OMIM ID:
External Ophthalmoplegia, Progressive, with mtDNA Deletions, AR 3
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
The ophthalmoplegia is adult in onset (approx. age 40 years) and progressive. Severe blepharoptosis is an associated sign.
Systemic Features
Proximal muscle weakness and atrophy in the shoulder girdle and legs were features in the two reported patients. Rising from a squatting position and walking up stairs may be particularly difficult. Dysarthria and dysphagia are associated findings.
Muscle biopsy showed mitochondrial myopathy. Multiple mtDNA deletions occur in skeletal muscles.
Genetics
Inheritance
One family with two sisters has been reported with this condition. Both had compound heterozygous mutations in the thymidine kinase gene (TK2) (16q21) and multiple deletions in mitochondrial DNA.
A similar condition, External Ophthalmoplegia, Progressive, with mtDNA Deletions, AR 4, (617070) is caused by mutations in the DGUOK 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.