P.151 - Limb girdle muscular dystrophy 2G in a religious minority of Bulgarian muslims homozygous for the c.75G>A, p.Trp25* TCAP mutation

Abstract

Mutations in TCAP gene cause autosomal recessive limb-girdle muscular dystrophy type 2G (LGMD2G), congenital muscular dystrophy and dilated and hypertrophic cardiomyopathy. To describe the phenotypic spectrum of LGMD 2G in a genetically homogeneous group of patients, belonging to a religious minority of Bulgarian muslims. Sixteen affected individuals (11 male and 5 female) from 10 pedigrees underwent neurological examination, including manual muscle testing, electromyography (EMG), cardiac evaluation, ventillatory assessment, evaluation of serum creatine kinase levels (CK) and molecular-genetic testing. The pattern of muscle involvement in the lower limbs was assessed in 2 patients by 3T MRI. Fifteen of the affected were homozygous for the c.75G>A, p.Trp25*mutation, whereas one was compound heterozygous, carrying Glu132Val in exon 2 as second mutation. The mean age at onset was 17.94 ± 3.97 years, ranging between 10 and 25 years. The initial manifestations in 12 patients included proximal muscle weakness in the lower limbs, followed by difficulties in ankle dorsiflexion. In 4 of the affected the proximal and distal weakness in the legs occurred simultaneously. The proximal muscles of the upper limbs became involved 5–9 years after the disease onset. Scapular winging and lumbar hyperlordosis developed late in the course of the disease. Respiratory and cardiac functions were spared. On the MRI the muscles in all three compartments of the thigh and anterior leg ones were predominantly affected, while m. sartorius, gracilis remained relatively spared. Homozygosity for c.75G>A, p.Trp25*mutation is associated with a homogeneous clinical presentation in terms of pattern of muscle involvement. The clinical course and severity of the disease however show inter- and intra-familial variation despite the mutation homogeneity.