OMIM ID:
Choroidal Dystrophy, Central Areolar 2
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Slowly progressive loss of vision is noted in the 4th and 6th decades with a mean age of onset at 46 years. ERG recordings suggest that the cone dysfunction is more severe and occurs earlier than rod deterioration. Night blindness is usually not a major complaint. A central scotoma is usually present but peripheral fields may be relatively intact. Dyschromatopsia is often present. Early in the disease the RPE may have a granular appearance but in later stages there is usually a sharply demarcated area of central RPE atrophy (sometimes called geographic atrophy).
Autoflourescence, pattern ERGs, and fine matrix mapping can reveal abnormalities before patients become symptomatic.
Systemic Features
No systemic features are known.
Genetics
Inheritance
This is a clinically and genetically heterozygous disorder. Multiple mutations in the PRPH2 gene (6p21.1) have been identified in this condition. Some of the clinical variation may be mutation-specific.
For a somewhat similar disorder see choroidal dystrophy, central areolar 1 (215500).
CACD is a genetically heterogeneous disorder with mutations in several genes responsible. The majority of patients have one of several mutations in the PRPH2 gene (6p21.1-cen) and the inheritance pattern seems to be autosomal recessive (CACD2). Other family trees in which mutations in PRPH2 were excluded suggest autosomal dominant inheritance (CACD3; 613144).
The gene product of PRPH2 is important to the integrity and stability of the structures that contain light-sensitive pigments (e.g., photoreceptors). More than 100 mutations have been identified. The resultant phenotype can be highly variable, even within members of the same family but most affected individuals have some degree of pigmentary retinopathy within the macula or throughout the posterior pole.
The altered gene product resulting from mutations in PRPH2 often leads to symptoms beginning in midlife as a result of the slow degeneration of photoreceptors. This database contains at least 11 disorders in which PRPH2 mutations have been found.
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