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.

Treatment
Treatment Options: 

Ptosis surgery may be of benefit.

References
Article Title: 

References

Ronchi D, Garone C, Bordoni A, Gutierrez Rios P, Calvo SE, Ripolone M, Ranieri M, Rizzuti M, Villa L, Magri F, Corti S, Bresolin N, Mootha VK, Moggio M, DiMauro S, Comi GP, Sciacco M. Next-generation sequencing reveals DGUOK mutations in adult patients with mitochondrial DNA multiple deletions. Brain. 2012 Nov;135(Pt 11):3404-15.

PubMedID: 23043144