Congenital Eye Research Articles

Longitudinal OCT and OCTA monitoring reveals accelerated regression of hyaloid vessels in retinal degeneration 10 (rd10) mice

The hyaloid vascular system (HVS) is known to have an important role in eye development. However, physiological mechanisms of HVS regression and their correlation with developmental eye disorders remain unclear due to technical limitations of conventional ending point examination with fixed tissues. Here, we report comparative optical coherence tomography (OCT) and OCT angiography (OCTA) monitoring of HVS regression in wild-type and retinal degeneration 10 (rd10) mice. Longitudinal OCTA monitoring revealed accelerated regression of hyaloid vessels correlated with retinal degeneration in rd10. Quantitative OCT measurement disclosed significant distortions of both retinal thickness and the vitreous chamber in rd10 compared to WT mice. These OCT/OCTA observations confirmed the close relationship between HVS physiology and retinal neurovascular development. The distorted HVS regression might result from retinal hyperoxia or dopamine abnormality due to retinal remodeling in rd10 retina. By providing a noninvasive imaging platform for longitudinal monitoring of HVS regression, further OCT/OCTA study may lead to in-depth understanding of the physiological mechanisms of HVS regression in normal and diseased eyes, which is not only important for advanced study of the nature of the visual system but also may provide insights into the development of better treatment protocols of congenital eye disorders.

Abnormal retinal pigment epithelium melanogenesis as a major determinant for radiation-induced congenital eye defects

Recent studies highlighted a link between ionizing radiation exposure during neurulation and birth defects such as microphthalmos and anophthalmos. Because the mechanisms underlying these defects remain largely unexplored, we irradiated pregnant C57BL/6J mice (1.0 Gy, X-rays) at embryonic day (E)7.5, followed by histological and gene/protein expression analyses at defined days. Irradiation impaired embryonic development at E9 and we observed a delayed pigmentation of the retinal pigment epithelium (RPE) at E11. In addition, a reduced RNA expression and protein abundance of critical eye-development genes (e.g. Pax6 and Lhx2) was observed. Furthermore, a decreased expression of Mitf, Tyr and Tyrp1 supported the radiation-induced perturbation in RPE pigmentation. Finally, via immunostainings for proliferation (Ki67) and mitosis (phosphorylated histone 3), a decreased mitotic index was observed in the E18 retina after exposure at E7.5. Overall, we propose a plausible etiological model for radiation-induced eye-size defects, with RPE melanogenesis as a major determining factor.

Uveitis associated with Toxocara; Clinic, Diagnosis, and Treatment

Ocular toxocariasis or ocular larva migrans is a parasitic infection via the ingestion of dog nematode Toxocara canis and cat nematode Toxocara cati larvae. It usually affects only one eye of the child under the age of sixteen. The most common clinical findings in ocular toxocariasis are peripheral granuloma, posterior pole chorioretinal eosinophilic granulomas, and endophthalmitis or pars planitis. It is diagnosed with clinical findings in developing countries, ELISA antibody tests, and, if necessary, intraocular fluid analysis can be made. Ocular toxocariasis must be distinguished from retinoblastoma and other congenital and inflammatory eye conditions of childhood. In treatment, besides anthelmintic agents, steroid use and vitreoretinal surgery may be needed.

Sostdc1 is expressed in all major compartments of developing and adult mammalian eyes.

This study was conducted in order to study Sostdc1 expression in rat and human developing and adult eyes. Using the yeast signal sequence trap screening method, we identified the Sostdc1 cDNA encoding a protein secreted by the adult rat retinal pigment epithelium. We determined by in situ hybridization, RT-PCR, immunohistochemistry, and western blot analysis Sostdc1 gene and protein expression in developing and postnatal rat ocular tissue sections. We also investigated Sostdc1 immunohistolocalization in developing and adult human ocular tissues. We demonstrated a prominent Sostdc1 gene expression in the developing rat central nervous system (CNS) and eyes at early developmental stages from E10.5days postconception (dpc) to E13dpc. Specific Sostdc1 immunostaining was also detected in most adult cells of rat ocular tissue sections. We also identified the rat ocular embryonic compartments characterized by a specific Sostdc1 immunohistostaining and specific Pax6, Sox2, Otx2, and Vsx2 immunohistostaining from embryonic stages E10.5 to E13dpc. Furthermore, we determined the localization of SOSTDC1 immunoreactivity in ocular tissue sections of developing and adult human eyes. Indeed, we detected SOSTDC1 immunostaining in developing and adult human retinal pigment epithelium (RPE) and neural retina (NR) as well as in several developing and adult human ocular compartments, including the walls of choroidal and scleral vessels. Of utmost importance, we observed a strong SOSTDC1 expression in a pathological ocular specimen of type 2 Peters' anomaly complicated by retinal neovascularization as well in the walls ofother pathological extra-ocular vessels. CONCLUSION: As rat Sostdc1 and human SOSTDC1 are dual antagonists of the Wnt/β-catenin and BMP signaling pathways, these results underscore the potential crucial roles of these pathways and their antagonists, such as Sostdc1 and SOSTDC1, in developing and adult mammalian normal eyes as well as in syndromic and nonsyndromic congenital eye diseases.

