proximal muscle weakness

External Ophthalmoplegia, Progressive, with mtDNA Deletions, AR 4

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

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
Treatment
Treatment Options: 

Ptosis surgery may be of benefit.

References
Article Title: 

External Ophthalmoplegia, Progressive, with mtDNA Deletions, AR 3

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

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
Treatment
Treatment Options: 

There is no treatment for the generalized condition but blepharoplasty may be required.

References
Article Title: 
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