura; Piquer-Gil, Marina; García-España, Antonio; Díaz-Llopis, Manuel; Millán, José M; Mullor, José L

2013-01-01

Patients suffering from Usher syndrome (USH) exhibit sensorineural hearing loss, retinitis pigmentosa (RP) and, in some cases, vestibular dysfunction. USH is the most common genetic disorder affecting hearing and vision and is included in a group of hereditary pathologies associated with defects in ciliary function known as ciliopathies. This syndrome is clinically classified into three types: USH1, USH2 and USH3. USH2 accounts for well over one-half of all Usher cases and mutations in the USH2A gene are responsible for the majority of USH2 cases, but also for atypical Usher syndrome and recessive non-syndromic RP. Because medaka fish (Oryzias latypes) is an attractive model organism for genetic-based studies in biomedical research, we investigated the expression and function of the USH2A ortholog in this teleost species. Ol-Ush2a encodes a protein of 5.445 aa codons, containing the same motif arrangement as the human USH2A. Ol-Ush2a is expressed during early stages of medaka fish development and persists into adulthood. Temporal Ol-Ush2a expression analysis using whole mount in situ hybridization (WMISH) on embryos at different embryonic stages showed restricted expression to otoliths and retina, suggesting that Ol-Ush2a might play a conserved role in the development and/or maintenance of retinal photoreceptors and cochlear hair cells. Knockdown of Ol-Ush2a in medaka fish caused embryonic developmental defects (small eyes and heads, otolith malformations and shortened bodies with curved tails) resulting in late embryo lethality. These embryonic defects, observed in our study and in other ciliary disorders, are associated with defective cell movement specifically implicated in left-right (LR) axis determination and planar cell polarity (PCP).

Twelve-year prevalence of common neonatal congenital malformations in Zhejiang Province, China.

PubMed

Sun, Ge; Xu, Zhe-Ming; Liang, Jian-Feng; Li, Lin; Tang, Da-Xing

2011-11-01

One of the challenges that pediatricians face when examining birth defects is to understand the trends in its occurrence and provide clues to etiology. This study was undertaken to retrospectively assess the prevalence of 10 common neonatal congenital malformations by reviewing a database of all deliveries from 28 weeks up until 7 days of birth from January 1998 to December 2009 in Zhejiang Province, China. Ten common neonatal congenital malformations were selected for analysis. The incidence and the Cochran-Armitage Trend were assessed via SAS9.2. A P value ≤0.05 was considered statistically significant. Of 83 888 perinatals, 374 (4.46‰) suffered from congenital heart diseases (CHD), 77 (0.92‰) from congenital hydrocephalus, 32 (0.38‰) from intestinal atresia/stenosis, 36 (0.43‰) from anorectal malformations, 149 (1.78‰) from kidney malformations, 139 (3.31‰) from hypospadias (male), 178 (2.12‰) from orofacial clefts (OFC), 188 (2.24‰) from polydactyly, 62 (0.74‰) from syndactyly, and 269 (3.21‰) from accessory auricle anomaly. Their trend of prevalence varied as follows: CHD, P=0.0026; hydrocephalus, P=0.0042; intestinal atresia/stenosis, P=0.0103; anorectal malformations, P=0.4332; kidney malformations, P<0.0001; hypospadias, P=0.0021; OFC, P=0.005; polydactyly, P=0.0867; syndactyly, P=0.1941; and accessory auricle anomaly, P=0.0011. The upward trend was as follows: CHD (P=0.0026), intestinal atresia/stenosis (P=0.0103), kidney malformations (P<0.0001), hypospadias (P=0.0021), OFC (P=0.005), and accessory auricle anomaly (P=0.0011). The incidence of hydrocephalus (P=0.0042) showed a downward trend. No statistical significant trend was found in anorectal malformations (P=0.4332), polydactyly (P=0.0867) and syndactyly (P=0.1941). The incidences of CHD, intestinal atresia/stenosis, kidney malformations, hypospadias, OFC, and accessory auricle anomaly have increased in the last 12 years, but the incidences of anorectal malformations, polydactyly and syndactyly remain stable. The incidence of hydrocephalus shows a downward trend.

ASSESSMENT OF ENVIRONMENTAL STRESSORS POTENTIALLY RESPONSIBLE FOR MALFORMATIONS IN NORTH AMERICAN ANURAN AMPHIBIANS

EPA Science Inventory

A number of species of anuran amphibians from different regions across North America have recently exhibited an increased occurrence of, predominantly, hind limb malformations. Research concerning factors potentially responsible for these malformations has focused extensively on ...

A proposal for classification of entities combining vascular malformations and deregulated growth.

PubMed

Oduber, Charlène E U; van der Horst, Chantal M A M; Sillevis Smitt, J Henk; Smeulders, Mark J C; Mendiratta, Vibhu; Harper, John I; van Steensel, Maurice A M; Hennekam, Raoul C M

2011-01-01

Agreement on terminology and nomenclature is fundamental and essential for effective exchange of information between clinicians and researchers. An adequate terminology to describe all patients showing vascular malformations combined with deregulated growth is at present not available. To propose a classification of patients with vascular malformations, not restricted to the face, and growth disturbances based on simple, clinically visible characteristics, on which clinicians and researchers can comment and which should eventually lead to an internationally accepted classification. Rooted in our joint experience we established a classification of vascular malformation not limited to the face, with growth disturbances. It is based on the nature and localization of the vascular malformations; the nature, localization and timing of growth disturbances; the nature of co-localization of the vascular malformations and growth disturbances; the presence or absence of other features. Subsequently a mixed (experienced and non-experienced) group of observers evaluated 146 patients (106 from the Netherlands; 40 from the UK) with vascular malformations and disturbed growth, using the classification. Inter-observer variability was assessed by estimating the Intra-Class Correlation (ICC) coefficient and its 95% confidence interval. We defined 6 subgroups within the group of entities with vascular malformation-deregulated growth. Scoring the patients using the proposed classification yielded a high inter-observer reproducibility (ICC varying between 0.747 and 0.895 for all levels of flow). The presently proposed classification was found to be reliable and easy to use for patients with vascular malformations with growth disturbances. We invite both clinicians and researchers to comment on the classification, in order to improve it further. This way we may obtain our final aim of an internationally accepted classification of patients, which should facilitate both clinical treatment and care of, as well as research into the molecular background of entities combining vascular malformation and deregulated growth. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Relationship between Cough-Associated Changes in CSF Flow and Disease Severity in Chiari I Malformation: An Exploratory Study Using Real-Time MRI.

PubMed

Bezuidenhout, A F; Khatami, D; Heilman, C B; Kasper, E M; Patz, S; Madan, N; Zhao, Y; Bhadelia, R A

2018-05-10

Currently no quantitative objective test exists to determine disease severity in a patient with Chiari I malformation. Our aim was to correlate disease severity in symptomatic patients with Chiari I malformation with cough-associated changes in CSF flow as measured with real-time MR imaging. Thirteen symptomatic patients with Chiari I malformation (tonsillar herniation of ≥5 mm) were prospectively studied. A real-time, flow-sensitized pencil-beam MR imaging scan was used to measure CSF stroke volume during rest and immediately following coughing and relaxation periods (total scan time, 90 seconds). Multiple posterior fossa and craniocervical anatomic measurements were also obtained. Patients were classified into 2 groups by neurosurgeons blinded to MR imaging measurements: 1) nonspecific Chiari I malformation (5/13)-Chiari I malformation with nonspecific symptoms like non-cough-related or mild occasional cough-related headache, neck pain, dizziness, paresthesias, and/or trouble swallowing; 2) specific Chiari I malformation (8/13)-patients with Chiari I malformation with specific symptoms and/or objective findings like severe cough-related headache, myelopathy, syringomyelia, and muscle atrophy. The Spearman correlation was used to determine correlations between MR imaging measurements and disease severity, and both groups were also compared using a Mann-Whitney U test. There was a significant negative correlation between the percentage change in CSF stroke volume (resting to postcoughing) and Chiari I malformation disease severity ( R = 0.59; P = .03). Mann-Whitney comparisons showed the percentage change in CSF stroke volume (resting to postcoughing) to be significantly different between patient groups ( P = .04). No other CSF flow measurement or anatomic measure was significantly different between the groups. Our exploratory study suggests that assessment of CSF flow response to a coughing challenge has the potential to become a valuable objective noninvasive test for clinical assessment of disease severity in patients with Chiari I malformation. © 2018 by American Journal of Neuroradiology.

Transverse Sinus Stenosis in Adult Patients With Chiari Malformation Type I

PubMed Central

Saindane, Amit M.; Bruce, Beau B.; Desai, Nilesh K.; Roller, Lauren A.; Newman, Nancy J.; Biousse, Valérie

2014-01-01

OBJECTIVE Transverse sinus stenosis is an imaging finding very highly associated with elevated intracranial pressure (ICP). Patients with the Chiari I malformation may potentially have elevated ICP due to impairment of CSF flow at the foramen magnum. This study evaluated whether patients with Chiari I malformation have transverse sinus stenosis and other imaging findings indicative of elevated ICP. MATERIALS AND METHODS Thirty patients with Chiari I malformation treated surgically and 76 control subjects were identified retrospectively. All control subjects and all patients with Chiari I malformation (preoperatively) underwent standardized contrast-enhanced brain MRI including a contrast-enhanced 3D T1-weighted sequence from which curved reformats of the transverse sinuses were generated. Two different readers blinded to the diagnosis then independently evaluated these curved reformats for severity of transverse sinus stenosis. Orbital and skull-base findings previously described in association with elevated ICP were also evaluated. Frequency of MRI findings between the two groups was compared. RESULTS Patients with Chiari I malformation had significantly greater frequency of unilateral or bilateral transverse sinus stenosis than did control subjects (p < 0.001). There was complete interreader agreement on presence or absence of transverse sinus stenosis by patient (κ = 1.0 [95% CI, 0.89–1.0]). Logistic regression analysis controlling for age, sex, and body mass index found that transverse sinus stenosis significantly predicted Chiari I malformation versus control status (odds ratio, 11.2 [95% CI, 2.1–59.0]; p = 0.004) but that no other features were significantly associated with the Chiari I malformation. Patients with Chiari I malformation who had transverse sinus stenosis had significantly greater pituitary flattening than did those without transverse sinus stenosis (p = 0.02). CONCLUSION Patients with Chiari I malformation have higher likelihood of trans-verse sinus stenosis, which may reflect associated elevated ICP. PMID:25247957

Ecotoxicology of organic contaminants to amphibians

USGS Publications Warehouse

Sparling, D.W.; Sparling, Donald W.; Linder, Greg L.; Bishop, Christine A.

2000-01-01

The effects of organic contaminants on amphibians are poorly known but of considerable interest. These contaminants include the highly toxic dioxins and furans as well as PCBs, PAHs and organochlorine pesticides. Although these compounds may have lower acute toxicity than dioxins and furans, they have been implicated in several problems associated with genotoxicity, endocrine disruption, malformations and reduced growth. There is evidence that amphibian tadpoles bioaccumulate these organic compounds and may have biological concentrating factors ranging in the hundreds. This chapter reviews what is known about the effects and concentrations of organic contaminants in amphibians and provides recommendations for further research

Chiari Malformation and Hydrocephalus Masking Neurocysticercosis.

PubMed

Rajpal, Sharad; Tomberlin, Colson; Bauer, Andrew; Forsythe, Robert C; Burneikiene, Sigita

2018-06-01

Various diagnostic characteristics associated with neurocysticercosis have been well studied; however, their potential to be implicated in other differential diagnoses has not been well demonstrated. We report the case of a 55-year-old Hispanic man who underwent a Chiari decompression surgery, which was complicated with hydrocephalus. Despite a ventriculoperitoneal shunt placement, he continued to have headaches and was soon found to have several skull base subarachnoid lesions, which were later diagnosed as the sequelae of an active neurocysticercosis infection. This case report highlights the importance of overlapping symptoms between diseases in a short temporal context. Copyright © 2018 Elsevier Inc. All rights reserved.

Pure pectus carinatum (not associated with pectus excavatum) solved by MIRPC (minimally invasive repair of pectus carinatum) associated with bilateral mamarian hypoplasia solved by bilateral breast implants.

PubMed

Ciurea, M; Ulmeanu, D; Popa, D; Mercuţ, R; Enache, M; Vânvu, A L; Demetrian, A

2014-01-01

We present the case of a young 24-year-old woman with an important but symmetrical pectus carinatum, not associated with pectus excavatum, without cardiorespiratory symptoms but with significant psychosocial implications for the patient, solved by the minimally invasive technique described by Abramson(reversed Nuss procedure) - MIRPC (Minimally invasive Repair of Pectus carinatum). The sternal malformation was associated with bilateral mammary hypoplasia, solved by bilateral breast implants 10 months later. The evolution was favorable and the aesthetic result was satisfactory for the patient. Celsius.

Congenital extrahepatic portosystemic shunts (Abernethy malformation): a histopathologic evaluation.

PubMed

Lisovsky, Mikhail; Konstas, Angelos A; Misdraji, Joseph

2011-09-01

Congenital extrahepatic portosystemic shunt, also known as Abernethy malformation, is a rare malformation in which intestinal and splenic venous blood bypasses the liver and drains into systemic veins. Aside from the complete or near-complete absence of portal veins, other histologic features of Abernethy malformation have not been evaluated in the literature. The goal of this study was to detail the hepatic histopathology in 5 patients with Abernethy malformation diagnosed at our institution. Paraffin-embedded tissue sections from 1 explant, 2 liver tumor resections, and 2 liver biopsies were evaluated using hematoxylin and eosin stains, reticulin, elastic, and trichrome stains, and immunohistochemistry for D2-40. Histologic findings included absence of portal veins in small portal tracts, absent or hypoplastic portal veins in medium-sized and large-sized portal tracts, isolated capillaries and arterioles in the lobules, hypertrophy of hepatic artery branches, remodeling of the liver architecture, and nodular regenerative hyperplasia in 1 case. Two patients had hepatocellular carcinoma without cirrhosis, and 2 had focal nodular hyperplasia. In addition to loss of portal veins, Abernethy malformation is characterized by multiple abnormalities due to remodeling of the hepatic vasculature. Abernethy malformation may also be associated with hepatocellular carcinoma and focal nodular hyperplasia in some patients.

Simultaneous and sequential hemorrhage of multiple cerebral cavernous malformations: a case report.

PubMed

Louis, Nundia; Marsh, Robert

2016-02-09

The etiology of cerebral cavernous malformation hemorrhage is not well understood. Causative physiologic parameters preceding hemorrhagic cavernous malformation events are often not reported. We present a case of an individual with sequential simultaneous hemorrhages in multiple cerebral cavernous malformations with a new onset diagnosis of hypertension. A 42-year-old white man was admitted to our facility with worsening headache, left facial and tongue numbness, dizziness, diplopia, and elevated blood pressure. His past medical history was significant for new onset diagnosis of hypertension and chronic seasonal allergies. Serial imaging over the ensuing 8 days revealed sequential hemorrhagic lesions. He underwent suboccipital craniotomy for resection of the lesions located in the fourth ventricle and right cerebellum. One month after surgery, he had near complete resolution of his symptoms with mild residual vertigo but symptomatic chronic hypertension. Many studies have focused on genetic and inflammatory mechanisms contributing to cerebral cavernous malformation rupture, but few have reported on the potential of hemodynamic changes contributing to cerebral cavernous malformation rupture. Systemic blood pressure changes clearly have an effect on angioma pressures. When considering the histopathological features of cerebral cavernous malformation architecture, changes in arterial pressure could cause meaningful alterations in hemorrhage propensity and patterns.

Percutaneous Sclerotherapy of Congenital Slow-Flow Vascular Malformations of the Orbit

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chiramel, George Koshy, E-mail: gkchiramel@gmail.com; Keshava, Shyamkumar Nidugala, E-mail: aparna-shyam@yahoo.com; Moses, Vinu, E-mail: vinu@cmcvellore.ac.in

PurposeThis manuscript describes the clinical features, imaging findings, treatment details, and short-term outcomes of a series of congenital slow-flow vascular malformations.MethodsThis was a prospective study of congenital slow-flow vascular malformations involving the orbital region treated at a single institution with percutaneous sclerotherapy.ResultsTen patients presented during the study period, comprising eight venous malformations, one lymphatic malformation, and one veno-lymphatic malformation. Nine patients underwent percutaneous sclerotherapy under digital subtraction angiography guidance, of which three developed marked rise in intraocular pressure requiring lateral canthotomy. The treatments were performed in the presence of an ophthalmologist who measured the intraorbital pressure during and after the procedure. Onmore » follow-up, some of the patients required repeat sessions of sclerotherapy. All patients had improvement of symptoms on follow up after the procedure.ConclusionCongenital slow-flow vascular malformations of the orbital region are rare lesions that should be treated using a multidisciplinary approach. Monitoring of the intraorbital pressure is required both during and after the procedure to decide about the need for lateral canthotomy to reduce the transiently increased intraorbital pressure.« less

Targeted Resequencing of 29 Candidate Genes and Mouse Expression Studies Implicate ZIC3 and FOXF1 in Human VATER/VACTERL Association.

PubMed

Hilger, Alina C; Halbritter, Jan; Pennimpede, Tracie; van der Ven, Amelie; Sarma, Georgia; Braun, Daniela A; Porath, Jonathan D; Kohl, Stefan; Hwang, Daw-Yang; Dworschak, Gabriel C; Hermann, Bernhard G; Pavlova, Anna; El-Maarri, Osman; Nöthen, Markus M; Ludwig, Michael; Reutter, Heiko; Hildebrandt, Friedhelm

2015-12-01

The VATER/VACTERL association describes the combination of congenital anomalies including vertebral defects, anorectal malformations, cardiac defects, tracheoesophageal fistula with or without esophageal atresia, renal malformations, and limb defects. As mutations in ciliary genes were observed in diseases related to VATER/VACTERL, we performed targeted resequencing of 25 ciliary candidate genes as well as disease-associated genes (FOXF1, HOXD13, PTEN, ZIC3) in 123 patients with VATER/VACTERL or VATER/VACTERL-like phenotype. We detected no biallelic mutation in any of the 25 ciliary candidate genes; however, identified an identical, probably disease-causing ZIC3 missense mutation (p.Gly17Cys) in four patients and a FOXF1 de novo mutation (p.Gly220Cys) in a further patient. In situ hybridization analyses in mouse embryos between E9.5 and E14.5 revealed Zic3 expression in limb and prevertebral structures, and Foxf1 expression in esophageal, tracheal, vertebral, anal, and genital tubercle tissues, hence VATER/VACTERL organ systems. These data provide strong evidence that mutations in ZIC3 or FOXF1 contribute to VATER/VACTERL. © 2015 WILEY PERIODICALS, INC.

Dlx5 Homeodomain: DNA Complex: Structure, Binding and Effect of Mutations Related to Split Hand and Foot Malformation Syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Proudfoot, Andrew; Axelrod, Herbert L.; Geralt, Michael

The Dlx5 homeodomain is a transcription factor related to the Drosophila Distal-less gene that is associated with breast and lung cancer, lymphoma, Rett syndrome and osteoporosis in humans. Mutations in the DLX5 gene have been linked to deficiencies in craniofacial and limb development in higher eukaryotes, including Split Hand and Foot Malformation-1 (SHFM-1) in humans. Our characterization of a Dlx5 homeodomain–(CGACTAATTAGTCG) 2 complex by NMR spectroscopy paved the way for determination of its crystal structure at 1.85 Å resolution that enabled rationalization of the effects of disease-related mutations on the protein function. A remarkably subtle mutation, Q186H, is linked tomore » SHFM-1; this change likely affects affinity of DNA binding by disrupting water-mediated interactions with the DNA major groove. A more subtle effect is implicated for the Q178P mutation, which is not in direct contact with the DNA. Our data indicate that these mutations diminish the ability of the Dlx5 homeodomain to recognize and bind target DNAs, and likely destabilize the formation of functional complexes.« less

Pulmonary Arteriovenous Malformations After the Superior Cavopulmonary Shunt: Mechanisms and Clinical Implications

PubMed Central

Kavarana, Minoo N.; Jones, Jeffrey A.; Stroud, Robert E.; Bradley, Scott M.; Ikonomidis, John S.; Mukherjee, Rupak

2015-01-01

Children with functional single ventricle heart disease are commonly palliated down a staged clinical pathway toward a Fontan completion procedure (total cavopulmonary connection). The Fontan physiology is fraught with long term complications associated with lower body systemic venous hypertension, eventually resulting in significant morbidity and mortality. The bidirectional Glenn shunt or superior cavopulmonary connection (SCPC) is commonly the transitional stage in single ventricle surgical management and provides excellent palliation. Some studies have demonstrated lower morbidity and mortality with the SCPC when compared with the Fontan. Unfortunately the durability of the SCPC is significantly limited by the development of pulmonary arteriovenous malformations (PAVMs) which have been commonly attributed to the absence of hepatic venous blood flow and the lack of pulsatile flow to the affected lungs. Abnormal angiogenesis has been suggested as a final common pathway to PAVM development. Understanding these fundamental mechanisms through the investigation of angiogenic pathways associated with the pathogenesis of PAVMs would help to develop medical therapies that could prevent or reverse this complication following SCPC. Such therapies could improve the longevity of the SCPC, potentially eliminate or significantly postpone the Fontan completion with its associated complications, and improve long-term survival in children with single ventricle disease. PMID:24758411

Dlx5 Homeodomain: DNA Complex: Structure, Binding and Effect of Mutations Related to Split Hand and Foot Malformation Syndrome

DOE PAGES

Proudfoot, Andrew; Axelrod, Herbert L.; Geralt, Michael; ...

2016-01-29

The Dlx5 homeodomain is a transcription factor related to the Drosophila Distal-less gene that is associated with breast and lung cancer, lymphoma, Rett syndrome and osteoporosis in humans. Mutations in the DLX5 gene have been linked to deficiencies in craniofacial and limb development in higher eukaryotes, including Split Hand and Foot Malformation-1 (SHFM-1) in humans. Our characterization of a Dlx5 homeodomain–(CGACTAATTAGTCG) 2 complex by NMR spectroscopy paved the way for determination of its crystal structure at 1.85 Å resolution that enabled rationalization of the effects of disease-related mutations on the protein function. A remarkably subtle mutation, Q186H, is linked tomore » SHFM-1; this change likely affects affinity of DNA binding by disrupting water-mediated interactions with the DNA major groove. A more subtle effect is implicated for the Q178P mutation, which is not in direct contact with the DNA. Our data indicate that these mutations diminish the ability of the Dlx5 homeodomain to recognize and bind target DNAs, and likely destabilize the formation of functional complexes.« less

The problem of vaginismus with congenital malformation of the genital tract.

PubMed

Jarząbek-Bielecka, Grażyna; Pisarska-Krawczyk, Magdalena; Kędzia, Witold; Mizgier, Małgorzata; Friebe, Zbigniew

2016-05-31

The persistent or recurrent difficulties of the woman to allow vaginal entry of a penis, a finger, and/or any object, despite the woman's expressed wish to do so" is vaginismus. Early traumatic sexual experiences (e.g. sexual abuse), religious orthodoxy, low self-esteem and body image, negative attitudes about sexuality, lack of knowledge about sex and fear responses are some of the traditional etiological correlates of vaginismus. Vaginismus is largely a diagnosis of exclusion. An interview is crucial in differentiating the causes of this disease and it should involve the following key questions: -whether the contraction of the vaginal muscles was recorded from the first sexual contact and still remains a need for sexual satisfaction is achieved without relations vaginal or -symptom occurs for some time and what circumstances it bound or -contraction of the muscles is independent of the will, reflex and is at the very idea of sexual intercourse, and -that the contraction of the vaginal muscles occurs when you try to enter the member into the vagina which is very painful. The physical, gynecological and sexuological examinations exclude local causes of the disease. The mainstay of treatment in the majority of cases is psychosexual support. The cause of organic vaginismus is congenital malformation of the genital tract. It results from abnormal development of genital paramesonephric (Müllerian) ducts and the urogenital sinus, which are structures involved in the process of oviduct, uterus, and vagina organogenesis. This has strong implications in the practices of gynecology and sexuology in general, not only in adolescent gynecology and sexuology. Vaginismus with congenital malformation is an important problem in these fields.

Syndromology: an updated conceptual overview. VI. Molecular and biochemical aspects of dysmorphology.

PubMed

Cohen, M M

1989-12-01

The role of chance using a stochastic single gene model has been shown to generate a continuous liability curve resembling that obtained from a multifactorial threshold model. Segregation of some malformations may be explained by a single defective gene that predisposes to, but does not necessarily result in, the malformation. Low penetrance and remarkably variable expressivity that characterize a number of presumed autosomal dominant malformation syndromes are possibly reflections of specific stochastic influences that are intrinsic to the embryonic process itself. Gene analysis is discussed and illustrated. Using polymorphic DNA probes to study cleft palate and ankyloglossia in males and ankyloglossia only in females in a large Icelandic family, the responsible gene was found to be located on the long arm of the X chromosome in the Xq21.1 region. In addition to gene analysis, some of the implications of transgenic analysis using mice are discussed. Among disorders of collagen metabolism, both the osteogenesis imperfectas and the Ehlers-Danlos syndromes are shown to represent genetically heterogeneous groups of connective tissue disorders. The days of thinking about osteogenesis imperfecta as one disorder and the Ehlers-Danlos syndrome as another are a thing of the past; persistence of such thinking is erroneous and misleading. Of the many disorders affecting bone mineral, the complexities of hypophosphatasia and pseudohypoparathyroidism are singled out for discussion. For lysosomal storage disorders, an overview of the mucopolysaccharidoses is provided. Finally, the recently delineated peroxisomal disorders--hyperpipecolic acidemia, rhizomelic chondrodysplasia, neonatal adrenoleukodystrophy, Zellweger syndrome, and infantile Refsum disease--are known to share a distinctive biochemical phenotype, although fibroblast complementation analysis suggests that some of these disorders are etiologically distinct.

Balloon-Occluded Retrograde Transvenous Embolization of a Pelvic Arteriovenous Malformation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mitsuzaki, Katsuhiko; Yamashita, Yasuyuki; Utsunomiya, Daisuke

1999-11-15

We successfully performed embolization therapy for a pelvic arteriovenous malformation by the retrograde transvenous approach using a liquid embolic material. This malformation was unique in that it had a single draining vein, which allowed this technique employing an occlusion balloon.

Hereditary hemorrhagic telangiectasia patient presenting with brain abscess due to silent pulmonary arteriovenous malformation.

PubMed

Themistocleous, Marios; Giakoumettis, Dimitrios; Mitsios, Andreas; Anagnostopoulos, Christos; Kalyvas, Aristoteles; Koutsarnakis, Christos

2016-01-01

Hereditary hemorrhagic telangiectasia is a rare autosomal dominant inherited disease that is usually complicated by visceral vascular malformations. Patients harboring such malformations are at increased risk of brain abscess formation, which despite advances in diagnostic and surgical methods remains a life threatening medical emergency with high mortality and morbidity rates. In the present report we describe a case of cerebral abscess due to silent pulmonary arteriovenous malformation (AVM) in a young patient previously undiagnosed for hereditary hemorrhagic telangiectasia syndrome (HHT).

Tessier 3 cleft with bilateral anophthalmia: case report and surgical treatment.

PubMed

Sesenna, Enrico; Anghinoni, Marilena L; Modugno, Alessandra C; Magri, Alice S

2012-12-01

Tessier clefts type 3 and 4 are rare. In this paper the authors report on the management of a wide Tessier 3 cleft. There is no standardized protocol or timing of the surgical procedures in this rare disfiguring condition. Generally speaking, the aim is to preserve the function of important anatomical structures (e.g., a seeing eye.) and reconstruct, as best as possible, harmonic facial features. The authors present a "step by step" solution of the malformation pointing out the limitations of the surgical procedures they used and the goals they wanted to obtain. Despite of the uniqueness and the complexity of the pathology, the authors think they obtained reasonable results both in term of function and aesthetics, permitting the patient to be accepted in the social environment. Copyright © 2012 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Craniofacial duplication (diprosopus).

