OMIM ID:
Macular Dystrophy, Patterned 3
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
This condition has been found in an extended pedigree among peoples originating in the West Indies. Vision loss is noted after the age of 50 years but clinical evidence can be seen in the fourth or fifth decades. The findings are primarily in the retinal pigment epithelium but Bruch’s membrane is also involved. Choroidal neovascularization and macular scarring may be present. The fundus pigmentary pattern has been described as resembling "dried-out soil" or crocodile skin. In late stages the fundus picture resembles retinitis pigmentosa with loss of the RPE and photoreceptors. The loss of photoreceptors continues throughout life. An 85 year old woman with light perception only has been described.
In early stages the full-field ERG can be nomal but later rod and cone responses are severely reduced. The OCT may show scalloped elevation at the borders of the scalloped patches corresponding to the irregular thickness of the RPE and Bruch membrance.
Knockout mice have both thickened and thinned areas of the Bruch membrane.
Systemic Features
No systemic abnormalities have been reported.
Genetics
Inheritance
This autosomal dominant condition results from heterozygous mutations in MAPKAPK3 (3p21.3), a mitogene-activated kinase of the p38 signaling pathway. It is highly expressed in the RPE.
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