UNUSUAL PRESENTATION AND CLINICAL VARIABILITY IN BELGIAN PEDIGREES WITH PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA AND MULTIPLE DELETIONS OF MITOCHONDRIAL-DNA

We studied 14 patients from three unrelated Belgian pedigrees with a f amilial mitochondrial disorder and multiple deletions of mitochondrial DNA (mtDNA). In one family with an oculopharyngeal presentation there is a clear autosomal dominant inheritance. Progressive external ophth almoplegia (PEO), ''ragged red fibres'' (RRF) and multiple deletions o f mtDNA are common to all three families. Therefore a diagnosis of aut osomal dominant progressive ophthalmoplegia with multiple deletions of mtDNA (adPEO) was made in one family at least. Our data confirm the p revious observations that adPEO is a systemic disorder rather than a p ure myopathy. In our pedigrees frequently associated features include axonal peripheral neuropathy, dysphagia, psychiatric illness, and sudd en death. Mild ataxia, pes cavus and mitral valve prolapse with associ ated mitral insufficiency also occur. In some cases onset is atypical with neuropathy, adolescent onset myopathy or psychiatric illness. In such cases the common features of PEO and muscle weakness always compl ete the clinical phenotype later during the course of the disease. Bio chemical studies on mitochondrial fractions prepared from one patient' s muscle, revealed no abnormalities of respiratory chain enzyme activi ties.