Objectives: We report here the clinical and genetic features of two new families with autosomal dominant progressive external ophthalmoplegia (adPEO). Patients and methods: The examination of index patients included a detailed clinical characterisation, histological analysis of muscle biopsy specimens, and genetic testing of mitochondrial and nuclear DNA extracted from muscle and leucocytes. Results: Index patients in both families presented with PEO and developed other clinical disease manifestations, such as myopathy and cardiomyopathy (patient 1) and axonal neuropathy, diabetes mellitus, hearing loss, and myopathy (patient 2), later in the course of illness. Both patients had ragged red fibres on muscle histology. Southern blot of mtDNA from muscle of patient 2 showed multiple deletions. In this case, a novel heterozygous missense mutation F485L was identified in the nuclear encoded putative mitochondrial helicase Twinkle. The mutation co-segregated with the clinical phenotype in the family and was not detected in 150 control chromosomes. In the other index patient, sequencing of ANT1, C10orf2 (encoding for Twinkle), and POLG1 did not reveal pathogenic mutations. Conclusions: Our cases illustrate the clinical variability of adPEO, add a novel pathogenic mutation in Twinkle (F485L) to the growing list of genetic abnormalities in adPEO, and reinforce the relevance of other yet unidentified genes in mtDNA maintenance and pathogenesis of adPEO.

Objective-To characterise the main clinical phenotypes of debrancher deficiency myopathy and to increase awareness for this probably underdiagnosed disorder. Methods-The diagnosis of debrancher deficiency was established by laboratory tests, EMG, and muscle and liver biopsy. Results-Four patients with debrancher deficiency myopathy were identified in the Tyrol, a federal state of Austria with half a million inhabitants. Clinical appearance was highly variable. The following phenotypes were diVerentiated: (1) adult onset distal myopathy; (2) subacute myopathy of the respiratory muscles; (3) severe generalised myopathy; and (4) minimal variant myopathy. Exercise intolerance was uncommon. The clinical course was complicated by advanced liver dysfunction in two patients and by severe cardiomyopathy in one. All had raised creatine kinase concentrations (263 to 810 U/l), myogenic and neurogenic features on EMG, and markedly decreased debrancher enzyme activities in muscle or liver biopsy specimens. The findings were substantiated by a review of 79 previously published cases with neuromuscular debrancher deficiency. Conclusions-This study illustrates the heterogeneity of neuromuscular manifestations in debrancher deficiency. Based on the clinical appearance, age at onset, and course of disease four phenotypes may be defined which diVer in prognosis, frequency of complications, and response to therapy. (J Neurol Neurosurg Psychiatry 1999;67:364-368)

We report on two cases of isolated damage to a muscle branch of the lateral pectoral nerve. Diagnosis was established by the clinical presentation and electromyographic examination. In the few reported cases of such injuries, the cause was trauma to this region. However, in both of our patients, focal muscle atrophy gradually developed after initiation of training schedules to increase the cross-section of the major pectoral muscle; we therefore assume that compression injury to the nerve by repetitive muscle contractions may be of pathogenic relevance. Anatomical studies of this region showed that the nerve branches of the lateral pectoral nerve, having to pierce through a connective tissue septum that is thicker here by a few millimeters, may be subjected to additional risk of compression. Early recognition and treatment are vital to prevent associated morbidity of these rare but serious injuries.