Familial exudative vitreoretinopathy (FEVR) is a severe clinically and genetically heterogeneous disease that is characterized by vascular disorder. FEVR exhibits strikingly variable clinical phenotypes, ranging from asymptomatic to total blindness. In this case, we present a patient who was first treated as having high myopia and retinopathy but was finally diagnosed with FEVR caused by the heterozygous deletion of exon 7 in TSPAN12 with the aid of whole genome sequencing (WGS). Typical vascular changes, including vascular leakage and an avascular zone in the peripheral retina, were observed in the proband using fundus fluorescein angiography (FFA), and the macular dragging was shown to be progressing in the follow-up visit. Furthermore, the proband showed unreported TSPAN12-related phenotypes of FEVR: ERG (full-field electroretinogram) abnormalities and retinoschisis. Only mild vascular changes were exhibited in the FFA for the other three family members who carried the same deletion of exon 7 in TSPAN12. This case expands our understanding of the phenotype resulting from TSPAN12 mutations and signifies the importance of combining both clinical and molecular analysis approaches to establish a complete diagnosis.

To report the concurrent presentation and management of IQCB1-associated Leber Congenital Amaurosis and NDP-associated Familial Exudative Vitreoretinopathy (FEVR).
A 6-month-old Caucasian infant presented with poor visual response, high hypermetropia, and infantile-nystagmus with a provisional diagnosis of Leber Congenital Amaurosis based on clinical findings. Genetic counseling and testing were performed with a 285 gene retinal dystrophy panel (Blueprint Genetics). Clinical characteristics, presentation, ancillary testing results, and management are described.
Two previously reported heterozygous pathogenic variants in ICQB1 were identified (c.1518_1519del (p.His506Glnfs*13) and c.1381C>T, p.Arg461*) segregating in trans. In addition, a variation of uncertain significance (VUS) was found in NDP (c.280C>T; p.His94Tyr). Fluorescein angiography was performed demonstrating peripheral avascularity and retinal telangiectasia without frank neovascularization. Peripheral ablative laser was applied to the avascular zone.
The NDP VUS likely represents a pathogenic variant given the FEVR phenotype in addition to retinal degeneration, creating a rare dual phenotype. The combination of low oxygen demand from the IQCB1-associated retinal degeneration and NDP variant may have led to a more attenuated FEVR presentation with uncertain prognosis. A molecular diagnosis informed ocular and renal surveillance, as well as the recurrence risk for future offspring.

BACKGROUND: Familial exudative vitreoretinopathy (FEVR) is an inherited disorder, which is mostly reported to be associated with the mutation of genes involved in the Wnt signaling pathway related to β-catenin. To the best of our knowledge, the involvement of Adams-Oliver syndrome (AOS) genes in FEVR patients have not been reported before.
METHODS: Two patients with FEVR presented with microcephaly. One of them showed slight scarring of the scalp vertex which is a typical manifestation of AOS. The whole exon sequencing confirmed the diagnosis of AOS with 2 AOS-gene mutations at DOCK6 and ARHGAP31. Further clinical examination revealed that their parents with the same mutations showed FEVR-like vascular anomalies.
METHODS: Both patients were diagnosed with AOS through whole exon sequencing, and they presented with some FEVR-like retinopathy including retinal detachment.
METHODS: Both patients received vitrectomy for tractional retinal detachment with proliferative vitreoretinopathy. During the follow-up, 1 patient received additional laser photocoagulation for tractional retinal detachment.
RESULTS: The 2 patients remained stable in the latest follow up after the treatment.
CONCLUSIONS: Microcephaly could be associated with some form of retinopathy. We proposed that mutation of DOCK6 and ARHGAP31 genes could be the possible cause of FEVR associated with microcephaly. Our study suggested that these genes may be candidate genes of FEVR.

Purpose: Neonatal retinal folds and/or vitreoretinal traction can be signs of isolated ocular or syndromic disorders. Etiologies include retinopathy of prematurity, perinatal infections or inherited vitreoretinal disorders such as familial exudative vitreoretinopathy (FEVR) or Norrie disease. We present the clinical and genetic findings of a two-month-old infant with microcephaly, mild motor developmental delay, and FEVR, who required urgent surgical interventions.Methods: The patient underwent an initial examination under anesthesia (EUA) with fluorescein angiography (FA) and subsequent medical and surgical treatments. Genetic testing was undertaken to identify the etiology.Results: Examination at 2 months of age demonstrated microcephaly with a head circumference smaller than the 1st percentile. Family history was negative for microcephaly or retinal disease. Anterior segment eye exam was normal OU. There were bilateral macular folds involving the fovea and extending from the disc to the temporal periphery. FA demonstrated bilateral incomplete vascularization of the retina most notable nasally. Indirect laser was applied to ischemic retina OU. Scleral buckling procedures were performed OU as well as a vitrectomy in the left eye. Follow-up examinations demonstrated the stable appearance of the folds and attached retinas OU. Genetic testing identified a novel dominant heterozygous c.2046_2047del [p.Phe683Glnfs*9] mutation in CTNNB1, predicted to result in a frameshift causing a truncated protein.Conclusions: CTNNB1 mutations are an uncommon cause of FEVR with microcephaly.

