Systemic Diagnostic Testing in Patients With Apparently Isolated Uveal Coloboma

Abstract

PURPOSE To investigate the frequency and types of systemic findings in patients with apparently isolated uveal coloboma. DESIGN Cross-sectional observational study. METHODS SETTING Single-center ophthalmic genetics clinic. STUDY POPULATION Ninety-nine patients with uveal coloboma seen at the National Eye Institute. OBSERVATIONAL PROCEDURE Results of audiology testing, echocardiogram, brain magnetic resonance imaging, renal ultrasound, and total spine radiographs. MAIN OUTCOME MEASURE Prevalence of abnormal findings on systemic testing. RESULTS Uveal coloboma affected only the anterior segment in 8 patients, only the posterior segment in 23 patients, and both anterior and posterior segments in 68 patients. Best-corrected visual acuity (BCVA) of eyes with coloboma was ≥20/40 in 45% of eyes; 23% of eyes had BCVA of ≤20/400. The majority of patients (74%) had good vision (>20/60) in at least 1 eye. Ten of the 19 patients (53%) who underwent echocardiography had abnormalities, with ventral septal defects being the most prevalent. Abnormal findings were observed in 5 of 72 patients (7%) who had a renal ultrasound and in 5 of 29 patients (17%) who underwent a brain MRI. Audiology testing revealed abnormalities in 13 of 75 patients (17%), and spine radiographs showed anomalies in 10 of 77 patients (13%). Most findings required no acute intervention. CONCLUSIONS Although some patients with coloboma had evidence of extraocular abnormalities, the majority of findings on routine clinical examination did not require acute intervention, but some warranted follow-up. Results from the systemic evaluation of patients with coloboma should be interpreted with caution and in view of their clinical context.

High‐throughput custom capture sequencing identifies novel mutations in coloboma‐associated genes: Mutation in DNA‐binding domain of retinoic acid receptor beta affects nuclear localization causing ocular coloboma

“…Trios for each of the families were assessed at a minimum, with further members, affected and unaffected, included for 17 of the families. For probands, a complete systemic work‐up tailored to phenotypic associations to coloboma was obtained (either from medical records or at the NIH Clinical Center; Huynh et al, ).…”

“…Ocular complications include decreased best-corrected visual acuity of varying severity, reduced visual field, photoaversion, and increased risk for retinal detachment, choroidal neovascularization, and cataracts (Chang et al, 2006;Onwochei et al, 2000). Syndromic cases of inherited coloboma can present with other defects such as spinal abnormalities, kidney and heart malformations, and central nervous system defects (Chang et al, 2006;Gregory-Evans, Vieira et al, 2004;Huynh et al, 2013;L. Wang et al, 2012).…”

EFTUD2 deficiency in vertebrates: Identification of a novel human mutation and generation of a zebrafish model

“…Microphthalmia or anophthalmia describe a small or an absent eye while coloboma is a segmental ocular defect which can affect multiple ocular structures and is typically caused by optic fissure closure defects (Morrison et al, ; Skalicky et al, ). Additional eye anomalies are often seen in patients with MAC and include cataract, glaucoma, anterior segment dysgenesis and posterior segment abnormalities (retinal detachment, hypoplasia of the optic nerve/disc, persistent fetal vasculature); retinal dystrophy is rarely reported (Morrison et al, ; Huynh et al, ). MAC phenotypes can be limited to the eye but are frequently associated with nonocular features, including neurological, craniofacial, hearing, skeletal, cardiac, and urogenital abnormalities, in a variety of known and not yet recognized heritable syndromes (Hornby et al, ; Morrison et al, ; Nakamura et al, ; Huynh et al, ; Skalicky et al, ).…”

“…The causes of syndromic and isolated MAC conditions are highly heterogeneous (Bardakjian and Schneider, ; Williamson and FitzPatrick, ) with many cases remaining unexplained. Common causes of syndromic MAC include CHD7 in CHARGE syndrome (which includes coloboma) and SOX2 or OTX2 in anophthalmia/microphthalmia syndromes (Huynh et al, ; Skalicky et al, ; Williamson and FitzPatrick, ); other genes associated with microcephaly, craniofacial anomalies, and ocular coloboma include TFAP2A in Branchiooculofacial syndrome (Gestri et al, ), ZEB2 in Mowat‐Wilson syndrome (Wenger et al, ), ACTB and ACTG1 in Baraitser‐Winter cerebrofrontofacial syndrome (Riviere et al, ), and occasionally SALL1 in Townes‐Brocks syndrome (Botzenhart et al, ) and PQBP1 in Renpenning syndrome (Kleefstra et al, ). For cases without causal variants in the most common MAC genes, whole exome sequencing represents an efficient method of screening numerous known ocular genes along with the entire exome to identify the causative variant (Need et al, ; Reis et al, ; Deml et al, ; Weh et al, ).…”

Uveal coloboma: about 3 cases at the University Teaching Hospital, Yaounde, Cameroon

“…Our patients did not present any clinically systemic abnormality. However, Nancy et al strongly recommended a physical examination by a clinician that may guide further evaluation, such as echocardiography, an audiology assessment, kidney ultrasound or spine X-ray, for all patients presenting with apparently isolated uveal colobomas [ 10 ]. Our patients did not undergo OCT examination because of our limited technical equipment.…”