Mitochondrial DNA Deletion Syndromes

Mitochondrial DNA (mtDNA) deletion syndromes predominantly comprise three overlapping phenotypes that are usually simplex (i.e., a single occurrence in a family), but rarely may be observed in different members of the same family or may evolve from one clinical syndrome to another in a given individual over time. The three classic phenotypes caused by mtDNA deletions are Kearns-Sayre syndrome (KSS), Pearson syndrome, and progressive external ophthalmoplegia (PEO). KSS is a progressive multisystem disorder defined by onset before age 20 years, pigmentary retinopathy, and PEO; additional features include cerebellar ataxia, impaired intellect (intellectual disability, dementia, or both), sensorineural hearing loss, ptosis, oropharyngeal and esophageal dysfunction, exercise intolerance, muscle weakness, cardiac conduction block, and endocrinopathy. Pearson syndrome is characterized by sideroblastic anemia and exocrine pancreas dysfunction and may be fatal in infancy without appropriate hematologic management. PEO is characterized by ptosis, impaired eye movements due to paralysis of the extraocular muscles (ophthalmoplegia), oropharyngeal weakness, and variably severe proximal limb weakness with exercise intolerance. Rarely, a mtDNA deletion can manifest as Leigh syndrome.

GeneReviews