Presence of Posterior Staphyloma in Congenital Cataract Children

ABSTRACTPurpose: To investigate the prevalence of posterior staphyloma (PS) in congenital cataract children and its role in predicting postoperative axial elongation.Materials and Methods: Preoperative prevalence of PS in 520 congenital cataract patients was reviewed and compared with that of the healthy eyes of 300 unilateral traumatic cataract children after 1:1 propensity score matching. Then, 32 pseudophakic children with preoperative PS and 48 age-matched pseudophakic controls without preoperative PS were followed up after the surgery, to compare their axial growth rates and refractive changes.Results: Congenital cataract was significantly associated with the presence of PS (OR: 14.88, P = .009) after propensity score matching. Even in congenital cataract eyes with axial length <26 mm, 5% were identified with PS on B-scan: ≤22 mm: 3%, 22–24 mm: 5% and 24–26 mm: 13%. Eyes with preoperative PS exhibited faster postoperative axial growth than those without, especially in bilateral cases or in children undergoing surgery before 8 years old (≤4 years: 0.53 ± 0.33 vs 0.30 ± 0.21 mm/y P = .028; 4–8 years: 0.37 ± 0.26 vs 0.23 ± 0.15 mm/y P = .044). Myopic shift after surgery was also more significant in children with preoperative PS than in those without (−1.10 ± 0.50 vs −0.60 ± 0.47D/y, P < .001).Conclusions: Congenital cataract is a risk factor for PS. Preoperative PS in pediatric cataract eyes may be an indicator of excessive postoperative axial elongation, especially in bilateral cases or in cases undergoing cataract surgery at a younger age. Our findings may also promote better clinical decision-making in intraocular lens power selection for pediatric population.

A SIX6 Nonsense Variant in Golden Retrievers with Congenital Eye Malformations.

Causative genetic variants for more than 30 heritable eye disorders in dogs have been reported. For other clinically described eye disorders, the genetic cause is still unclear. We investigated four Golden Retriever litters segregating for highly variable congenital eye malformations. Several affected puppies had unilateral or bilateral retina dysplasia and/or optic nerve hypoplasia. The four litters shared the same father or grandfather suggesting a heritable condition with an autosomal dominant mode of inheritance. The genome of one affected dog was sequenced and compared to 601 control genomes. A heterozygous private nonsense variant, c.487C>T, was found in the SIX6 gene. This variant is predicted to truncate about a third of the open reading frame, p.(Gln163*). We genotyped all available family members and 464 unrelated Golden Retrievers. All three available cases were heterozygous. Five additional close relatives including the common sire were also heterozygous, but did not show any obvious eye phenotypes. The variant was absent from the 464 unrelated Golden Retrievers and 17 non-affected siblings of the cases. The SIX6 protein is a homeobox transcription factor with a known role in eye development. In humans and other species, SIX6 loss of function variants were reported to cause congenital eye malformations. This strongly suggests that the c.487C>T variant detected contributed to the observed eye malformations. We hypothesize that the residual amount of functional SIX6 protein likely to be expressed in heterozygous dogs is sufficient to explain the observed incomplete penetrance and the varying severity of the eye defects in the affected dogs.

Association of KIF26B and COL4A4 gene polymorphisms with the risk of keratoconus in a sample of Iranian population.

