Macular dystrophy

Macular dystrophies typically present with progressive impairment of central visual acuity, often accompanied by central visual-field defects and, depending on the specific condition, dyschromatopsia or photophobia. Age at onset varies considerably, ranging from childhood or adolescence in conditions such as and to adulthood in adult-onset vitelliform macular dystrophy, pattern dystrophy and Sorsby fundus dystrophy. Peripheral vision is usually preserved, although retinal involvement may extend beyond the macula in some conditions. Fundus appearances vary according to the underlying condition and include the characteristic vitelliform lesion of Best disease, retinal flecks and macular atrophy in Stargardt disease, and an apparently normal fundus in occult macular dystrophy. Macular dystrophies are predominantly non-syndromic, although they may occasionally occur as part of a syndromic disorder.

The overall prevalence of inherited macular dystrophies is not well established. Stargardt disease is the most common inherited macular dystrophy, with an estimated prevalence of approximately 1 in 8,000 to 1 in 10,000 individuals. Best disease is another relatively common inherited macular dystrophy, although reliable prevalence estimates are limited.

Macular dystrophies are genetically heterogeneous and comprise several clinically overlapping disease groups. The most common form is ABCA4-associated (STGD1), caused by biallelic pathogenic variants in ABCA4. Other well-recognised forms include BEST1-associated and PRPH2-associated pattern dystrophy. Considerable phenotypic variability and overlap with other inherited retinal dystrophies may complicate the clinical and molecular classification.

The genetic conditions associated with macular dystrophies show heterogeneous inheritance patterns, including autosomal dominant, autosomal recessive and X-linked inheritance. is a well-recognised autosomal dominant form, whereas ABCA4-associated follows autosomal recessive inheritance.

• Molecular genetic testing can establish the underlying genetic diagnosis, confirm the clinical suspicion, enable predictive testing of at-risk family members and provide information relevant to family planning.
• The identified entity supports condition-specific monitoring and management decisions; therapeutic options are evaluated individually by the treating physicians.

Raimondi R, D’Esposito F, Sorrentino T, Tsoutsanis P, De Rosa FP, Stradiotto E, et al. How to set up genetic counselling for inherited macular dystrophies: focus on genetic characterization. Int J Mol Sci. 2023;24(11):9722. doi:10.3390/ijms24119722. PMID:; PMCID:PMC10253739.