PubMed

Turpin, I M; Furnas, D W; Amlie, R N

1981-02-01

No congenital malformation in infants is more profound than anterior craniofacial duplication. The precise term for this rare anomaly is diprosopus, referring to a fetus with a single trunk, normal limbs, and varying degrees of facial duplication. A search of the world literature produced only 16 cases of diprosopus since 1864. Despite the rarity of this anomaly, three such infants were born in the Southern California area during the past year, making this the largest reported series to date. The three infants were born with two distinctly formed faces. Each had four separate eyes, two mouths, two noses, and two ears with a primitive ear or sinus tract at the plane of fusion. In addition, multiple congenital aberrations existed which involved a variety of internal organs. The pathogenesis of diprosopus is not well understood, but environmental stress early in embryologic development has been suggested as a possible factor. The apparent mechanism is a slowing of pregastrulation oxidation with resultant focal developmental arrests.

Multisegment coloboma in a case of Marfan syndrome: another possible effect of increased TGFβ signaling.

PubMed

LeBlanc, Shannon K; Taranath, Deepa; Morris, Scott; Barnett, Christopher P

2014-02-01

Colobomata are etiologically heterogeneous and may occur as an isolated defect or as a feature of a variety of single-gene disorders, chromosomal syndromes, or malformation syndromes. Although not classically associated with Marfan syndrome, colobomata have been described in several reports of Marfan syndrome, typically involving the lens and rarely involving other ocular structures. While colobomata of the lens have been described in Marfan syndrome, there are very few reports of coloboma involving other ocular structures. We report a newborn boy presenting with coloboma of the iris, lens, retina, and optic disk who was subsequently diagnosed with Marfan syndrome. Marfan syndrome is a disorder of increased TGFβ signaling, and recent work in the mouse model suggests a role for TGFβ signaling in eye development and coloboma formation, suggesting a causal association between Marfan syndrome and coloboma. Crown Copyright © 2014. Published by Mosby, Inc. All rights reserved.

Massive Bilateral Serous Retinal Detachment in a Case of Hypertensive Chorioretinopathy

PubMed Central

Villalba-Pinto, Luis; Hernández-Ortega, M. Ángeles; de los Mozos, F. Javier Lavid; Pascual-Camps, Isabel; Dolz-Marco, Rosa; Arevalo, J. Fernando; Gallego-Pinazo, Roberto

2014-01-01

Introduction Systemic high blood pressure is related to a variety of retinal manifestations. We present an atypical case of hypertensive chorioretinopathy with massive bilateral serous retinal detachment. Case Report A 26-year-old male with a genitourinary malformation and secondary grade IV chronic kidney failure as well as high blood pressure complained of acute vision loss. Dilated fundus examination evidenced a bilateral serous retinal detachment with macular involvement. The patient was unresponsive to oral antihypertensive therapy and dialysis treatment. The serous retinal detachment progressively decreased after the restoration of dialysis and antihypertensive therapy. The final visual acuity was 0.50 in both eyes. Discussion In cases of serous macular detachment, it is mandatory to rule out different systemic and ocular diseases. The presence of uncontrolled high blood pressure may produce aggressive bilateral retinal changes, thus hypertension must be under early and strict control in order to improve the visual outcomes. PMID:25120474

Prenatal Diagnosis of Persistent Hyperplastic Primary Vitreous: Report of 2 Cases and Review of the Literature.

PubMed

Esmer, Aytul Corbacioglu; Sivrikoz, Tugba Sarac; Gulec, Elif Yilmaz; Sezer, Salim; Kalelioglu, Ibrahim; Has, Recep; Yuksel, Atil

2016-10-01

Persistent hyperplastic primary vitreous is a spectrum of congenital ocular abnormalities characterized by leukocoria, microphthalmia, cataracts, extensive intravitreal hemorrhage, persistence of the hyaloid artery, glaucoma, and retinal detachment. It might be isolated or associated with congenital syndromes such as trisomy 13, Walker-Warburg syndrome, and Norrie disease. We present 2 cases of persistent hyperplastic primary vitreous diagnosed by prenatal sonography in the early third trimester. Bilateral hyperechoic lenses and retinal nonattachment were detected in the sonographic examination of the first case, whereas irregular echogenic bands between the lenses and posterior walls of the eyes were prominent in the second case. In both of the cases, ocular findings were accompanied by intracranial findings, including severe hydrocephalus, an abnormal gyral pattern, and cerebellar hypoplasia, suggesting the diagnosis of Walker-Warburg syndrome. We also present a review of the literature regarding the prenatal diagnosis of this malformation.

The Sony PlayStation II EyeToy: low-cost virtual reality for use in rehabilitation.

PubMed

Rand, Debbie; Kizony, Rachel; Weiss, Patrice Tamar L

2008-12-01

The objective of this study was to investigate the potential of using a low-cost video-capture virtual reality (VR) platform, the Sony PlayStation II EyeToy, for the rehabilitation of older adults with disabilities. This article presents three studies that were carried out to provide information about the EyeToy's potential for use in rehabilitation. The first study included the testing of healthy young adults (N = 34) and compared their experiences using the EyeToy with those using GestureTek's IREX VR system in terms of a sense of presence, level of enjoyment, control, success, and perceived exertion. The second study aimed to characterize the VR experience of healthy older adults (N = 10) and to determine the suitability and usability of the EyeToy for this population and the third study aimed to determine the feasibility of the EyeToy for use by individuals (N = 12) with stroke at different stages. The implications of these three studies for applying the system to rehabilitation are discussed.

The impact of fatigue on latent print examinations as revealed by behavioral and eye gaze testing.

PubMed

Busey, Thomas; Swofford, Henry J; Vanderkolk, John; Emerick, Brandi

2015-06-01

Eye tracking and behavioral methods were used to assess the effects of fatigue on performance in latent print examiners. Eye gaze was measured both before and after a fatiguing exercise involving fine-grained examination decisions. The eye tracking tasks used similar images, often laterally reversed versions of previously viewed prints, which holds image detail constant while minimizing prior recognition. These methods, as well as a within-subject design with fine grained analyses of the eye gaze data, allow fairly strong conclusions despite a relatively small subject population. Consistent with the effects of fatigue on practitioners in other fields such as radiology, behavioral performance declined with fatigue, and the eye gaze statistics suggested a smaller working memory capacity. Participants also terminated the search/examination process sooner when fatigued. However, fatigue did not produce changes in inter-examiner consistency as measured by the Earth Mover Metric. Implications for practice are discussed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Induction of mortality and malformation in Xenopus laevis embryos by water sources associated with field frog deformities.

PubMed

Burkhart, J G; Helgen, J C; Fort, D J; Gallagher, K; Bowers, D; Propst, T L; Gernes, M; Magner, J; Shelby, M D; Lucier, G

1998-12-01

Water samples from several ponds in Minnesota were evaluated for their capacity to induce malformations in embryos of Xenopus laevis. The FETAX assay was used to assess the occurrence of malformations following a 96-hr period of exposure to water samples. These studies were conducted following reports of high incidences of malformation in natural populations of frogs in Minnesota wetlands. The purpose of these studies was to determine if a biologically active agent(s) was present in the waters and could be detected using the FETAX assay. Water samples from ponds with high incidences of frog malformations (affected sites), along with water samples from ponds with unaffected frog populations (reference sites), were studied. Initial experiments clearly showed that water from affected sites induced mortality and malformation in Xenopus embryos, while water from reference sites had little or no effect. Induction of malformation was dose dependent and highly reproducible, both with stored samples and with samples taken at different times throughout the summer. The biological activity of the samples was reduced or eliminated when samples were passed through activated carbon. Limited evidence from these samples indicates that the causal factor(s) is not an infectious organism nor are ion concentrations or metals responsible for the effects observed. Results do indicate that the water matrix has a significant effect on the severity of toxicity. Based on the FETAX results and the occurrence of frog malformations observed in the field, these studies suggest that water in the affected sites contains one or more unknown agents that induce developmental abnormalities in Xenopus. These same factors may contribute to the increased incidence of malformation in native species.

Induction of mortality and malformation in Xenopus laevis embryos by water sources associated with field frog deformities.

PubMed Central

Burkhart, J G; Helgen, J C; Fort, D J; Gallagher, K; Bowers, D; Propst, T L; Gernes, M; Magner, J; Shelby, M D; Lucier, G

1998-01-01

Water samples from several ponds in Minnesota were evaluated for their capacity to induce malformations in embryos of Xenopus laevis. The FETAX assay was used to assess the occurrence of malformations following a 96-hr period of exposure to water samples. These studies were conducted following reports of high incidences of malformation in natural populations of frogs in Minnesota wetlands. The purpose of these studies was to determine if a biologically active agent(s) was present in the waters and could be detected using the FETAX assay. Water samples from ponds with high incidences of frog malformations (affected sites), along with water samples from ponds with unaffected frog populations (reference sites), were studied. Initial experiments clearly showed that water from affected sites induced mortality and malformation in Xenopus embryos, while water from reference sites had little or no effect. Induction of malformation was dose dependent and highly reproducible, both with stored samples and with samples taken at different times throughout the summer. The biological activity of the samples was reduced or eliminated when samples were passed through activated carbon. Limited evidence from these samples indicates that the causal factor(s) is not an infectious organism nor are ion concentrations or metals responsible for the effects observed. Results do indicate that the water matrix has a significant effect on the severity of toxicity. Based on the FETAX results and the occurrence of frog malformations observed in the field, these studies suggest that water in the affected sites contains one or more unknown agents that induce developmental abnormalities in Xenopus. These same factors may contribute to the increased incidence of malformation in native species. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:9831545

Classification of Newborn Ear Malformations and their Treatment with the EarWell Infant Ear Correction System.

PubMed

Daniali, Lily N; Rezzadeh, Kameron; Shell, Cheryl; Trovato, Matthew; Ha, Richard; Byrd, H Steve

2017-03-01

A single practice's treatment protocol and outcomes following molding therapy on newborn ear deformations and malformations with the EarWell Infant Ear Correction System were reviewed. A classification system for grading the severity of constricted ear malformations was created on the basis of anatomical findings. A retrospective chart/photograph review of a consecutive series of infants treated with the EarWell System from 2011 to 2014 was undertaken. The infants were placed in either deformation or malformation groups. Three classes of malformation were identified. Data regarding treatment induction, duration of treatment, and quality of outcome were collected for all study patients. One hundred seventy-five infant ear malformations and 303 infant ear deformities were treated with the EarWell System. The average age at initiation of treatment was 12 days; the mean duration of treatment was 37 days. An average of six office visits was required. Treated malformations included constricted ears [172 ears (98 percent)] and cryptotia [three ears (2 percent)]. Cup ear (34 ears) was considered a constricted malformation, in contrast to the prominent ear deformity. Constricted ears were assigned to one of three classes, with each subsequent class indicating increasing severity: class I, 77 ears (45 percent); class II, 81 ears (47 percent); and class III, 14 ears (8 percent). Molding therapy with the EarWell System reduced the severity by an average of 1.2 points (p < 0.01). Complications included minor superficial excoriations and abrasions. The EarWell System was shown to be effective in eliminating or reducing the need for surgery in all but the most severe malformations. Therapeutic, IV.

Trends over time in congenital malformations in live-born children conceived after assisted reproductive technology.

PubMed

Henningsen, Anna-Karina A; Bergh, Christina; Skjaerven, Rolv; Tiitinen, Aila; Wennerholm, Ulla-Britt; Romundstad, Liv B; Gissler, Mika; Opdahl, Signe; Nyboe Andersen, Anders; Lidegaard, Øjvind; Forman, Julie L; Pinborg, Anja

2018-07-01

Children born after assisted reproductive technology, particularly singletons, have been shown to have an increased risk of congenital malformations compared with children born after spontaneous conception. We wished to study whether there has been a change in the past 20 years in the risk of major congenital malformations in children conceived after assisted reproductive technology compared with children spontaneously conceived. Population-based cohort study including 90 201 assisted reproductive technology children and 482 552 children spontaneously conceived, born in Denmark, Finland, Norway and Sweden. Both singletons and twins born after in vitro fertilization, intracytoplasmatic sperm injection and frozen embryo transfer were included. Data on children were taken from when the national Nordic assisted reproductive technology registries were established until 2007. Multiple logistic regression analyses were used to estimate the risks and adjusted odds ratios for congenital malformations in four time periods: 1988-1992, 1993-1997, 1998-2002 and 2003-2007. Only major malformations were included. The absolute risk for singletons of being born with a major malformation was 3.4% among assisted reproductive technology children vs. 2.9% among children spontaneously conceived during the study period. The relative risk of being born with a major congenital malformation between all assisted reproductive technology children and children spontaneously conceived remained similar through all four time periods (p = 0.39). However, we found that over time the number of children diagnosed with a major malformation increased in both groups across all four time periods. When comparing children conceived after assisted reproductive technology and spontaneously conceived, the relative risk of being born with a major congenital malformation did not change during the study period. © 2018 Nordic Federation of Societies of Obstetrics and Gynecology.

RASA1 analysis guides management in a family with capillary malformation-arteriovenous malformation

PubMed Central

Flore, Leigh Anne; Leon, Eyby; Maher, Tom A.; Milunsky, Jeff M.

2012-01-01

Capillary malformation-arteriovenous malformation (CM-AVM; MIM 60354) is an autosomal dominant disorder characterized by multifocal cutaneous capillary malformations, often in association with fast-flow vascular lesions, which may be cutaneous, subcutaneous, intramuscular, intraosseus, or cerebral arteriovenous malformations or arteriovenous fistulas. CM-AVM results from heterozygous mutations in the RASA1 gene. Capillary malformations of the skin are common, and clinical examination alone may not be able to definitively diagnose-or exclude- CM-AVM. We report a family in which the proband was initially referred for a genetic evaluation in the neonatal period because of the presence of a cardiac murmur and minor dysmorphic features. Both he and his mother were noted to have multiple capillary malformations on the face, head, and extremities. Echocardiography revealed dilated head and neck vessels and magnetic resonance imaging and angiography of the brain revealed a large infratentorial arteriovenous fistula, for which he has had two embolization procedures. RASA1 sequence analysis revealed a heterozygous mutation, confirming his diagnosis of CM-AVM. We established targeted mutation analysis for the proband's mother and sister, the latter of whom is a healthy 3-year-old whose only cutaneous finding is a facial capillary malformation. This revealed that the proband's mother is also heterozygous for the RASA1 mutation, but his sister is negative. Consequently, his mother will undergo magnetic resonance imaging and angiography screening for intracranial and spinal fast-flow lesions, while his sister will require no imaging or serial evaluations. Targeted mutation analysis has been offered to additional maternal family members. This case illustrates the benefit of molecular testing in diagnosis and making screening recommendations for families with CM-AVM. PMID:27625812

RASA1 analysis guides management in a family with capillary malformation-arteriovenous malformation.

PubMed

Flore, Leigh Anne; Leon, Eyby; Maher, Tom A; Milunsky, Jeff M

2012-06-01

Capillary malformation-arteriovenous malformation (CM-AVM; MIM 60354) is an autosomal dominant disorder characterized by multifocal cutaneous capillary malformations, often in association with fast-flow vascular lesions, which may be cutaneous, subcutaneous, intramuscular, intraosseus, or cerebral arteriovenous malformations or arteriovenous fistulas. CM-AVM results from heterozygous mutations in the RASA1 gene. Capillary malformations of the skin are common, and clinical examination alone may not be able to definitively diagnose-or exclude- CM-AVM. We report a family in which the proband was initially referred for a genetic evaluation in the neonatal period because of the presence of a cardiac murmur and minor dysmorphic features. Both he and his mother were noted to have multiple capillary malformations on the face, head, and extremities. Echocardiography revealed dilated head and neck vessels and magnetic resonance imaging and angiography of the brain revealed a large infratentorial arteriovenous fistula, for which he has had two embolization procedures. RASA1 sequence analysis revealed a heterozygous mutation, confirming his diagnosis of CM-AVM. We established targeted mutation analysis for the proband's mother and sister, the latter of whom is a healthy 3-year-old whose only cutaneous finding is a facial capillary malformation. This revealed that the proband's mother is also heterozygous for the RASA1 mutation, but his sister is negative. Consequently, his mother will undergo magnetic resonance imaging and angiography screening for intracranial and spinal fast-flow lesions, while his sister will require no imaging or serial evaluations. Targeted mutation analysis has been offered to additional maternal family members. This case illustrates the benefit of molecular testing in diagnosis and making screening recommendations for families with CM-AVM.

Biology of vascular malformations of the brain.

PubMed

Leblanc, Gabrielle G; Golanov, Eugene; Awad, Issam A; Young, William L

2009-12-01

This review discusses recent research on the genetic, molecular, cellular, and developmental mechanisms underlying the etiology of vascular malformations of the brain (VMBs), including cerebral cavernous malformation, sporadic brain arteriovenous malformation, and the arteriovenous malformations of hereditary hemorrhagic telangiectasia. Summary of Review- The identification of gene mutations and genetic risk factors associated with cerebral cavernous malformation, hereditary hemorrhagic telangiectasia, and sporadic arteriovenous malformation has enabled the development of animal models for these diseases and provided new insights into their etiology. All of the genes associated with VMBs to date have known or plausible roles in angiogenesis and vascular remodeling. Recent work suggests that the angiogenic process most severely disrupted by VMB gene mutation is that of vascular stabilization, the process whereby vascular endothelial cells form capillary tubes, strengthen their intercellular junctions, and recruit smooth muscle cells to the vessel wall. In addition, there is now good evidence that in some cases, cerebral cavernous malformation lesion formation involves a genetic 2-hit mechanism in which a germline mutation in one copy of a cerebral cavernous malformation gene is followed by a somatic mutation in the other copy. There is also increasing evidence that environmental second hits can produce lesions when there is a mutation to a single allele of a VMB gene. Recent findings begin to explain how mutations in VMB genes render vessels vulnerable to rupture when challenged with other inauspicious genetic or environmental factors and have suggested candidate therapeutics. Understanding of the cellular mechanisms of VMB formation and progression in humans has lagged behind that in animal models. New knowledge of lesion biology will spur new translational work. Several well-established clinical and genetic database efforts are already in place, and further progress will be facilitated by collaborative expansion and standardization of these.

Atlas Assimilation Patterns in Different Types of Adult Craniocervical Junction Malformations.

PubMed

Ferreira, Edson Dener Zandonadi; Botelho, Ricardo Vieira

2015-11-01

This is a cross-sectional analysis of resonance magnetic images of 111 patients with craniocervical malformations and those of normal subjects. To test the hypothesis that atlas assimilation is associated with basilar invagination (BI) and atlas's anterior arch assimilation is associated with craniocervical instability and type I BI. Atlas assimilation is the most common malformation in the craniocervical junction. This condition has been associated with craniocervical instability and BI in isolated cases. We evaluated midline Magnetic Resonance Images (MRIs) (and/or CT scans) from patients with craniocervical junction malformation and normal subjects. The patients were separated into 3 groups: Chiari type I malformation, BI type I, and type II. The atlas assimilations were classified according to their embryological origins as follows: posterior, anterior, and both arches assimilation. We studied the craniometric values of 111 subjects, 78 with craniocervical junction malformation and 33 without malformations. Of the 78 malformations, 51 patients had Chiari type I and 27 had BI, of whom 10 presented with type I and 17 with type II BI. In the Chiari group, 41 showed no assimilation of the atlas. In the type I BI group, all patients presented with anterior arch assimilation, either in isolation or associated with assimilation of the posterior arch. 63% of the patients with type II BI presented with posterior arch assimilation, either in isolation or associated with anterior arch assimilation. In the control group, no patients had atlas assimilation. Anterior atlas assimilation leads to type I BI. Posterior atlas assimilation more frequently leads to type II BI. Separation in terms of anterior versus posterior atlas assimilation reflects a more accurate understanding of the clinical and embryological differences in craniocervical junction malformations. N/A.

Placenta previa and risk of major congenital malformations among singleton births in Finland.

PubMed

Kancherla, Vijaya; Räisänen, Sari; Gissler, Mika; Kramer, Michael R; Heinonen, Seppo

2015-06-01

Placenta previa has been associated with adverse birth outcomes, but its association with congenital malformations is inconclusive. We examined the association between placenta previa and major congenital malformations among singleton births in Finland. We performed a retrospective population register-based study on all singletons born at or after 22+0 weeks of gestation in Finland during 2000 to 2010. We linked three national health registers: the Finnish Medical Birth Register, the Hospital Discharge Register, and the Register of Congenital Malformations, and examined several demographic and clinical characteristics among women with and without placenta previa, in association with major congenital malformations. We estimated adjusted odds ratios and 95% confidence intervals using multivariable logistic regression models. The prevalence of placenta previa was estimated as 2.65 per 1000 singleton births in Finland (95% confidence interval, 2.53-2.79). Overall, 6.2% of women with placenta previa delivered a singleton infant with a major congenital malformation, compared with 3.8% of unaffected women (p ≤ 0.001). Placenta previa was positively associated with almost 1.6-fold increased risk of major congenital malformations in the offspring, after controlling for maternal age, parity, fetal sex, smoking, socio-economic status, chorionic villus biopsy, In vitro fertilization, pre-existing diabetes, depression, preeclampsia, and prior caesarean section (adjusted odds ratio = 1.55; 95% confidence interval, 1.27-1.90). Using a large population-based study, we found that placenta previa was weakly, but significantly associated with an increased risk of major congenital malformations in singleton births. Future studies should examine the association between placenta previa and individual types of congenital malformations, specifically in high-risk pregnancies. © 2015 Wiley Periodicals, Inc.

Antipsychotic Use in Pregnancy and the Risk for Congenital Malformations

PubMed Central

Huybrechts, Krista F.; Hernández-Díaz, Sonia; Patorno, Elisabetta; Desai, Rishi J.; Mogun, Helen; Dejene, Sara Z.; Cohen, Jacqueline M.; Panchaud, Alice; Cohen, Lee; Bateman, Brian T.

2017-01-01

IMPORTANCE The frequency of antipsychotic (AP) use during pregnancy has approximately doubled during the last decade. However, little is known about their safety for the developing fetus, and concerns have been raised about a potential association with congenital malformations. OBJECTIVE To examine the risk for congenital malformations overall and cardiac malformations associated with first-trimester exposure to APs. DESIGN, SETTING, AND PARTICIPANTS This nationwide sample of 1 360 101 pregnant women enrolled in Medicaid with a live-born infant constituted the pregnancy cohort nested in the Medicaid Analytic Extract database, which included data from January 1, 2000, to December 31, 2010. Participants were enrolled in Medicaid from 3 months before their last menstrual period through at least 1 month after delivery. Relative risks (RRs) were estimated using generalized linear models with fine stratification on the propensity score to control for the underlying psychiatric disorders and other potential confounders. Data were analyzed during 2015. EXPOSURES Use of APs during the first trimester, the etiologically relevant period for organogenesis. MAIN OUTCOMES AND MEASURES Major congenital malformations overall and cardiac malformations identified during the first 90 days after delivery. RESULTS Of the 1 341 715 pregnancies that met inclusion criteria (mean [SD] age of women, 24.02 [5.77] years), 9258 (0.69%) filled at least 1 prescription for an atypical AP and 733 (0.05%) filled at least 1 prescription for a typical AP during the first trimester. Overall, 32.7 (95% CI, 32.4–33.0) per 1000 births not exposed to APs were diagnosed with congenital malformations compared with 44.5 (95% CI, 40.5–48.9) per 1000 births exposed to atypical and 38.2 (95% CI, 26.6–54.7) per 1000 births exposed to typical APs. Unadjusted analyses suggested an increased risk for malformations overall for atypical APs (RR, 1.36; 95% CI, 1.24–1.50) but not for typical APs (RR, 1.17; 95% CI, 0.81–1.68). After confounding adjustment, the RR was reduced to 1.05 (95% CI, 0.96–1.16) for atypical APs and 0.90 (95% CI, 0.62–1.31) for typical APs. The findings for cardiac malformations were similar. For the individual agents examined, a small increased risk in overall malformations (RR, 1.26; 95% CI, 1.02–1.56) and cardiac malformations (RR, 1.26; 95% CI, 0.88–1.81) was found for risperidone that was independent of measured confounders. CONCLUSIONS AND RELEVANCE Evidence from this large study suggests that use of APs early in pregnancy generally does not meaningfully increase the risk for congenital malformations overall or cardiac malformations in particular. The small increase in the risk for malformations observed with risperidone requires additional study. PMID:27540849

Monocular Perceptual Deprivation from Interocular Suppression Temporarily Imbalances Ocular Dominance.

PubMed

Kim, Hyun-Woong; Kim, Chai-Youn; Blake, Randolph

2017-03-20

Early visual experience sculpts neural mechanisms that regulate the balance of influence exerted by the two eyes on cortical mechanisms underlying binocular vision [1, 2], and experience's impact on this neural balancing act continues into adulthood [3-5]. One recently described, compelling example of adult neural plasticity is the effect of patching one eye for a relatively short period of time: contrary to intuition, monocular visual deprivation actually improves the deprived eye's competitive advantage during a subsequent period of binocular rivalry [6-8], the robust form of visual competition prompted by dissimilar stimulation of the two eyes [9, 10]. Neural concomitants of this improvement in monocular dominance are reflected in measurements of brain responsiveness following eye patching [11, 12]. Here we report that patching an eye is unnecessary for producing this paradoxical deprivation effect: interocular suppression of an ordinarily visible stimulus being viewed by one eye is sufficient to produce shifts in subsequent predominance of that eye to an extent comparable to that produced by patching the eye. Moreover, this imbalance in eye dominance can also be induced by prior, extended viewing of two monocular images differing only in contrast. Regardless of how shifts in eye dominance are induced, the effect decays once the two eyes view stimuli equal in strength. These novel findings implicate the operation of interocular neural gain control that dynamically adjusts the relative balance of activity between the two eyes [13, 14]. Copyright © 2017 Elsevier Ltd. All rights reserved.

Physiological implications of the abnormal absence of the parietal foramen in a late Permian cynodont (Therapsida)

NASA Astrophysics Data System (ADS)

Benoit, Julien; Abdala, Fernando; Van den Brandt, Marc J.; Manger, Paul R.; Rubidge, Bruce S.

2015-12-01

The third eye (pineal eye), an organ responsible for regulating exposure to sunlight in extant ectotherms, is located in an opening on the dorsal surface of the skull, the parietal foramen. The parietal foramen is absent in extant mammals but often observed in basal therapsids, the stem-group to true mammals. Here, we report the absence of the parietal foramen in a specimen of Cynosaurus suppostus, a Late Permian cynodont from South Africa (SA). Comparison with Procynosuchus delaharpeae, a contemporaneous non-mammalian cynodont from SA, demonstrates that the absence of this foramen is an abnormal condition for such a basal species. Because seasonality was marked during the Late Permian in SA, it is proposed that the third eye was functionally redundant in Cynosaurus, possibly due to the acquisition of better thermoregulation or the evolution of specialized cells in the lateral eyes to compensate for the role of the third eye.

A fuzzy system for helping medical diagnosis of malformations of cortical development.

PubMed

Alayón, Silvia; Robertson, Richard; Warfield, Simon K; Ruiz-Alzola, Juan

2007-06-01

Malformations of the cerebral cortex are recognized as a common cause of developmental delay, neurological deficits, mental retardation and epilepsy. Currently, the diagnosis of cerebral cortical malformations is based on a subjective interpretation of neuroimaging characteristics of the cerebral gray matter and underlying white matter. There is no automated system for aiding the observer in making the diagnosis of a cortical malformation. In this paper a fuzzy rule-based system is proposed as a solution for this problem. The system collects the available expert knowledge about cortical malformations and assists the medical observer in arriving at a correct diagnosis. Moreover, the system allows the study of the influence of the various factors that take part in the decision. The evaluation of the system has been carried out by comparing the automated diagnostic algorithm with known case examples of various malformations due to abnormal cortical organization. An exhaustive evaluation of the system by comparison with published cases and a ROC analysis is presented in the paper.

Analysis of Lethality and Malformations During Zebrafish (Danio rerio) Development.

PubMed

Raghunath, Azhwar; Perumal, Ekambaram

2018-01-01

The versatility offered by zebrafish (Danio rerio) makes it a powerful and an attractive vertebrate model in developmental toxicity and teratogenicity assays. Apart from the newly introduced chemicals as drugs, xenobiotics also induce abnormal developmental abnormalities and congenital malformations in living organisms. Over the recent decades, zebrafish embryo/larva has emerged as a potential tool to test teratogenicity potential of these chemicals. Zebrafish responds to compounds as mammals do as they share similarities in their development, metabolism, physiology, and signaling pathways with that of mammals. The methodology used by the different scientists varies enormously in the zebrafish embryotoxicity test. In this chapter, we present methods to assess lethality and malformations during zebrafish development. We propose two major malformations scoring systems: binomial and relative morphological scoring systems to assess the malformations in zebrafish embryos/larvae. Based on the scoring of the malformations, the test compound can be classified as a teratogen or a nonteratogen and its teratogenic potential is evaluated.