Keratoconus (KTCN) is a congenital corneal eye disorder which correlates with abnormal distribution of the collagen fiber and causes loss of visual acuity. COLA4A gene has a substantive role in collagen synthesis, whereas KIF26B as a new candidate gene belonging to kinesin superfamily (KIFs) has been suggested to be associated with this disease. So, in this preliminary study, we simultaneously evaluated the effects of two single nucleotide polymorphisms, 222855rs7C/T and rs12407427C/T, on KTCN susceptibility in a sample of Iranian population. The present case-control study consists of 144 patients confirmed with KTCN and 153 healthy controls. The variants are genotyped by using amplification refractory mutation system-polymerase chain reaction method. The findings disclosed that rs2228557C/T and rs12407427C/T polymorphisms significantly increased the risk of KTCN in measured (codominant1; p = 0.0001, codominant2; p = 0.0001, codominant3; p = 0.0006, dominant; p = 0.0001, over-dominant; p = 0.0005) and (codominant1; p = 0.0001, codominant3; p = 0.0005, recessive; p = 0.0001) inheritance patterns, respectively. Our results did prove a statistical association of both rs2228557 and rs12407427 genotypes (TT and CT + CC) and allele (T) with KTCN susceptibility in Iranian population. Further studies in other ethnicities are required to verify our results.

SUN-288 Severe Growth Hormone Deficiency in a 13-Year-Old Girl with Congenital Eye Anomalies, Secondary to Transsphenoidal Encephalocele

Background: Transphenoidal encephaloceles are very rare with estimated incidence of 1 in 700,000 live births. They can be associated with pituitary hormonal deficiencies, facial midline defects or eye anomalies. Lack of feeding problems, respiratory difficulties and/or characteristic facies can lead to delayed diagnosis to adolescence or adulthood. Clinical Case: a 13 year old female was referred for evaluation of short stature. She had history of left microophthalmia, congenital coloboma, persistent hyperplastic primary vitreous (PHPV), and subsequent enucleation. She had no other congenital anomalies. She described some discomfort of left eye prosthesis. No headache or nasal symptoms. She maintained height around 2%tile (Z= -2.09) until the age of 6 yrs with subsequent slowing to less than 1%tile (Z= -2.49). She slowed down further (Z= -2.66) over the last year despite showing pubertal changes including breast and pubic hair development. Weight was around 27% tile (Z= - 0.61) until the age of 10 yrs with subsequent acceleration up to 54%tile (Z= 0.10) at time of presentation, despite healthy diet and scheduled physical activities. On physical exam, she was overweight (BMI 91%tile, Z= 1.25), positive left eye prosthesis, no other congenital anomalies, and Tanner stage III breasts/pubic hair. Bone age was normal at 13 years 6 months. IGF-1 level was low for pubertal stage at 183 ng/ml with normal IGFBP-3 of 4.61 mg/l. Other pituitary hormonal studies were completely normal. Peak growth hormone level was only 1.3 ng/ml on Arginine-Glucagon tolerance test. Brain MRI showed considerable deformity of sella turcica with encephalocele extending through the inferior and anterior aspects into the nasopharyngeal region. Pituitary gland was flattened and deformed by the encephalocele. Pituitary stalk was partially visualized, with inferior coursing of optic chiasm and optic nerves. Conclusions: Pituitary hormonal deficiencies including growth hormone have been described rarely in association with transphenoidal encephaloceles and congenital eye anomalies, typically “morning glory” anomaly of optic disc. Transphenoidal encephalocele and subsequent pituitary dysfunction should be considered early when a child with any eye congenital anomaly presents with short stature/growth failure, even without other midline/facial abnormalities or symptoms.

Prevalence of childhood ocular morbidity in a peri-urban setting in Bangladesh: a community-based study

ObjectivesTo test a model of integrated pediatric eye care delivery and examine the prevalence and factors associated with childhood ocular morbidity in a peri-urban setting in Bangladesh. Study designCross-sectional, population-based study. MethodsThe study was conducted in three phases among children aged ≤15 years. Trained community health workers (CHWs) conducted awareness intervention and identified children with ocular problems. These children were then referred to the base hospital for examination and treatment by ophthalmologists. A pediatric ophthalmologist further examined the children with complicated eye diseases and ensured treatment at a tertiary public eye hospital. Awareness, referral patterns, and health-seeking behavior were also examined. All data were analyzed statistically using Statistical Package for Social Sciences. ResultsCHWs screened 33,549 eligible children and identified 1887 cases with ocular morbidity. The prevalence of ocular morbidity and childhood blindness were 5.63% (95% confidence interval [CI] = 5.27–6.16) and 0.060% (95% CI = 0.03–0.11), respectively. The most commonly observed ocular morbidities were refractive error (3.24%; 95% CI = 3.11–3.45), allergic eye conditions (1.2%; 95% = CI 0.74–1.27), and nasolacrimal duct obstruction (0.52%; 95% CI = 0.25–0.74). Blindness was more frequently seen in children aged <5 years than in those aged 5–15 years (χ2 = 7.25; P = 0.007). The causes of blindness were corneal opacity, congenital eye anomaly, cataract, retinopathy of prematurity, and retinoblastoma. The prevalence of ocular morbidity was higher among older children, boys, children with low parental education and income, and children from households dwelling in slums. ConclusionsThis study demonstrated that in a setting where screening and treatment for vision problems remain low, ocular morbidity among children could be easily identified through well-designed community-based screening programs involving appropriately trained CHWs. Community mobilization, awareness, and early detection of childhood eye diseases, with effective referral mechanisms for accessing appropriate care, are crucially important to improve service delivery.

