Eye Anomalies Research Articles

Limbal Stem Cell Transplantation for Limbal Dermoid in a Case of Goldenhar Syndrome

Goldenhar Syndrome (known as Oculoauriculovertebral Syndrome (OAVS) or facioauriculovertebral dysplasia) is a rare congenital defect classically involving eye anomalies with or without anomalous development of the ear, nose, lips, soft palate, mandible and vertebra. It is a morphogenetic anomaly associated with the 1st and 2nd branchial arches. We report a case of 9 months old male child presented with ocular abnormalities. On evaluation, he had the classical signs of this syndrome like limbal dermoids, eyelid coloboma, preauricular skin tags and hemi facial microsomia. This patient was first seen in January 2010 and has been followed and treated for the same. The patient underwent a surgery for right eye limbal dermoid at the age of 4 years. The initial presentation with course of the disease and Post-Surgical outcome is described here. The Authors performed dermoid excision with autologous conjunctiva along with limbal stem cells transplantation and achieved a satisfactory surgical outcome.

Inversion duplication deletions involving the long arm of chromosome 13: phenotypic description of additional three fetuses and genotype-phenotype correlation.

Inversion duplication and terminal deletion of the long arm of chromosome 13 (inv dup del 13q) is a rare chromosomal rearrangement: only five patients have been reported, mostly involving a ring chromosome 13. We report on additional three fetuses with pure inv dup del 13q: Patient 1 had macrosomia, enlarged kidneys, hypersegmented lungs, unilateral moderate ventriculomegaly, and a mild form of hand and feet preaxial polydactyly; Patient 2 had intrauterine growth retardation, widely spaced eyes, left microphthalmia, right anophthalmia, short nose, bilateral absent thumbs, cutaneous syndactyly of toes 4 and 5, bifid third metacarpal, a small left kidney, hyposegmented lungs, and partial agenesis of the corpus callosum; Patient 3 had widely spaced eyes, long and smooth philtrum, low-set ears, median notch in the upper alveolar ridge, bifid tongue, cutaneous syndactyly of toes 2 and 3, enlarged kidneys and pancreas, arhinencephaly, and partial agenesis of the corpus callosum. We compared the phenotypes of these patients to those previously reported for ring chromosome 13, pure 13q deletions and duplications. We narrowed some critical regions previously reported for lung, kidney and fetal growth, and for thumb, cerebral, and eye anomalies.

Rapid Involuting Congenital Hemangioma in the Setting of PHACE Association

Rapidly involuting congenital hemangioma (RICH) is an uncommon vascular tumor that, unlike infantile hemangioma, is largely developed at birth and undergoes rapid postnatal involution. To date, RICH has often been described in the setting of an isolated lesion, whereas infantile hemangioma is a well-known feature of numerous syndromes and associations, including the association of posterior fossa anomalies, hemangioma, arterial anomalies, cardiac anomalies, and eye anomalies. The authors report a unique case of RICH in the setting of this association.

CHD7 deficiency in "Looper", a new mouse model of CHARGE syndrome, results in ossicle malformation, otosclerosis and hearing impairment.

CHARGE syndrome is a rare human disorder caused by mutations in the gene encoding chromodomain helicase DNA binding protein 7 (CHD7). Characteristics of CHARGE are varied and include developmental ear and hearing anomalies. Here we report a novel mouse model of CHD7 dysfunction, termed Looper. The Looper strain harbours a nonsense mutation (c.5690C>A, p.S1897X) within the Chd7 gene. Looper mice exhibit many of the clinical features of the human syndrome, consistent with previously reported CHARGE models, including growth retardation, facial asymmetry, vestibular defects, eye anomalies, hyperactivity, ossicle malformation, hearing loss and vestibular dysfunction. Looper mice display an otosclerosis-like fusion of the stapes footplate to the cochlear oval window and blepharoconjunctivitis but not coloboma. Looper mice are hyperactive and have vestibular dysfunction but do not display motor impairment.

