Familial mitochondrial chronic progressive external ophthalmoplegia.: Five families with different genetics

Chronic progressive external ophthalmoplegia (CPEO) is considered the most frequent form of mitochondrial encephalomyopathies. Most cases occur sporadically. We investigated 18 consecutive patients with CPEO. Thirteen cases were sporadic and five cases were familial. In one family with maternal inheritance the mitochondrial point mutation A3243G was identified. In index patients of three other families multiple deletions of mitochondrial DNA were found. One of these families showed autosomal recessive inheritance. In the two other pedigrees a definitive determination of the mode of inheritance was impossible. The fifth family revealed autosomal dominant or maternal inheritance. In their index patient no alteration of mitochondrial DNA could be identified (including sequencing of hot spots for mitochondrial mutations). Conclusions. CPEO was familial in 28% of our patients. There are three different modes of inheritance: (i) maternal transmission associated with mitochondrial point mutations as it is known for other mitochondrial disorders, (ii) autosomal recessive, and (iii) autosomal dominant inheritance. In contrast to sporadic cases with single mitochondrial deletions autosomal inheritance can be associated with multiple deletions of mitochondrial DNA. They are due to so far unknown nuclear mutations.