A High-Throughput Assay for Congenital and Age-Related Eye Diseases in Zebrafish.

Debilitating visual impairment caused by cataracts or microphthalmia is estimated to affect roughly 20 million people in the United States alone. According to the National Eye Institute, by 2050 that number is expected to more than double to roughly 50 million. The identification of candidate disease-causing alleles for cataracts and microphthalmia has been accelerated with advanced sequencing technologies creating a need for verification of the pathophysiology of these genes. Zebrafish pose many advantages as a high-throughput model for human eye disease. By 5 days post-fertilization, zebrafish have quantifiable behavioral responses to visual stimuli. Their small size, many progeny, and external fertilization allows for rapid screening for vision defects. We have adapted the OptoMotor Response to assay visual impairment in zebrafish models of cataracts and microphthalmia. This research demonstrates an inexpensive, high-throughput method for analyzing candidate genes involved in visual impairment.

Clinical Characteristics in Congenital Cataract Eyes

Clinical Characteristics in Congenital Cataract Eyes

Contrast Sensitivity Affection: A Comparative Study between Photorefractive Keratectomy and Small Incision Lenticule Extraction Pre and Postoperative

Background: the cornea is a transparent dome shaped structure at the front of the eye separated from the iris and pupil by the anterior chamber. It is one of the main refractive media of the eye. Refractive surgery includes several types such as Photorefractive Refractive Keratectomy (PRK) and Small incision lenticule extraction (SMILE). Objective: contrast sensitivity affection in comparative study between patients undergoing photorefractive keratectomy (PRK) or small incision lenticule extraction (SMILE) surgery. Patients and Methods: twenty cases of different patients’ ages; 18-30 years old with myopia from -0.5 D to - 9.00 D were included in this comparative study. Patient with corneal infection, trauma, opacities, operation, ocular disease or congenital eye disease were excluded from our study. All the selected patients were submitted to full ophthalmological examination (visual acuity, fundus examination, pantacam, and assess contrast sensitivity degree before operation and one month after refractive surgery. Measurement of contrast sensitivity was done by Function Acuity Contrast Test (FACT) before and one month after refractive surgery through several spatial frequencies (1.5, 3, 6, 12 and 18). Results: we found that contrast sensitivity was affected one month after refractive surgery in both groups but it is affected in group 1 after PRK more than group 2 that had femto SMILE. Conclusion: contrast sensitivity was affected in both patients who had PRK or Femto SMILE after one month from operation but it is more stable after Femto SMILE.

Contrast Sensitivity Affection: A Comparative Study between Photorefractive Keratectomy and Small Incision Lenticule Extraction Pre and Postoperative

Background: the cornea is a transparent dome shaped structure at the front of the eye separated from the iris and pupil by the anterior chamber. It is one of the main refractive media of the eye. Refractive surgery includes several types such as Photorefractive Refractive Keratectomy (PRK) and Small incision lenticule extraction (SMILE). Objective: contrast sensitivity affection in comparative study between patients undergoing photorefractive keratectomy (PRK) or small incision lenticule extraction (SMILE) surgery. Patients and Methods: twenty cases of different patients’ ages; 18-30 years old with myopia from -0.5 D to - 9.00 D were included in this comparative study. Patient with corneal infection, trauma, opacities, operation, ocular disease or congenital eye disease were excluded from our study. All the selected patients were submitted to full ophthalmological examination (visual acuity, fundus examination, pantacam, and assess contrast sensitivity degree before operation and one month after refractive surgery. Measurement of contrast sensitivity was done by Function Acuity Contrast Test (FACT) before and one month after refractive surgery through several spatial frequencies (1.5, 3, 6, 12 and 18). Results: we found that contrast sensitivity was affected one month after refractive surgery in both groups but it is affected in group 1 after PRK more than group 2 that had femto SMILE. Conclusion: contrast sensitivity was affected in both patients who had PRK or Femto SMILE after one month from operation but it is more stable after Femto SMILE.

