OMIM ID:
Macular Dystrophy, Vitelliform 5
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
This is a late onset form of vitelliform macular dystrophy with symptoms noted by the 5th decade or later. Only central vision seems to be impacted and a central scotoma may be demonstrable. The ERG, EOG and color vision responses may be normal. Mild autofluorescence has been reported. The vitelliform lesions are small and may be multiple. No drusen-like lesions have been seen. Visual acuity is variable, ranging from normal to a mild decrease.
Systemic Features
No systemic abnormalities have been reported.
Genetics
Inheritance
This form of vitelliform dystrophy results from heterozygous mutations in the IMPG2 gene (3q12). Patients with homozygous mutations have also been reported.
Genotyping has identified at least 5 forms of vitelliform macular dystrophy. In addition to the iconic Best disease (VMD2, 153700) apparently first described by Friedreich Best in 1905 and now attributed to mutations in the Best1 gene, we know of at least 4 more and specific mutations have been identified in three. No mutation or locus has yet been identified in VMD1 (153840) but it is likely a unique condition since mutations in other genes known to cause vitelliform dystrophy have been ruled out. Other forms are VMD3 (608161) due to mutations in the PRPH2 gene, VMD4 (616151) resulting from mutations in the IMPG1 gene, and VMD5 described here.
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
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.