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 sporad ically. We investigated 18 consecutive patients with CPEO. Thirteen cases w ere sporadic and five cases were familial. In one family with maternal inhe ritance the mitochondrial point mutation A3243G was identified. In index pa tients of three other families multiple deletions of mitochondrial DNA were found. One of these families showed autosomal recessive inheritance. In th e two other pedigrees a definitive determination of the mode of inheritance was impossible. The fifth family revealed autosomal dominant or maternal i nheritance. In their index patient no alteration of mitochondrial DNA could be identified (including sequencing of hot spots for mitochondrial mutatio ns). Conclusions. CPEO was familial in 28% of our patients. There are three diff erent modes of inheritance: (i) maternal transmission associated with mitoc hondrial point mutations as it is known for other mitochondrial disorders, (ii) autosomal recessive, and (iii) autosomal dominant inheritance. In cont rast to sporadic cases with single mitochondrial deletions autosomal inheri tance can be associated with multiple deletions of mitochondrial DNA. They are due to so far unknown nuclear mutations.