A Newborn With Complex Skeletal Abnormalities, Joint Contractures, and Bilateral Corneal Clouding With Sclerocornea

A newborn presented to genetics with complex skeletal abnormalities, joint contractures, and bilateral corneal clouding with sclerocornea. The patient survived for 8 months before succumbing to respiratory failure. Exome sequencing revealed a compound heterozygous mutation in theB3GALT6gene. Mutations in this gene have been associated with both Ehlers- Danlos syndrome, progeroid type 2 and spondyloepimetaphyseal dysplasia with joint laxity type 1. These diagnoses encompass the skeletal and joint findings. Our patient expands the phenotype of these diagnoses, as anterior segment eye anomalies have not been described with either syndrome, and he is much more profoundly affected. Interestingly, our patient fits the description of a rare genetic disease referred to as Al-Gazali syndrome, for which the genetic cause is unknown.

Effects of gestational administration of nickel on postnatal development in Swiss albino mice

Effects on postnatal development of Swiss albino mice exposed to nickel (Ni(2+)) ions as nickel chloride haxahydrate (NiCl2·6H2O) during the gestation periods were evaluated in this study. Administration of Ni to pregnant females by gavage (46.125, 92.25, and 184.5 mg Ni/kg body weight (b.w.)) at doses below median lethal dose during 0-5 (preimplantation period), 6-13 (organogenetic period), and 14-18 days (fetal period) postconception. The dams were allowed to deliver and raise their pups. Significant (p < 0.05) decrease in litter size was observed after 184.5 mg Ni/kg b.w. during the three gestation periods particularly from preimplantation period as compared to organogenetic and fetal periods in comparison with the control group. Exposure to 184.5 mg Ni/kg b.w. during fetal period revealed higher mortality as compared to organogenetic period. Exposure to 184.5 mg Ni/kg b.w. increased the eye, limb, and tail anomalies during organogenetic period. Gestation index from preimplantation period was low at all the doses. Live birth index decreased during preimplantation and organogenetic periods after 184.5 mg Ni/kg b.w. The viability and weanling of pups decreased during all periods after 92.25 and 184.5 mg Ni/kg b.w. doses. A dose-dependent highly significant (p < 0.01) decrease in the body weight of offspring from day 0 to 6 weeks of age at all the doses during different gestation periods were observed. Maximum body weight decrease was observed in offspring from organogenetic period. This study concludes that young ones are vulnerable during different gestational and lactation period which indicates that Ni ingested by mothers constitutes a great threat to the progeny.

Growth Hormone Replacement in Patients with PHACE Association and Hypopituitarism

Partially empty sella with growth hormone (GH) deficiency is rarely reported in association with PHACE (posterior fossa anomalies, cervicofacial infantile hemangiomas [IHs], arterial anomalies, cardiac defects, eye anomalies, and midline/ventral defects). Consequently, little is known about the effect of GH replacement on the proliferation and involution of IHs in children with PHACE. We describe two children with PHACE and partially empty sella, both of whom received GH replacement for treatment of hypopituitarism. In our first patient we observed erythema and prominence of the vasculature in the hemangioma shortly after initiation of therapy at age 20 months, although after 4 weeks of treatment the appearance of the hemangioma stabilized and little change was seen during eight additional years of therapy. In our second patient we noted enlargement of the hemangioma after starting low-dose GH at age 5 years, prompting discontinuation of GH replacement after 3 months of therapy. The hemangiomas continued to grow after discontinuation of GH treatment. GH administration in our patients was associated with erythema and prominence of IHs. Our findings suggest that GH replacement therapy may promote transient or more prolonged proliferation of IHs and should be administered with close clinical monitoring.

Diffuse Cerebral Atrophy, Central Sinus Venous Thrombosis, Hypoplastic Carpus Callosum, Adhd and Vsd in A Child; Anaesthestic Implications

Attention deficit hyperkinetic disorder (ADHD ) is characterized by inattention, poor impulse control, motor overactivity and restlessness.The clinical features most commonly seen in patients with hypoplastic carpus callosum syndrome are microcephaly, seizures, developmental delay or retardation, hypotonia, spasticity and multiple somatic anomalies including arthrogryposis, eye anomalies, syringomyelia in the spinal cord and facial dysmorphisms. The response to general anaesthesia with sevoflurane in this rare complex combination of disorders and its postoperative outcomes were observed.

