Limb-Girdle Muscular Dystrophy and Distal Myopathy

Gene: LAMA2

Green List (high evidence)

Well established gene-disease association. Recent review of 86 individuals. Phenotype varies in severity, likely represents a single disorder rather than distinct entities. The majority of individuals have a congenital muscular dystrophy (CMD) phenotype classified as type 1A (MDC1A; MIM# 607855). The classical phenotype manifests as neonatal hypotonia or muscle weakness during the first months of life and reduced spontaneous movements. As muscle weakness persists during development, it compromises the achievement of normal motor milestones (no cephalic control or inability to sit unsupported) and frequently gives rise to failure to thrive. Other manifestations such as gastroesophageal reflux, aspiration, recurrent chest infections, and even respiratory failure are reported. Facial muscle weakness, ophthalmoparesis, and macroglossia are also features present in these patients but are often beyond early childhood. Other relevant clinical hallmarks of MDC1A include elevated creatine kinase (CK) levels and dystrophic changes (necrosis and regeneration of fibers, chronic inflammation, and fibrosis) recognizable in muscle biopsies of these patients. Structural brain abnormalities, seizures, and intellectual disability reported. Also note reports of late‐onset LAMA2‐MD patients, mainly characterised by proximal muscle weakness with onset during childhood, delayed motor milestones, achievement of independent ambulation, and persistently elevated CK levels.

Created: 27 Aug 2020, 11:42 p.m. | Last Modified: 27 Aug 2020, 11:42 p.m.

Panel Version: 0.3958

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Muscular dystrophy, congenital, merosin deficient or partially deficient, MIM# 607855; Muscular dystrophy, limb-girdle, autosomal recessive 23, MIM# 618138

Publications

• 30055037