| #613204 | ||||||||||||
| MUSCULAR DYSTROPHY, CONGENITAL, DUE TO INTEGRIN ALPHA-7 DEFICIENCY | ||||||||||||
| Alternative titles; symbols | ||||||||||||
| MYOPATHY, CONGENITAL, DUE TO INTEGRIN ALPHA-7 DEFICIENCY | ||||||||||||
| Phenotype Gene Relationships | ||||||||||||
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| A number sign (#) is used with this entry because this form of congenital muscular dystrophy is caused by mutation in the ITGA7 gene (600536). | ||||||||||||
| Clinical Features | ||||||||||||
| Hayashi et al. (1998) reported 2 unrelated Japanese patients with a congenital myopathy or muscular dystrophy. The first, a 3-year-old boy, showed delayed psychomotor milestones; he acquired the ability to roll over at 9 months, and walked at 2.5 years. He could not jump or run. Mental retardation was also observed, and verbal abilities were limited to only a few words. Serum creatine kinase (CK) activity was mildly elevated. Brain MRI and EEG were normal. Muscle biopsy at 15 months showed changes consistent with congenital myopathy. The second patient was an 11-year-old girl who 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. Serum CK was mildly elevated. Muscle biopsy showed changes consistent with muscular dystrophy, with substantial fatty replacement and fiber size variation. In contrast to the first child, she had no cognitive impairment. A third patient with congenital myopathy and marked deficiency of ITGA7 mRNA showed hypotonia and torticollis from birth; however, no mutation was identified in the ITGA7 cDNA. Nakashima et al. (2009) reported follow-up of the third patient reported by Hayashi et al. (1998). He had hypotonia from birth, sat without support at 1 year 2 months, and moved on his knees at 2 years 8 months. His motor development then stopped and started regressing at age 5 years. He had progressive, predominantly proximal, muscle weakness and atrophy, as well as scoliosis. He could only move by bottom shuffling at 7 years of age, and became wheelchair-bound at age 12 years. He also had gradually progressive dyspnea resulting from respiratory muscle weakness. Cardiac function was normal. Brain MRI showed no abnormalities and cognitive development was normal. | ||||||||||||
| Molecular Genetics | ||||||||||||
| In a Japanese boy with congenital muscular dystrophy, Hayashi et al. (1998) identified compound heterozygosity for 2 truncating mutations in the ITGA7 gene (600536.0001 and 600536.0002). An unrelated girl was also compound heterozygous for 2 truncating mutations in the ITGA7 gene (600536.0002 and 600536.0003). | ||||||||||||
| Nomenclature | ||||||||||||
| In a review of congenital muscular dystrophies, Reed (2009) stated that the phenotype associated with ITGA7 deficiency is better characterized as a 'muscular dystrophy' than a 'myopathy' since knockout mice show clinical and histopathologic features of a progressive muscular dystrophy (Mayer et al., 1997). | ||||||||||||
| Animal Model | ||||||||||||
| Mayer et al. (1997) found that homozygous Itga7-null mice developed a typical progressive muscular dystrophy starting soon after birth. Histologic analysis of skeletal muscle showed muscular dystrophy with a distinct variability in different muscle types. The histopathologic changes indicated an impairment of function of the myotendinous junctions. | ||||||||||||
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