Optic Disc Anomalies With Retinal And/or Macular Dystrophy

A number sign (#) is used with this entry because of evidence that optic disc anomalies with retinal and/or macular dystrophy (ODRMD) is caused by homozygous mutation in the SIX6 gene (606326) on chromosome 14q23.

Clinical Features

Aldahmesh et al. (2013) reported 2 brothers, born of healthy first-cousin Syrian parents, who had optic nerve dysplasia, retinal dystrophy, and microphthalmia. In addition to small ocular globes, the 5-year-old brother had bilateral dystrophic retinas with small dysplastic optic nerve heads. His 16-month-old brother had buphthalmos and corneal scarring of the right eye that was presumed to be the result of neglected infantile glaucoma; no eye was visible on the left. Ocular ultrasound revealed large optic nerve cupping and retinal detachment in the right eye, whereas the left eye was extremely short and without retinal detachment. The brothers had no other associated signs or symptoms.

Yariz et al. (2015) studied a sister and 2 brothers, born of healthy first-cousin Turkish parents, who had bilateral colobomatous optic discs, retinal vessels arising from the peripheral optic disc, and macular atrophy. The 2 older sibs had peripapillary chorioretinal changes or atrophy, and the oldest sib also exhibited unilateral iris and chorioretinal coloboma. Anteroposterior globe measurements were 28 mm in the 14-year-old sister, 25 mm in the 5-year-old brother, and 23 mm in the 2-year-old brother. All had poor visual acuity and horizontal nystagmus since birth. Brain MRI was normal in all 3 sibs, and thyroid, renal, and pelvic ultrasounds in the oldest sib were normal.

Mapping

Yariz et al. (2015) genotyped 3 affected and 5 unaffected members of a consanguineous Turkish family with optic disc anomalies and chorioretinal and macular atrophy, and identified an autozygous region at chr14:59,247,009-75,949,378 (GRCh37).

Molecular Genetics

In 2 Syrian brothers with optic nerve dysplasia, retinal dystrophy, and microphthalmia, and their unaffected first-cousin parents, Aldahmesh et al. (2013) performed genotyping and autozygome analysis. The authors identified a homozygous frameshift deletion in the SIX6 gene (606326.0002) that segregated with disease in the family and was not found in 200 Saudi exomes or in the 1000 Genomes Project database.

In a consanguineous Turkish family in which 3 sibs had optic disc anomalies as well as chorioretinal and macular atrophy mapping to chromosome 14, Yariz et al. (2015) analyzed 2 candidate genes within the critical interval and identified homozygosity for a missense mutation in the SIX6 gene (L37P; 606236.0003). The mutation, which segregated with disease in the family, was not found in 342 ethnically matched controls or in the Exome Variant Server or dbSNP (build 137) databases.