Neurodevelopmental Malformations of the Cerebellar Vermis in Genetically Engineered Rats.

PubMed

Ramos, Raddy L; Van Dine, Sarah E; Gilbert, Mary E; Leheste, Joerg R; Torres, German

2015-12-01

The cerebellar vermis is particularly vulnerable to neurodevelopmental malformations in humans and rodents. Sprague-Dawley, and Long-Evans rats exhibit spontaneous cerebellar malformations consisting of heterotopic neurons and glia in the molecular layer of the vermis. Malformations are almost exclusively found along the primary fissure and are indicative of deficits of neuronal migration during cerebellar development. In the present report, we test the prediction that genetically engineered rats on Sprague-Dawley or Long-Evans backgrounds will also exhibit the same cerebellar malformations. Consistent with our hypothesis, we found that three different transgenic lines on two different backgrounds had cerebellar malformations. Heterotopia in transgenic rats had identical cytoarchitecture as that observed in wild-type rats including altered morphology of Bergmann glia. In light of the possibility that heterotopia could affect results from behavioral studies, these data suggest that histological analyses be performed in studies of cerebellar function or development when using genetically engineered rats on these backgrounds in order to have more careful interpretation of experimental findings.

A Fuzzy System for Helping Medical Diagnosis of Malformations of Cortical Development

PubMed Central

Alayón, Silvia; Robertson, Richard; Warfield, Simon K.; Ruiz-Alzola, Juan

2007-01-01

Malformations of the cerebral cortex are recognized as a common cause of developmental delay, neurological deficits, mental retardation and epilepsy. Currently, the diagnosis of cerebral cortical malformations is based on a subjective interpretation of neuroimaging characteristics of the cerebral gray matter and underlying white matter. There is no automated system for aiding the observer in making the diagnosis of a cortical malformation. In this paper a fuzzy rule-based system is proposed as a solution for this problem. The system collects the available expert knowledge about cortical malformations and assists the medical observer in arriving at a correct diagnosis. Moreover, the system allows the study of the influence of the various factors that take part in the decision. The evaluation of the system has been carried out by comparing the automated diagnostic algorithm with known case examples of various malformations due to abnormal cortical organization. An exhaustive evaluation of the system by comparison with published cases and a ROC analysis is presented in the paper. PMID:17197247

Liquid nitrogen cryotherapy for lip mucous membrane venous malformation in infants.

PubMed

Zhang, Da-Ming; Wang, You-Yuan; Lin, Zhao-Yu; Yang, Zhao-Hui; Chen, Wei-Liang

2015-03-01

Lip mucous membrane venous malformations are common benign lesions in infants. This clinical study evaluates the efficacy and safety of liquid nitrogen cryotherapy used to treat this condition. A total of 84 pediatric patients undergoing liquid nitrogen cryotherapy for venous malformations involving the lips were reviewed, with 45 males and 39 females treated. The overall median age at mucous membrane venous malformation diagnosis was 5.6 months (range 2-18 months). The venous malformations involved the vermilion of the lower lip in 44 cases, the vermilion of the upper lip in 31 cases, and both vermilions in 9 cases. No complications due to anesthesia occurred. After a follow-up period of 2-38 months (mean 25 months), 65 lesions (77.4 %) were completely involuted, 14 lesions (16.7 %) were mostly involuted, and 5 lesions (5.9 %) were partially involuted; no lesions showed a minor amount of involution. Liquid nitrogen cryotherapy is an effective, simple, and safe management tool for mucous membrane venous malformations of the lip in infants.

Comparative transcriptomic analyses of normal and malformed flowers in sugar apple (Annona squamosa L.) to identify the differential expressed genes between normal and malformed flowers.

PubMed

Liu, Kaidong; Li, Haili; Li, Weijin; Zhong, Jundi; Chen, Yan; Shen, Chenjia; Yuan, Changchun

2017-10-23

Sugar apple (Annona squamosa L.), a popular fruit with high medicinal and nutritional properties, is widely cultivated in tropical South Asia and America. The malformed flower is a major cause for a reduction in production of sugar apple. However, little information is available on the differences between normal and malformed flowers of sugar apple. To gain a comprehensive perspective on the differences between normal and malformed flowers of sugar apple, cDNA libraries from normal and malformation flowers were prepared independently for Illumina sequencing. The data generated a total of 70,189,896 reads that were integrated and assembled into 55,097 unigenes with a mean length of 783 bp. A large number of differentially expressed genes (DEGs) were identified. Among these DEGs, 701 flower development-associated transcript factor encoding genes were included. Furthermore, a large number of flowering- and hormone-related DEGs were also identified, and most of these genes were down-regulated expressed in the malformation flowers. The expression levels of 15 selected genes were validated using quantitative-PCR. The contents of several endogenous hormones were measured. The malformed flowers displayed lower endogenous hormone levels compared to the normal flowers. The expression data as well as hormone levels in our study will serve as a comprehensive resource for investigating the regulation mechanism involved in floral organ development in sugar apple.

Radiation-free quantification of head malformations in craniosynostosis patients from 3D photography

NASA Astrophysics Data System (ADS)

Tu, Liyun; Porras, Antonio R.; Oh, Albert; Lepore, Natasha; Mastromanolis, Manuel; Tsering, Deki; Paniagua, Beatriz; Enquobahrie, Andinet; Keating, Robert; Rogers, Gary F.; Linguraru, Marius George

2018-02-01

The evaluation of cranial malformations plays an essential role both in the early diagnosis and in the decision to perform surgical treatment for craniosynostosis. In clinical practice, both cranial shape and suture fusion are evaluated using CT images, which involve the use of harmful radiation on children. Three-dimensional (3D) photography offers noninvasive, radiation-free, and anesthetic-free evaluation of craniofacial morphology. The aim of this study is to develop an automated framework to objectively quantify cranial malformations in patients with craniosynostosis from 3D photography. We propose a new method that automatically extracts the cranial shape by identifying a set of landmarks from a 3D photograph. Specifically, it registers the 3D photograph of a patient to a reference template in which the position of the landmarks is known. Then, the method finds the closest cranial shape to that of the patient from a normative statistical shape multi-atlas built from 3D photographs of healthy cases, and uses it to quantify objectively cranial malformations. We calculated the cranial malformations on 17 craniosynostosis patients and we compared them with the malformations of the normative population used to build the multi-atlas. The average malformations of the craniosynostosis cases were 2.68 +/- 0.75 mm, which is significantly higher (p<0.001) than the average malformations of 1.70 +/- 0.41 mm obtained from the normative cases. Our approach can support the quantitative assessment of surgical procedures for cranial vault reconstruction without exposing pediatric patients to harmful radiation.

Are congenital malformations more frequent in fetuses with intrahepatic persistent right umbilical vein? A comparative study.

PubMed

Adiego-Calvo, Ignacio; Saviron-Cornudella, Ricardo; Martinez-Payo, Cristina; Rubio-Aranda, Encarna; Sancho-Sauco, Javier; Cisneros-Gimeno, Ana Isabel; Perez-Perez, Pilar; Lerma-Puertas, Diego; Whyte-Orozco, Jaime

2016-12-01

Persistent right umbilical vein (PRUV) is a vascular anomaly where the right umbilical vein remains as the only conduit that returns oxygenated blood to the fetus. It has classically been described as associated with numerous defects. We distinguish the intrahepatic variant (better prognosis) and the extrahepatic variant (associated with worse prognosis). The objective of this study was to compare rates of congenital malformations in fetuses with intrahepatic PRUV (I-PRUV) versus singleton pregnancies without risk factors. A multicenter, crossover design, comparative study was performed between 2003 and 2013 on fetuses diagnosed with I-PRUV (n=56), and singleton pregnancies without congenital malformation risk factors (n=4050). Fifty-six cases of I-PRUV were diagnosed (incidence 1:770). A statistically significant association between I-PRUV and the presence of congenital malformations (odds ratio 4.321; 95% confidence interval 2.15-8.69) was found. This positive association was only observed with genitourinary malformations (odds ratio 3.038; 95% confidence interval 1.08-8.56). Our rate of malformations associated with I-PRUV (17.9%) is similar to previously published rates. I-PRUV has shown a significant increase in the rate of associated malformations, although this association has only been found to be statistically significant in the genitourinary system. Noteworthy is the fact that this comparative study has not pointed to a significant increase in the congenital heart malformation rate. Diagnosis of isolated I-PRUV does not carry a worse prognosis. Copyright © 2016. Published by Elsevier B.V.

Risk of major congenital malformations in relation to maternal overweight and obesity severity: cohort study of 1.2 million singletons.

PubMed

Persson, Martina; Cnattingius, Sven; Villamor, Eduardo; Söderling, Jonas; Pasternak, Björn; Stephansson, Olof; Neovius, Martin

2017-06-14

Objective  To estimate the risks of major congenital malformations in the offspring of mothers who are underweight (body mass index (BMI) <18.5), overweight (BMI 25 to <30), or in obesity classes I (BMI 30 to <35), II (35 to <40), or III (≥40) compared with offspring of normal weight mothers (BMI 18.5 to <25) in early pregnancy. Design  Population based cohort study. Setting  Nationwide Swedish registries. Participants  1 243 957 liveborn singleton infants from 2001 to 2014 in Sweden. Data on maternal and pregnancy characteristics were obtained by individual record linkages. Exposure  Maternal BMI at the first prenatal visit. Main outcome measures  Offspring with any major congenital malformation, and subgroups of organ specific malformations diagnosed during the first year of life. Risk ratios were estimated using generalised linear models adjusted for maternal factors, sex of offspring, and birth year. Results  A total of 43 550 (3.5%) offspring had any major congenital malformation, and the most common subgroup was for congenital heart defects (n=20 074; 1.6%). Compared with offspring of normal weight mothers (risk of malformations 3.4%), the proportions and adjusted risk ratios of any major congenital malformation among the offspring of mothers with higher BMI were: overweight, 3.5% and 1.05 (95% confidence interval 1.02 to 1.07); obesity class I, 3.8% and 1.12 (1.08 to 1.15), obesity class II, 4.2% and 1.23 (1.17 to 1.30), and obesity class III, 4.7% and 1.37 (1.26 to 1.49). The risks of congenital heart defects, malformations of the nervous system, and limb defects also progressively increased with BMI from overweight to obesity class III. The largest organ specific relative risks related to maternal overweight and increasing obesity were observed for malformations of the nervous system. Malformations of the genital and digestive systems were also increased in offspring of obese mothers. Conclusions  Risks of any major congenital malformation and several subgroups of organ specific malformations progressively increased with maternal overweight and increasing severity of obesity. For women who are planning pregnancy, efforts should be encouraged to reduce adiposity in those with a BMI above the normal range. 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.

Growth mixture modelling in families of the Framingham Heart Study

PubMed Central

2009-01-01

Growth mixture modelling, a less explored method in genetic research, addresses unobserved heterogeneity in population samples. We applied this technique to longitudinal data of the Framingham Heart Study. We examined systolic blood pressure (BP) measures in 1060 males from 692 families and detected three subclasses, which varied significantly in their developmental trajectories over time. The first class consisted of 60 high-risk individuals with elevated BP early in life and a steep increase over time. The second group of 131 individuals displayed first normal BP, but showed a significant increase over time and reached high BP values late in their life time. The largest group of 869 individuals could be considered a normative group with normal BP on all exams. To identify genetic modulators for this phenotype, we tested 2,340 single-nucleotide polymorphisms on chromosome 8 for association with the class membership probabilities of our model. The probability of being in Class 1 was significantly associated with a very rare variant (rs1445404) present in only four individuals from four different families located in the coding region of the gene EYA (eyes absent homolog 1 in Drosophila) (p = 1.39 × 10-13). Mutations in EYA are known to cause brachio-oto-renal syndrome, as well as isolated renal malformations. Renal malformations could cause high BP early in life. This result awaits replication; however, it suggests that analyzing genetic data stratified for high-risk subgroups defined by a unique development over time could be useful for the detection of rare mutations in common multi-factorial diseases. PMID:20017979

Somatic KRAS mutation in an infant with linear nevus sebaceous syndrome associated with lymphatic malformations: A case report and literature review.

PubMed

Lihua, Jiang; Feng, Gao; Shanshan, Mao; Jialu, Xu; Kewen, Jiang

2017-11-01

Linear nevus sebaceous syndrome (LNSS) is a rare neurocutaneous syndrome, characterized by nevus sebaceous,central nervous system (CNS), ocular and skeletal abnormalities. The present study describes KRAS somatic mosaic mutation in a case of LNSS with lymphatic malformations (LMs). A 4-month-old female with a clinical diagnosis of LNSS presented with infantile spasms, mental retardation, skull dysplasia, ocular abnormalities, congenital atrial septal defect, and LMs. Cervical ultrasonography revealed a 4.6 × 4.6 × 2.2cm no echo packet with clear boundary in the subcutaneous tissues of the right neck. The neck MRI indicated a cyst in the subcutaneous tissues of the right neck. Whole-exome sequencing revealed a low-level heterozygous mutation of the KRAS gene (c.35C > T; p.G12D, 19%) in the skin lesion sample. This mutation was not present in the blood samples of the patient and her parents. The patient received sclerotherapy with paicibanil (OK-432) injection for the cyst. Following 1 year of treatment, the patient exhibited fewer seizures. The mental and motor development was significantly improved. The patient can currently walk with assistance and speak simple words. LNSS is a rare, congenital neurocutaneous syndrome consisting of a spectrum of abnormalities involving the skin, central nervous system, eyes, LMs and other systems. LNSS can be caused by postzygotic somatic mutation in the RAS family of genes. Multidisciplinary evaluation and treatment is needed. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Massive obesity and hyperphagia in posterior bilateral periventricular heterotopias: case report.

PubMed

Guglielmi, Valeria; Floris, Roberto; D'Adamo, Monica; Garaci, Francesco; Novelli, Giuseppe; Sbraccia, Paolo

2016-03-09

Bilateral posterior periventricular nodular heterotopia PNH is a complex malformation of cortical development with imaging features distinguishing it from classic bilateral PNH associated with filamin (FLNA) mutations. It distinctively consists of variably sized nodules of neurons along the trigones and temporal or occipital horns of the lateral ventricles and spectrum of developmental disorders of the mid-/hindbrain. This association suggests that pPNH is part of a more diffuse process of posterior or infrasylvian brain developmental abnormalities other than just a disorder of neuronal migration. This report describes the first case of an Italian young girl featuring pPNH and severe hyperphagic obesity. At the time of our first examination at age 3 years of age she was severely obese (body mass index, BMI 45.9 Kg/m(2)) and food-seeking behavior in the free-living situation was reported by the relatives. She showed normal linear growth and cognition, but mildly dysmorphic facial traits including deeply-set eyes, prominent zygomatic bones, downturned mouth corners and low-set ears. Over the years, the patient progressively developed further massive weight gain (at age 9 years, her BMI was 60.4 Kg/m(2)) and hyperphagia was confirmed by an ad libitum test meal. During follow-up, she presented limitations in walking capacity and in physical functioning due to the disabling obesity. On the basis of distinctive neuro-radiological findings pPNH was diagnosed, in absence of history of seizures. The present case may contribute to the expansion of the phenotypic expressions of this distinctive complex malformation.

Elevation of autophagy markers in Sjögren syndrome dry eye.

PubMed

Byun, Yong-Soo; Lee, Hyun Jung; Shin, Soojung; Chung, So-Hyang

2017-12-08

Autophagy is known to be implicated in the pathogenesis of Sjögren syndrome (SS), but evidences are limited. We aimed to examine the levels of autophagy markers in tear film and conjunctival epithelial cells from SS dry eye patients, and analyze their correlations with clinical features. Patients with SS dry eye exhibited lower Schirmer values, lower tear breakup time, and higher ocular staining scores. In tears, ATG5 and LC3B-II/I levels were significantly higher in SS dry eye. ATG5 and LC3B-II mRNA in the conjunctiva were also elevated in SS dry eye compared with non-SS dry eye. The immunostaining of conjunctival epithelium showed a punctate pattern of ATG5 and LC3B-II in SS dry eye. These staining patterns were also observed in the lacrimal gland of SS animal models. ATG5 levels in tears and the conjunctival epithelium strongly correlated with ocular staining scores, and one month of topical corticosteroid treatment reduced both ATG5 and LC3B-II/I levels in tear film and the conjunctival epithelium of patients with SS dry eye. Our results suggest that autophagy is enhanced or dysregulated in SS and autophagy markers may be serve as both diagnostic and therapeutic biomarkers in SS dry eye.

INVESTIGATIONS INTO THE CAUSES OF AMPHIBIAN MALFORMATIONS IN THE LAKE CHAMPLAIN BASIN OF NEW ENGLAND (AWARDED PROJECT)

EPA Science Inventory

The concurrent geographic extent and rate of amphibian malformations appear to have markedly increased above background levels in recent years in many states and Canadian provinces as documented by the North American Reporting Center for Amphibian Malformations (www.npwrc.usgs.go...

COMPARING THE EFFECTS OF RETINOIC ACID ON AMPHIBIAN LIMB DEVELOPMENT AND LETHALITY: CHRONIC EXPOSURE RESULTS IN LETHALITY NOT LIMB MALFORMATIONS

EPA Science Inventory

Recently, high frequencies of malformations have been reported in amphibians across the United States. It has been suggested that the malformations may be the result of xenobiotic disruption of retinoid signaling pathways during embryogenesis and tadpole development. Therefore, a...

Definitions and Anatomic Considerations in Chiari I Malformation and Associated Syringomyelia.

PubMed

Tubbs, R Shane

2015-10-01

Current understanding of the hindbrain hernias known as Chiari I malformations is based on more than 100 years of pathologic and clinical experience. Over time, the definition of this finding has been analyzed and altered. The term Chiari I malformation is currently used to describe tonsillar ectopia in a wide range of patients with varying embryonic derailments. This article discusses this malformation, its various definitions, and varied anatomic traits. In addition, the morphology of the commonly associated syringomyelia is reviewed. Copyright © 2015 Elsevier Inc. All rights reserved.

Chiari I malformation as part of the Floating-Harbor syndrome?

PubMed

Kurzbuch, Arthur R; Magdum, Shailendra

2016-12-01

We report the first case of a patient diagnosed with Floating-Harbor syndrome (FHS) and Chiari I malformation. The 3-year-old girl was of proportional short stature, had delay of language development, conductive hearing loss and a high threshold of pain. Diagnosis of Chiari I malformation may be difficult in FHS patients who present with communication problems. Clinicians following patients with FHS should be aware of a possible relation between FHS and Chiari I malformation. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Acquired Chiari malformation secondary to atlantoaxial vertical subluxation in a patient with rheumatoid arthritis combined with atlanto-occipital assimilation.

PubMed

Kimura, Yuiko; Seichi, Atsushi; Gomi, Akira; Kojima, Masahiro; Inoue, Hirokazu; Kimura, Atsushi

2012-01-01

A 65-year-old woman with a history of rheumatoid arthritis presented with a rare case of acquired Chiari malformation secondary to atlantoaxial vertical subluxation, associated with congenital atlanto-occipital assimilation. Syringomyelia and tetraparesis improved immediately after posterior fossa decompression and simultaneous occipito-cervical junction fusion. The progression of acquired Chiari malformation is not well known. We concluded that coexisting assimilation accelerated crowded foramen magnum following atlantoaxial vertical subluxation and induced acquired Chiari malformation over the course of a few years.

Dandy-Walker malformation: a rare association with hypoparathyroidism.

PubMed

Coban, Dilek; Akin, Mustafa Ali; Kurtoglu, Selim; Oktem, Suat; Yikilmaz, Ali

2010-12-01

Dandy-Walker malformation is characterized by cystic dilatation of the fourth ventricle and an enlarged posterior cranial fossa with upward displacement of the tentorium, lateral sinuses, and torcular, with agenesis or hypoplasia of the cerebellar vermis. Dandy-Walker malformation occurs in approximately the 4th week of gestation and is associated with various abnormalities involving the cardiac, skeletal, genitourinary, and gastrointestinal systems. The parathyroid gland also forms in the 3rd and 4th gestational weeks. Reported here is the case of a male infant with Dandy-Walker malformation with ventricular and atrial septal defect, unilateral renal agenesis, and hypoparathyroidism. To our knowledge, this rare association with neural crest events during the development of Dandy-Walker malformation has not been reported previously. Crown Copyright © 2010. Published by Elsevier Inc. All rights reserved.

Isolated unilateral trismus as a presentation of Chiari malformation: case report.

PubMed

Feinberg, Michelle; Babington, Parker; Sood, Shawn; Keating, Robert

2016-05-01

The authors present a case of Chiari malformation manifesting as isolated trismus, describe the typical symptoms associated with Chiari malformation, and discuss the potential anatomical causes for this unique presentation. A 3-year-old boy presented with inability to open his jaw for 6 weeks with associated significant weight loss. The results of medical and radiological evaluation were negative except for Type I Chiari malformation with cerebellar tonsils 12 mm below the level of the foramen magnum. The patient underwent Chiari decompression surgery. Postoperatively, his ability to open his mouth was significantly improved, allowing resumption of a regular diet. Postoperative MRI revealed almost complete resolution of the syringobulbia. To the best of the authors' knowledge, this is the first reported case of isolated trismus from Chiari malformation with syringobulbia.

Severe malformations of eelpout (Zoarces viviparus) fry are induced by maternal estrogenic exposure during early embryogenesis.

PubMed

Morthorst, Jane E; Korsgaard, Bodil; Bjerregaard, Poul

2016-02-01

Pregnant eelpout were exposed via the water to known endocrine disrupting compounds (EDCs) to clarify if EDCs could be causing the increased eelpout fry malformation frequencies observed in coastal areas receiving high anthropogenic input. The presence of a teratogenic window for estrogen-induced malformations was also investigated by starting the exposure at different times during eelpout pregnancy. Both 17α-ethinylestradiol (EE2) (17.8 ng/L) and pyrene (0.5 μg/L) significantly increased fry malformation frequency whereas 4-t-octylphenol (4-t-OP) up to 14.3 μg/L did not. Vitellogenin was significantly induced by EE2 (5.7 and 17.8 ng/L) but not by 4-t-OP and pyrene. A critical period for estrogen-induced fry malformations was identified and closed between 14 and 22 days post fertilization (dpf). Exposure to 17β-estradiol (E2) between 0 and 14 dpf caused severe malformations and severity increased the closer exposure start was to fertilization, whereas malformations were absent by exposure starting later than 14 dpf. Data on ovarian fluid volume and larval length supported the suggested teratogenic window. Larval mortality also increased when exposure started right after fertilization. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cancer and congenital abnormalities in Asian children: a population-based study from the West Midlands.

PubMed Central

Powell, J. E.; Kelly, A. M.; Parkes, S. E.; Cole, T. R.; Mann, J. R.

1995-01-01

Cancer and associated congenital abnormalities were investigated in Muslim and non-Muslim Asian children from the West Midlands. Cancer incidence rates were calculated for Indian (non-Muslim), Pakistani/Bangladeshi (Muslim) and white children diagnosed from 1978 to 1992. Incidence was significantly higher in the Pakistanis, with an age-standardised rate (ASR) of 163 cases per million per year, compared with 115 for Indian and 125 for white children. Among Asian cancer patients, congenital malformations were significantly more common in Muslim (21%) compared with non-Muslim (7%). In Muslims the malformation excess was caused by autosomal recessive and dominant disorders (in 8% and 5% of cases respectively). Cancer malformation/predisposition syndromes were found in 10% of Muslims, compared with 2% of non-Muslims. In 33% of the Muslims with malformations, childhood cancer and a malformation were also present in a close relative. None of the non-Muslims with malformations had a relative with childhood cancer. The cancer excess in Muslims may be partly related to inherited genes causing both malformations and cancer. The prevalence of autosomal recessive disorders may be related to consanguinity, which is common in the Pakistani Muslim population. The high incidence of autosomal dominant disorders may be related to older paternal age at conception, giving rise to spontaneous mutations. PMID:8519679

Evolution of congenital malformations of the umbilical-portal-hepatic venous system.

PubMed

Scalabre, Aurelien; Gorincour, Guillaume; Hery, Geraldine; Gamerre, Marc; Guys, Jean-Michel; de Lagausie, Pascal

2012-08-01

The objective of this study is to describe the evolution of 8 cases of congenital malformations of the umbilical-portal-hepatic venous system diagnosed before the first month of life. All cases of congenital malformation of the portal and hepatic venous system diagnosed prenatally or during the first month of life in our institution were systematically reviewed since November 2000. Clinical features, imaging, and anatomical findings were reviewed, focusing primarily on clinical and radiologic evolution. Eight cases of congenital malformation of the umbilical-portal-hepatic venous system were studied. Fifty percent of these malformations were diagnosed prenatally. We report 4 portosystemic shunts. Three involuted spontaneously, and the fourth one required surgical treatment. We report a variation of the usual anatomy of portal and hepatic veins that remained asymptomatic, an aneurysmal dilatation of a vitelline vein causing portal vein thrombosis that needed prompt surgical treatment with good result, a complex portal and hepatic venous malformation treated operatively, and a persistent right umbilical vein that remained asymptomatic. Prenatal diagnosis of malformations of the umbilical-portal-hepatic venous network is uncommon. Little is known about the postnatal prognosis. Clinical, biologic, and radiologic follow-up by ultrasonography is essential to distinguish pathologic situations from normal anatomical variants. Copyright © 2012 Elsevier Inc. All rights reserved.

Impaired autophagy in macrophages promotes inflammatory eye disease.

PubMed

Santeford, Andrea; Wiley, Luke A; Park, Sunmin; Bamba, Sonya; Nakamura, Rei; Gdoura, Abdelaziz; Ferguson, Thomas A; Rao, P Kumar; Guan, Jun-Lin; Saitoh, Tatsuya; Akira, Shizuo; Xavier, Ramnik; Virgin, Herbert W; Apte, Rajendra S

2016-10-02

Autophagy is critical for maintaining cellular homeostasis. Organs such as the eye and brain are immunologically privileged. Here, we demonstrate that autophagy is essential for maintaining ocular immune privilege. Deletion of multiple autophagy genes in macrophages leads to an inflammation-mediated eye disease called uveitis that can cause blindness. Loss of autophagy activates inflammasome-mediated IL1B secretion that increases disease severity. Inhibition of caspase activity by gene deletion or pharmacological means completely reverses the disease phenotype. Of interest, experimental uveitis was also increased in a model of Crohn disease, a systemic autoimmune disease in which patients often develop uveitis, offering a potential mechanistic link between macrophage autophagy and systemic disease. These findings directly implicate the homeostatic process of autophagy in blinding eye disease and identify novel pathways for therapeutic intervention in uveitis.

Abnormal notochord branching is associated with foregut malformations in the adriamycin treated mouse model.

PubMed

Hajduk, Piotr; Sato, Hideaki; Puri, Prem; Murphy, Paula

2011-01-01

Oesophageal atresia (OA) and tracheooesophageal fistula (TOF) are relatively common human congenital malformations of the foregut where the oesophagus does not connect with the stomach and there is an abnormal connection between the stomach and the respiratory tract. They require immediate corrective surgery and have an impact on the future health of the individual. These abnormalities are mimicked by exposure of rat and mouse embryos in utero to the drug adriamycin. The causes of OA/TOF during human development are not known, however a number of mouse mutants where different signalling pathways are directly affected, show similar abnormalities, implicating multiple and complex signalling mechanisms. The similarities in developmental outcome seen in human infants and in the adriamycin treated mouse model underline the potential of this model to unravel the early embryological events and further our understanding of the processes disturbed, leading to such abnormalities. Here we report a systematic study of the foregut and adjacent tissues in embryos treated with adriamycin at E7 and E8 and analysed between E9 and E12, comparing morphology in 3D in 149 specimens. We describe a spectrum of 8 defects, the most common of which is ventral displacement and branching of the notochord (in 94% of embryos at E10) and a close spatial correspondence between the site of notochord branching and defects of the foregut. In addition gene expression analysis shows altered dorso-ventral foregut patterning in the vicinity of notochord branches. This study shows a number of features of the adriamycin mouse model not previously reported, implicates the notochord as a primary site of disturbance in such abnormalities and underlines the importance of the model to further address the mechanistic basis of foregut congenital abnormalities.