Transmission of Zika Virus Through the Rectal Route Leads to Mucosal and Systemic Infection with Reduced Neuropathology in Mice

Zika virus (ZIKV) is a mosquito‐borne flavivirus originally confined to Africa and Asia that has most recently spread to the Americas and the Caribbean. ZIKV circulates in sylvatic and urban transmission cycles and causes asymptomatic infection in most affected individuals, while the rest of the population experiences mild febrile syndrome. In some adults, ZIKV causes neurotropic Guillain–Barré syndrome. Vertical transmission of ZIKV in infected mothers causes fetal growth restriction, microcephaly, and congenital eye disease. There have been reports of infected individuals transmitting ZIKV sexually from male to female, male to male, and a suspected case of female to male. ZIKV has been detected in the semen of infected males months after symptom onset and thus, ZIKV persistence in the semen and testes can increase the risk of viral transmission for men having sex with men (MSM) and between heterosexual partners through rectal route. To further understand the risk of ZIKV acquisition through this route, we established a rectal route of infection model using immunocompromised (Ifnar1−/−) mice to investigate the sexual (rectal) and mosquito (subcutaneous) modes of transmission and their resulting systemic and mucosal responses to infection. Rectal inoculation of ZIKV results in viremia with non‐lethal infection, while establishing active rectal and testicular infection that persists for at least 21 days. We found that after one day of infection, ZIKV infects epithelial cells comprising the mucosal epithelium and dendritic cells within the lamina propria and submucosa. Significantly increased levels of the chemokine CCL2 and CD4+ T‐cell response were observed at 3 and 7 days post‐infection, respectively, relative to the subcutaneously infected group. Moreover, rectal route of infection results in reduced immune cell infiltration and inflammation in the brain with a robust CCL2 and CXCl10 response, while subcutaneous infection caused severe brain pathology and induces a more robust CD8+ T‐cell response. Lastly, at 21 days, the rectal group had specific anti‐ZIKV antiviral response suggesting the role of adaptive immune response in restricting lethal viral infection. Our studies provide comprehensive insight of ZIKV transmission through rectal route and the resulting reduced neuropathology and control of disease progression in mice due to early virological and immunological events following infection of the rectal mucosa.Support or Funding InformationThis research was funded by Cedars‐Sinai Medical Center's Institutional Research Award to V.A., the California Institute for Regenerative Medicine (CIRM) Quest – Discovery Stage Research Projects Grant (DISC2‐10188) to V.A. at UCLA, and the UCLA Interdisciplinary Postdoctoral Training Grant (T32) in Virology and Gene Therapy to L.E.M.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

A recurrent de novo missense pathogenic variant in SMARCB1 causes severe intellectual disability and choroid plexus hyperplasia with resultant hydrocephalus

PurposeSMARCB1 encodes a subunit of the SWI/SNF complex involved in chromatin remodeling. Pathogenic variants (PV) in this gene can give rise to three conditions. Heterozygous loss-of-function germline PV cause rhabdoid tumor predisposition syndrome and schwannomatosis. Missense PV and small in-frame deletions in exons 8 and 9 result in Coffin–Siris syndrome, which is characterized by intellectual disability (ID), coarse facial features, and fifth digit anomalies. MethodsBy a gene matching approach, individuals with a similar SMARCB1 PV were identified. Informed consent was obtained and patient data were collected to further establish genotype–phenotype relationship. ResultsA recurrent de novo missense PV (c.110G>A;p.Arg37His) in exon 2 of SMARCB1, encoding the DNA-binding domain, was identified in four individuals from different genetic centers. They shared a distinct phenotype consisting of profound ID and hydrocephalus due to choroid plexus hyperplasia. Other shared features include severe neonatal feeding difficulties; congenital heart, kidney, and eye anomalies; obstructive sleep apnea; and anemia. ConclusionThe p.Arg37His PV in the DNA-binding domain of SMARCB1 causes a distinctive syndrome, likely through a gain-of-function or dominant-negative effect, which is characterized by severe ID and hydrocephalus resulting from choroid plexus hyperplasia. This report broadens the phenotypic spectrum associated with PV in SMARCB1.

