Myopathy, myasthenic syndrome, and epidermolysis bullosa simplex due to plectin deficiency

Plectin, an intermediate filament linking protein, is normally associated w ith the sarcolemma, nuclear membrane, and intermyofibrillar network in musc le, and with hemisdesmosomes in skin. A 20-year-old female with epidermolys is bullosa simplex since birth had progressive ocular, facial, limb, and tr unkal weakness and fatigability since age 9, fivefold CK elevation, a 25% d ecrement with myopathic motor unit potentials and increased electrical irri tability on electromyography, and no anti-acetylcholine receptor (AChR) ant ibodies. Plectin expression was absent in muscle and severe plectin deficie ncy was noted in skin. Morphologic studies revealed necrotic and regenerati ng fibers and a wide spectrum of ultrastructural abnormalities: large accum ulations of heterochromatic and lobulated nuclei, rare apoptotic nuclei, nu merous cytoplasmic and few intranuclear nemaline rods, disarrayed myofibril s, thick-filament loss, vacuolar change, and pathologic alterations in memb ranous organelles. Many endplates (EPs) had an abnormal configuration with chains of small regions over the fiber surface and a few displayed focal de generation of the junctional folds. The EP AChR content was normal. In vitr o electrophysiologic studies showed normal quantal release by nerve impulse , small miniature EP potentials, and fetal as well as adult AChR channels a t the EP. Our findings support the notion that plectin is essential for the structural integrity of muscle and skin, and for normal neuromuscular tran smission.