Lymphatic Malformation Architecture: Implications for Treatment With OK-432.

PubMed

Malic, Claudia C; Guilfoyle, Regan; Courtemanche, Rebecca J M; Arneja, Jugpal S; Heran, Manraj K S; Courtemanche, Douglas J

2017-10-01

Herein, the authors aim to describe their findings of novel architectural types of lymphatic malformations (LM) and explain the relationship between these architectures and OK-432 treatment outcomes. A retrospective review was conducted of all patients diagnosed with a LM treated with OK-432 at the Vascular Anomalies Clinic at BC Children's Hospital from December 2002 to January 2012. Twenty-seven patients were included in the study. Sixty percent of lesions were present by 2 years of age with the majority located in the head and neck (59%). The average number of sclerotherapy procedures was 1.4 per patient. Treatment under fluoroscopic guidance revealed 3 new LM architectures: open-cell microcystic, closed-cell microcystic, and lymphatic channel. Response to treatment was complete or good for 14/19 macrocystic and for 1/2 mixed lesions. Open-cell microcystic LMs gave a complete or good response for 3/3, which was attributed to OK-432 freely communicating between cysts. Closed-cell microcystic LM had localized cysts that did not allow OK-432 to freely communicate and were associated with partial responses, 2/2. The lymphatic channel had a partial response. There were 2 minor complications and 1 instance of recurrence. The identification of 3 new LM architectures expands the current accepted classification to include: open-cell microcystic, closed-cell microcystic, and lymphatic channels. The majority of complete responses to OK-432 were found with macrocystic lesions. Open-cell microcystic lesions respond better to OK-432 than closed-cell microcystic lesions, and lymphatic channels may respond to OK-432. These key architecture-response relationships have direct clinical implications for treatment with OK-432 sclerotherapy.

Abnormal Notochord Branching Is Associated with Foregut Malformations in the Adriamycin Treated Mouse Model

PubMed Central

Hajduk, Piotr; Sato, Hideaki; Puri, Prem; Murphy, Paula

2011-01-01

Oesophageal atresia (OA) and tracheooesophageal fistula (TOF) are relatively common human congenital malformations of the foregut where the oesophagus does not connect with the stomach and there is an abnormal connection between the stomach and the respiratory tract. They require immediate corrective surgery and have an impact on the future health of the individual. These abnormalities are mimicked by exposure of rat and mouse embryos in utero to the drug adriamycin. The causes of OA/TOF during human development are not known, however a number of mouse mutants where different signalling pathways are directly affected, show similar abnormalities, implicating multiple and complex signalling mechanisms. The similarities in developmental outcome seen in human infants and in the adriamycin treated mouse model underline the potential of this model to unravel the early embryological events and further our understanding of the processes disturbed, leading to such abnormalities. Here we report a systematic study of the foregut and adjacent tissues in embryos treated with adriamycin at E7 and E8 and analysed between E9 and E12, comparing morphology in 3D in 149 specimens. We describe a spectrum of 8 defects, the most common of which is ventral displacement and branching of the notochord (in 94% of embryos at E10) and a close spatial correspondence between the site of notochord branching and defects of the foregut. In addition gene expression analysis shows altered dorso-ventral foregut patterning in the vicinity of notochord branches. This study shows a number of features of the adriamycin mouse model not previously reported, implicates the notochord as a primary site of disturbance in such abnormalities and underlines the importance of the model to further address the mechanistic basis of foregut congenital abnormalities. PMID:22132119

Impact of nest predators, competitors, and ectoparasites on Pearly-eyed Thrashers, with comments on the potential implications for Puerto Rican Parrot recovery

Treesearch

Wayne J. Arendt

2000-01-01

Over the past 17 years, research on a rain forest population of the Pearly-eyed Thrasher (Margarops fuscatus), with additional observations on nesting Puerto Rican Parrots (Amazona vittata) within the Sierra de Luquillo, Puerto Rico, has shown that reproductive success of thrashers and parrots is often greatly reduced as a result of the additive effects of a diverse...

Eye movement difficulties in autism spectrum disorder: implications for implicit contextual learning.

PubMed

Kourkoulou, Anastasia; Kuhn, Gustav; Findlay, John M; Leekam, Susan R

2013-06-01

It is widely accepted that we use contextual information to guide our gaze when searching for an object. People with autism spectrum disorder (ASD) also utilise contextual information in this way; yet, their visual search in tasks of this kind is much slower compared with people without ASD. The aim of the current study was to explore the reason for this by measuring eye movements. Eye movement analyses revealed that the slowing of visual search was not caused by making a greater number of fixations. Instead, participants in the ASD group were slower to launch their first saccade, and the duration of their fixations was longer. These results indicate that slowed search in ASD in contextual learning tasks is not due to differences in the spatial allocation of attention but due to temporal delays in the initial-reflexive orienting of attention and subsequent-focused attention. These results have broader implications for understanding the unusual attention profile of individuals with ASD and how their attention may be shaped by learning. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

Age-related differences in memory expression during infancy: using eye-tracking to measure relational memory in 6- and 12-month-olds.

PubMed

Richmond, Jenny L; Power, Jessica

2014-09-01

Relational memory, or the ability to bind components of an event into a network of linked representations, is a primary function of the hippocampus. Here we extend eye-tracking research showing that infants are capable of forming memories for the relation between arbitrarily paired scenes and faces, by looking at age-related changes in relational memory over the first year of life. Six- and 12-month-old infants were familiarized with pairs of faces and scenes before being tested with arrays of three familiar faces that were presented on a familiar scene. Preferential looking at the face that matches the scene is typically taken as evidence of relational memory. The results showed that while 6-month-old showed very early preferential looking when face/scene pairs were tested immediately, 12-month-old did not exhibit evidence of relational memory either immediately or after a short delay. Theoretical implications for the functional development of the hippocampus and practical implications for the use of eye tracking to measure memory during early life are discussed. © 2014 Wiley Periodicals, Inc.

Congenital Malformations of the Central Nervous System in Rural Western Honduras: A 6-Year Report on Trends.

PubMed

Estevez-Ordonez, Dagoberto; Dewan, Michael C; Feldman, Michael J; Montalvan-Sanchez, Eleazar E; Montalvan-Sanchez, Daniela M; Rodriguez-Murillo, Aida A; Urrutia-Argueta, Samuel A; Cherry, Charlotte B; Morgan, Douglas R; Alvarez-Rodriguez, Roberto; Bonfield, Christopher M

2017-11-01

Central nervous system (CNS) malformations, including neural tube defects (NTDs), are the second most common type of birth defects worldwide and are major causes of childhood disability and mortality. We report the first analysis of birth prevalence in Western Honduras of CNS malformations including NTDs over 6 consecutive years. Data from all patients with congenital CNS malformations and total live births for the period 2010-2015 were obtained through institution and regional registries from all 3 public referral hospitals in Western Honduras, representing 67 municipalities. Cases were identified using the International Classification of Diseases, Tenth Revision CNS malformation codes. Birth prevalence was calculated as cases per 10,000 live births. From 123,903 live births, 275 cases of CNS malformations were identified (54% females, 58% NTDs). Six-year birth prevalence of CNS malformations was 13.9-31.1. Spina bifida variants and anencephaly represented 80% and 19% of reported NTDs, respectively. Total 6-year prevalence of NTDs in Western Honduras was 7.0-17.4 over years studied. In 6 municipalities, average prevalence was >30 (maximum 49.0). This is the first study reporting disease burden of CNS malformations in Western Honduras. The nationwide birth prevalence of NTDs in rural Honduras may have decreased since the implementation of prenatal health policies in 2005. However, we identified regions with unexpectedly elevated prevalence, indicating high regional prevalence that could be targeted for improved preventive efforts, ultimately decreasing the burden of these conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

Annual trends in use of periconceptional folic acid and birth prevalence of major congenital malformations.

PubMed

Richard-Tremblay, Audrey-Ann; Sheehy, Odile; Bérard, Anick

2013-07-01

Recent evidence suggests that periconceptional folic acid use could not only prevent neural tube defects but also other malformations. The objectives of this study were to assess trends in dispensed high dose periconceptional folic acid (5 mg) and birth prevalence of major congenital malformations. The Quebec Pregnancy Registry, an administrative database with information on periconceptional prescribed medication and diagnostic codes was used to conduct this study. All pregnant women insured by the Quebec public drug plan between January 1(st) 1998 and December 31(st) 2008 were included. The exposure was defined as the use of high dose periconceptional folic acid 30 days before, and during the first 70 days of pregnancy. The outcome measured was the birth prevalence of major congenital malformations among live births. We identified 152,392 pregnancies and babies. The annual prevalence of high dose periconceptional folic acid use increased from 0.17% to 0.80% (p<0.05) during the study period; birth prevalence of congenital malformations increased by 15% (3.35% to 3.87%, p<0.05). More specifically, a 23% increase in the prevalence of cardiac malformation and 23% increase in musculoskeletal defects were observed, whereas there was no change in the prevalence of malformations of the nervous system. Although there was an increase in the use of periconceptional high dose folic acid over the past decade, there was no decrease in the prevalence of major congenital malformations. A limitation of this study is the absence of data on low dose folic acid use, available over the counter, in our administrative database.

Analysis of the Volumes of the Posterior Cranial Fossa, Cerebellum, and Herniated Tonsils Using the Stereological Methods in Patients with Chiari Type I Malformation

PubMed Central

Vurdem, Ümit Erkan; Acer, Niyazi; Ertekin, Tolga; Savranlar, Ahmet; İnci, Mehmet Fatih

2012-01-01

Objective. The aim of this study was to determine the posterior cranial fossa volume, cerebellar volume, and herniated tonsillar volume in patients with chiari type I malformation and control subjects using stereological methods. Material and Methods. These volumes were estimated retrospectively using the Cavalieri principle as a point-counting technique. We used magnetic resonance images taken from 25 control subjects and 30 patients with chiari type I malformation. Results. The posterior cranial fossa volume in patients with chiari type I malformation was significantly smaller than the volume in the control subjects (P < 0.05). In the chiari type I malformation group, the cerebellar volume was smaller than the control group, but this difference was not statistically significant (P > 0.05). In the chiari type I malformation group, the ratio of cerebellar volume to posterior cranial fossa volume was higher than in the control group. We also found a positive correlation between the posterior cranial fossa volume and cerebellar volume for each of the groups (r = 0.865, P < 0.001). The mean (±SD) herniated tonsillar volume and length were 0.89 ± 0.50 cm3 and 9.63 ± 3.37 mm in the chiari type I malformation group, respectively. Conclusion. This study has shown that posterior cranial fossa and cerebellum volumes can be measured by stereological methods, and the ratio of these measurements can contribute to the evaluation of chiari type I malformation cases. PMID:22629166

Phenotype in girls and women with Turner syndrome: Association between dysmorphic features, karyotype and cardio-aortic malformations.

PubMed

Noordman, Iris; Duijnhouwer, Anthonie; Kapusta, Livia; Kempers, Marlies; Roeleveld, Nel; Schokking, Michiel; Smeets, Dominique; Freriks, Kim; Timmers, Henri; van Alfen-van der Velden, Janiëlle

2018-06-01

Turner syndrome (TS) is a genetic disorder characterized by the (partial) absence or a structural aberration of the second sex chromosome and is associated with a variety of phenotypes with specific physical features and cardio-aortic malformations. The objective of this study was to gain a better insight into the differences in dysmorphic features between girls and women with TS and to explore the association between these features, karyotype and cardio-aortic malformations. This prospective study investigated 14 dysmorphic features of TS girls and women using a checklist. Three major phenotypic patterns were recognized (severe phenotype, lymphatic phenotype and skeletal phenotype). Patient data including karyotype and cardio-aortic malformations (bicuspid aortic valve (BAV) and aortic coarctation (COA)) were collected. Associations between the prevalence of dysmorphic features, karyotype and cardio-aortic malformations were analysed using chi 2 -test and odds ratios. A total of 202 patients (84 girls and 118 women) were analysed prospectively. Differences in prevalence of dysmorphic features were found between girls and women. A strong association was found between monosomy 45,X and the phenotypic patterns. Furthermore, an association was found between COA and lymphatic phenotype, but no association was found between karyotype and cardio-aortic malformations. This study uncovered a difference in dysmorphic features between girls and women. Monosomy 45,X is associated with a more severe phenotype, lymphatic phenotype and skeletal phenotype. All patients with TS should be screened for cardio-aortic malformations, because in contrast to previous reports, karyotype and cardio-aortic malformations showed no significant association. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Temperature profiles of patient-applied eyelid warming therapies.

PubMed

Wang, Michael T M; Gokul, Akilesh; Craig, Jennifer P

2015-12-01

To compare temperature profile characteristics (on and off eye) of two patient-applied heat therapies for meibomian gland dysfunction (MGD): an eye mask containing disposable warming units (EyeGiene(®)) and a microwave-heated flaxseed eye bag(®) (MGDRx EyeBag(®)). In vitro evaluation: surface temperature profiles of activated eye masks and heated eye bags(®) (both n=10), were tracked every 10s until return to ambient temperature. Heat-transfer assessment: outer and inner eyelid temperature profiles throughout the eye mask and eye bag(®) treatment application period (10min) were investigated in triplicate. The devices were applied for 12 different time intervals in a randomised order, with a cool-down period in between to ensure ocular temperatures returned to baseline. Temperature measurements were taken before and immediately after each application. In vitro evaluation: on profile, the eye bag(®) surface temperature peaked earlier (0±0 s vs. 100±20 s, p<0.001), cooled more slowly and displayed less variability than the eye mask (all p<0.05). Heat-transfer assessment: the eye bag(®) effected higher peak inner eyelid temperatures (38.1±0.4°C vs. 37.4±0.2°C, p=0.04), as well as larger inner eyelid temperature increases over the first 2 min, and between 9 and 10 min (all p<0.05). The eye bag(®) surface temperature profile displayed greater uniformity and slower cooling than the eye mask, and was demonstrated to be significantly more effective in raising ocular temperatures than the eye mask, both statistically and clinically. This has implications for MGD treatment, where the melting points of meibomian secretions are likely to be higher with increasing disease severity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Abernethy malformation with portal vein aneurysm in a child.

PubMed

Chandrashekhara, Sheragaru H; Bhalla, Ashu Seith; Gupta, Arun Kumar; Vikash, C S; Kabra, Susheel Kumar

2011-01-01

Abernethy malformation is an extremely rare anomaly of the splanchnic venous system. We describe multidetector computed tomography findings of an incidentally detected Abernethy malformation with portal vein aneurysm in a two-and-half-year old child. The computed tomography scan was performed for the evaluation of respiratory distress, poor growth, and loss of appetite.

Klippel-Feil syndrome and Dandy-Walker malformation.

PubMed

Karaman, A; Kahveci, H

2011-01-01

The Klippel-Feil deformity is a complex of osseous and visceral anomalies, which include low hairline, platybasia, fused cervical vertebrae with a short neck, and deafness. Associated central nervous system abnormalities include occipital cephalocele, Chiari I malformation, syrinx, microcephaly, and hydrocephalus. Herein, we report a case with Klippel-Feil syndrome and Dandy-Walker malformation.

[Anatomy and malformations of the posterior cranial fossa].

PubMed

Struffert, T

2016-11-01

Many important structures are located in the confined space within the posterior cranial fossa. This article describes the main aspects of the anatomy. As a uniform classification of malformations of the posterior cranial fossa does not exist the main syndromes, such as Chiari malformations, zerebellar hypoplasia and dysplasia are discussed separately.

Cerebral dominance for speech and handwriting of patients with cortical vascular malformations.

PubMed

Sass, K J; Buchanan, C P; Westerveld, M; Spencer, D D

1994-10-01

Lateralization of speech dominance was established using amobarbital for 22 patients with vascular malformations lateralized to the left cerebral hemisphere. Patients' histories were negative for clinically evident neurological events (e.g., seizures or hemorrhage) prior to adulthood. The vascular lesions were categorized as high flow arteriovenous malformations (AVMs) (n = 4), low flow AVMs (n = 6), cavernous hemangiomas (n = 10), or venous angiomas (n = 2) by reviewing angiographic findings and surgical pathology for those patients whose lesions were excised. Three of the malformations encroached upon primary language areas. The frequency of right hemisphere speech dominance was not significantly elevated in comparison with the normal population, even though the incidence of nonright-handedness was. Ninety-five percent of the patients were left hemisphere dominant for speech: only one patient, with a parietal lobe cavernous hemangioma, was found to be right hemisphere dominant for speech. This malformation did not involve the primary language areas. These findings suggest that vascular malformations do not affect speech dominance as readily as other neurological diseases, but frequently affect manual dominance.

Long-Term Follow-up After Embolization of Pulmonary Arteriovenous Malformations with Detachable Silicone Balloons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andersen, Poul Erik; Kjeldsen, Anette D.

2008-05-15

Long-term follow-up results after embolization of 13 pulmonary arteriovenous malformations in 10 patients by use of 14 detachable silicone balloons are given. Patients were followed for a mean of 99 months (range, 63-123 months) with chest x-rays and for a mean of 62 months (range, 3-101 months) with pulmonary angiography. Fifty-four percent of the balloons were deflated at latest radiographic chest film follow-up, but at pulmonary angiographic follow-up all embolized malformations were without flow irrespective of whether or not the balloons were visible. Detachable silicone balloons are not available anymore, but use of these balloons for embolization of pulmonary arteriovenousmore » malformations has been shown to be a safe and precise method, with immediate occlusion of the feeding artery and with long-lasting occlusion, even though many balloons deflate with time, leaving a fibrotic scar replacing the pulmonary arteriovenous malformation. No case of recanalization has been discovered, and these results seem to justify a reduced number of controls of these balloon-embolized malformations.« less

[Study of the radioprotective effects of TMG on teratogenic malformations in irradiated mice].

PubMed

Gu, Y; Hasegawa, T; Kim, H; Suzuki, I; Mori, T; Yamamoto, Y

2000-12-01

ICR mice fetuses in the organogenesis stage were used to clarify experimentally the mechanism of the protective effect of vitamin E derivant (TMG: 2-(alpha-D-Glucopyranosyl) methyl-2, -5, -7, -8-Teramethylchorman-6-working woman) on the effects of radiation. The authors paid careful attention to radiation, and the radioprotective effects of TMG on the induction of malformations was examined. Radiation is an important consideration because of its widespread use in the areas of medicine, nuclear energy, and industry. Malformations induced by radiation at the organogenesis stage, skeletal malformations, and the effects at the cellular level of embryos were examined in this research. Further, the mechanism of the protection effect of TMG against radiation-induced malformations was analyzed and observed experimentally. Thus, this study was done to provide fundamental data on the radioprotective agent TMG. It was clear that TMG exerted radioprotective effects against embryonic death and the rate of teratogenesis when administered before exposure. Such effects were also exerted against skeletal malformations and fetal body weight. In summary, radioprotective effects were observed at the whole-body level as well as at the cellular level.

Chiari III malformation: a comprehensive review of this enigmatic anomaly.

PubMed

Ivashchuk, Galyna; Loukas, Marios; Blount, Jeffrey P; Tubbs, R Shane; Oakes, W Jerry

2015-11-01

Chiari III is one of the rarest of the Chiari malformations and is characterized by a high cervical or low occipital encephalocele and osseous defect with or without spinal cord involvement and may include many of the anatomical characteristics seen in the Chiari II malformation. Herein, we provide a comprehensive review of this rare anomaly as well as a translation of Chiari's original description. We review all reported cases of Chiari III malformation found in the extant literature. Out of 57 reported cases of Chiari III malformation, encephaloceles were in a high cervical/low occipital position in 23, 8 were in a high cervical position, 17 were in low occipital position, and the position in 9 cases was not reported. The pathogenesis of Chiari III malformation remains unclear. The majority of patients have concomitant hydrocephalus. Brain parts occurring in the sac from the most to least common include the following: cerebellum, occipital lobe, and parietal lobe. The severity of symptoms is correlated with the amount of brain structures within the encephalocele. Neurologic functional outcomes have been varied and depend on the neurological status of the patient before surgery.

[Nephrourologic pathology in girls with Turner syndrome].

PubMed

Di Pinto, Diana; Balestracci, Alejandro; Dujovne, Noelia; de Palma, Isabel; Adragna, Marta; Delgado, Norma

2010-08-01

Nephrourologic malformations in Turner syndrome are frequent, its diagnosis and follow-up is important in order to diminish the morbidity of this disease. The aim of this retrospective study was to analyze the nephrourologic pathology in 72 girls with Turner syndrome followed between 1989 and 2008 at Garrahan Hospital. The prevalence of nephrourologic involvement was 33% (24 patients). The most frequent findings were urinary system malformations, isolated (10 pacientes, 42%) or associated with renal malformations (9 patients, 37%); 5 patients (21%) had only renal malformations. Fifty percent of patients developed complications (8 urinary tract infection, 2 proteinuria and 2 arterial hypertension); however, none progressed to chronic renal failure. The prevalence of nephrourologic involvement was 33% and a half of these girls developed complications, our findings show the need of routine nephrological follow-up of girls with Turner syndrome and nephrourologic malformations.

Frontal Lobe Cavernous Malformations in Pediatric Patients: Clinical Features and Surgical Outcomes.

PubMed

Wang, Chengjun; Zhao, Meng; Wang, Jia; Wang, Shuo; Jiang, Zhongli; Zhao, Jizong

2018-01-01

The purpose of this study is to investigate the clinical manifestations, surgical treatment, and neurologic outcomes of frontal lobe cavernous malformations in children. A retrospective analysis of 23 pediatric frontal lobe cavernous malformation patients who underwent surgical treatment in Beijing Tiantan Hospital was performed. The case series included 16 boys and 7 girls. Gross total removal without surgical mortality was achieved in all patients. The mean follow-up period after surgery was 33.1 months. Two patients who left hospital with motor deficits gradually recovered after rehabilitative treatment, and other patients were considered to be in excellent clinical condition. For symptomatic frontal lobe cavernous malformations, neurosurgical management should be the treatment of choice. Conservative treatment may be warranted in asymptomatic frontal lobe cavernous malformations, especially the deep-seated or eloquently located cases.

Update on the management of anorectal malformations.

PubMed

Bischoff, Andrea; Levitt, Marc A; Peña, Alberto

2013-09-01

Thirty-three years ago, on 10 August 1980, in Mexico City, the first patient with an anorectal malformation was operated on using the posterior sagittal approach. At that time it was not obvious that we were actually opening a "Pandora's box" that continues to give many positive surprises, a few disappointments, and the constant hope that each day we can learn more about how to improve the quality of life of children born with all different types of anorectal malformations. In November 2012, patient number 3000 in our database was operated in the city of Cochabamba, Bolivia; during one of our International Courses of Anorectal Malformations and Colorectal Problems in Children. The goal of this article is to give a brief update on the current management of patients with anorectal malformation, based on the multiple lessons learned during this period.

Müllerian Agenesis in Cat Eye Syndrome and 22q11 Chromosome Abnormalities: A Case Report and Literature Review.

PubMed

AlSubaihin, Abdulmajeed; VanderMeulen, John; Harris, Kate; Duck, John; McCready, Elizabeth

2018-04-01

Although Müllerian agenesis is the second most common cause of primary amenorrhea the underlying etiology in most cases is unknown. Müllerian agenesis has been reported as a rare finding associated with chromosomal aberrations of the 22q11 chromosomal region including at least 1 individual with cat eye syndrome (CES) and 10 individuals with deletions or duplications of the 22q11.2 region. However, a potential link between 22q11 abnormalities and uterine malformations has been difficult to adequately ascertain because of the limited case reports in the literature. We report a second case of Müllerian agenesis in a girl with CES. A 16-year-old girl presented with bilateral colobomata, primary amenorrhea, and absence of the uterus and upper vagina on pelvic magnetic resonance imaging. Microarray analysis showed tetrasomy of the pericentromeric region of chromosome 22 diagnostic of CES. Müllerian aplasia/hypoplasia might represent a rare feature in CES and should be considered in the investigation of young girls with this syndrome. An increasing number of cases with 22q11 chromosome abnormalities and Müllerian agenesis further highlights the possibility of a gene within the 22q11 region that might mediate normal Müllerian development in girls. Copyright © 2017 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Loss of function mutations in EPHB4 are responsible for vein of Galen aneurysmal malformation.

PubMed

Vivanti, Alexandre; Ozanne, Augustin; Grondin, Cynthia; Saliou, Guillaume; Quevarec, Loic; Maurey, Helène; Aubourg, Patrick; Benachi, Alexandra; Gut, Marta; Gut, Ivo; Martinovic, Jelena; Sénat, Marie Victoire; Tawk, Marcel; Melki, Judith

2018-04-01

See Meschia (doi:10.1093/brain/awy066) for a scientific commentary on this article.Vein of Galen aneurysmal malformation is a congenital anomaly of the cerebral vasculature representing 30% of all paediatric vascular malformations. We conducted whole exome sequencing in 19 unrelated patients presenting this malformation and subsequently screened candidate genes in a cohort of 32 additional patients using either targeted exome or Sanger sequencing. In a cohort of 51 patients, we found five affected individuals with heterozygous mutations in EPHB4 including de novo frameshift (p.His191Alafs*32) or inherited deleterious splice or missense mutations predicted to be pathogenic by in silico tools. Knockdown of ephb4 in zebrafish embryos leads to specific anomalies of dorsal cranial vessels including the dorsal longitudinal vein, which is the orthologue of the median prosencephalic vein and the embryonic precursor of the vein of Galen. This model allowed us to investigate EPHB4 loss-of-function mutations in this disease by the ability to rescue the brain vascular defect in knockdown zebrafish co-injected with wild-type, but not truncated EPHB4, mimicking the p.His191Alafs mutation. Our data showed that in both species, loss of function mutations of EPHB4 result in specific and similar brain vascular development anomalies. Recently, EPHB4 germline mutations have been reported in non-immune hydrops fetalis and in cutaneous capillary malformation-arteriovenous malformation. Here, we show that EPHB4 mutations are also responsible for vein of Galen aneurysmal malformation, indicating that heterozygous germline mutations of EPHB4 result in a large clinical spectrum. The identification of EPHB4 pathogenic mutations in patients presenting capillary malformation or vein of Galen aneurysmal malformation should lead to careful follow-up of pregnancy of carriers for early detection of anomaly of the cerebral vasculature in order to propose optimal neonatal care. Endovascular embolization indeed greatly improved the prognosis of patients.

Vascular Anomalies (Part I): Classification and Diagnostics of Vascular Anomalies.

PubMed

Sadick, Maliha; Müller-Wille, René; Wildgruber, Moritz; Wohlgemuth, Walter A

2018-06-06

 Vascular anomalies are a diagnostic and therapeutic challenge. They require dedicated interdisciplinary management. Optimal patient care relies on integral medical evaluation and a classification system established by experts in the field, to provide a better understanding of these complex vascular entities.  A dedicated classification system according to the International Society for the Study of Vascular Anomalies (ISSVA) and the German Interdisciplinary Society of Vascular Anomalies (DiGGefA) is presented. The vast spectrum of diagnostic modalities, ranging from ultrasound with color Doppler, conventional X-ray, CT with 4 D imaging and MRI as well as catheter angiography for appropriate assessment is discussed.  Congenital vascular anomalies are comprised of vascular tumors, based on endothelial cell proliferation and vascular malformations with underlying mesenchymal and angiogenetic disorder. Vascular tumors tend to regress with patient's age, vascular malformations increase in size and are subdivided into capillary, venous, lymphatic, arterio-venous and combined malformations, depending on their dominant vasculature. According to their appearance, venous malformations are the most common representative of vascular anomalies (70 %), followed by lymphatic malformations (12 %), arterio-venous malformations (8 %), combined malformation syndromes (6 %) and capillary malformations (4 %).  The aim is to provide an overview of the current classification system and diagnostic characterization of vascular anomalies in order to facilitate interdisciplinary management of vascular anomalies.   · Vascular anomalies are comprised of vascular tumors and vascular malformations, both considered to be rare diseases.. · Appropriate treatment depends on correct classification and diagnosis of vascular anomalies, which is based on established national and international classification systems, recommendations and guidelines.. · In the classification, diagnosis and treatment of congenital vascular anomalies, radiology plays an integral part in patient management.. · Sadick M, Müller-Wille R, Wildgruber M et al. Vascular Anomalies (Part I): Classification and Diagnostics of Vascular Anomalies. Fortschr Röntgenstr 2018; DOI: 10.1055/a-0620-8925. © Georg Thieme Verlag KG Stuttgart · New York.

