PEOA2

External Ophthalmoplegia, ANT1 and mtDNA Mutations

Clinical Characteristics
Ocular Features: 

Ptosis and progressive external ophthalmoplegia are the outstanding features of this form of external ophthalmoplegia.  These symptoms may appear in early adulthood.  A few patients have had thyroid disease as well.  Muscle biopsies from limb muscles show the characteristic ragged red appearance of myopathy in a minority of fibers.  Multiple deletions occur in the mitochondria of skeletal muscles.  EMG studies show myopathy while nerve conduction studies are normal.  Respiratory chain analysis often shows evidence of mitochondrial dysfunction.

Systemic Features: 

Adult patients with SLC25A4 (4q35.1) and mtDNA (ANT1) mutations have exercise intolerance and sometimes skeletal muscle weakness.  They are less likely to have symptoms of parkinsonism or peripheral neuropathy than those with mutations in POLG.  Hearing loss is minimal.

Genetics

This autosomal dominant disorder results from the combination of a mutation in the ANT1 (SLC25A4) gene (4q35) (encoding the adenine nucleotide translocator-1) and mitochondrial DNA deletions.  About 11% of autosomal dominant cases with progressive external ophthalmoplegia have mutations in this gene.  Most reported families have been from Italy.

External ophthalmoplegia may also result from mutations in POLG (most common), and in C10ORF2.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

No effective treatment is available.

References
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