General Genetic Considerations

All inheritance patterns are represented among currently known inherited retinal dystrophies. Thus, obtaining an accurate and complete family history is essential in determining the dystrophy’s inheritance pattern (ie, autosomal dominant, autosomal recessive, X-linked recessive, X-linked dominant, or mitochondrial). However, patients with retinal dystrophies may have a negative family history for a variety of reasons, including lack of information, variable expressivity and/or incomplete penetrance within the family, or de novo mutations. It is helpful to examine relatives for any signs of asymptomatic retinal degeneration.

Molecular genetic testing can help establish an inheritance pattern; de novo mutations in X-linked and autosomal dominant genes can be occasionally observed in sporadic rod–cone or cone dystrophy cases. The expression of these disorders can vary widely even within family members that share the same causative mutations. Molecular genetic testing helps differentiate the specific causative genes within this phenotypic group; it can be useful for family planning purposes because of the multiple possible inheritance patterns.

Genes that were previously thought to only give rise to stationary conditions, such as congenital stationary night blindness and achromatopsias, have since been linked to some progressive cases. In some cases, both dominant and recessive forms have been seen, resulting from mutations in the same gene. Molecular genetic testing is also useful for identifying syndromic versus nonsyndromic causes of retinal dystrophies, but it does not predict the penetrance, expressivity, and/or rate of progression of these conditions. Testing in asymptomatic individuals to determine a potential future risk of vision loss is generally not warranted (unless a treatment is available). Clinicians can consult the American Academy of Ophthalmology’s guidelines for genetic testing and consider the use of genetic counseling services when offering testing to their patients and family members.

• Stone EM, Aldave AJ, Drack AV, et al. Recommendations for genetic testing of inherited eye diseases: report of the American Academy of Ophthalmology task force on genetic testing. Ophthalmology. 2012;119(11):2408–2410.

Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.