Defining the molecular pathologies in cloaca malformation: similarities between mouse and human

PubMed Central

Runck, Laura A.; Method, Anna; Bischoff, Andrea; Levitt, Marc; Peña, Alberto; Collins, Margaret H.; Gupta, Anita; Shanmukhappa, Shiva; Wells, James M.; Guasch, Géraldine

2014-01-01

Anorectal malformations are congenital anomalies that form a spectrum of disorders, from the most benign type with excellent functional prognosis, to very complex, such as cloaca malformation in females in which the rectum, vagina and urethra fail to develop separately and instead drain via a single common channel into the perineum. The severity of this phenotype suggests that the defect occurs in the early stages of embryonic development of the organs derived from the cloaca. Owing to the inability to directly investigate human embryonic cloaca development, current research has relied on the use of mouse models of anorectal malformations. However, even studies of mouse embryos lack analysis of the earliest stages of cloaca patterning and morphogenesis. Here we compared human and mouse cloaca development and retrospectively identified that early mis-patterning of the embryonic cloaca might underlie the most severe forms of anorectal malformation in humans. In mouse, we identified that defective sonic hedgehog (Shh) signaling results in early dorsal-ventral epithelial abnormalities prior to the reported defects in septation. This is manifested by the absence of Sox2 and aberrant expression of keratins in the embryonic cloaca of Shh knockout mice. Shh knockout embryos additionally develop a hypervascular stroma, which is defective in BMP signaling. These epithelial and stromal defects persist later, creating an indeterminate epithelium with molecular alterations in the common channel. We then used these animals to perform a broad comparison with patients with mild-to-severe forms of anorectal malformations including cloaca malformation. We found striking parallels with the Shh mouse model, including nearly identical defective molecular identity of the epithelium and surrounding stroma. Our work strongly suggests that early embryonic cloacal epithelial differentiation defects might be the underlying cause of severe forms of anorectal malformations in humans. Moreover, deranged Shh and BMP signaling is correlated with severe anorectal malformations in both mouse and humans. PMID:24524909

The relationship between some neonatal and maternal factors during pregnancy with the prevalence of congenital malformations in Iran: a systematic review and meta-analysis.

PubMed

Daliri, Salman; Safarpour, Hamid; Bazyar, Jafar; Sayehmiri, Kourosh; Karimi, Arezoo; Anvary, Rahman

2018-05-08

Congenital malformations are one of the main causes of death and disability in children. These malformations arise during embryogenesis and fetal development during pregnancy due to exposure to some environmental factors and genetic mutations. Given the high prevalence of congenital malformations in Iran, the current study was conducted to investigate the relationship between some neonatal and maternal factors during pregnancy with the prevalence of congenital malformations in Iran. This was a systematic review and meta-analysis study. All studies conducted in Iran were extracted between 2000 and 2016 during a search in internal and external databases of Medlib, Medline, Pubmed, Web of Science, Google Scholar, Scopus, Magiran, SID, Cochrane, Irandoc, and all articles published. Then, the required data were entered into the Spss16 software (SPSS Inc., Chicago, IL); and the model of fixed and random effects was analyzed in meta-analysis, Cochran, meta-regression using statistical tests. A total of 30 studies with a sample size of 928,311 patients were enrolled. Baby's gender (1-1.55: CI95%) OR: 1.25, preterm delivery (1.71-3.69: CI 95%) OR: 2.51, low birth weight (1.13-2.67: CI95%) OR: 1.74, age older than 35 for the pregnant mother (1.41-6.3: CI 95%) OR: 2.98, multiple births (1.14-3.46: CI 95%) OR: 1.99, mother suffering from chronic diseases (1.68-3.31: CI 95%) OR: 2.36 are significantly related with the risk of congenital malformations. Based on the results the baby's gender, premature birth, low birth weight, mother's age, consanguineous marriages, multiple births, family history of congenital malformations, and the risk of chronic diseases in the mother during pregnancy increase the birth of children with congenital malformations. As a result, control or modification of the above factors implementing a health and education intervention program can reduce the birth of children with congenital malformations.

[Cerebrovenous orthostatic reactivity in pathology of the craniovertebral junction (Chiari malformation)].

PubMed

Shakhnovich, V A; Mitrofanova, E V; Shimanskiy, V N; Konovalov, N A; Shkarubo, A N

2015-01-01

Chiari malformation is characterized by herniation of the cerebellar tonsils into the foramen magnum, which leads to disturbance of CSF circulation through the craniovertebral junction. Orthostatic stress, which leads to the movement of SCF through the craniovertebral junction, is an adequate method to detect these disorders. It is accompanied by changes in the intracranial pressure, affecting the cerebrovenous orthostatic reactivity (CVOR), which is noninvasively assessed in patients with Chiari malformation. The study involved 35 patients with Chiari malformation (26 patients with Chiari I and 9 patients with Chiari II) aged 4 to 58 years (of them 12 males). Hydrocephalus was diagnosed in 4 examined patients and myelosyringosis was diagnosed in 6 patients. Transcranial Doppler sonography was used to record the venous blood flow in the tentorial sinus of the brain while changing body position on the fracture table from +90° to -30°. There is significant CVOR abnormality in most patients with Chiari malformation (more than 90%), which is characterized by either increased CVOR (sometimes 5-6-fold compared to the upper normal level (considerable hyperreactivity) or complete absence of any changes during the orthostatic load (areactivity). Before surgical treatment, CVOR of patients with Chiari malformation is often characterized by areactivity, as well as a moderate or significant hyperreactivity. After surgical treatment (decompression of the foramen magnum), patients with Chiari malformation demonstrate significant normalization of the craniovertebral volumetric ratios and CVOR if often characterized by normoreactivity (in 63%) or, more rarely, moderate hyperreactivity. The rate of venous blood flow in the tentorial sinus of the brain in patients with Chiari malformation can be increased before the surgery and normalizes after surgery. The high incidence of disturbance of CVOR (over 90%) in patients with Chiari malformation was revealed. After surgical treatment, complete normalization of CVOR was observed in more than half of these patients (63%).

Lamina cribrosa position and Bruch's membrane opening differences between anterior ischemic optic neuropathy and open-angle glaucoma.

PubMed

Rebolleda, Gema; Pérez-Sarriegui, Ane; Díez-Álvarez, Laura; De Juan, Victoria; Muñoz-Negrete, Francisco J

2018-06-01

To compare the optic nerve head morphology among primary open-angle glaucoma, non-arteritic anterior ischemic optic neuropathy eyes, their fellow healthy eyes and control eyes, using spectral-domain optical coherence tomography with enhanced depth imaging. Observational cross-sectional study including 88 eyes of 68 patients. In this study, 23 non-arteritic anterior ischemic optic neuropathy eyes, 17 fellow unaffected eyes, 25 primary open-angle glaucoma eyes, and 23 age-matched control eyes were included. Peripapillary retinal nerve fiber layer thickness and optic disk area were evaluated. Bruch's membrane opening diameter, optic cup depth, anterior lamina cribrosa depth, and prelaminar tissue thickness were assessed. Non-arteritic anterior ischemic optic neuropathy and primary open-angle glaucoma eyes had similar visual field mean deviation and peripapillary retinal nerve fiber layer thickness (P = 0.6 and P = 0.56, respectively). Bruch's membrane opening diameter was significantly larger in primary open-angle glaucoma eyes than in control eyes (P = 0.02). Lamina cribrosa and disk cup were deeper in eyes with primary open-angle glaucoma than both control and non-arteritic anterior ischemic optic neuropathy eyes (P < 0.001). Prelaminar tissue thickness was significantly thinner in primary open-angle glaucoma eyes than in non-arteritic anterior ischemic optic neuropathy eyes (P < 0.001). Lamina cribrosa was shallower in both non-arteritic anterior ischemic optic neuropathy and unaffected fellow eyes compared to healthy eyes (P < 0.001 and P = 0.04, respectively). No differences were found in the optic disk area. A forward lamina cribrosa placement and not a smaller disk could be involved in the pathogenesis of non-arteritic anterior ischemic optic neuropathy. A significantly larger Bruch's membrane opening diameter was found in primary open-angle glaucoma eyes compared with control eyes. This issue has clinical implications because Bruch's membrane opening has been considered a stable reference for disk-related measures.

Practice Patterns in Retinopathy of Prematurity Treatment for Disease Milder than Recommended by Guidelines

PubMed Central

Gupta, Mrinali Patel; Chan, RV. Paul; Anzures, Rachelle; Ostmo, Susan; Jonas, Karyn; Chiang, Michael F.

2015-01-01

Purpose To characterize the frequency of and clinical indications for which experts treat retinopathy of prematurity (ROP) milder than Type 1 disease, the recommended threshold for treatment from established consensus guidelines. Design Descriptive analysis Methods Setting: Multicenter. Study Population: A database of 1444 eyes generated prospectively from all babies screened for ROP at one of 6 major ROP centers whose parents provided informed consent. Intervention: Retrospective review of the database and charts to identify all patients treated for ROP milder than Type 1. Main Outcome Measure: Indication(s) for treatment. Results 137 eyes of 70 infants were treated for ROP. Of these 137 eyes, 13 (9.5%) were treated despite a clinical diagnosis milder than Type 1 ROP. Indications for treatment included: active ROP with the fellow eye being treated for Type 1 ROP (2 eyes, 15.4%); concerning structural changes (9 eyes, 69.2%), including tangential traction with temporal vessel straightening concerning for macular dragging (8 eyes, 61.5%) and thick stage 3 membranes with anteroposterior traction concerning for progression to stage 4 ROP (3 eyes, 23.1%); persistent ROP at an advanced postmenstrual age (4 eyes, 30.8%); and/or vitreous hemorrhage (3 eyes, 23.1%). Conclusion Experts in this study occasionally recommended treatment in eyes with disease less than Type 1 ROP. This study has important clinical implications and highlights the role of individual clinical judgment in situations not covered by evidence-based treatment guidelines. PMID:26705094

Exploring topical anti-glaucoma medication effects on the ocular surface in the context of the current understanding of dry eye.

PubMed

Wong, Aaron B C; Wang, Michael T M; Liu, Kevin; Prime, Zak J; Danesh-Meyer, Helen V; Craig, Jennifer P

2018-07-01

To assess tear film parameters, ocular surface characteristics, and dry eye symptomology in patients receiving topical anti-glaucoma medications. Thirty-three patients with a diagnosis of open angle glaucoma or ocular hypertension, receiving unilateral topical anti-glaucoma medication for at least 6 months, were recruited in a cross-sectional, investigator-masked, paired-eye comparison study. Tear film parameters, ocular surface characteristics, and dry eye symptomology of treated and fellow eyes were evaluated and compared. The mean ± SD age of the participants was 67 ± 12 years, and the mean ± SD treatment duration was 5.3 ± 4.4 years. Treated eyes had poorer non-invasive tear film breakup time (p = 0.03), tear film osmolarity (p = 0.04), bulbar conjunctival hyperaemia (p = 0.04), eyelid margin abnormality grade (p = 0.01), tear meniscus height (p = 0.03), and anaesthetised Schirmer value (p = 0.04) than fellow eyes. There were no significant differences in dry eye symptomology, meibomian gland assessments, and ocular surface staining between treated and fellow eyes (all p > 0.05). Adverse changes in tear film stability, tear osmolarity, conjunctival hyperaemia, and eyelid margins were observed in treated eyes. This suggests that inflammatory mechanisms may be implicated in the development of dry eye in patients receiving long term topical anti-glaucoma therapy. Copyright © 2018 Elsevier Inc. All rights reserved.

Prenatal diagnosis and molecular characterization of a novel locus for Dandy-Walker malformation on chromosome 7p21.3.

PubMed

Liao, Can; Fu, Fang; Li, Ru; Yang, Xin; Xu, Qing; Li, Dong-Zhi

2012-01-01

We present three foetuses with Dandy-Walker malformation, intra-uterine growth restriction and multiple congenital abnormalities, who were studied by array-based comparative genomic hybridization and revealed a novel locus on chromosome 7p21.3. The association of pure chromosome 7p aberrations with Dandy-Walker malformation has rarely been reported. The present study suggests that the critical region associated with Dandy-Walker malformation is restricted to 7p21.3, including the cerebellar disease associated genes NDUFA4 and PHF14. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Management of Low-Flow Vascular Malformations: Clinical Presentation, Classification, Patient Selection, Imaging and Treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCafferty, Ian, E-mail: ian.mccafferty@uhb.nhs.uk

This review article aims to give an overview of the current state of imaging, patient selection, agents and techniques used in the management of low-flow vascular malformations. The review includes the current classifications for low-flow vascular malformations including the 2014 updates. Clinical presentation and assessment is covered with a detailed section on the common sclerosant agents used to treat low-flow vascular malformations, including dosing and common complications. Imaging is described with a guide to a simple stratification of the use of imaging for diagnosis and interventional techniques.

Description and initial evaluation of an educational and psychosocial support model for adults with congenitally malformed hearts.

PubMed

Rönning, Helén; Nielsen, Niels Erik; Swahn, Eva; Strömberg, Anna

2011-05-01

Various programmes for adults with congenitally malformed hearts have been developed, but detailed descriptions of content, rationale and goals are often missing. The aim of this study was to describe and make an initial evaluation of a follow-up model for adults with congenitally malformed hearts, focusing on education and psychosocial support by a multidisciplinary team (EPS). The model is described in steps and evaluated with regards to perceptions of knowledge, anxiety and satisfaction. The EPS model included a policlinic visit to the physician/nurse (medical consultation, computer-based and individual education face-to-face as well as psychosocial support) and a 1-month telephone follow-up. Fifty-five adults (mean age 34, 29 women) with the nine most common forms of congenitally malformed hearts participated in the EPS model as well as the 3-months follow-up. Knowledge about congenital heart malformation had increased in 40% of the participants at the 3-months follow-up. This study describes and evaluates a model that combines a multidisciplinary approach and computer-based education for follow-up of adults with congenitally malformed hearts. The EPS model was found to increase self-estimated knowledge, but further evaluations need to be conducted to prove patient-centred outcomes over time. The model is now ready to be implemented in adults with congenitally malformed hearts. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

The role of eye movements in decision making and the prospect of exposure effects.

PubMed

Bird, Gary D; Lauwereyns, Johan; Crawford, Matthew T

2012-05-01

The aim of the current study was to follow on from previous findings that eye movements can have a causal influence on preference formation. Shimojo et al. (2003) previously found that faces that were presented for a longer duration in a two alternative forced choice task were more likely to be judged as more attractive. This effect only occurred when an eye movement was made towards the faces (with no effect when faces were centrally presented). The current study replicated Shimojo et al.'s (2003) design, whilst controlling for potential inter-stimuli interference in central presentations. As per previous findings, when eye movements were made towards the stimuli, faces that were presented for longer durations were preferred. However, faces that were centrally presented (thus not requiring an eye movement) were also preferred in the current study. The presence of an exposure duration effect for centrally presented faces casts doubt on the necessity of the eye movement in this decision making process and has implications for decision theories that place an emphasis on the role of eye movements in decision making. Copyright © 2012 Elsevier Ltd. All rights reserved.

Comparison of distance and near visual acuity in patients with vision loss due to cataract.

PubMed

Mercado, Carmel L; Doroslovački, Pavle; Wang, Jiangxia; Siddiqui, Aazim A; Kolker, Andrew F; Kolker, Richard J

2017-02-01

The purpose of this study was to assess whether there is a disparity in distance and near best-corrected visual acuity (BCVA) in cataract eyes. 102 patients with cataract (N = 121 eyes) were seen in clinic between January and November 2013 at the Wilmer Eye Institute Comprehensive Eye Service. An age-related macular degeneration (ARMD) group (N = 27 eyes) was also identified for comparison. Distance and near BCVA were measured as part of the standard ophthalmic evaluation. Snellen measurements were converted to their LogMAR equivalents for statistical analysis. Near was better than distance BCVA with mean difference of 1.38 lines (P < 0.001) in the cataract eyes. This disparity was not seen in the ARMD eyes. Near-distance BCVA disparity is a statistically significant finding seen with cataracts. This may have further implications in patients with both cataract and ARMD as the presence of disparity may suggest a cataract etiology playing a greater role in vision loss. This comparison may be useful for surgical prognostication and as a quick triage tool in conjunction with, or in place of, a potential acuity meter and dilated near-pinhole test.

Ophthalmological implications of the chronic infections with the hepatitis C Virus.

PubMed

Anisia-Iuliana, Alexa; Alina, Cantermir; Elena, Ciuntu Roxana; Dorin, Chiseliţă

2015-01-01

Objectives. Report of a clinical case reuniting the dry eye syndrome in a severe form, the Mooren's ulcer and necrotizing anterior scleritis with inflammation, with bilateral affectation in the context of chronic infection with the hepatitis C virus. Methods. A female patient aged 66 diagnosed with chronic hepatitis with HCV, with ophthalmological antecedents of Mooren's ulcer and severe form of dry eye syndrome in both eyes, comes to the emergency unit with hypopyon corneal ulcer in the right eye, shortly afterwards developing necrotizing anterior scleritis with inflammation. The patient is administered treatment for chronic hepatitis C, following which the ARN-HCV viremia decreases without ocular exacerbations. When the viremia level increases again, two lesions indicating necrotizing anterior scleritis are observed in the left eye. The evolution is favourable with topical and systemic treatment with corticosteroids. Complicated cataract is surgically treated in the right eye and vitreous humour is collected during surgery. Results. Visual acuity increases in the right eye after the surgery, while antibodies-HCV are identified in the vitreous humour. Conclusions. Chronic infection with hepatitis C virus displays multiple extra-hepatic manifestations and the ophthalmological ones require a multidisciplinary approach from both the chronic diseases practitioner and the ophthalmologist.

Ophthalmological implications of the chronic infections with the hepatitis C Virus

PubMed Central

Anisia-Iuliana, Alexa; Alina, Cantermir; Elena, Ciuntu Roxana; Dorin, Chiseliţă

2015-01-01

Objectives. Report of a clinical case reuniting the dry eye syndrome in a severe form, the Mooren’s ulcer and necrotizing anterior scleritis with inflammation, with bilateral affectation in the context of chronic infection with the hepatitis C virus. Methods. A female patient aged 66 diagnosed with chronic hepatitis with HCV, with ophthalmological antecedents of Mooren’s ulcer and severe form of dry eye syndrome in both eyes, comes to the emergency unit with hypopyon corneal ulcer in the right eye, shortly afterwards developing necrotizing anterior scleritis with inflammation. The patient is administered treatment for chronic hepatitis C, following which the ARN-HCV viremia decreases without ocular exacerbations. When the viremia level increases again, two lesions indicating necrotizing anterior scleritis are observed in the left eye. The evolution is favourable with topical and systemic treatment with corticosteroids. Complicated cataract is surgically treated in the right eye and vitreous humour is collected during surgery. Results. Visual acuity increases in the right eye after the surgery, while antibodies-HCV are identified in the vitreous humour. Conclusions. Chronic infection with hepatitis C virus displays multiple extra-hepatic manifestations and the ophthalmological ones require a multidisciplinary approach from both the chronic diseases practitioner and the ophthalmologist. PMID:29450318

Post-Doctoral Research Award

DTIC Science & Technology

1988-12-01

day old tadpoles have completed most of organogenesis and, therefore, are usually not susceptible to malformation . An exception is limb development...antagonistic response may have b.een the result of poorer absorption of hydroxyurea by the severly malformed embryos, as isoniazid had a much greater...Short-chain carboxylic acids showed concentration additive joint actionsfor induction of malformation . Combinations of DNA synthesis inhibitors

Abernethy malformation with portal vein aneurysm in a child

PubMed Central

Chandrashekhara, Sheragaru H.; Bhalla, Ashu Seith; Gupta, Arun Kumar; Vikash, C. S.; Kabra, Susheel Kumar

2011-01-01

Abernethy malformation is an extremely rare anomaly of the splanchnic venous system. We describe multidetector computed tomography findings of an incidentally detected Abernethy malformation with portal vein aneurysm in a two-and-half-year old child. The computed tomography scan was performed for the evaluation of respiratory distress, poor growth, and loss of appetite. PMID:21430844

Angiotensin converting enzyme inhibitors and aortic arch obstructive malformations.

PubMed

Maliheh, Kadivar; Abdorrazagh, Kiani; Armen, Kocharian; Reza, Shabanian

2006-10-01

We describe two newborn infants with aortic arch obstructive malformations who became anuric after initiation of captopril. Since angiotensin converting enzyme inhibitors can alter renal blood flow by reduction in angiotensin II and blocking autoregulation phenomenon, it is important to use them with great caution in neonates with aortic arch obstructive malformations, while monitoring their renal function closely.

[Expansive suboccipital cranioplasty in Chiari 1 malformation (a case report and technical notes)].

PubMed

Korshunov, A E; Kushel', Yu V

In this case report, we describe the use of expansive suboccipital cranioplasty in Chiari-1 malformation. The technique improves the efficacy and safety of treatment for Chiari-1 malformation. The technique can be used as an adjunct treatment together with any variant of posterior fossa decompression, including duroplasty and extradural decompression.

Arteriovenous malformation of the external ear: a clinical assessment with a scoping review of the literature.

PubMed

Kim, Shin Hye; Han, Seung Hoon; Song, Yoonjae; Park, Chang Sik; Song, Jae-Jin

Auricular Arteriovenous Malformation of the external ear is a rarely encountered disease; in particular, arteriovenous malformation arising from the auricle, with spontaneous bleeding, has seldom been reported. In the current study, we report an unusual case of late-onset auricular arteriovenous malformation originating from the posterior auricular artery that was confirmed by computed tomographic angiography. The case was successfully managed by pre-surgical intravascular embolization followed by total lesion excision. Prompted by this case, we also present a scoping review of the literature. A case of a 60 year-old man with right auricular arteriovenous malformation treated in our tertiary care center, and 52 patients with auricular arteriovenous malformation described in 10 case reports and a retrospective review are presented. Auricular arteriovenous malformation can manifest as swelling of the ear, pulsatile tinnitus, pain, and/or bleeding. On physical examination, a pulsatile swelling and/or a tender mass is evident. When arteriovenous malformation is suspected, the lesions should be visualized using imaging modalities that optimally detect vascular lesions, and managed via embolization, mass excision, or auricular resection. Effectiveness of the various diagnostic methods used and the treatment outcomes were analyzed. Various imaging modalities including Doppler sonography, computed tomographic angiography, magnetic resonance angiography, and/or transfemoral cerebral angiography were used to diagnose 38 cases reported in the literature. In another 15 cases, no imaging was performed; treatment was determined solely by physical examination and auscultation. Of the total of 53 cases, 12 were not treated (their symptoms were merely observed) whereas 20 underwent therapeutic embolization. In total, 32 patients, including 1 patient who was not treated and 10 with persistent or aggravated arteriovenous malformation after previous embolization, underwent mass excision or auricular resection depending on the extent of the lesion. No major postoperative complication was recorded. The postoperative follow-up duration varied from 1 month to 19 years, and only one case of unresectable, residual cervicofacial arteriovenous malformation was recorded. Auricular arteriovenous malformation is a rarely encountered disease, but should be suspected if a patient presents with a swollen ear and pulsatile tinnitus. Appropriate imaging is essential for diagnosis and evaluation of the extent of disease. As embolization affords only relatively poor control, total surgical removal of the vascular mass is recommended. Copyright © 2016 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

The Cotard syndrome. Report of two patients: with a review of the extended spectrum of 'délire des négations'.

PubMed

Gardner-Thorpe, C; Pearn, J

2004-08-01

The Cotard syndrome is characterized by the delusion where an individual insists that he has died or part of his body has decayed. Although described classically in schizophrenia and bipolar disorder, physical disorders including migraine, tumour and trauma have also been associated with the syndrome. Two new cases are described here, the one associated with arteriovenous malformations and the other with probable multiple sclerosis. The delusion has been embarrassing to each patient. Study of such cases may have wider implications for the understanding of the psychotic interpretation of body image, for example that occurring in anorexia nervosa.

Surgical implications of portal venous system malformation

PubMed Central

Marks, Charles

1974-01-01

The significance of congenital abnormalities in predisposing to portal hypertension and variceal haemorrhage needs to be remembered when these effects manifest in childhood, as portal venography will permit elucidation of the complicated congenital developmental abnormalities underlying the pathological condition and permit rational surgical amelioration. In the presence of portal hypertension the development of a collateral venous circulation may be represented by a hepatopetal or hepatofugal circulatory pattern and will closely parallel the developmental areas where portal and systemic venous circulations meet, being representative of the embryological anastomosis between the vitelloumbilical system and the posterior cardinal system of veins. ImagesFig. 3Fig. 5Fig. 6 PMID:4614690

Beta-lactam antibiotics during pregnancy: a cross-sectional comparative study Zagreb-Novi Sad.

PubMed

Erić, M; Leppée, M; Sabo, A; Culig, J

2012-01-01

During pregnancy, a number of changes occur in women's body, and some medications are safe and some are not. The aim of our study was to establish the possible correlation between use of beta-lactam antibiotics in pregnancy and occurrence of congenital malformations. The study included 893 pregnant women from Zagreb and 6099 pregnant women from Novi Sad. 527 pregnant women used beta-lactams. First part of the study (one month study) was performed at four maternity hospitals in Zagreb, Croatia. Second part were collected as a part of the study analysing the teratogenicity of drugs used in pregnancy, a longitudinal study performed in Novi Sad district. Pregnant women most frequently used antibacterial agents in the first trimester of pregnancy. They used 15 different antibacterial medications, most often beta-lactams. In Zagreb arm, out of the total number of pregnant women that used medications during pregnancy (859), 231 (26.9%) used beta-lactam antibiotics. Malformations were detected in 8 (3.5%) cases. The prevalence of malformations in newborns whose mothers did not take beta-lactam antibiotics in pregnancy (662) was 2.7% (18 newborns with malformations). In Novi Sad arm, out of the total number of pregnant women that used medications during pregnancy (2013), 296 (14.7%) used beta-lactam antibiotics. Malformations were detected in 14 (4.7%) cases. The prevalence of malformations in newborns whose mothers did not take beta-lactam antibiotics in pregnancy (5803) was 1.7% (99 newborns with malformations). The results show possible teratogenic potential even with those antibacterials which are considered safe (amoxicillin) but as those are usually minor malformations they often pass undetected. International pharmacoepidemiological studies of drug use in pregnancy could substantially contribute to the improvement of pharmacotherapy, and could be of great help in assessing the fetal risks.

Malformations among 289,365 Births Attributed to Mutations with Autosomal Dominant and Recessive and X-Linked Inheritance.

PubMed

Toufaily, M Hassan; Westgate, Marie-Noel; Nasri, Hanah; Holmes, Lewis B

2018-01-01

The number of malformations attributed to mutations with autosomal or X-linked patterns of inheritance has increased steadily since the cataloging began in the 1960s. These diagnoses have been based primarily on the pattern of phenotypic features among close relatives. A malformations surveillance program conducted in consecutive pregnancies can identify both known and "new" hereditary disorders. The Active Malformations Surveillance Program was carried out among 289,365 births over 41 years (1972-2012) at Brigham and Women's Hospital in Boston. The findings recorded by examining pediatricians and all consultants were reviewed by study clinicians to establish the most likely diagnoses. The findings in laboratory testing in the newborn period were reviewed, as well. One hundred ninety-six (0.06%) infants among 289,365 births had a malformation or malformation syndrome that was attributed to Mendelian inheritance. A total of 133 (68%) of the hereditary malformations were attributed to autosomal dominant inheritance, with 94 (71%) attributed to apparent spontaneous mutations. Forty-six (23%) were attributed to mutations with autosomal recessive inheritance, 17 associated with consanguinity. Seventeen (9%) were attributed to X-linked inheritance. Fifteen novel familial phenotypes were identified. The family histories showed that most (53 to 71%) of the affected infants were born, as a surprise, to healthy, unaffected parents. It is important for clinicians to discuss with surprised healthy parents how they can have an infant with an hereditary condition. Future studies, using DNA samples from consecutive populations of infants with malformations and whole genome sequencing, will identify many more mutations in loci associated with mendelizing phenotypes. Birth Defects Research 110:92-97, 2018.© 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Sella turcica morphology and the pituitary gland-a new contribution to craniofacial diagnostics based on histology and neuroradiology.

