Predictive genetic testing in minors for Myocilin juvenile onset open angle glaucoma

Abstract

Myocilin glaucoma is an autosomal dominant disorder leading to irreversible blindness, but early intervention can minimize vision loss and delay disease progression. The purpose of this study was to discuss the benefits of predictive genetic testing in minors for Myocilin mutations associated with childhood onset glaucoma. Three families with Myocilin mutations associated with an age of onset before 18 years and six unaffected at‐risk children were identified. Predictive genetic testing was discussed with the parents and offered for at‐risk minors. Parents opted for genetic testing in half of the cases. None carried the familial mutation. The age of disease onset in the family, the severity of the condition, and the age of the child are all factors that appear to influence the decision of the parent to test their children. Predictive genetic testing for early onset Myocilin glaucoma can facilitate early detection of disease or discharge from routine ophthalmic examinations.

Myocilin Predictive Genetic Testing for Primary Open-Angle Glaucoma Leads to Early Identification of At-Risk Individuals

“…In these families, we would expect cascade genetic testing to have similar positive outcomes if conducted at an early age, and we have previously discussed the benefits of a genetic testing approach for minors in these families. 23 Our numbers were too small to analyze this group separately in this study but future studies should examine the clinical utility of genetic testing in individuals carrying MYOC variants associated with early glaucoma onset. Similarly, our findings could be extrapolated to other monogenic rarer forms of the disease such as Optineurin and TBK1 glaucoma associated variants.…”

Major review: Molecular genetics of primary open-angle glaucoma

“…Genetic screening and counseling should be considered for affected family members in families where MYOC-associated glaucoma has been found. Since mutations are autosomal dominant, highly penetrant, clinically severe, and usually present early in life, carriers can be identified in early stages of glaucoma or screening can be initiated in those without evidence of disease (Gharahkhani et al, 2015; Hewitt et al, 2008; Souzeau et al, 2013; Souzeau et al, 2014; Souzeau et al, 2015). …”

Are we ready for genetic testing for primary open-angle glaucoma?

“…There are situations when genetic testing can be helpful for managing families with inherited POAG. For example, a young member of a family with severe, early onset, autosomal dominant POAG may benefit from knowing their likelihood of developing the disease [32]. If the mutation causing POAG in that family is identified (e.g., by testing for myocilin mutations in affected family members), then the individual concerned can be tested for that mutation.…”

“…If the mutation causing POAG in that family is identified (e.g., by testing for myocilin mutations in affected family members), then the individual concerned can be tested for that mutation. If they do not carry the myocilin mutation, then their risk of developing POAG will be similar to the risk in the general population, and this would allow discharge from routine ophthalmic examinations [32]. Such information may even inform life choices such as occupation, especially if the disease is of early onset.…”