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.  


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. 

Treatment Options: 

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

Article Title: 


Tyynismaa H, Sun R, Ahola-Erkkila S, Almusa H, Poyhonen R, Korpela M, Honkaniemi J, Isohanni P, Paetau A, Wang L, Suomalainen A. Thymidine kinase 2 mutations in autosomal recessive progressive external ophthalmoplegia with multiple mitochondrial DNA deletions. Hum Mol Genet. 2012 Jan 1;21(1):66-75.

PubMedID: 21937588