BACKGROUND: To report a case of familial exudative vitreoretinopathy (FEVR) complicated with full-thickness macular hole (FTMH).
UNASSIGNED: A 39-year-old male presented after becoming aware of metamorphopsia in his left eye.
UNASSIGNED: Fundus examination showed a retinal avascular area, retinal vascular abnormality, and yellow exudation at the peripheral retina in both eyes. Optical coherence tomography findings revealed impending MH (IMH) due to posterior vitreous detachment (PVD) in his left eye. Despite of the occurrence of spontaneous complete PVD, an FTMH developed at 4 months after the onset of IMH.
METHODS: To treat the FTMH, vitreous surgery was performed. Intraoperative findings revealed that the thick posterior vitreous membrane (PVM) had no adhesions with the edge of the FTMH. However, a thin epiretinal membrane (ERM) was observed around the MH.
RESULTS: Postoperatively, the FTMH was closed, and the patient\'s corrected visual acuity improved from (0.4) to (0.8).
CONCLUSIONS: In this present case, an IMH developed via traction by a thick PVM, characteristic of FEVR, with FTMH then developing via traction by a thin ERM. Our findings reveal that it is vital to fully understand these anatomical features before performing vitreous surgery for FTMH complicated with FEVR.

The constellation of signs including microcephaly, retinal colobomas, and exudative vitreo-retinopathy suggests a mutation of the KIF-11 gene on chromosome 10q. We report a female infant with these features but due, instead, to a contiguous gene deletion on chromosome Xp including the OMIM morbid genes CASK, KDM6A, NDP, MAOA, NYX, and DDX3X. The NDP deletion could account for the exudative retinopathy and the CASK deletion for the microcephaly, while CASK and KDM6A have both been associated with coloboma. This case highlights genetic heterogeneity for the clustering of these signs.

OBJECTIVE: To report a familial case of Familial Exudative Vitreoretinopathy (FEVR) with an autosomal dominant inheritance pattern identified with the molecular analysis of FZD4.
METHODS: The proband is a 13 year-old boy who consulted for low vision. Fundus examination revealed a peripheral avascular zone and macular dragging, consistent with FEVR. Molecular analysis demonstrated a mutation of FZD4 in DNA from both the patient and his asymptomatic mother.
CONCLUSIONS: This familial case was identified with the molecular analysis of FZD4 and shows the importance to explore first degree relatives in a sporadic FEVR case.

In this communication, we report the case of a four year old boy who presented with reduced vision in the right eye. He had visual acuity of light perception right eye and 6/12 in the left eye and anterior segment examination was normal. Fundus examination of the right eye showed a falciform retinal fold extending from the optic nerve temporally involving the entire retina with exudates within the falciform fold and dense pigmentation peripherally. The left eye showed mild macular temporal dragging of the vessels and 360° of peripheral laser scars. In addition he also had some characteristic systemic features such as developmental delay, obesity, dysmorphic facies and tapered fingers. Using this case as an example, we present a systematic, logical approach to a patient with a possible genetic disorder. The growing field of ocular genetics now allows for improved diagnosis using step-wise cost efficient testing as demonstrated herein.

Familial exudative vitreoretinopathy and osteoporosis pseudoglioma syndrome are conditions that result from mutations in the LRP5 gene. Persistent fetal vasculature is a rare congenital malformation that can mimic end-stage familial exudative vitreoretinopathy. The authors report a case of familial exudative vitreoretinopathy in the spectrum of osteoporosis pseudoglioma syndrome associated with novel mutations of the LRP5 and TSPAN12 genes that resulted in a phenotype similar to bilateral persistent fetal vasculature. Both conditions can result in bilateral early-onset blindness. A high index of suspicion, dilated fundus examination and angiography of the parents, and genetic testing are necessary to ensure a correct diagnosis.

We report the case of a 21-month-old girl who was found to have familial exudative vitreoretinopathy after genetic testing revealed a genetic deletion at 7q22. She had previously been followed for exotropia; however, fundus examinations in the office were thought to be normal. After the pediatric geneticist identified the link between 7q22 deletions and vitreoretinopathies an examination under anesthesia was performed. Fluorescein angiography during this examination confirmed the presence of avascular areas of the retina.