Congenital Muscular Dystrophy with Integrin-Alpha-7 Deficiency
This form of congenital muscular dystrophy is characterized by neonatal hypotonia, proximal muscle weakness and atrophy, delayed motor development, cognitive impairment, scoliosis, dyspnea due to respiratory muscle weakness, mildly increased CK levels, and dystrophic changes in muscle biopsy with lack of integrin-alpha-7 staining, due to mutations in the ITGA7 gene. Integrin-alpha-7/beta-1 is a specific receptor for the basal membrane proteins laminin-1 and laminin-2; it is expressed mainly in striated muscle, and it may have a critical role in the maintenance of muscle integrity by providing mechanical links between muscle fibers and the basal membrane and in differentiation and migration processes during myogenesis.
Of the few cases reported, one 3-year-old boy with delayed psychomotor milestones acquired the ability to roll over at 9 months and walked at 2.5 years. He could not jump or run. Mental retardation was present, and verbal abilities were limited to only a few words. Brain MRI and EEG were normal. Muscle biopsy showed changes consistent with congenital myopathy. Another 11-year-old girl was diagnosed at 2 months of age with congenital dislocation of the hip and torticollis, which required surgical intervention. She acquired independent ambulation at 2 years, but Gowers’ sign and waddling gait were observed. She had never been able to climb stairs without support and could not run. Muscle biopsy showed dystrophic changes, substantial fatty replacement, and fiber size variation.
KeywordsSevere CMD Integrin-alpha-7 deficiency Cortical atrophy