P.47 - Congenital centronuclear myopathy and epidermolysis bullosa due to two novel mutations in the plectin gene

Abstract

We report on a Turkish patient with congenital myopathy with a fiber type disproportion and central myonuclei comparable to a centronuclear myopathy and skin blistering (epidermolysis bullosa simplex, EBS) due to a novel homozygous mutation in the plectin gene, a cytoskeleton-membrane anchorage protein. So far, EBS has only been described to be associated with congenital or limb girdle muscular dystrophy, myasthenic syndrome, or pyloric atresia. A clubfoot and hypotonia were noted directly at birth, skin blistering was identified shortly after cast treatment of the foot malposition. Motor milestones were only mildly delayed; walking was possible with 18 months of age. The parents are first grade cousins; the patient has no siblings. There are no other affected family members, offspring of the parents siblings are reported healthy. Clinical examination at age 25 revealed bilateral ptosis, normal eye movement, long facial bones, high palate, scoliosis, rigid neck and spine, severe contractures of elbow, wrist, knee and ankle joints, scapular winging, slim muscles, and a cachectic phenotype with an BMI of 15.7. Serum CK was elevated with 1500 U/ml, EMG revealed myopathic changes, repetitive stimulation showed a 12% decrement. Lung function showed respiratory involvement with vital capacity 50% of predicted, heart ultrasound was normal. Multigene panel diagnostics for congenital and distal myopathies (55 genes) revealed a homozygous missense mutation in the plectin gene c.8306C > G (p.Pro2769Arg). Even though plectinopathy represents a rare condition, testing should be included into the diagnostic work-up of congenital myopathies with or even without skin blistering.