Prevalence, prenatal diagnosis and clinical features of oculo-auriculo-vertebral spectrum: a registry-based study in Europe

Oculo-auriculo-vertebral spectrum is a complex developmental disorder characterised mainly by anomalies of the ear, hemifacial microsomia, epibulbar dermoids and vertebral anomalies. The aetiology is largely unknown, and the epidemiological data are limited and inconsistent. We present the largest population-based epidemiological study to date, using data provided by the large network of congenital anomalies registries in Europe. The study population included infants diagnosed with oculo-auriculo-vertebral spectrum during the 1990-2009 period from 34 registries active in 16 European countries. Of the 355 infants diagnosed with oculo-auriculo-vertebral spectrum, there were 95.8% (340/355) live born, 0.8% (3/355) fetal deaths, 3.4% (12/355) terminations of pregnancy for fetal anomaly and 1.5% (5/340) neonatal deaths. In 18.9%, there was prenatal detection of anomaly/anomalies associated with oculo-auriculo-vertebral spectrum, 69.7% were diagnosed at birth, 3.9% in the first week of life and 6.1% within 1 year of life. Microtia (88.8%), hemifacial microsomia (49.0%) and ear tags (44.4%) were the most frequent anomalies, followed by atresia/stenosis of external auditory canal (25.1%), diverse vertebral (24.3%) and eye (24.3%) anomalies. There was a high rate (69.5%) of associated anomalies of other organs/systems. The most common were congenital heart defects present in 27.8% of patients. The prevalence of oculo-auriculo-vertebral spectrum, defined as microtia/ear anomalies and at least one major characteristic anomaly, was 3.8 per 100,000 births. Twinning, assisted reproductive techniques and maternal pre-pregnancy diabetes were confirmed as risk factors. The high rate of different associated anomalies points to the need of performing an early ultrasound screening in all infants born with this disorder.

Fryns syndrome without diaphragmatic hernia, DOOR syndrome or Fryns‐like syndrome? Report on patients from Indian Ocean islands

We report on six patients (five unpublished patients) from the Indian Ocean islands, with coarse face, cleft lip or palate, eye anomalies, brachytelephalangy, nail hypoplasia, various malformations (genitourinary or cerebral), abnormal electroencephalograms with impaired neurological examination and lethal outcome. Massive polyhydramnios was noted in the third trimester of pregnancy and neonatal growth was normal or excessive. The combination of the features is consistent with the diagnosis of Fryns syndrome (FS) without congenital diaphragmatic hernia. Besides chromosomal aberrations and microdeletion syndrome, differential diagnoses include conditions overlapping with FS such as Simpson-Golabi-Behmel, and conditions with hypoplasia/absence of the distal phalanges such as DOOR syndrome, Schinzel-Giedion syndrome, and Rudiger syndrome.

How should propranolol be initiated for infantile hemangiomas: Inpatient versus outpatient?

How should propranolol be initiated for infantile hemangiomas: Inpatient versus outpatient?

PHACES syndrome associated with carcinoid endobronchial tumor

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.

Propranolol for the treatment of infantile haemangiomas: our experience with 44 patients

Propranolol is an effective, safe treatment for complicated infantile haemangiomas (IH). We evaluated all patients (n = 44) with IH treated with propranolol in our department. Of the 44 patients who were begun on propranolol therapy, 26 patients have completed the treatment to date and all had a good response. The mean duration of treatment was 45.7 weeks. Four patients developed rebound growth of their IH, which responded to the reintroduction of propranolol. Two patients with PHACES (posterior fossa malformations, haemangiomas, arterial anomalies, coarctation of the aorta/cardiac abnormalities, eye anomalies and sternal defects/supraumbilical raphe) syndrome were treated with lower than standard doses, because of concern about possible cerebrovascular compromise. Adverse effects were minor in most patients. Three patients discontinued propranolol because of vomiting, wheeze, and hypoglycaemia, respectively. Our duration of treatment was longer than that of other series, and may be due to our group having higher rates of hypotension, recorded in 27.3% of patients, precluding an increase in propranolol dose. Our experience supports that propranolol is an effective first-line agent for complicated IH.

Environmental and public health effects of polluting industries in Tulkarm, West Bank, occupied Palestinian territory: an ethnographic study

