Phenotypic Variability of LGMD 2C/R5 in a Genetically Homogenous Group of Bulgarian Muslim Roma

Abstract

Sarcoglycanopathies are among the most frequent and severe forms of autosomal recessive forms of limb-girdle muscular dystrophies (LGMDs) with childhood onset. Four subtypes are known: LGMDR3, LGMDR4, LGMDR5 and LGMDR6, which are caused, respectively, by mutations in the SGCA, SGCB, SGCG and SGCD genes. We present the clinical variability of LGMD 2C/R5 among a genetically homogeneous group of 57 patients, belonging to 35 pedigrees. Molecular genetic analysis showed that all 57 patients were homozygous for the C283Y variant. The muscles of the pelvic girdle and the trunk were affected early and were more severely affected, followed by the shoulder girdle. Macroglossia, hypertrophy of the calves, scapular winging and lumbar hyperlordosis were common in the ambulatory phase. A great intra and interfamilial variability in the clinical presentation of LGMD 2C/R5 was observed, despite having the same underlying molecular defect. Females demonstrated a relatively milder clinical course compared to males. Mean creatine phosphokinase (CK) CK levels were 20 times above normal values. Muscle computer tomography (CT) CT or MRIs showed earlier and more severe involvement of the flexor proximal limb muscles in comparison to extensor muscles.