PubMed

Kjær, Inger

2015-02-01

The present review summarizes two decades of published and unpublished studies on normal and pathological development of sella turcica and pituitary gland in humans. The pathological conditions are studied in known genotype deviations, syndromes, and other malformations. The studies include histological analyses of human prenatal material and profile radiographic analyses of human postnatal material, supplemented in a few cases with neuroradiology. Prenatal and postnatal results are compared. Similarities between prenatal and postnatal deviations in sella turcica morphology were demonstrated. Malformations in the pituitary gland were observed in several cases. For diagnostic purposes, the review distinguishes between deviations in the anterior wall and in the posterior wall of the sella turcica. Deviations in the anterior wall seem to be associated with deviations specifically in the frontonasal developmental field, while deviations in the posterior wall are often connected with malformations in the posterior structures, e.g. the cerebellum. In normal cases, minor variations in morphology are observed. In each pathological case, a specific malformation pattern was observed in sella turcica morphology, varying from mild to severe phenotype. The malformation in the sella turcica/pituitary gland can be associated with a malformation within a developmental field that forms the craniofacial region (frontonasal, maxillary, palatal, and mandibular fields), sometimes also involving the brain stem, thymus, thyroid, and heart (velocardiofacial syndrome). Pathological sella turcica morphology can also be associated with malformations in the cerebellum and larynx (Cri-du-Chat syndrome). This review demonstrates the value of combining profile radiographic diagnostics with neuroradiological diagnostics in cases with malformed sella turcicae. © The Author 2012. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Time-resolved magnetic resonance angiography (MRA) at 3.0 Tesla for evaluation of hemodynamic characteristics of vascular malformations: description of distinct subgroups.

PubMed

Hammer, Simone; Uller, Wibke; Manger, Florentine; Fellner, Claudia; Zeman, Florian; Wohlgemuth, Walter A

2017-01-01

Quantitative evaluation of hemodynamic characteristics of arteriovenous and venous malformations using time-resolved magnetic resonance angiography (MRA) at 3.0 Tesla. Time-resolved MRA with interleaved stochastic trajectories (TWIST) at 3.0 Tesla was studied in 83 consecutive patients with venous malformations (VM) and arteriovenous malformations (AVM). Enhancement characteristics were calculated as percentage increase of signal intensity above baseline over time. Maximum percentage signal intensity increase (signal max ), time intervals between onset of arterial enhancement and lesion enhancement (t onset ), and time intervals between beginning of lesion enhancement and maximum percentage of lesion enhancement (t max ) were analyzed. All AVMs showed a high-flow hemodynamic pattern. Two significantly different (p < 0.001) types of venous malformations emerged: VMs with arteriovenous fistulas (AVF) (median signal max 737 %, IQR [interquartile range] = 511 - 1182 %; median t onset 5 s, IQR = 5 - 10 s; median t max 35 s, IQR = 26 - 40 s) and without AVFs (median signal max 284 %, IQR = 177-432 %; median t onset 23 s, IQR = 15 - 30 s; median t max 60 s, IQR = 55 - 75 s). Quantitative evaluation of time-resolved MRA at 3.0 Tesla provides hemodynamic characterization of vascular malformations. VMs can be subclassified into two hemodynamic subgroups due to presence or absence of AVFs. • Time-resolved MRA at 3.0 Tesla provides quantitative hemodynamic characterization of vascular malformations. • Malformations significantly differ in time courses of enhancement and signal intensity increase. • AVMs show a distinctive high-flow hemodynamic pattern. • Two significantly different types of VMs emerged: VMs with and without AVFs.

[Focus on Dandy-Walker malformation].

PubMed

Klein, O; Pierre-Kahn, A

2006-09-01

The aim of this review is to summarize our knowledge about Dandy-Walker malformation (DWM) and introduce recent notions about its prognosis. DWM is a malformation associating hypoplasia of the vermis, pseudocystic fourth ventricle, upward displacement of the tentorium, torcular and lateral sinuses and anterio-posterior enlargement of the posterior fossa. It is frequently associated with genetic anomalies, brain malformations (anomalies of gyration, grey matter heterotopias, meningoceles, corpus callosum agenesis...) or systemic malformations (heart, orthopedic, intestinal, urogenital and facial anomalies). It is also part of many syndromes. Its rarity, the difficulty of its diagnosis, the fact that the malformation is mainly known through hospitalized patients, mainly from neurosurgical departments, have made its definition variable and prevents us from having an accurate knowledge of its natural history and prognosis. Hydrocephalus, so frequent in neurosurgical series that some have included it in the definition, is actually rare as has been seen in prenatal series. Treatment, when necessary, is still controversial, the main options remaining cyst fenestration, ventriculo- and/or cystoperitoneal shunts and more recently endoscopic third ventriculostomy. The prognosis, commonly said to be unpredictable, is actually foreseeable after scrutinous observation of the brain anatomy, and mainly of the vermis. A cerebellar vermis with three groups of lobes and two main fissures, as identified on MRI T2 sagittal views, not only has the greatest chance to not be associated with other malformation but also to have a favorable neurocognitive outcome. On the contrary, a deeply dysgenetic vermis with only two or one recognizable lobes is not only constantly associated with other brain malformation but also with poor prognosis. This is a recent advance that may be important for those involved in prenatal counselling.

Neurosurgical Issues in Pregnancy.

PubMed

Can, Anil; Du, Rose

2017-12-01

Although rare, intracranial hemorrhage due to rupture of cerebral vascular malformations or intracranial aneurysms during pregnancy is a potentially devastating and life-threatening disorder, posing a diagnostic and therapeutic challenge to a multidisciplinary team of neurosurgeons, neurologists, obstetricians, and anesthesiologists. Despite the significant risk of morbidity and mortality affecting both the mother and the unborn child, knowledge of the natural history, epidemiology, and appropriate management of cerebral vascular malformations and intracranial aneurysms in pregnant women is limited. Although emergent neurosurgical concerns usually outweigh obstetric considerations, and treatment of these disorders is generally similar in pregnant and nonpregnant women, any necessary and feasible modifications to protect the unborn child should be made. This article reviews the management of ruptured intracranial aneurysms and cerebral vascular malformations, including arteriovenous malformations, cavernous malformations, and moyamoya disease, in women during pregnancy, partus, and puerperium. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Type I Chiari malformation presenting central sleep apnea.

PubMed

Kitamura, Takuro; Miyazaki, Soichiro; Kadotani, Hiroshi; Kanemura, Takashi; Okawa, Masako; Tanaka, Toshihiko; Komada, Ichiro; Hatano, Taketo; Suzuki, Hideaki

2014-04-01

Sleep apnea is a rare but a well-known clinical feature of type I Chiari malformation. It may be obstructive or central in nature. Sleep apnea in patients with type I Chiari malformation rarely presents without accompanying neurological signs or symptoms. We here report a case of a 10-year-old girl who presented with central sleep apnea without any other neurological signs but was ultimately diagnosed with type I Chiari malformation. The patient initially showed mild improvement in symptoms after administration of an acetazolamide. Finally, posterior fossa decompression dramatically improved her respiratory status during sleep, both clinically and on polysomnography. This case suggests that type I Chiari malformation should be considered in the differential diagnoses of central apneas in children, even if there are no other neurological signs and symptoms. Furthermore, sagittal craniocervical magnetic resonance imaging may be necessary for a definitive diagnosis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Chiari I Malformation in Nephropathic Cystinosis

PubMed Central

Rao, Kavya I; Hesselink, John; Trauner, Doris A

2015-01-01

Objective To determine the relative incidence of Chiari I malformations in children with cystinosis compared with those in the general population. Study design Magnetic resonance imaging (MRI) scans were performed on 53 patients with nephropathic cystinosis and 120 controls, age range 3-18 years. Results Ten of 53 (18.9%) cystinosis patients had Chiari I or tonsillar ectopia, and only 2 of 120 controls (1.6%) had a similar finding. At least 2 of the patients had symptoms or signs thought to be related to the malformation, and one had surgical decompression. Two had an associated cervical syrinx. Conclusions Children with cystinosis have a 12-fold higher prevalence of Chiari I malformations than the general pediatric population. Chiari I malformations should be high on the differential diagnosis when individuals with cystinosis develop neurologic signs and symptoms, and MRI scans should be performed on children with cystinosis who present with new-onset headache, ataxia, incontinence, or other unexplained neurologic symptoms. PMID:26265281

Inner ear abnormalities in patients with Goldenhar syndrome.

PubMed

Bisdas, Sotirios; Lenarz, Minoo; Lenarz, Thomas; Becker, Hartmut

2005-05-01

The objective of this study is to investigate the inner ear malformations in patients with Goldenhar syndrome and to hypothesize the potential embryopathogenesis of these malformations. Retrospective case review. Tertiary referral center. Fourteen patients with Goldenhar syndrome. Each patient underwent hearing tests and high-resolution computed tomography (CT) of the temporal bone. In six patients, magnetic resonance imaging of the temporal bone also was performed. Among the 14 patients with Goldenhar syndrome, 13 had outer and middle ear anomalies and 5 (36%) had inner ear malformations, including one case of common cavity. Our observations regarding inner ear anomalies in Goldenhar syndrome correlate with the reported cases in the literature and may help to hypothesize the embryological origin of these malformations, which can caused by an early developmental arrest in the fourth gestational week. Specialists evaluating patients with Goldenhar syndrome should be aware of the possibility of inner ear malformations, which could be diagnosed earlier with appropriate imaging studies.

[Genetic deafness].

PubMed

Marcolla, A; Bouchetemble, P; Lerosey, Y; Marie, J-P; Dehesdin, D

2006-06-01

The aim of this study was to review the different types of genetic deafness. We describe syndromic and isolated sensorineural deafness and transmission deafness. Genetic sensorineural syndromic deafness represents 30% of cases of genetic deafness. A frequent cause is Pendred syndrome, which associates congenital sensorineural deafness with goitre and malformations of the inner ear which can be identified on computed tomography scan. Isolated deafness which is responsible for 70% of cases of genetic deafness is then outlined. Among the different types of isolated deafness, 80% are autosomal recessive disorders. A frequent form of autosomal recessive deafness is due to mutations in the connexin 26 gene. Lastly, we detail transmission deafness dominated by aplasia. Major aplasia is characterized by a malformation of the external ear associated with malformations of the middle ear whereas, minor aplasia corresponds to a malformation of the middle ear, sometimes associated with minor external ear malformations. For each type of deafness we propose a systematic assessment.

The relationship between temperamental traits and the level of performance of an eye-hand co-ordination task in jet pilots.

PubMed

Biernacki, Marcin; Tarnowski, Adam

2008-01-01

When assessing the psychological suitability for the profession of a pilot, it is important to consider personality traits and psychomotor abilities. Our study aimed at estimating the role of temperamental traits as components of pilots' personality in eye-hand co-ordination. The assumption was that differences in the escalation of the level of temperamental traits, as measured with the Formal Characteristic of Behaviour-Temperament Inventory (FCB-TI), will significantly influence eye-hand co-ordination. At the level of general scores, enhanced briskness proved to be the most important trait for eye-hand co-ordination. An analysis of partial scores additionally underlined the importance of sensory sensitivity, endurance and activity. The application of eye-hand co-ordination tasks, which involve energetic and temporal dimensions of performance, helped to disclose the role of biologically-based personality traits in psychomotor performance. The implication of these findings for selecting pilots is discussed.

Nutrients for the aging eye

PubMed Central

Rasmussen, Helen M; Johnson, Elizabeth J

2013-01-01

The incidence of age-related eye diseases is expected to rise with the aging of the population. Oxidation and inflammation are implicated in the etiology of these diseases. There is evidence that dietary antioxidants and anti-inflammatories may provide benefit in decreasing the risk of age-related eye disease. Nutrients of interest are vitamins C and E, β-carotene, zinc, lutein, zeaxanthin, and the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid. While a recent survey finds that among the baby boomers (45–65 years old), vision is the most important of the five senses, well over half of those surveyed were not aware of the important nutrients that play a key role in eye health. This is evident from a national survey that finds that intake of these key nutrients from dietary sources is below the recommendations or guidelines. Therefore, it is important to educate this population and to create an awareness of the nutrients and foods of particular interest in the prevention of age-related eye disease. PMID:23818772

The eyes don't have it: lie detection and Neuro-Linguistic Programming.

PubMed

Wiseman, Richard; Watt, Caroline; ten Brinke, Leanne; Porter, Stephen; Couper, Sara-Louise; Rankin, Calum

2012-01-01

Proponents of Neuro-Linguistic Programming (NLP) claim that certain eye-movements are reliable indicators of lying. According to this notion, a person looking up to their right suggests a lie whereas looking up to their left is indicative of truth telling. Despite widespread belief in this claim, no previous research has examined its validity. In Study 1 the eye movements of participants who were lying or telling the truth were coded, but did not match the NLP patterning. In Study 2 one group of participants were told about the NLP eye-movement hypothesis whilst a second control group were not. Both groups then undertook a lie detection test. No significant differences emerged between the two groups. Study 3 involved coding the eye movements of both liars and truth tellers taking part in high profile press conferences. Once again, no significant differences were discovered. Taken together the results of the three studies fail to support the claims of NLP. The theoretical and practical implications of these findings are discussed.

The Eyes Don’t Have It: Lie Detection and Neuro-Linguistic Programming

PubMed Central

Wiseman, Richard; Watt, Caroline; ten Brinke, Leanne; Porter, Stephen; Couper, Sara-Louise; Rankin, Calum

2012-01-01

Proponents of Neuro-Linguistic Programming (NLP) claim that certain eye-movements are reliable indicators of lying. According to this notion, a person looking up to their right suggests a lie whereas looking up to their left is indicative of truth telling. Despite widespread belief in this claim, no previous research has examined its validity. In Study 1 the eye movements of participants who were lying or telling the truth were coded, but did not match the NLP patterning. In Study 2 one group of participants were told about the NLP eye-movement hypothesis whilst a second control group were not. Both groups then undertook a lie detection test. No significant differences emerged between the two groups. Study 3 involved coding the eye movements of both liars and truth tellers taking part in high profile press conferences. Once again, no significant differences were discovered. Taken together the results of the three studies fail to support the claims of NLP. The theoretical and practical implications of these findings are discussed. PMID:22808128

Effects of individual differences in verbal skills on eye-movement patterns during sentence reading

PubMed Central

Kuperman, Victor; Van Dyke, Julie A.

2011-01-01

This study is a large-scale exploration of the influence that individual reading skills exert on eye-movement behavior in sentence reading. Seventy one non-college-bound 16–24 year-old speakers of English completed a battery of 18 verbal and cognitive skill assessments, and read a series of sentences as their eye movements were monitored. Statistical analyses were performed to establish what tests of reading abilities were predictive of eye-movement patterns across this population and how strong the effects were. We found that individual scores in rapid automatized naming and word identification tests (i) were the only participant variables with reliable predictivity throughout the time-course of reading; (ii) elicited effects that superceded in magnitude the effects of established predictors like word length or frequency; and (iii) strongly modulated the influence of word length and frequency on fixation times. We discuss implications of our findings for testing reading ability, as well as for research of eye-movements in reading. PMID:21709808

Drainage of the Left Hepatic Vein into the Coronary Sinus, a Rare Intraoperative Finding.

PubMed

Morshuis, Wouter G; de Lind van Wijngaarden, Robert A F; Kik, Charles; Bogers, Ad J J C

2015-11-01

In a 76-year-old female undergoing coronary artery bypass surgery, a persistent left hepatic vein was observed. Draining of this vein into the coronary sinus is an extremely rare embryological malformation and this is the first case to be reported as a solitary malformation in absence of other cardiac malformations. © 2015 Wiley Periodicals, Inc.

Joint Actions of Developmental Toxicants.

DTIC Science & Technology

1991-06-01

antagonistic response may have been the result of poorer absorption of hydroxyurea by the severly malformed embryos, as isoniazid had a much greater...chain carboxylic acids showed concentration additive joint actions for induction of malformation . Combinations of DNA synthesis inhibitors showed...response additive to antagonistic joint actions at malformation -inducing con- centrations. Since each compound inhibits a different enzyme in the process of

Cerebellar and Brainstem Malformations.

PubMed

Poretti, Andrea; Boltshauser, Eugen; Huisman, Thierry A G M

2016-08-01

The frequency and importance of the evaluation of the posterior fossa have increased significantly over the past 20 years owing to advances in neuroimaging. Conventional and advanced neuroimaging techniques allow detailed evaluation of the complex anatomic structures within the posterior fossa. A wide spectrum of cerebellar and brainstem malformations has been shown. Familiarity with the spectrum of cerebellar and brainstem malformations and their well-defined diagnostic criteria is crucial for optimal therapy, an accurate prognosis, and correct genetic counseling. This article discusses cerebellar and brainstem malformations, with emphasis on neuroimaging findings (including diagnostic criteria), neurologic presentation, systemic involvement, prognosis, and recurrence. Copyright © 2016 Elsevier Inc. All rights reserved.

Parasitic twin--a supernumerary limb associated with spinal malformations. A case report.

PubMed

Sahlu, Abat; Mesfin, Brook; Tirsit, Abenezer; Debebe, Tequam; Wester, Knut

2016-03-01

We describe a case of rachipagus parasitic twin with spinal cord malformations (lipomyelomeningocele and tethered cord) in a 7-month-old Ethiopian infant. The parasitic mass had a well-formed foot, ankle and lower leg and a small sinus that resembled an anus. Magnetic resonance imaging scans revealed spinal malformations including a distal syringohydromyelia. The mass was successfully resected and the dural attachment was closed. Histopathological examination confirmed the diagnosis. Postoperatively, the child had unchanged, intact neurological function in both lower limbs. Almost all rachipagus parasitic twins are associated with spinal malformations. They should, therefore, be operated on by surgeons experienced in myelomeningocele surgery.

Pediatric neuroanesthesia. Arteriovenous malformations.

PubMed

Newfield, P; Hamid, R K

2001-06-01

Intracranial arteriovenous malformations can occur singly, multiply, and in conjunction with aneurysms and denovo, family, or in conjunction with connective-tissue disorders. Intracranial hemorrhage is the most common presentation, occurring in 20% to 50% of cases. In children, seizures are the second most common presentation occurring in 15% to 20% of cases. The modalities available treatment of arteriovenous malformations are microsurgery, embolization, and stereotactic radiosurgery with heavy particles, alpha knife, or linear accelerator. Induction, maintenance, and emergence from anesthesia are designed to prevent rupture of arteriovenous malformation and aneurysm and to improve intracranial compliance in the presence of an intracranial hematoma, during both diagnostic (CT, MR scanning) and therapeutic procedures.

Management of lymphatic malformations in children.

PubMed

Bagrodia, Naina; Defnet, Ann M; Kandel, Jessica J

2015-06-01

To review the literature on lymphatic malformations and to provide current opinion about the management of these lesions. Current treatment options include nonoperative management, surgery, sclerotherapy, radiofrequency ablation, and laser therapy. New therapies are emerging, including sildenafil, propranolol, sirolimus, and vascularized lymph node transfer. The primary focus of management centers on the patient's quality of life. Multimodal treatment of lymphatic malformations continues to expand as new information about the biology and genetics of these lesions is discovered, in addition to knowledge gained from clinical practice. A patient-centered approach should guide timing and modality of treatment. Continued study of lymphatic malformations will increase and solidify a treatment algorithm for these complicated lesions.

Rare association of spondylo costal dysostosis with split cord malformations type II: A case report and a brief review of literature

PubMed Central

Srinivas, Bhavanam Hanuma; Puligopu, Aneel Kumar; Sukhla, Dinesh; Ranganath, Prajnya

2014-01-01

Spondylo costal dysostosis (SCD) is a genetic skeletal disorder characterized by a variety of costo-vertebral malformations. SCD with type I split cord malformation (SCM) have been reported in the literature. We report an unusual association of SCD with type II SCM. Imaging studies revealed multiple vertebral segmentations, rib malformations, spina bifida and low lying cord with type II SCM at the D12-L3 level. She underwent detethering of the cord. To the best of our knowledge, this is the first report of the association of SCD with type II SCM. PMID:25250070

Fiber 1.56-1.9 μm lasers in treatment of vascular malformations in children and adults

NASA Astrophysics Data System (ADS)

Abushkin, Ivan A.; Privalov, Valeriy A.; Lappa, Alexander V.; Minaev, Vladimir P.

2013-03-01

A few new low invasive fiber laser technologies for treatment of 1) capillary malformations (port-wine stains), 2) venous, arterial, and arteriovenous malformations, 3) lymphatic malformations of 3 types: micro, small and large-cystic lymphangiomas are presented in this work. There were applied 1.56 μm laser distant photocoagulation, 1.56 μm laser endovascular thermotherapy, 1.9 μm laser instant ablation, 1.9 μm laser interstitial thermotherapy, and 1.9 μm laser excision. The technologies were applied to about 300 patients. Good clinical and esthetic results have been achieved in great majority cases.

Arnold Chiari Malformation With Sponastrime (Spondylar and Nasal Changes, With Striations of the Metaphyses) Dysplasia: A Case Report.

PubMed

Jeong, Je Hoon; Lee, A Leum; Cho, Sung Yoon; Jin, Dong Kyu; Im, Soo-Bin

2016-05-01

SPOndylar and NAsal changes, with STRIations of the Metaphyses (SPONASTRIME) dysplasia (SD) is a dwarfing autosomal recessive syndrome, characterized by a variety of clinical and radiographic features, which form the basis for diagnosis. We describe the presentation of an Arnold Chiari malformation in a patient with a clinical diagnosis of SD. The malformation was successfully treated by decompression of the foramen magnum and elevation of the cerebellum, with complete resolution of pain.We report a rare case of Arnold Chiari malformation in a patient presenting with clinical and radiographic features strongly suggestive of SD and be successfully treated.

Defining anural malformations in the context of a developmental problem

USGS Publications Warehouse

Meteyer, C.U.; Cole, Rebecca A.; Converse, K.A.; Docherty, D.E.; Wolcott, M.; Helgen, J.C.; Levey, R.; Eaton-Poole, L.; Burkhart, J.G.

2000-01-01

This paper summarizes terminology and general concepts involved in animal development for the purpose of providing background for the study and understanding of frog malformations. The results of our radiographic investigation of rear limb malformations in Rana pipiens provide evidence that frog malformations are the product of early developmental errors. Although bacteria, parasites and viruses were identified in these metamorphosed frogs, the relevant window to look for the teratogenic effect of these agents is in the early tadpole stage during limb development. As a result, our microbiological findings must be regarded as inconclusive relative to determining their contribution to malformations because we conducted our examinations on metamorphosed frogs not tadpoles. Future studies need to look at teratogenic agents (chemical, microbial, physical or mechanical) that are present in the embryo, tadpole, and their environments at the stages of development that are relevant for the malformation type. The impact of these teratogenic agents then needs to be assessed in appropriate animal models using studies that are designed to mimic field conditions. The results of these laboratory tests should then be analyzed in such a way that will allow comparison with the findings in the wild-caught tadpoles and frogs.

Ultrasound features in trisomy 13 (Patau syndrome) and trisomy 18 (Edwards syndrome) in a consecutive series of 47 cases.

PubMed

Kroes, I; Janssens, S; Defoort, P

2014-01-01

To determine and list the variety of the predominant appeal signs leading to referral and their accompanying features found during specialized ultrasound evaluation in foetuses with trisomy 13 and trisomy 18. In a period of thirty years, 1110 cases of foetal malformations were detected during specialized echographic evaluation. 47 Of these cases were foetuses with trisomy 13 or trisomy 18. We evaluated the predominant signs leading to referral, the difference and overlap in presenting signs between both syndromes and when the data were available, we also compared the echographic signs with the foetal pathology. In foetuses with trisomy 13 the most common malformations were craniofacial defects, cerebral malformations and genitourinary tract anomalies. The most common malformations associated with trisomy 18 were limb abnormalities and intrauterine growth restriction. Most malformations were predominant in trisomy 18, except for genitourinary tract anomalies. In most cases the sonographic signs correlated with the pathology findings. Trisomy 13 as well as trisomy 18 are characterized by a number of various malformations in the foetus. Most of the ultrasound features were predominant in foetuses with trisomy 18. Mostly the foetal pathology correlated with the sonographic evaluation.

Epilepsy surgery in patients with malformations of cortical development.

PubMed

Lüders, Hans; Schuele, Stephan U

2006-04-01

Patients with malformations of cortical development often suffer from intractable focal epilepsy. This review considers recent progress in the selection and seizure outcome of patients undergoing resective epilepsy surgery for this condition. Patients with malformations of cortical development restricted to part or even a whole hemisphere may be candidates for epilepsy surgery even when, due to microscopic malformations, magnetic resonance imaging shows no detectable lesion. Despite recent advances in structural and functional imaging, the majority of patients with this condition undergo invasive evaluation. Patients with focal cortical dysplasia, with and without a detectable lesion on magnetic resonance imaging, often have a favorable outcome with epilepsy surgery. The underlying pathological substrate seems to be a better predictor for surgical outcome in patients with focal cortical dysplasia than the presence of a lesion on magnetic resonance imaging. Epilepsy surgery can be offered in a highly selected subgroup of patients with unilateral nodular heterotopia. Seizures in hemimegalencephaly may respond favorably to hemispherectomy, although most children will continue to have seizures and significant functional impairments. Patients with focal epilepsy due to malformations of cortical development are often intractable to medical management. Resective epilepsy surgery can be beneficial, particularly for patients with focal cortical dysplasia and unilateral hemispheric malformations.

Hemifacial spasm associated with type 1 Chiari malformation: a retrospective study of 13 cases.

PubMed

Li, Ning; Zhao, Wei-Guo; Pu, Chun-Hua; Yang, Wen-Lei

2017-04-01

Hemifacial spasm (HFS) associated with type 1 Chiari malformation is particularly uncommon and is limited to isolated case report. The aims of this study were to report the clinical correlates of patients who had simultaneously HFS and type 1 Chiari malformation and to present the outcome of these patients treated with microvascular decompression (MVD) surgery. We retrospectively evaluated 13 patients who had simultaneously HFS and type 1 Chiari malformation among 675 HFS patients. Clinical features and radiological findings were collected from each patient and analyzed. All these 13 patients were surgically treated with MVD through retro-mastoid microsurgical approach, and postoperative outcomes were evaluated. A review of literature about this association was also provided. In this study, the frequency of type 1 Chiari malformation in HFS patients was 1.9 %. The clinical profile of this series of patients did not differ from typical form of primary HFS. MVD achieved satisfactory results in 11 patients (85 %) in short- and long-term follow-up. There was no mortality or severe complication occurred postoperatively. Although rare, clinician should be aware of the association of HFS and type 1 Chiari malformation and consider MVD as an effective surgical management.

The possible association between exposure to air pollution and the risk for congenital malformations.

PubMed

Farhi, Adel; Boyko, Valentina; Almagor, Jonatan; Benenson, Itzhak; Segre, Enrico; Rudich, Yinon; Stern, Eli; Lerner-Geva, Liat

2014-11-01

Over the last decade, there is growing evidence that exposure to air pollution may be associated with increased risk for congenital malformations. To evaluate the possible association between exposures to air pollution during pregnancy and congenital malformations among infants born following spontaneously conceived (SC) pregnancies and assisted reproductive technology (ART) pregnancies. This is an historical cohort study comprising 216,730 infants: 207,825 SC infants and 8905 ART conceived infants, during the periods 1997-2004. Air pollution data including sulfur dioxide (SO2), particulate matter <10 µm (PM10), nitrogen oxides (NOx) and ozone (O3) were obtained from air monitoring stations database for the study period. Using a geographic information system (GIS) and the Kriging procedure, exposure to air pollution during the first trimester and the entire pregnancy was assessed for each woman according to her residential location. Logistic regression models with generalized estimating equation (GEE) approach were used to evaluate the adjusted risk for congenital malformations. In the study cohort increased concentrations of PM10 and NOx pollutants in the entire pregnancy were associated with slightly increased risk for congenital malformations: OR 1.06(95% CI, 1.01-1.11) for 10 µg/m(3) increase in PM10 and OR 1.03(95% CI, 1.01-1.04) for 10 ppb increase in NOx. Specific malformations were evident in the circulatory system (for PM10 and NOx exposure) and genital organs (for NOx exposure). SO2 and O3 pollutants were not significantly associated with increased risk for congenital malformations. In the ART group higher concentrations of SO2 and O3 in entire pregnancy were associated (although not significantly) with an increased risk for congenital malformations: OR 1.06(95% CI, 0.96-1.17) for 1 ppb increase in SO2 and OR 1.15(95% CI, 0.69-1.91) for 10 ppb increase in O3. Exposure to higher levels of PM10 and NOx during pregnancy was associated with an increased risk for congenital malformations. Specific malformations were evident in the circulatory system and genital organs. Among ART pregnancies possible adverse association of SO2 and O3 exposure was also observed. Further studies are warranted, including more accurate exposure assessment and a larger sample size for ART pregnancies, in order to confirm these findings. Copyright © 2014 Elsevier Inc. All rights reserved.