Background Since the 1980s, several factories that cause pollution have been relocated from Israel to areas in the occupied Palestinian territory (oPt). Most prominent of these is Geshuri, a privately owned Israeli agrochemicals company operating in Tulkarm, West Bank, oPt. Results of several empirical studies suggest that as a result of proximity to industrial zones that house Geshuri and other factories that cause pollution, residents of Tulkarm have among the highest rates of cancer, asthma, and eye and respiratory health anomalies compared with residents in other districts. Because of the paucity of qualitative data to show the effect of polluting industries, our aim was to build a framework to understand the perceived adverse role of industrial pollution on the environment, economy, and public health of Tulkarm's residents. Methods In this ethnographic study, participants were selected using a snowball sampling method generated from initial contacts within Tulkarm. We analysed qualitative data from in-depth, semistructured interviews of former employees of Geshuri factory (n=3), their families (n=6), and other adult residents (n=24). Participants were interviewed from June to August, 2011. Interviews were done in Arabic, audio recorded with verbal consent of the participants, and transcribed for review and analysis. Using a grounded-theory ethnographic approach and an open-coding method of data review, we reviewed both interview transcripts and the original recordings to identify key themes in perceptions of the environmental, economic, and health effects of the factories. The institutional review board of Brown University, Providence, RI, USA, approved this study. Findings Key themes that emerged from the qualitative data analysis were that the most prominent acute health effects of industrial pollution were respiratory and psychosocial; there was a consensus that rates of cancer and asthma in Tulkarm were disproportionately higher than were those in other districts directly as a result of pollution from factories; pollution and waste produced by the industries had devastated agriculture, business, and land, and thus local economy and livelihoods of Tulkarm's residents who were reliant on the land for income; frustration at the researchers and journalists who had investigated the illegal practices by Geshuri but had yet to hold the responsible parties accountable for their actions; conflicting beliefs about whether some employees would have economic insecurity if Geshuri and similar factories should cease operation; concern about unsafe factory working conditions and violent management practices; and a long-held belief that working towards closing these factories would be a tangible affirmation of a commitment to environmental justice in the oPt. Interpretation Most of the participants believed that the pollution caused by Geshuri has adversely affected the public health and livelihood of the community in Tulkarm. In the absence of resources required for advanced environmental epidemiological modelling, we suggest the incorporation of community voices in any effort to challenge such industries. Furthermore, gathering of rigorous environmental exposure data is warranted and should be encouraged. The main limitations of this study were the inability to ascertain the representativeness of our sample to the experience of all Tulkarm's residents; and because of the qualitative design, our inability to identify precise sources of pollution apart from that caused by agrochemical manufacturers. Funding Alpert Medical School at Brown University.

Prevalence of congenital eye anomalies in a paediatric clinic in Ghana

There is little information about the epidemiology of congenital eye anomalies in Ghana. We retrospectively reviewed the clinical records of 485 admissions to the paediatric eye centre of the Korle-Bu Teaching Hospital, Ghana (2004-2009) and 263 were diagnosed with at least one anomaly. Visual acuity was quantitatively assessed in 209 patients and 130 had some visual impairment; 49 with bilateral and 64 with unilateral blindness. The most frequent congenital anomaly overall was cataract (n = 44). In infants, cataract was the most frequent finding (28/121). Toddlers most frequently presented with retinoblastoma (10/65). Glaucoma was the most frequent anomaly in preschool (9/39) and school (10/38) children. We conclude that avoidable causes of childhood blindness caused most congenital eye anomalies. Intensification of community-based health promotion and preventive eye care, early detection and provision of adequate resources for effective therapy could reverse these trends.

A novel heterozygous SOX2 mutation causing congenital bilateral anophthalmia, hypogonadotropic hypogonadism and growth hormone deficiency

Heterozygous de novo mutations in SOX2 have been reported in approximately 10–20% of patients with unilateral or bilateral anophthalmia or microphthalmia. An additional phenotype of hypopituitarism, with anterior pituitary hypoplasia and hypogonadotropic hypogonadism, has been reported in patients carrying SOX2 alterations. We report a novel heterozygous mutation in the SOX2 gene in a male affected with congenital bilateral anophthalmia, hypogonadotrophic hypogonadism and growth hormone deficiency. The mutation we describe is a cytosine deletion in position 905 (c905delC) which causes frameshift and an aberrant C-terminal domain. Our report highlights the fact that subjects affected with eye anomalies and harboring SOX2 mutations are at high risk for gonadotropin deficiency, which has important implications for their clinical management.

