Patients with autosomal dominant MYH2 myopathy presented with joint contractures preferentially involved the fingers and/or hips and generally resolved early in childhood. Hypotonia was not a prominent feature and the early development was normal. External ophthalmoplegia was present in all patients, ranging from a slight impairment of upward gaze in affected children to a generalized ophthalmoparesis in some adult cases. The muscle weakness and atrophy predominantly involved proximal muscles of the shoulder and pelvic girdles, and also back and hand muscles. Atrophy of the quadriceps muscles was prominent in the more severely affected adults. The muscle weakness was remarkably variable. Most children and adolescents and some adults were mildly affected, whereas some adults had experienced progressive muscle weakness affecting ambulation from age 30 to 50 years. While mildly affected cases had normal serum creatine kinase (s-CK) levels, it was slightly elevated in the family members showing a progressive course. A fine action hand tremor has been noticed in several cases.
Patients with recessive MyHC IIa mutations, homozygous or compound heterozygous for truncating mutations in MYH2, accompanied by complete loss of MyHC IIa protein and absence of type 2A muscle fibers. The clinical picture was surprisingly mild with minor or moderate generalized muscle weakness including facial muscle weakness. A consistent finding was external ophthalmoplegia, which was only occasionally associated with ptosis. Magnetic resonance imaging (MRI) of lower limb muscles in two cases demonstrated selective involvement of certain muscles with fatty infiltration. There was predominant involvement of medial gastrocnemius in the lower legs, combined with predominant involvement of the semitendinosus, gracilis and vastus lateralis muscles in the thigh.
MYH2