OMIM ID:
Doyne Honeycomb Macular Dystrophy
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Beginning usually in midlife, the retina has radially localized white, large drusen in the posterior pole. These may begin as small drusen that later enlarge and become confluent creating a honeycomb pattern. The disease begins as an accumulation of material between the Bruch membrane and the RPE. Eventually drusen occupy the entire thickness of the Bruch membrane and are continuous with or internal to the RPE basement membrane. Vision early is normal and a slow loss of vision occurs sometime after the drusen appear in most individuals. In some patients geographic atrophy, pigmentary changes, and a subfoveal neovascular net develops with macular scarring, vitreous hemorrhage, and severe reduction of vision.
Systemic Features
No systemic disease is associated.
Genetics
Inheritance
Doyne honeycomb macular disease, or dominant drusen, is the result of mutations in the EFEMP1 gene at 2p16 in the majority of cases. It is an autosomal dominant disorder. The mutant protein product (a member of the fibulin famiy) is folded abnormally and secreted inefficiently. It is also resistant to degradation which may lead to receptor damage by limiting access to nutrients from the choriocapillaris. Some genetic heterogeneity may exist since a few cases seem to be linked to a locus at 6q14. Some have considered Malattia Leventinese and Doyne honeycomb retinal dystrophy as separate entities but mutations in the same gene seem to be responsible for both conditions suggesting they are clinical variations of the same disorder.
Pedigree
Autosomal dominant
Autosomal dominant disorders require only one mutation for the disease to be expressed. Since an affected parent has two chromosomes, only one of which has the mutant gene, parents can expect that half (50%) of their children will receive that one and inherit the disease. It is common for individuals that inherit the mutation, however, to not have evidence of the disease (nonpenetrance).
Autosomal dominant inheritance leads to a vertical pattern of transmission