Expanding the phenotype of IFAP/BRESECK syndrome: A new case with severe hypogammaglobulinemia

The ichthyosis follicular with atrichia and photophobia syndrome (IFAP) is a rare X-linked multiple congenital malformation syndrome. Some male patients have additional features including brain anomalies, intellectual disability, ectodermal dysplasia, skeletal deformities, ear or eye anomalies and kidney dysplasia/hypoplasia (BRESEK syndrome) sometimes associated with Hirschsprung disease and cleft palate or cryptorchidism (BRESHECK syndrome). We report a 5 months-old male patient with the p.R429H mutation in MBTPS2 protein, which has been reported to be associated with the most severe phenotype of patients with IFAP/BRESHECK syndrome. This patient presented with a severe IFAP/BRESHECK phenotype including ichthyosis follicular, atrichia, photophobia, brain anomalies, global developmental delay, Hirschsprung disease and kidney hypoplasia. Additional features not previously reported in IFAP syndrome, include severe hypogammaglobulinemia and congenital rectourethral fistula.

Coloboma and anorectal malformations: a rare association with important clinical implications

In a patient with an anorectal malformation (ARM), the presence of a coloboma is commonly associated with other serious anomalies. Our database and the world literature were reviewed searching for associated defects in patients with ARM and coloboma. Of 2,482 ARMs in our database, 11 had coloboma (0.4%): 2 were females. No specific associated type of ARM was identified. Six patients were developmentally delayed. Eight had a cardiac anomaly (3 had TAPVR, 2 VSD, 3 ASD), five required a cardiac operation. Five had a gastrointestinal anomaly (3 malrotation, 1 biliary and 1 duodenal atresia). Six had eye and seven had ear anomalies. Five had a genetic abnormality. In the literature, 71 patients with ARM and coloboma were found: 65 % were females. 24% died prematurely. 74% were developmentally delayed. 70% had a cardiac malformation (35% had TAPVR, 38% required an operation). 57% had gastrointestinal anomalies (31% malrotation, 31 % biliary atresia, 17% Hirschsprung disease). Eye and ear anomalies were present in 80 and 97% of patients, respectively. 81% had a genetic abnormality. An ocular inspection in patients born with ARM is crucial. The finding of a coloboma should increase awareness to evaluate for a developmental, cardiologic or gastrointestinal anomaly.

Familial Peters Plus syndrome with absent anal canal, sacral agenesis and sensorineural hearing loss: Expanding the clinical spectrum

Peters anomaly is a rare form of anterior segment dysgenesis in which abnormal cleavage of the anterior chamber occurs involving the central or entire cornea. It may be associated with other ocular or systemic abnormalities. Peters Plus syndrome, also known as Krause–Kivlin syndrome, characterized by additional anomalies including short stature with developmental delay, facial dysmorphism, genitourinary abnormalities; syndactyly; brachycephaly; and cardiac, neural, and hearing abnormalities. Here we report an 8month old boy with typical features of Peters Plus syndrome including eye anomalies, dysmorphic features, global developmental delay, growth retardation, bilateral talipes equinovarus, complex renal anomalies, absent anal canal, sacral agenesis and sensorineural hearing loss. To our knowledge, the last three features were not reported before.

Mutations in PIK3R1 Cause SHORT Syndrome

SHORT syndrome is a rare, multisystem disease characterized by short stature, anterior-chamber eye anomalies, characteristic facial features, lipodystrophy, hernias, hyperextensibility, and delayed dentition. As part of the FORGE (Finding of Rare Disease Genes) Canada Consortium, we studied individuals with clinical features of SHORT syndrome to identify the genetic etiology of this rare disease. Whole-exome sequencing in a family trio of an affected child and unaffected parents identified a de novo frameshift insertion, c.1906_1907insC (p.Asn636Thrfs*18), in exon 14 of PIK3R1. Heterozygous mutations in exon 14 of PIK3R1 were subsequently identified by Sanger sequencing in three additional affected individuals and two affected family members. One of these mutations, c.1945C>T (p.Arg649Trp), was confirmed to be a de novo mutation in one affected individual and was also identified and shown to segregate with the phenotype in an unrelated family. The other mutation, a de novo truncating mutation (c.1971T>G [p.Tyr657*]), was identified in another affected individual. PIK3R1 is involved in the phosphatidylinositol 3 kinase (PI3K) signaling cascade and, as such, plays an important role in cell growth, proliferation, and survival. Functional studies on lymphoblastoid cells with the PIK3R1 c.1906_1907insC mutation showed decreased phosphorylation of the downstream S6 target of the PI3K-AKT-mTOR pathway. Our findings show that PIK3R1 mutations are the major cause of SHORT syndrome and suggest that the molecular mechanism of disease might involve downregulation of the PI3K-AKT-mTOR pathway.