A Japanese case of oto-palato-digital syndrome type II: an apparent lack of phenotype–genotype correlation

Abstract

We report the case of a 12 year-old boy with oto-palato-digital syndrome type II (OPD II). He had various anomalies at birth, including bilateral cataracts, bilateral glaucoma, bilateral severe hearing impairment, congenital heart defect, umbilical herniation, bowed extremities and constrictions of various joints. These clinical features and whole body X-ray findings were compatible with OPD II. However, his ocular disorders such as congenital cataract and glaucoma, and congenital heart defect have never been associated with OPD II as far as we know. His chromosomal analysis revealed normal karyotype, 46,XY. Analysis of the filamin A gene using a standard PCRdirect sequencing method determined a C586T (Arg196Trp) missense mutation in exon 3. Interestingly, the same C586T mutation was reported previously in a patient with OPD I (mild form). Thus, phenotype-genotype correlation of OPD is lacking in those patients. Further clinical and genetic studies are needed to clarify the relationship between phenotypes and genotypes, or to identify other factor(s) that influence the clinical features of this syndrome.

Differences in Copy Number Variation between Discordant Monozygotic Twins as a Model for Exploring Chromosomal Mosaicism in Congenital Heart Defects

“…Loss-of-function mutations in FLNA have been described in families with X-linked cardiac valvular dysplasia [Kyndt et al, 2007] and in boys with CHDs associated with nodular periventricular heterotopias [Jefferies et al, 2010] or otopalatodigital syndrome [Kondoh et al, 2007]. A similar duplication partially comprising FLNA and EMD was detected once, in a normal control from the HAPMAP population [Perry et al, 2008].…”

Whole exome sequence analysis of Peters anomaly

“…Corneal opacity has been reported in one patient with a missense mutation in FLNA [c.514C>G, p.(Leu172Val)] and features consistent with OPD2 (Murphy-Ryan et al 2011). Congenital glaucoma and cataracts were reported in another patient with OPD2 and a missense mutation in FLNA [c.586C>T, p.(Arg196Trp)] (Kondoh et al 2007). And finally, two unrelated patients with MNS and missense mutations in FLNA (c.3776_3777delinsAT, p.(Gly1176Asp); c.3596C>T, p.(Ser1199Leu) were reported with sclerocornea, exophthalmos, and congenital cataracts (Santos et al 2010).…”

Bifid tongue, corneal clouding, and Dandy-Walker malformation in a male infant with otopalatodigital syndrome type 2

“…However, a change in the same codon resulting in a Leu172Phe substitution has been reported as a familial FLNA mutation in a male with OPD type 1. Changes in codon 196 from arginine to glycine or tryptophan have been reported to lead to OPD type 2 or 1, respectively [Robertson et al, 2003], and in another instance an identical mutation (C.568C>T, Arg196Trp) was found in one child with severe OPD2 and another unrelated individual with mild OPD1 [Kondoh et al, 2007]. The unpredictable phenotype–genotype correlation illustrated by these patients suggests that there is still much to learn about the factors contributing to severity in the OPD‐spectrum disorders.…”

“…Ophthalmologic findings are relatively uncommon in patients with OPD2. Both congenital glaucoma and congenital cataracts have both been described in a patient with OPD2 [Kondoh et al, 2007] and congenital corneal clouding has been reported only once in this condition [Stratton and Bluestone, 1991]. With an estimated prevalence of 3/100,000 newborns, congenital corneal opacity is an uncommon clinical finding that can result from a variety of genetic, metabolic, developmental, and idiopathic causes [Bermejo and Martinez‐Frias, 1998].…”