Myopathy, Myasthenic Syndrome, and Epidermolysis Bullosa Simplex Due to Plectin Deficiency

• Published in: Journal of neuropathology and experimental neurology 1999-08, Vol.58 (8), p.832-846
• Main Authors: Banwell, Brenda L, Russel, James, Fukudome, Takayasu, Shen, Xin-Ming, Stilling, Gail, Engel, Andrew G
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; Diseases of striated muscles. Neuromuscular diseases; Electrophysiology; Epidermolysis bullosa; Epidermolysis Bullosa Simplex - metabolism; Epidermolysis Bullosa Simplex - pathology; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins - deficiency; Intestinal Pseudo-Obstruction - metabolism; Intestinal Pseudo-Obstruction - pathology; Keratin; Medical sciences; Motor Endplate - metabolism; Motor Endplate - pathology; Motor Endplate - physiopathology; Motor Endplate - ultrastructure; Muscle Fibers, Skeletal - pathology; Muscle Fibers, Skeletal - ultrastructure; Muscle Weakness - metabolism; Muscle Weakness - pathology; Muscles - metabolism; Muscles - pathology; Muscles - ultrastructure; Myofibrils - pathology; Myofibrils - ultrastructure; Neurology; Plectin; Receptors, Cholinergic - drug effects; Receptors, Cholinergic - metabolism; Skin - pathology; Skin - ultrastructure; Syndrome
• ISSN: 0022-3069; 1554-6578
• DOI: 10.1097/00005072-199908000-00006

Plectin, an intermediate filament linking protein, is normally associated with the sarcolemma, nuclear membrane, and intermyofibrillar network in muscle, and with hemisdesmosomes in skin. A 20-year-old female with epidermolysis bullosa simplex since birth had progressive ocular, facial, limb, and trunkal weakness and fatigability since age 9, fivefold CK elevation, a 25% decrement with myopathic motor unit potentials and increased electrical irritability on electromyography, and no anti-acetylcholine receptor (AChR) antibodies. Plectin expression was absent in muscle and severe plectin deficiency was noted in skin. Morphologic studies revealed necrotic and regenerating fibers and a wide spectrum of ultrastructural abnormalitieslarge accumulations of heterochromatic and lobulated nuclei, rare apoptotic nuclei, numerous cytoplasmic and few intranuclear nemaline rods, disarrayed myofibrils, thick-filament loss, vacuolar change, and pathologic alterations in membranous organelles. Many endplates (EPs) had an abnormal configuration with chains of small regions over the fiber surface and a few displayed focal degeneration of the junctional folds. The EP AChR content was normal. In vitro electrophysiologic studies showed normal quantal release by nerve impulse, small miniature EP potentials, and fetal as well as adult AChR channels at the EP. Our findings support the notion that plectin is essential for the structural integrity of muscle and skin, and for normal transmission.