Microcornea, Myopic Chorioretinal Atrophy, And Telecanthus

A number sign (#) is used with this entry because of evidence that microcornea with myopic chorioretinal atrophy and telecanthus is caused by homozygous mutation in the ADAMTS18 gene (607512) on chromosome 16q23.

Clinical Features

Khan (2012) described 5 boys, ranging in age from 4 to 10 years at presentation, from 4 unrelated consanguineous Saudi Arabian families with microcornea and myopic chorioretinal atrophy. In addition to ocular findings, all 5 boys had telecanthus and posteriorly rotated ears, which were not present in unaffected parents or sibs and were not normative for the ethnic population. Horizontal corneal diameters ranged from 9.8 to 10.5 mm; anterior chambers were not shallow. Three unrelated boys had severe chorioretinal atrophy, whereas 2 affected brothers had milder disease. Pupillary examination and intraocular pressures were normal for all 5 boys, and no coloboma or other developmental eye disease was detected. In the 2 patients who were old enough to cooperate for electroretinography, there was mild depression and delay in both scotopic and photopic function. Parents did not notice progressive deterioration in vision or significant preference for day or night vision in any of the children. One boy had an affected father, with telecanthus, posteriorly rotated ears, bilateral best-corrected visual acuity of 20/50, horizontal corneal diameters of 10.5 mm, and moderate myopic chorioretinal atrophy bilaterally.

Aldahmesh et al. (2013) studied a 9-year-old girl from a consanguineous family who had microcornea, myopic chorioretinal degeneration, telecanthus, posteriorly rotated ears, and a broad nasal tip. Best corrected visual acuity was 20/50 bilaterally, and horizontal corneal diameters were 9.9 mm and 10.2 mm.

Mapping

Aldahmesh et al. (2013) performed homozygosity mapping in the 4 consanguineous Saudi Arabian families with microcornea and myopic chorioretinal atrophy described by Khan (2012) as well as in 1 additional affected consanguineous family, and identified a single run of homozygosity at chromosome 16q23.1 that was shared among all affected individuals. Linkage analysis confirmed the locus with a peak corresponding to a lod of 3. In addition, 4 of the 5 families had different haplotypes at the locus, suggesting the presence of 4 different ancestral mutations.

Molecular Genetics

In a boy with microcornea and myopic chorioretinal atrophy from the father-son pedigree previously described by Khan (2012), Aldahmesh et al. (2013) performed exome sequencing and filtering and identified homozygosity for a missense mutation in the ADAMTS18 gene (C577W; 607512.0002). Full sequencing of ADAMTS18 in the other 4 families revealed homozygosity for another missense and 2 nonsense mutations in affected individuals from each family (607512.0003-607512.0005).