Genotype-phenotype correlations and differential diagnosis in autosomal dominant macular disease

Abstract

In the past few years, great progress has been made in the understanding of macular diseases. A number of disease-causing genes have been cloned, and numerous loci for other conditions have been mapped. The purpose of this article is to provide an overview of the current understanding of the genotype-phenotype correlations in autosomal dominant macular diseases with an emphasis on differential diagnostic issues. Whenever possible, the molecular correlates have been reviewed and the implications for age-related macular degeneration have been discussed. The many similarities of these diseases to age-related macular degeneration of the atrophic or exudative type, which can be misleading in elderly subjects, have also been addressed. While some conditions yield disease truly confined to the macula, others show widespread retinal involvement on functional testing. Clear-cut genotype-phenotype correlations are possible only for some forms of macular diseases. To further complicate the diagnostic process, there is a considerable degree of clinical overlap between many of them, making the differential diagnostic process potentially challenging. Functional testing, careful assessment of family history and extensive family work-up are essential in differentiating at the clinical level most, but not all, of these disease entities. Awareness of all of these conditions is required to direct correctly diagnostic investigations, to formulate an accurate prognosis, and for proper genetic counseling.