F42. EMG findings in patients with limb-girdle muscular dystrophy due to heterozygous CAPN3 mutations

Abstract

Introduction Limb-girdle muscular dystrophy type 2A (LGMD2A) is the most common autosomal recessive (AR) LGMD subtype worldwide. The disease is caused by homozygous pathogenic mutations in the calpain 3 gene (CAPN3). Although strict AR inheritance is assumed for CAPN3-related myopathies, recent reports described symptomatic patients carrying a single CAPN3 mutation. The LGMDs share common clinical and laboratory findings such as weakness and atrophy of proximal muscles, often affecting lower extremities first; elevated creatine kinase (CK) levels; and dystrophic findings on muscle biopsy. Some clinical and imaging findings help to differentiate LGMD2A, such as asymmetric weakness and atrophy and early scapular winging. On muscle MRI, calpain deficiency characteristically reveals preferential involvement of posterior thigh muscles and the adductor magnus muscle with relative sparing of the anterior thigh muscles. There are few reports on EMG findings in patients with single CAPN3 mutations. Methods Two unrelated patients with LGMD and harboring single CAPN3 mutations were identified. They underwent detailed neurological evaluation, muscle biopsy, muscle MRI and electroneuromyography (ENMG). Results Patient one: man, 28 years old, born from nonconsanguineous parents, presenting progressive calves atrophy since 24 years old. Genetic analysis showed the variant c.258dupT;p. (Leu87Serfs*4) at CAPN3 in heterozygosity. ENMG showed myopathic motor unit action potential (MUAP) on left gastrocnemius and pectoralis major, and on right biceps brachii, without fibs or positive sharp waves. Right gastrocnemius muscle biopsy showed moderate myopathic changes. Patient two: woman, 77 years old, born from nonconsanguineous parents, presenting progressive proximal lower limb weakness in the last 2 years. Genetic analysis revealed the heterozygous frameshift variant c.550delA; p. (Thr184Argfs*36) in the CAPN3 gene. ENMG showed moderate diffuse myopathy, with preferential involvement of posterior tigh muscles and gastrocnemius with fibs and positive sharp waves. MRI showed severe atrophy of posterior tight muscles. Right quadriceps femoris biopsy revealed minimal myopathic changes. Conclusion The typical clinical, imaging and electrophysiological findings from LGMD2A can be found in patients presenting heterozygous pathogenic mutations in CAPN3 gene, indicating that a dominantly inherited form of calpainopathy exists, but with a milder fenotype. EMG reveals a predominantly posterior leg pattern of involvement.