A Good Family History , the First Step in Reaching a Diagnosis

The authors review the utility of genetic testing in ophthalmic disorders – precise diagnosis, accurate prognosis, genetic counseling, prenatal diagnosis, and entry into gene-specific therapeutic trials. The prerequisites for a successful outcome of a genetic test are an accurate clinical diagnosis, a careful family history that guides which genes to study, and genetic counseling (both pretest and post-test). The common eye disorders for which genetic testing is commonly requested are briefly discussed – anophthalmia, microphthalmia, coloboma, anterior segment dysgenesis, corneal dystrophies, cataracts, optic atrophy, congenital glaucoma, congenital amaurosis, retinitis pigmentosa, color blindness, juvenile retinoshisis, retinoblastoma etc. A protocol for genetic testing is presented. If specific mutations in a gene are common, they should form the first tier test, as the mutations in Leber hereditary optic neuropathy. If mutations in one gene are likely, sequencing of that gene should be carried out, e.g. GALT gene in galactosemia, RS1 gene in retinoshisis. Disorders with genetic heterogeneity require multi-gene panel tests, and if these show no abnormality, then deletion / duplication or microarray studies are recommended, followed in sequence by clinical exome (5000 to 6000 genes), full exome (about 20,000 genes or whole genome studies (includes all introns). It is fortunate that most genetic tests in ophthalmology are available in India, including gene panel and whole exome/genome sequencing tests.