Recurrent and founder mutations in the Netherlands: the cardiac phenotype of DES founder mutations p.S13F and p.N342D
A syndrome of slowly progressive muscle weakness with scapulo-ilio-peroneal distribution and cardiopathy was identified in 26 members of two families. Inheritance was autosomal dominant. Onset of the disease was between 17 and 42 years. Cardiopathy did not antedate skeletal muscle disease and patients had no symptoms of cardiopathy until a late phase of the disease. Initial ECG changes were non-specific, disturbances of conduction and impulse formation developed subsequently. Skeletal muscle biopsies showed neurogenic and myopathic changes with inflammatory cell reaction and perivascular cuffing. The combination of myopathy with neurogenic-like changes is characteristic of many cases of SPA. The inflammatory cell reaction is considered as part of a secondary polymyositis which is at leart partly responsible for muscle pathology.