Acidic mammalian chitinase in dry eye conditions.

PubMed

Musumeci, Maria; Aragona, Pasquale; Bellin, Milena; Maugeri, Francesco; Rania, Laura; Bucolo, Claudio; Musumeci, Salvatore

2009-07-01

An acidic mammalian chitinase (AMCase) seems to be implicated in allergic asthma and allergic ocular pathologies. The aim of this work was to investigate the role of AMCase during Sjögren's Syndrome (SS) and Meibomian Gland Dysfunction (MGD) dry eye diseases. Six patients with MGD dry eye (20-58 years, median 40) and six patients with dry eye associated to SS (32-60 years, median 47) were enrolled in this study. AMCase activity was measured in tears and AMCase mRNA expression was evaluated by real-time polymerase chain reaction from RNA extracted from epithelial cells of the conjunctiva. Six healthy adult subjects of the same age (34-44 years, median 39) were also studied as the control group. AMCase activity was significantly increased in patients affected by MGD dry eye (18.54 +/- 1.5 nmol/ml/h) and SS dry eye (8.94 +/- 1.0 nmol/ml/h) respectively, compared to healthy controls (1.6 +/- 0.2 nmol/ml/h). AMCase activity was higher in the tears of subjects with MGD dry eye (P < 0.001). AMCase mRNA was detected in conjunctival epithelial cells and the expression was significantly higher in MGD dry eye than SS dry eye. A significant correlation between AMCase activity in the tears and mRNA in conjunctival epithelial cells was found. AMCase may be an important marker in the pathogenesis of dry eye, suggesting the potential role of AMCase as a therapeutic target in these frequent pathologies.

Effect of the embolization material in the dose calculation for stereotactic radiosurgery of arteriovenous malformations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Galván de la Cruz, Olga Olinca; Lárraga-Gutiérrez, José Manuel, E-mail: jlarraga@innn.edu.mx; Laboratorio de Física Médica, Instituto Nacional de Neurología y Neurocirugía

2013-07-01

It is reported in the literature that the material used in an embolization of an arteriovenous malformation (AVM) can attenuate the radiation beams used in stereotactic radiosurgery (SRS) up to 10% to 15%. The purpose of this work is to assess the dosimetric impact of this attenuating material in the SRS treatment of embolized AVMs, using Monte Carlo simulations assuming clinical conditions. A commercial Monte Carlo dose calculation engine was used to recalculate the dose distribution of 20 AVMs previously planned with a pencil beam dose calculation algorithm. Dose distributions were compared using the following metrics: average, minimal and maximummore » dose of AVM, and 2D gamma index. The effect in the obliteration rate was investigated using radiobiological models. It was found that the dosimetric impact of the embolization material is less than 1.0 Gy in the prescription dose to the AVM for the 20 cases studied. The impact in the obliteration rate is less than 4.0%. There is reported evidence in the literature that embolized AVMs treated with SRS have low obliteration rates. This work shows that there are dosimetric implications that should be considered in the final treatment decisions for embolized AVMs.« less

Effect of abnormal notochord delamination on hindgut development in the Adriamycin mouse model.

PubMed

Sato, Hideaki; Hajduk, Piotr; Furuta, Shigeyuki; Wakisaka, Munechika; Murphy, Paula; Puri, Prem; Kitagawa, Hiroaki

2013-11-01

Adriamycin mouse model (AMM) is a model of VACTERL anomalies. Sonic hedgehog (Shh) pathway, sourced by the notochord, is implicated of anorectal malformations. We hypothesized hindgut anomalies observed in the AMM are the result of abnormal effect of the notochord. Time-mated CBA/Ca mice received two intraperitoneal injections of Adriamycin (6 mg/kg) or saline as control on embryonic day (E) 7 and 8. Fetuses were harvested from E9 to E11, stained following whole mount in situ hybridization with labeled RNA probes to detect Shh and Fork head box F1(Foxf1) transcripts. Immunolocalization with endoderm marker Hnf3β was used to visualize morphology. Embryos were scanned by OPT to obtain 3D representations of expressions. In AMM, the notochord was abnormally displaced ventrally with attachment to the hindgut endoderm in 71 % of the specimens. In 32 % of the treated embryos abnormal hindgut ended blindly in a cystic structure, and both of types were remarked in 29 % of treated embryos. Endodermal Shh and mesenchymal Foxf1 genes expression were preserved around the hindgut cystic malformation. The delamination of the developing notochord in the AMM is disrupted, which may influence signaling mechanisms from the notochord to the hindgut resulting in abnormal patterning of the hindgut.

[Risk for congenital malformations in pregnant women exposed to pesticides in the state od Nayarit, Mexico].

PubMed

Medina-Carrilo, L; Rivas-Solis, F; Fernández-Argüelles, R

2002-11-01

To measure the association between the use of pesticides and congenital malformations. We studied 279 newborn from mothers living in rural area of Nayarit, a state in the northwest region of México. Cases (n = 93) were defined as newborn with central nervous, face, genital, hip, foot or finger congenital malformations. Controls (n = 186) were newborns without any malformation. We considered as exposure any type of contact with any of the agrochemicals used as pesticides. We evaluated other risk factors such as medical drugs, fever, exposure to radiation, obstetric and family factors, as confoundings. We registered 22 genital malformations, 20 from hip, 19 from the central nervous system, 18 from extremities and 14 cleft-lip or palate. Exposed mothers had high risk of having a malformed child (OR = 3.5, CI95% 2.05-6.34, p < 0.05). Risk was higher if the mother had occupational exposure to pesticides (OR = 6.33, CI95% 2.95-13.7, p < 0.0001) and in mothers living near areas under pesticides treatment (OR = 3.47, CI95% 1.91-6.33, p < 0.0001). Among obstetric factors, abortion and early delivery (OR = 15.05, CI95% 1.82-124.30, p < 0.01) were significant. This study shows association between exposure to pesticides and congenital malformation. This is a public health problem in Nayarit state and in other rural areas with similar exposure to pesticides.

Dandy-Walker malformation: analysis of 38 cases.

PubMed

Pascual-Castroviejo, I; Velez, A; Pascual-Pascual, S I; Roche, M C; Villarejo, F

1991-04-01

Thirty-eight cases of Dandy-Walker malformation (DWM) are presented. A female predominance of 3:1 was found. Thirty-two cases (84%) were diagnosed within the 1st year of life. Of these, 17 cases (44.7%) were diagnosed at birth. Ten (26%) were delivered by cesarean section. Thirteen infants (34%) had a birth weight below 3000 g. Several associated malformations were observed, the most frequent being capillary angioma (6 cases); cardiac malformations, ophthalmic anomalies, agenesis of the corpus callosum, malformed limbs, and occipital meningocele were also seen. These observations indicate that DWM represents a disorder of the midline central nervous system indicative of marked genetic and etiologic heterogeneity with the possibility of showing clinical and pathological alterations intra- and extracranially. Macrocephaly was the most frequent physical finding, appearing in 31 cases (82%). Seventeen (44.7%) patients died, 11 before 6 months of age, 3 between 6 and 12 months, and 3 after 1 year. Postmortem studies were performed in 13 patients. Three cases have been lost to follow-up. Mental retardation (IQ below 70) was found in 11 cases (58% of survivors), low intellect (IQ between 70 and 85) in 4, and only 2 patients showed normal intellectual development (IQ more than 85). The high incidence of malformations having several genetic and environmental origins, as well as the high early mortality of patients with DWM, indicate the complexity of this syndrome, which involves the midline developmental field structures. It is not an isolated malformation of the posterior fossa in most cases.

Ethanol-Gel Sclerotherapy of Venous Malformations: Effectiveness and Safety.

PubMed

Teusch, Veronika I; Wohlgemuth, Walter A; Hammer, Simone; Piehler, Armin P; Müller-Wille, René; Goessmann, Holger; Uller, Wibke

2017-12-01

In the treatment of venous malformations, ethanol may be administered in a gelified form to increase local effects and reduce systemic ones. The purpose of this prospective study was to evaluate the efficacy and safety of a commercially available viscous ethanol gel in the treatment of venous malformations. Thirty-one patients (mean age, 23.4 years; age range, 6.6-46.5 years) with venous malformations were prospectively scheduled for two ethanol-gel sclerotherapy sessions. Venous malformations were located at the lower extremity (n = 18), the upper extremity (n = 9), and the face (n = 4). Questionnaires to assess pain, clinical examinations, professional photographs, and contrast-enhanced MRI of the venous malformations were performed before and after therapy to measure therapy-induced changes. Two experienced radiologists blinded to the examination date and clinical status compared photographs and MR images before and after treatment. A mean of 4.2 mL of ethanol gel were administered per session. The technical success rate was 100%. Clinical success, defined as improvement or resolution of symptoms, was noted in 81% of patients. Mean pain score decreased, and the difference was statistically significant (3.9 vs 3.1, p = 0.005). In 54 treatment sessions where follow-up was available, four minor complications occurred. Comparison of photographs and MR images before and after treatment showed improvement in 35% and 93% of patients, respectively. Ethanol gel is an effective and safe sclerosing agent in the treatment of venous malformations.

Report of Task Group on the implications of the implementation of the ICRP recommendations for a revised dose limit to the lens of the eye.

PubMed

Broughton, J; Cantone, M C; Ginjaume, M; Shah, B

2013-12-01

This report was commissioned by the IRPA President to provide an assessment of the impact on members of IRPA Associate Societies of the introduction of ICRP recommendations for a reduced dose limit for the lens of the eye. The report summarises current practice and considers possible changes that may be required. Recommendations for further collaboration, clarification and changes to working practices are suggested.

Tear clearance implications for ocular surface health.

PubMed

de Paiva, Cintia Sade; Pflugfelder, Stephen C

2004-03-01

Tear clearance/turnover provides a global assessment of the function of the lacrimal functional unit and of tear exchange on the ocular surface. It is an indirect measure of dry eye induced inflammation on the ocular surface. It shows better correlation with the severity of ocular irritation symptoms and corneal epithelial disease in dry eye than the Schirmer 1 test. Delayed tear clearance may prove to be the best measure for identifying patients with tear film disorders who may respond to anti-inflammatory therapy.

Effects of Pollutants on Eggs, Embryos and Larvae of Amphibian Species

DTIC Science & Technology

1976-04-01

of octyl-phenyl-,- naphthylamine may retard the growth rate of tadpoles . However, histological study indicated that these animals were not malformed ...all embryos become malformed if treatment 6 begins prior to completion of neurulation. Embryos exposed to trypan blue after closure of the neural...folds are not affected. The syndrome of malformations exhibited includes microcephaly, tailessness, and re- duction of mesonephros (fig. 1). Lithium

Pathogenesis and Cerebrospinal Fluid Hydrodynamics of the Chiari I Malformation.

PubMed

Buell, Thomas J; Heiss, John D; Oldfield, Edward H

2015-10-01

This article summarizes the current understanding of the pathophysiology of the Chiari I malformation that is based on observations of the anatomy visualized by modern imaging with MRI and prospective studies of the physiology of patients before and after surgery. The pathogenesis of a Chiari I malformation of the cerebellar tonsils is grouped into 4 general mechanisms. Copyright © 2015 Elsevier Inc. All rights reserved.

Miscarriage, stillbirth and congenital malformation in the offspring of UK veterans of the first Gulf war.

PubMed

Doyle, Pat; Maconochie, Noreen; Davies, Graham; Maconochie, Ian; Pelerin, Margo; Prior, Susan; Lewis, Samantha

2004-02-01

To assess whether the offspring of UK veterans of the first Gulf war are at increased risk of fetal death or congenital malformation. This was a retrospective reproductive cohort study of UK Gulf war veterans and a demographically similar comparison group who were in service at the time but were not deployed to the Gulf. Reproductive history was collected by means of a validated postal questionnaire between 1998 and 2001. In all, 27 959 pregnancies reported by men and 861 pregnancies reported by women were conceived after the first Gulf war and before November 1997. The risk of reported miscarriage was higher among pregnancies fathered by Gulf war veterans than by non-Gulf war veterans (OR = 1.4, 95% CI: 1.3, 1.5). Stillbirth risk was similar in both groups. Male Gulf war veterans reported a higher proportion of offspring with any type of malformation than the comparison cohort (OR = 1.5, 95% CI: 1.3, 1.7). Examination by type of malformation revealed some evidence for increased risk of malformations of the genital system, urinary system (renal and urinary tract), and 'other' defects of the digestive system, musculo-skeletal system, and non-chromosomal (non-syndrome) anomalies. These associations were weakened when analyses were restricted to clinically confirmed conditions. There was little or no evidence of increased risk for other structural malformations, specific syndromes, and chromosomal anomalies. Among female veterans, no effect of Gulf war service was found on the risk of miscarriage. The numbers of stillbirths and malformations reported by women were too small to allow meaningful analyses. We found no evidence for a link between paternal deployment to the Gulf war and increased risk of stillbirth, chromosomal malformations, or congenital syndromes. Associations were found between fathers' service in the Gulf war and increased risk of miscarriage and less well-defined malformations, but these findings need to be interpreted with caution as such outcomes are susceptible to recall bias. The finding of a possible relationship with renal anomalies requires further investigation. There was no evidence of an association between risk of miscarriage and mothers' service in the gulf.

Impaired reproduction of mallards fed an organic form of selenium

USGS Publications Warehouse

Heinz, G.H.; Hoffman, D.J.; Gold, L.G.

1989-01-01

We fed mallards (Anas platyrhynchos) diets supplemented with 0-, 1-, 2-, 4-, 8-, or 16-ppm selenium in the form of selenomethionine. We fed another group of mallards a diet containing 16-ppm selenium as selenocystine. Females fed the control diet produced a mean of 8.1 ducklings that survived to 6 days of age, which was significantly greater than the 4.6 young produced by females fed 8-ppm selenium as selenomethionine and the zero surviving young of females fed 16-ppm selenium as selenomethionine. Selenocystine did not impair reproduction. Diets containing 8- and 16-ppm selenium as selenomethionine caused malformations in 6.8 and 67.9%, respectively, of unhatched eggs compared with 0.6% for controls. The most common malformations were of eyes, bill, legs, and feet. Selenium did not affect the onset or frequency of egg laying, egg size, shell thickness, fertility of eggs, or sex ratio of ducklings. Reduced survival and growth occurred in ducklings hatched from groups whose parents had received 8- or 16-ppm selenium as selenomethionine, even though all ducklings were fed a control diet. Concentrations of selenium in eggs and liver of adults could be predicted from dietary concentrations. We conclude that the dietary threshold of selenium as selenomethionine necessary to impair reproduction is between 4 and 8 ppm. It is difficult to identify 1 level of selenium in eggs that will be diagnostic of reproductive impairment in the field because different chemical forms of selenium appear to have different toxicities in eggs. However, when eggs from a wild population contain .gtoreq. 1-ppm selenium on a wet-weight basis, reproductive impairment may be possible and should be evaluated in that population. At 5-ppm selenium in eggs, reproductive impairment is much more likely to occur.

[Outcome at two years corrected age of a cohort of very low birth weight infants from hospitals within the neonatal SEN1500 network].

PubMed

García, P; San Feliciano, L; Benito, F; García, R; Guzmán, J; Salas, S; Fernández, C; Del Prado, N; Ciprián, D; Figueras, J

2013-11-01

To describe growth and neurodevelopmental status of 4,944 children who completed a follow-up at two years of corrected age out of the 10,456 newborns with weight ≤1500g born between the years 2002-2007 and discharged from hospitals within the network SEN1500. A total of 522 newborns were excluded as they had some type of malformation. The total number of children assessed represents the 49.76% of children discharged alive and without malformations. A retrospective review was conducted using prospectively collected data in the SEN1500 database. We compared growth data at two years of corrected age according to birth weight and sex. Motor impairment, incidence of cerebral palsy, visual and hearing disabilities, and abnormal neurodevelopment for gestational age were analysed between groups. We studied the associations between cerebral palsy (CP) and perinatal factors. At 2 years of age 44.2% of children had a weight <2 SD for corrected age. Children with birth weight ≤1000g showed worse outcomes in growth. Some type of motor impairment was observed in 6.96% of the infants, and 4.56% of them were diagnosed with CP. The incidence was higher among males with birth weight ≤1000g. There was an incidence of 5.21% of visual disability, with 0.5% of children being blind in one or both eyes. Cerebral palsy was associated with retinopathy of prematurity, severe intraventricular haemorrhage, and periventricular leukomalacia, in particular cystic periventricular leukomalacia. Copyright © 2012 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Noonan like appearance and familial deletion of the 22q11 Shprintzen-DiGeorge critical region

DOE Office of Scientific and Technical Information (OSTI.GOV)

Piussan, C.; Mathieu, M.; Boudailliez, B.

1994-09-01

Shprintzen velocardiofacial syndrome (VCFS) and reported cases of autosomal dominant DiGeorge sequence (DGS) both belong to a heterogeneous developmental field defect due to the familial segregation of a 22q11 deletion. Two sisters present with mental retardation, dysmorphia and multiple congenital anomalies. The eldest has a Noonan-like appearance; short stature, short webbed neck, low posterior hairline, widely spaced nipples, hemivertebrae, speech disability and mild hypoparathyroidism. Her younger sister has prominent eyes, floppy ears, pulmonary valvular stenosis, hypoplastic right kidney, left multicystic kidney, hypoparathyroidism and renal failure causing death at age 3. Their retarded mother has a typical Shprintzen phenotype and nomore » hypoparathyroidism. A deletion of the critical DiGeorge-Shprintzen conotruncal malformation region was found by FISH in the mother and her Noonan-like daughter. In the mother`s family exist 3 cleft palates, an imperforate anus, a stillbirth and one infant died at age 3 months because of heart malformation. To our knowledge, another case of Noonan-like appearance in a DG patient affected with monosomy 22q11 has been reported in 1992 by Wilson et al. Whether resulting from the hemizygosity of a gene or from the deletion of contiguous genes, the wide DGS-VCFS spectrum encompasses quite variable phenotypes, discordant for palatal and conotruncal defects as well as for hypoparathyroidism, dysmorphic features and multiple congenital anomalies. Physical mapping of both the large 22q11 region commonly lost and the smallest deletion sufficient to produce DGS has been done and may account for the broadening spectrum, the variable expression and the frequently delayed diagnosis of this syndrome.« less

Improvement of perinatal outcome in diabetic pregnant women.

PubMed

Szilagyi, A; Szabo, I

2001-01-01

Obstetrical and perinatal outcomes in newborns of diabetic pregnant women depend on metabolic control and fetal surveillance during pregnancy. The effects of fetal surveillance on perinatal mortality and morbidity was analyzed in diabetic pregnant women with appropriate glucose control in our regional center for diabetes and pregnancy. 480 deliveries complicated by frank or gestational diabetes occurred in our Department in the period of 1988-1999. Perinatal mortality and morbidity, prevalence of premature deliveries, methods of fetal surveillance, options for respiratory distress syndrome (RDS) profilaxis, cesarean section rate, timing of delivery and its indications and occurrence of malformations have been analyzed. It was found that malformation rate and perinatal mortality may be reduced to even lower level than that of in healthy pregnant women by appropriate glucose control and by using the latest methods of intrauterine fetal surveillance including cardiotocography (non stress test and oxytocin challenge test), doppler fetal artery velocimetry and fetal pulse oximetry. Timing of delivery was needed in 35% of the cases with IDDM and 15% of gestational diabetes due to chronic placental insufficiency. If labour induction was needed before the 38 weeks, amniocentesis was performed to test fetal lung maturity. Direct fetal glucocorticoid administration was used to enhance fetal lung maturation in 14 cases. C-section rate was slightly higher than that of in non diabetic pregnant women. Our perinatal morbidity data (macrosomia, hyperbilirubinemia, hypoglycemia, injuries, infections) are comparable with the data from the literature. Although perinatal mortality with the help of thorough fetal surveillance is even better in diabetic pregnant women than in non diabetic patients, future eye should be focused on factors affecting perinatal morbidity, because it is still higher than in newborns of healthy mothers.

OPTICS OF CONDUCTIVE KERATOPLASTY: IMPLICATIONS FOR PRESBYOPIA MANAGEMENT

PubMed Central

Hersh, Peter S

2005-01-01

Purpose To define the corneal optics of conductive keratoplasty (CK) and assess the clinical implications for hyperopia and presbyopia management. Methods Four analyses were done. (1) Multifocal effects: In a prospective study of CK, uncorrected visual acuity (UCVA) for a given refractive error in 72 postoperative eyes was compared to control eyes. (2) Surgically induced astigmatism (SIA): 203 eyes were analyzed for magnitude and axis of SIA. (3) Higher-order optical aberrations: Corneal higher-order optical aberrations were assessed for 36 eyes after CK and a similar patient population after hyperopic laser in situ keratomileusis (LASIK). (4) Presbyopia clinical trial: Visual acuity, refractive result, and patient questionnaires were analyzed for 150 subjects in a prospective, multicenter clinical trial of presbyopia management with CK. Results (1) 63% and 82% of eyes after CK had better UCVA at distance and near, respectively, than controls. (2) The mean SIA was 0.23 diopter (D) steepening at 175° (P < .001); mean magnitude was 0.66 D (SD, 0.43 D). (3) After CK, composite fourth- and sixth-order spherical aberration increased; change in (Z12) spherical aberration alone was not statistically significant. When compared to hyperopic LASIK, there was a statistically significant increase in composite fourth- and sixth-order spherical aberration (P < .01) and spherical aberration (Z12) alone (P < .02); spherical aberration change was more prolate after CK. (4) After the CK monovision procedure, 80% of patients had J3 or better binocular UCVA at near; 84% of patients were satisfied. Satisfaction was associated with near UCVA of J3 or better in the monovision eye (P = .001) and subjectively good postoperative depth perception (P = .038). Conclusions CK seems to produce functional corneal multifocality with definable introduction of SIA and higher-order optical aberrations, and development of a more prolate corneal contour. These optical factors may militate toward improved near vision function. PMID:17057812

The eyes have it: Using eye tracking to inform information processing strategies in multi-attributes choices.

PubMed

Ryan, Mandy; Krucien, Nicolas; Hermens, Frouke

2018-04-01

Although choice experiments (CEs) are widely applied in economics to study choice behaviour, understanding of how individuals process attribute information remains limited. We show how eye-tracking methods can provide insight into how decisions are made. Participants completed a CE, while their eye movements were recorded. Results show that although the information presented guided participants' decisions, there were also several processing biases at work. Evidence was found of (a) top-to-bottom, (b) left-to-right, and (c) first-to-last order biases. Experimental factors-whether attributes are defined as "best" or "worst," choice task complexity, and attribute ordering-also influence information processing. How individuals visually process attribute information was shown to be related to their choices. Implications for the design and analysis of CEs and future research are discussed. Copyright © 2017 John Wiley & Sons, Ltd.

Quantifying Pilot Visual Attention in Low Visibility Terminal Operations

NASA Technical Reports Server (NTRS)

Ellis, Kyle K.; Arthur, J. J.; Latorella, Kara A.; Kramer, Lynda J.; Shelton, Kevin J.; Norman, Robert M.; Prinzel, Lawrence J.

2012-01-01

Quantifying pilot visual behavior allows researchers to determine not only where a pilot is looking and when, but holds implications for specific behavioral tracking when these data are coupled with flight technical performance. Remote eye tracking systems have been integrated into simulators at NASA Langley with effectively no impact on the pilot environment. This paper discusses the installation and use of a remote eye tracking system. The data collection techniques from a complex human-in-the-loop (HITL) research experiment are discussed; especially, the data reduction algorithms and logic to transform raw eye tracking data into quantified visual behavior metrics, and analysis methods to interpret visual behavior. The findings suggest superior performance for Head-Up Display (HUD) and improved attentional behavior for Head-Down Display (HDD) implementations of Synthetic Vision System (SVS) technologies for low visibility terminal area operations. Keywords: eye tracking, flight deck, NextGen, human machine interface, aviation

Long-Range Correlation in alpha-Wave Predominant EEG in Human

NASA Astrophysics Data System (ADS)

Sharif, Asif; Chyan Lin, Der; Kwan, Hon; Borette, D. S.

2004-03-01

The background noise in the alpha-predominant EEG taken from eyes-open and eyes-closed neurophysiological states is studied. Scale-free characteristic is found in both cases using the wavelet approach developed by Simonsen and Nes [1]. The numerical results further show the scaling exponent during eyes-closed is consistently lower than eyes-open. We conjecture the origin of this difference is related to the temporal reconfiguration of the neural network in the brain. To further investigate the scaling structure of the EEG background noise, we extended the second order statistics to higher order moments using the EEG increment process. We found that the background fluctuation in the alpha-predominant EEG is predominantly monofractal. Preliminary results are given to support this finding and its implication in brain functioning is discussed. [1] A.H. Simonsen and O.M. Nes, Physical Review E, 58, 2779¡V2748 (1998).

A late presentation of Dandy-Walker malformation and aortic coarctation.

PubMed

Venturini, Elio; Magni, Lucia; Pucci, Giovanna; Mazzinghi, Fabio

2017-05-01

The Dandy-Walker malformation is a rare anomaly of the posterior cranial fossa. Concomitant brain or systemic malformations are frequent and can influence the outcome. Associated cardiac congenital defects usually induce a poor prognosis. We report a case of a 58-yearold man with hydrocephalus, in whom Dandy-Walker malformation was diagnosed, for the first time, after the demonstration of aortic coarctation. This association is very rare and only a few cases have been described; moreover, to our knowledge, this is the first description of this incidence in a middle-aged patient. The characteristic of diseases and physiopathologic features are discussed, focusing attention on the rare and late clinical manifestations.

Computed tomography of congenital brain malformations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sarwar, M.

1984-01-01

This book is illustrated showing each condition. This book is designed to correlate the pathology of CNS malformations with their CT scan appearance, mainly on the axial images. The author has drawn upon his personal experience and the information gleaned from the literature dealing with the description of the CT scan findings of these malformations. The emphasis is on simplicity of description. Since a large degree of morphological variation exists in each entity, numerous illustrations (wherever applicable) are shown to depict those variations. When appropriate, deficiency of the CT scan in the evaluation of these CNS malformations also is indicated.more » A description of CNS embryology is included as well.« less

CARDIO-VASCULAR MALFORMATIONS PROVOKED IN THE CHICKEN AFTER IRRADIATION WITH X RAYS OF THE EMBRYONIC REGION LOCATED BEHIND THE HEART RUDIMENT (in French)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Le Douarin, N.

BS>The x-ray destruction of the embryonic region intended to form the neck modifies the topographic ratios of the cardiac rudiment, causing a constraint in the normal pattem of morphogenetic movements. Malformations of the heart and the arterial trunks result. The cardio-vascular malformations are, moreover, more frequent and significant when the anterior radiation level is nearer the heart and when the region destroyed is wider. The vascular anomalies concern generally the brachiocephalic trunks and less frequently the aortal bend. The heart malformations affect the rotation of the arterial bud and the achievement of cardiac partitioning. (tr-auth)

Chiari type 1 malformation in a pseudotumour cerebri patient: is it an acquired or congenital Chiari malformation?

PubMed

Istek, Seref

2014-06-04

Chiari malformation type 1 (CM1) is a developmental abnormality of the cerebellar tonsils. Patients with CM1 commonly present with headache. Papilloedema is rarely seen in CM1. However, a 52-year-old woman presented to the hospital with a headache and her ophthalmological examination revealed bilateral papilloedema. Her cranial MRI was compatible with borderline CM1. Bilateral papilloedema and headache suggested idiopathic intracranial hypertension (IIH) as the preliminary diagnosis. IIH is a rare case in CM1. This article argues about this association and discusses as to whether it is an acquired or congenital Chiari malformation. 2014 BMJ Publishing Group Ltd.

