Zhang et al. (2007) reported a man who presented with proximal upper limb weakness and winged scapulae at age 8 years. Serum creatine kinase was increased and he later developed minor respiratory insufficiency. Skeletal muscle biopsy at age ... Zhang et al. (2007) reported a man who presented with proximal upper limb weakness and winged scapulae at age 8 years. Serum creatine kinase was increased and he later developed minor respiratory insufficiency. Skeletal muscle biopsy at age 16 showed dystrophic changes. There was no apparent cardiac involvement. The paternal grandfather and paternal uncle had a history of premature heart failure, consistent with autosomal dominant inheritance. The proband's sister had transient cardiac arrhythmia at age 10 to 14 years and abnormal myocardial compliance. The proband's father had general weakness since age 37 years and later developed ptosis and increased serum creatine kinase. Cardiac workup showed left ventricular hypertrophy and abnormal compliance. In a second family, the authors reported a woman with a history of muscular weakness died at age 30 years of a cardiomyopathy. Her son had proximal muscle weakness with impaired ambulation since childhood. Muscle biopsy showed dystrophic changes and serum creatine kinase was increased. He developed heart rhythm disturbances at age 17, which progressed to dilated cardiomyopathy requiring heart transplant at age 26 years.
In 3 affected individuals from a family with autosomal dominant EDMD, Zhang et al. (2007) identified a heterozygous mutation in the SYNE2 gene (T89M; 608442.0001) that segregated with the disorder. In a second family, the affected mother was ... In 3 affected individuals from a family with autosomal dominant EDMD, Zhang et al. (2007) identified a heterozygous mutation in the SYNE2 gene (T89M; 608442.0001) that segregated with the disorder. In a second family, the affected mother was heterozygous for the SYNE2 T89M mutation and her son was compound heterozygous for the T89M mutation and a variant in the SYNE1 gene (V572L; 608441.0009), which was also identified in heterozygosity in the unaffected father, raising some doubt about the pathogenicity of the V572L variant. Zhang et al. (2007) postulated a dominant-negative effect of the SYNE2 mutations, with the possibility of more severe manifestations in the compound heterozygote.