Transcriptome profiling of zebrafish optic fissure fusion

Incomplete fusion of the optic fissure leads to ocular coloboma, a congenital eye defect that affects up to 7.5 per 10,000 births and accounts for up to 10 percent of childhood blindness. The molecular and cellular mechanisms that facilitate optic fissure fusion remain elusive. We have profiled global gene expression during optic fissure morphogenesis by transcriptome analysis of tissue dissected from the margins of the zebrafish optic fissure and the opposing dorsal retina before (32 hours post fertilisation, hpf), during (48 hpf) and after (56 hpf) optic fissure fusion. Differential expression analysis between optic fissure and dorsal retinal tissue resulted in the detection of several known and novel developmental genes. The expression of selected genes was validated by qRT-PCR analysis and localisation investigated using in situ hybridisation. We discuss significantly overrepresented functional ontology categories in the context of optic fissure morphogenesis and highlight interesting transcripts from hierarchical clustering for subsequent analysis. We have identified netrin1a (ntn1a) as highly differentially expressed across optic fissure fusion, with a resultant ocular coloboma phenotype following morpholino antisense translation-blocking knockdown and downstream disruption of atoh7 expression. To support the identification of candidate genes in human studies, we have generated an online open-access resource for fast and simple quantitative querying of the gene expression data. Our study represents the first comprehensive analysis of the zebrafish optic fissure transcriptome and provides a valuable resource to facilitate our understanding of the complex aetiology of ocular coloboma.

A Rare Case of Left Sided Anophthalmos with Congenital Cystic Eyeball with Right Sided Microphthalmos

Congenital cystic eye, also known as anophthalmos with cyst, is an extremely rare congenital anomaly, first described by Mann in 1939 with a prevalence of 3 per 1,00,000. Congenital micropthalmos is also a rare condition with prevalence rates of 1.4 - 3.5 per 10,000 births. The objective is to report a case of a 19 year old male who was born to non-consanguineous marriage, presenting with left sided anophthalmos with right sided microphthalmos, with horizontal nystagmus and healed perforated corneal ulcer. Differential diagnosis include encephalocele, dermoid cyst, congenital cystic eye and tumors. Early visual rehabilitation is advised.

Children and Infant’s Vision and Measure for Detecting Congenital Eye Diseases

Children and Infant’s Vision and Measure for Detecting Congenital Eye Diseases

SCF/SCFR signaling plays an important role in the early morphogenesis and neurogenesis of human embryonic neural retina.

The stem cell factor receptor (SCFR) has been demonstrated to be expressed in the neural retina of mice, rat and human for decades. Previous reports indicated that the SCFR correlates with glia differentiation of late retinal progenitor cells (RPCs), retinal vasculogenesis and homeostasis of the blood-retinal barrier. However, the role of SCF/SCFR signaling in the growth and development of the neural retina (NR), especially in the early embryonic stage, remains poorly understood. Here, we show that SCF/SCFR signaling orchestrates invagination of the human embryonic stem cell (hESC)-derived NR via regulation of cell cycle progression, cytoskeleton dynamic and apical constriction of RPCs in the ciliary marginal zone (CMZ). Furthermore, activation of SCF/SCFR signaling promotes neurogenesis in the central-most NR via acceleration of the migration of immature ganglion cells and repressing apoptosis. Our study reveals an unreported role for SCF/SCFR signaling in controlling ciliary marginal cellular behaviors during early morphogenesis and neurogenesis of the human embryonic NR, providing a new potential therapeutic target for human congenital eye diseases such as anophthalmia, microphthalmia and congenital high myopia.

An update on oculocerebrocutaneous (Delleman-Oorthuys) syndrome.

Oculocerebrocutaneous syndrome (OCCS) is a rare disorder characterized primarily by congenital skin, eye, and brain anomalies. The most distinctive findings are hypoplastic or aplastic skin defects; pedunculated, typically hamartomatous, or nodular skin appendages; cystic microphthalmia; and a combination of forebrain anomalies and a specific mid-hindbrain malformation. Based on a review of 40 patients with OCCS, existing clinical criteria have been revised. Because of the asymmetric and patchy distribution of features, lack of recurrence in families, male preponderance and completely skewed X-inactivation in one female, OCCS is hypothesized to result from postzygotic mosaic variants in an X-linked gene. Whole exome and genome sequencing on blood DNA in two patients failed to identify pathogenic variants so far. In view of the overlapping features, in particular of the brain, of OCCS and Aicardi syndrome, both may be pathogenetically related or even result from different variants in the same gene. For the elucidation of the cause of OCCS, exome or genome sequencing on multiple lesional tissues is the primary goal.