A severe form of epidermal nevus syndrome associated with brainstem and cerebellar malformations and neonatal medulloblastoma.

PubMed

Okumura, Akihisa; Lee, Tsubasa; Ikeno, Mitsuru; Shimojima, Keiko; Kajino, Kazunori; Inoue, Yuka; Yoshikawa, Naomi; Suganuma, Hiroki; Suzuki, Mitsuyoshi; Hisata, Ken; Shoji, Hiromichi; Takanashi, Jun-ichi; Barkovich, A James; Shimizu, Toshiaki; Yamamoto, Toshiyuki; Hayashi, Masaharu

2012-11-01

Here we report a boy with epidermal nevus syndrome associated with brainstem and cerebellar malformations and neonatal medulloblastoma. The patient had epidermal nevi and complicated brain malformations including macrocephaly with polymicrogyria, dysmorphic and enlarged midbrain tectum, enlarged cerebellar hemispheres with small and maloriented folia. The patient died after surgical resection of medulloblastoma which was newly recognized on MRI at 51 days of age. Postmortem pathological examinations showed very unique and bizarre malformation of the midbrain and hindbrain. The cerebellar cortex exhibited a coarse, irregular and bumpy surface, blurred border between the Purkinje cell layer and internal granule cell layer, and many foci of heterotopia in the cerebellar white matter. The brainstem showed multiple anomalies, including enlargement of superior colliculi, hypoplasia of pyramidal tracts and dysplasia of inferior olivary nuclei. The unusual constellation of brain malformations of our patient will widen the spectrum of epidermal nevus syndrome. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

[Application of 1% lauromacrogol in the treatment of facial refractory hemangioma and vascular malformations].

PubMed

Wang, Yin; Zhu, Fei; Ning, Jin-long; Li, Xiao-jing; Liu, Ye

2012-11-01

To investigate the clinical effect of 1% lauromacrogol for the treatment of facial refractory hemangioma and vascular malformation. From Sept 2009 to Nov 2011, 55 patients (20 male, 35 female, 1 month to 30 years) with different types of facial hemangiorwa and vascular malformation about 1.0 cm x (0. 5-5.0) cm x 10.0 cm in size, underwent 1% lauromacrogol intratumor injection therapy. Generally, the injection dose, concentration, frequency were determined by the age of the patients, the volume and depth of the lesion. The dose was limited to 10 mg every time. The injection interval is 14 weeks. After followed up for 3-16 months, 41 cases were cured, 9 cases were greatly improved, and 5 were partially improved. Skin necrosis happened in only 2 cases. Lauromacrogol is safe, simple and effective as a sderosing agent for the treatment of facial refractory hemangioma and vascular malformation. It provides a new and alternative way for the treatment of facial refractory hemangioma and vascular malformation.

Nannoplankton malformation during the Paleocene-Eocene Thermal Maximum and its paleoecological and paleoceanographic significance

USGS Publications Warehouse

Bralower, Timothy J.; Self-Trail, Jean

2016-01-01

The Paleocene-Eocene Thermal Maximum (PETM) is characterized by a transient group of nannoplankton, belonging to the genus Discoaster. Our investigation of expanded shelf sections provides unprecedented detail of the morphology and phylogeny of the transient Discoasterduring the PETM and their relationship with environmental change. We observe a much larger range of morphological variation than previously documented suggesting that the taxa belonged to a plexus of highly gradational morphotypes rather than individual species. We propose that the plexus represents malformed ecophenotypes of a single species that migrated to a deep photic zone refuge during the height of PETM warming and eutrophication. Anomalously, high rates of organic matter remineralization characterized these depths during the event and led to lower saturation levels, which caused malformation. The proposed mechanism explains the co-occurrence of malformed Discoaster with pristine species that grew in the upper photic zone; moreover, it illuminates why malformation is a rare phenomenon in the paleontological record.

Seckel's syndrome and malformations of cortical development: report of three new cases and review of the literature.

PubMed

Capovilla, G; Lorenzetti, M E; Montagnini, A; Borgatti, R; Piccinelli, P; Giordano, L; Accorsi, P; Caudana, R

2001-05-01

Seckel's syndrome is a rare form of primordial dwarfism, characterized by peculiar facial appearance. In the past, this condition was overdiagnosed, and most attention was given to the facial and skeletal features to define more precise diagnostic criteria. The presence of mental retardation and neurologic signs is one of the peculiar features of this syndrome, but only recently were rare cases of malformation of cortical development described, as documented by magnetic resonance imaging (MRI). Here, we present three new cases of Seckel's syndrome showing different malformations of cortical development (one gyral hypoplasia, one macrogyria and partial corpus callosum agenesis, and one bilateral opercular macrogyria). We hypothesize that the different types of clinical expression of our patients could be explained by different malformation of cortical development types. We think that MRI studies could be performed in malformative syndromes because of the possible correlations between type and extent of the lesion and the clinical picture of any individual case.

Cranial Nerve Palsy after Onyx Embolization as a Treatment for Cerebral Vascular Malformation

PubMed Central

Lee, Jong Min; Whang, Kum; Cho, Sung Min; Kim, Jong Yeon; Oh, Ji Woong; Koo, Youn Moo; Hu, Chul; Pyen, Jinsoo

2017-01-01

The Onyx liquid embolic system is a relatively safe and commonly used treatment for vascular malformations, such as arteriovenous fistulas and arteriovenous malformations. However, studies on possible complications after Onyx embolization in patients with vascular malformations are limited, and the occurrence of cranial nerve palsy is occasionally reported. Here we report the progress of two different types of cranial nerve palsy that can occur after embolization. In both cases, Onyx embolization was performed to treat vascular malformations and ipsilateral oculomotor and facial nerve palsies were observed. Both patients were treated with steroids and exhibited symptom improvement after several months. The most common types of neuropathy that can occur after Onyx embolization are facial nerve palsy and trigeminal neuralgia. Although the mechanisms underlying these neuropathies are not clear, they may involve traction injuries sustained while extracting the microcatheter, mass effects resulting from thrombi and edema, or Onyx reflux into the vasa nervorum. In most cases, the neuropathy spontaneously resolves several months following the procedure. PMID:29159152

Cranial Nerve Palsy after Onyx Embolization as a Treatment for Cerebral Vascular Malformation.

PubMed

Lee, Jong Min; Whang, Kum; Cho, Sung Min; Kim, Jong Yeon; Oh, Ji Woong; Koo, Youn Moo; Hu, Chul; Pyen, Jinsoo; Choi, Jong Wook

2017-09-01

The Onyx liquid embolic system is a relatively safe and commonly used treatment for vascular malformations, such as arteriovenous fistulas and arteriovenous malformations. However, studies on possible complications after Onyx embolization in patients with vascular malformations are limited, and the occurrence of cranial nerve palsy is occasionally reported. Here we report the progress of two different types of cranial nerve palsy that can occur after embolization. In both cases, Onyx embolization was performed to treat vascular malformations and ipsilateral oculomotor and facial nerve palsies were observed. Both patients were treated with steroids and exhibited symptom improvement after several months. The most common types of neuropathy that can occur after Onyx embolization are facial nerve palsy and trigeminal neuralgia. Although the mechanisms underlying these neuropathies are not clear, they may involve traction injuries sustained while extracting the microcatheter, mass effects resulting from thrombi and edema, or Onyx reflux into the vasa nervorum. In most cases, the neuropathy spontaneously resolves several months following the procedure.

Hydrocephalus in Dandy-Walker malformation.

PubMed

Spennato, Pietro; Mirone, Giuseppe; Nastro, Anna; Buonocore, Maria Consiglio; Ruggiero, Claudio; Trischitta, Vincenzo; Aliberti, Ferdinando; Cinalli, Giuseppe

2011-10-01

Even if the first description of Dandy-Walker dates back 1887, difficulty in the establishment of correct diagnosis, especially concerning differential diagnosis with other types of posterior fossa CSF collection, still persists. Further confusion is added by the inclusion, in some classification, of different malformations with different prognosis and therapeutic strategy under the same label of "Dandy-Walker". An extensive literature review concerning embryologic, etiologic, pathogenetic, clinical and neuroradiological aspects has been performed. Therapeutic options, prognosis and intellectual outcome are also reviewed. The correct interpretation of the modern neuroradiologic techniques, including CSF flow MR imaging, may help in identifying a "real" Dandy-Walker malformation. Among therapeutical strategies, single shunting (ventriculo-peritoneal or cyst-peritoneal shunts) appears effective in the control of both ventricle and cyst size. Endoscopic third ventriculostomy may be considered an acceptable alternative, especially in older children, with the aim to reduce the shunt-related problems. Prognosis and intellectual outcome mostly depend on the presence of associated malformations, the degree of vermian malformation and the adequate control of hydrocephalus.

Intestinal atresia, encephalocele, and cardiac malformations in infants with 47,XXX: Expansion of the phenotypic spectrum and a review of the literature.

PubMed

Bağci, Soyhan; Müller, Andreas; Franz, Axel; Heydweiller, Andreas; Berg, Christoph; Nöthen, Markus M; Bartmann, Peter; Reutter, Heiko

2010-01-01

Identification of the 47,XXX karyotype often occurs adventitiously during prenatal fetal karyotyping in cases of advanced maternal age. Although most females with 47,XXX appear healthy at birth, various types of congenital malformations have been reported, of which urinary tract anomalies are the most frequent. We report on 2 newborns with 47,XXX and congenital cardiac defects, one of whom had duodenal atresia and the other an occipital encephalocele. This expands the spectrum of malformations reported in association with the triple-X syndrome. We also present a review of the literature on non-urinary tract malformations in females with 47,XXX. We conclude that prenatal identification of the 47,XXX karyotype is an indication for detailed fetal ultrasonography which should include examination of multiple organ systems. Such prenatal screening for possible associated congenital malformations should help to ensure optimal perinatal clinical management of 47,XXX cases. 2010 S. Karger AG, Basel.

Dcx Re-expression Reduces Subcortical Band Heterotopia and Seizure Threshold in an Animal Model of Neuronal Migration Disorder

PubMed Central

Manent, Jean-Bernard; Wang, Yu; Chang, YoonJeung; Paramasivam, Murugan; LoTurco, Joseph J

2009-01-01

Disorders of neuronal migration can lead to malformations of the cerebral neocortex that greatly increase the risk of seizures. It remains untested whether malformations caused by disorders in neuronal migration can be reduced by reactivating cellular migration, and whether such repair can decrease seizure risk. Here we show, in a rat model of subcortical band heterotopia (SBH) generated by in utero RNAi of Dcx, that aberrantly positioned neurons can be stimulated to migrate by re-expressing Dcx after birth. Re-starting migration in this way both reduces neocortical malformations and restores neuronal patterning. We find further that the capacity to reduce SBH has a critical period in early postnatal development. Moreover, intervention after birth reduces convulsant-induced seizure threshold to levels similar to that of malformation-free controls. These results suggest that disorders of neuronal migration may be eventually treatable by re-engaging developmental programs both to reduce the size of cortical malformations and to reduce seizure risk. PMID:19098909

Nannoplankton malformation during the Paleocene-Eocene Thermal Maximum and its paleoecological and paleoceanographic significance

NASA Astrophysics Data System (ADS)

Bralower, Timothy J.; Self-Trail, Jean M.

2016-10-01

The Paleocene-Eocene Thermal Maximum (PETM) is characterized by a transient group of nannoplankton, belonging to the genus Discoaster. Our investigation of expanded shelf sections provides unprecedented detail of the morphology and phylogeny of the transient Discoaster during the PETM and their relationship with environmental change. We observe a much larger range of morphological variation than previously documented suggesting that the taxa belonged to a plexus of highly gradational morphotypes rather than individual species. We propose that the plexus represents malformed ecophenotypes of a single species that migrated to a deep photic zone refuge during the height of PETM warming and eutrophication. Anomalously, high rates of organic matter remineralization characterized these depths during the event and led to lower saturation levels, which caused malformation. The proposed mechanism explains the co-occurrence of malformed Discoaster with pristine species that grew in the upper photic zone; moreover, it illuminates why malformation is a rare phenomenon in the paleontological record.

Roles of ADAM13-regulated Wnt activity in early Xenopus eye development

PubMed Central

Wei, Shuo; Xu, Guofeng; Bridges, Lance C.; Williams, Phoebe; Nakayama, Takuya; Shah, Anoop; Grainger, Robert M.; White, Judith M.; DeSimone, Douglas W.

2012-01-01

Pericellular proteolysis by ADAM family metalloproteinases has been widely implicated in cell signaling and development. We recently found that Xenopus ADAM13, an ADAM metalloproteinase, is required for activation of canonical Wnt signaling during cranial neural crest (CNC) induction by regulating a novel crosstalk between Wnt and ephrin B (EfnB) signaling pathways (Wei et al., 2010b). In the present study we show that the metalloproteinase activity of ADAM13 also plays important roles in eye development in X. tropicalis. Knockdown of ADAM13 results in reduced expression of eye field markers pax6 and rx1, as well as that of the pan-neural marker sox2. Activation of canonical Wnt signaling or inhibition of forward EfnB signaling rescues the eye defects caused by loss of ADAM13, suggesting that ADAM13 functions through regulation of the EfnB-Wnt pathway interaction. Downstream of Wnt, the head inducer Cerberus was identified as an effector that mediates ADAM13 function in early eye field formation. Furthermore, ectopic expression of the Wnt target gene snail2 restores cerberus expression and rescues the eye defects caused by ADAM13 knockdown. Together these data suggest an important role of ADAM13-regulated Wnt activity in eye development in Xenopus. PMID:22227340

Alternative arrangements for the delivery of eye care services within staff model managed care organizations.

PubMed

Soroka, Mort; Reis, Lesley; Krumholz, David; Krasner, Mel; Portello, Joan

2003-11-01

Eye care services, though accounting for only a small fraction of healthcare costs, encompass a unique spectrum of professional staffing options that can enhance efficiency and decrease costs within staff model managed care organizations. This study was designed to describe and assess alternative staffing arrangements and cost implications for the delivery of eye care services by optometrists, ophthalmologists, and primary care physicians within staff model managed care organizations. The clinical records of individual patients--rather than administrative and billing files--at three managed care organizations are the principal source of information. Clinical auditors extracted data on ambulatory eye care services provided for conjunctivitis, corneal abrasion/erosion, cataract, diabetic retinopathy, glaucoma, and macular degeneration. Our findings document the substantial role optometrists play in the delivery of eye care, whether they provide the care independently or in collaboration with an ophthalmologist. The levels of remuneration for optometrists are roughly one third to one half the annual rate for ophthalmologists. Staffing arrangements that use optometrists to the full extent of their professional training can provide significant cost savings. The cost-effectiveness of using the services of optometrists capable of delivering high-quality eye care can be demonstrated. Potential cost savings for staff model managed care organizations may accrue if the roles, functions, and availability of eye providers are adjusted.

Effects of visual expertise on a novel eye-size illusion: Implications for holistic face processing

PubMed Central

Fu, Genyue; Dong, Yan; Quinn, Paul C.; Xiao, Wen S.; Wang, Qiandong; Chen, Guowei; Pascalis, Olivier; Lee, Kang

2015-01-01

The present study examined the effect of visual experience on the magnitude of a novel eye-size illusion: when the size of a face’s frame is increased or decreased but eye size is unchanged, observers judge the size of the eyes to be different from that in the original face frame. In the current study, we asked Chinese and Caucasian participants to judge eye size in different pairs of faces and measured the magnitude of the illusion when the faces were own- or other-age (adult vs. infant faces) and when the faces were own- or other-race (Chinese vs. Caucasian faces). We found an other-age effect and an other-race effect with the eye-size illusion: The illusion was more pronounced with own-race and own-age faces than with other-race and other-age faces. These findings taken together suggest that visual experience with faces influences the magnitude of this novel illusion. Extensive experience with certain face categories strengthens the illusion in the context of these categories, but lack of it reduces the magnitude of the illusion. Our results further imply that holistic processing may play an important role in engendering the eye-size illusion. PMID:26048685

Evaluation of the Embryotoxicity of Hydrazine in Rats

DTIC Science & Technology

1982-08-01

HYDRONEPHROSIS, MODERATE DILATION OF BRAIN VENTRICLES AND OTHER SIMILAR BUT LESS FREQUENTLY OCCURRING ABNORMALITIES E MAJOR MALFORMATION WAS ANOPHTHALMIA F...THREE FETUSES WITH ANOPHTHALMIA WERE FOUND IN ONE LITTER G MAJOR MALFORMATIONS WERE ANOPHTHALMIA (2) RIGHT SIDE AORTA (1) AND MONORCHID (1) 5 60 - 0 o...MALFORMATIONS CONSISTED OF ANOPHTHALMIA AND ADRENAL AGENESIS F ANOMALIES DETECTED IN THE 7-9 DAY TREATMENT GROUP WERE SUPERNUMERARY RIBS (2) MODERATE

[Sirenomelia].

PubMed

García, J; Romero-Araus, J

1996-09-01

Sirenomelia is an uncommon congenital malformation of unknown etiology characterized by all degrees of severity in merning, malrotation, and dysgenesis of the lower limbs, combining as it does malformation with several anomalies of the external and internal organs, specially of the urogenital and gastrointestinal systems and other lumbosacral vertebral abnormalities; the severity of the associated malformations are not compatible with life. A genetic mechanism leading to sirenomelia is unlikely, due to the absence of the familial cases.

Cyclical vomiting syndrome secondary to a Chiari I malformation-a case report.

PubMed

White, William L; Bagga, Veejay; Campbell, David I; Hart, Anthony R; Ushewokunze, Shungu

2017-12-01

Cyclical vomiting syndrome is a disorder characterised by recurrent episodes of profuse vomiting. There are no cases in the literature on the management of children with presenting with cyclical vomiting syndrome and a Chiari malformation type I. We report the case of a 12-year-old child diagnosed with cyclical vomiting syndrome and a Chiari malformation type I. The patient received symptomatic relief following a craniocervical decompression.

Potential ecotoxic effects of polychlorinated biphenyls on Xenopus laevis.

PubMed

Qin, Zhan-Fen; Zhou, Jing-Ming; Cong, Lin; Xu, Xiao-Bai

2005-10-01

We examined potential ecotoxic effects of polychlorinated biphenyl (PCB)3, PCB5, Aroclor 1254, and Aroclor 1242 on Xenopus laevis. Tadpoles were exposed to PCBs from stage 46/47 (system of Nieuwkoop and Faber) to the completion of metamorphosis. We demonstrated, to our knowledge for the first time, forelimb malformations caused by PCBs (malformation rate, > 70%). The malformed forelimbs were fixed in the adduction-backward rotation position and could not move. Therefore, malformed male frogs were destined to have no offspring, because they could not grasp the females with their forelimbs to mate. Alcian blue-alizarin red double-staining indicated that the forelimb malformation resulted from the shoulder abnormality. Compared with the normal shoulder joint, the proximal humerus with the humerus inter-rotated 90 degrees in the abnormal shoulder joint. Moreover, testes from more than a third of male frogs with exposed to PCBs exhibited feminization to different degrees at gross morphology and histology, with fewer or abnormal spermatogonia and oocytes. Gonadal abnormalities would lead directly to reproductive dysfunction and population decline. These results suggest that PCBs have potentially ecotoxic effects on amphibian populations. We infer that PCBs could play roles in amphibian malformations and population declines, at least at sites that are polluted heavily with PCBs.

The Hemodynamic Changes in Patients with Cerebral Arteriovenous Malformations before and after Interventional Embolization Therapy with Glubran 2 Acrylic Glue.

PubMed

Chen, Qi-Yu; Zhu, Xiao-Rui; Zhang, Yu

2017-01-01

The study explored hemodynamic changes in patients with cerebral arteriovenous malformations (CAVM) before and -after interventional embolization therapy with Glubran 2 acrylic glue and analyzed the related factors. CAVM patients received endovascular embolization therapy with Glubran 2. Patients' systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), blood flow velocity (BFV), and pulsatility index (PI) were measured. The location of malformed vessels, Spetzler-Martin (SM) grade, CAVM size, and type of feeding artery and venous drainage were analyzed. CAVM patients showed increased DBP, SBP, MAP, and PI and decreased average BFV compared to before therapy. CAVM patients with big CAVM size, SM grade IV/V, deep location malformed vessels, deep, and mixed venous drainage, and cortical branch and mixed artery blood-supply exhibited lower DBP, SBP, MAP, and PI but higher average BFV. Hypertensive CAVM patients showed lower DBP, SBP, MAP, average BFV, and PI before or after embolization. Hypertension, SM grade, CAVM size, malformed vessels location, venous drainage, and artery blood-supply were correlated to the hemodynamic changes of CAVM patients. Embolization with Glubran 2 acrylic glue could enhance hemodynamics in CAVM patients, and the hemodynamic changes were in correlation with the SM grade, CAVM size, and malformed vessels location. © 2017 S. Karger AG, Basel.

Single-stage excision of localized head and neck venous malformations using preoperative glue embolization.

PubMed

Tieu, David D; Ghodke, Basavaraj V; Vo, Nghia J; Perkins, Jonathan A

2013-04-01

Describe single-stage removal of head and neck venous malformations using percutaneous embolization with n-butyl cyanoacrylate (n-BCA) glue prior to surgical resection. Case series with chart review. Tertiary-care pediatric hospital. A total of 169 venous malformations were identified between 2000 and 2012, and 102 (60.1%) were in the head and neck. Thirty-five of 102 (34.3%) were observed, 56 of 102 (54.9%) had invasive therapy, and 11 of 102 (10.8%) underwent n-BCA embolization and surgery ("GES procedure"). The median age of the glue embolization and surgery cohort was 14 years (range, 6-19), and 7 of 11 (63.6%) were female. Treated venous malformations involved the oral cavity/tongue (4/11; 36.4%) and parotid/face (7/11; 63.6%). During facial lesion excision, intraoperative facial nerve monitoring was used. All surgical sites (11/11) were closed primarily. No patient in this cohort had any posttreatment nerve deficits, dysarthria, and dysphagia or lesion persistence. Localized venous malformations can be treated with preoperative percutaneous embolization with n-BCA glue followed by surgical excision. This technique, with selective motor nerve monitoring, appears safe and allows for complete venous malformation removal with limited nerve dissection, to allow maximal tissue and functional preservation.

Different protein profile in amniotic fluid with nervous system malformations by surface-enhanced laser desorption-ionization/time-of-flight mass spectrometry (SELDI-TOF-MS) technology.

PubMed

Ma, Zhe; Liu, Cun; Deng, Biping; Dong, Shaogang; Tao, Guowei; Zhan, Xinfeng; Wang, Chuner; Liu, Shaoping; Qu, Xun

2010-12-01

To detect the distinct proteins in amniotic fluid (AF) between nervous system malformations fetuses and normal fetuses. Surface-enhanced laser desorption-ionization/time-of-flight mass spectrometry was used to characterize AF peptides in AF between nervous system malformations fetuses and normal fetuses. WCX2 protein chips were used to characterize AF peptides in AF. Protein chips were examined in a PBSIIC protein reader, the protein profiling was collected by ProteinChip software version 3.1 (Ciphergen Biosystems, Fremont, CA, USA) and analyzed by Biomarker Wizard software (Ciphergen Biosystems). Nine distinct proteins were identified in AF between nervous system malformations fetuses and normal fetuses. Compared with the control group, three proteins with m/z 4967.5 Da, 5258.0 Da, and 11,717.0 Da were down-regulated, and six proteins with m/z 2540.4 Da, 3107.1 Da, 3396.8 Da, 4590.965 Da, 5589.2 Da and 6429.4 Da up-regulated in nervous system malformations fetuses. The results suggest that there are distinct proteins in protein profiling of AF between nervous system malformations fetuses and normal fetuses. © 2010 The Authors. Journal of Obstetrics and Gynaecology Research © 2010 Japan Society of Obstetrics and Gynecology.

Ultrasound features in trisomy 13 (Patau syndrome) and trisomy 18 (Edwards syndrome) in a consecutive series of 47 cases

PubMed Central

Kroes, I.; Janssens, S.; Defoort, P.

2014-01-01

Objective: To determine and list the variety of the predominant appeal signs leading to referral and their accompanying features found during specialized ultrasound evaluation in foetuses with trisomy 13 and trisomy 18. Materials and Methods: In a period of thirty years, 1110 cases of foetal malformations were detected during specialized echographic evaluation. 47 Of these cases were foetuses with trisomy 13 or trisomy 18. We evaluated the predominant signs leading to referral, the difference and overlap in presenting signs between both syndromes and when the data were available, we also compared the echographic signs with the foetal pathology. Results: In foetuses with trisomy 13 the most common malformations were craniofacial defects, cerebral malformations and genitourinary tract anomalies. The most common malformations associated with trisomy 18 were limb abnormalities and intrauterine growth restriction. Most malformations were predominant in trisomy 18, except for genitourinary tract anomalies. In most cases the sonographic signs correlated with the pathology findings. Conclusion: Trisomy 13 as well as trisomy 18 are characterized by a number of various malformations in the foetus. Most of the ultrasound features were predominant in foetuses with trisomy 18. Mostly the foetal pathology correlated with the sonographic evaluation. PMID:25593701

Cerebrospinal fluid leakage and Chiari I malformation with Gorham's disease of the skull base: A case report.

PubMed

Nagashima, Hiroaki; Mizukawa, Katsu; Taniguchi, Masaaki; Yamamoto, Yusuke; Kohmura, Eiji

Gorham's syndrome is a rare bone disorder characterized by massive osteolysis of unknown etiology. There are no reports of comorbidity involving cerebrospinal fluid (CSF) leakage and Chiari I malformation with Gorham's syndrome. Here, we report an unusual case of an acute presyrinx state complicated by bacterial meningitis due to CSF leakage and Chiari I malformation associated with Gorham's disease of the skull base. A 25-year-old woman with Chiari I malformation associated with Gorham's syndrome presented with aggressive paresthesia following bacterial meningitis. Axial magnetic resonance imaging (MRI) and computed tomography (CT) cisternography revealed CSF leakage in the right petrous apex. A presyrinx state was diagnosed based on the clinical symptoms and MRI findings. With resolution of the bacterial meningitis, the spinal edema and tonsillar ectopia also improved. Surgical repair of the CSF leakage was performed by an endoscopic endonasal transsphenoidal approach to prevent recurrence of meningitis. The postoperative course was uneventful. Skull base osteolysis in Gorham's syndrome may induce Chiari I malformation and CSF leakage. We should pay attention to acute progression of clinical symptoms because Gorham's syndrome may predispose to development of Chiari I malformation and may be complicated by CSF leakage. Copyright © 2017 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Intravitreal bevacizumab versus laser treatment in type 1 retinopathy of prematurity: report on fluorescein angiographic findings.

PubMed

Lepore, Domenico; Quinn, Graham E; Molle, Fernando; Baldascino, Antonio; Orazi, Lorenzo; Sammartino, Maria; Purcaro, Velia; Giannantonio, Carmen; Papacci, Patrizia; Romagnoli, Costantino

2014-11-01

To compare the structural outcome at 9 months of eyes treated with intravitreal injection of bevacizumab with fellow eyes treated with conventional laser photoablation in zone I type 1 retinopathy of prematurity (ROP). Single randomized controlled trial. All inborn babies with type 1 zone I ROP at a single institution were included in the study. One eye was randomized to receive an intravitreal injection of 0.5 mg bevacizumab; the fellow eye received conventional laser photoablation. Digital fundus photographs and fluorescein angiography (FA) using the RetCam (Clarity Medical Systems Inc., Pleasanton, CA) were performed before treatment and 9 months after treatment. Presence of retinal and choroidal abnormalities on FA at 9 months. Thirteen infants were enrolled; 1 died 3 months after birth. One laser-treated eye progressed to stage 5 retinal detachment. The remaining 23 eyes had favorable structural results at the 9-month follow-up and provided FA results. At 9 months of age, all eyes treated with a bevacizumab injection were noted to have abnormalities at the periphery (large avascular area, abnormal branching, shunt) or the posterior pole (hyperfluorescent lesion, absence of foveal avascular zone). These posterior and peripheral lesions were not observed in the majority of the lasered eyes. This study documents significant vascular and macular abnormalities of eyes in the bevacizumab group. Long-lasting implications of these abnormalities for visual function of the child need to be studied. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.