OMIM ID:
External Ophthalmoplegia, Progressive, with mtDNA Deletions, AR 4
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Patients have adult onset (6th to 7th decade of life) and progressive ptosis and external ophthalmoplegia of variable severity.
Systemic Features
There is a great deal of clinical heterogeneity in this condition. Some patients have adult onset proximal and limb girdle progressive muscle weakness. Other individuals complain of exercise-induced muscle pain and increased weakness. Dysphagia and dysphagia may be present. More widespread signs such as peripheral neuropathy, hearing impairment, cortical atrophy, and liver disease are variably present.
Genetics
Inheritance
Compound heterozygous mutations in the DGUOK (deoxyguanosine kinase) gene (2p13) have been identified in this disorder. Multiple deletions in the mitochondrial DNA of skeletal muscle have been found as well.
Biallelic mutations in the DGUOK gene also cause more widespread disease as evidenced in the mitochondrial DNA depletion syndrome MTDPS3 (251880).
A similar condition, External Ophthalmoplegia, Progressive, with mtDNA Deletions, AR 3, (617069) is caused by mutations in the TK2 gene.
Pedigree
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.