ZASPopathy with childhood-onset distal myopathy

We report on a German family presenting with a predominantly distal myopathy primarily affecting anterior compartments of lower legs in childhood. Proximal lower limb and hip girdle weakness developed later in early adulthood in the female index patient and likewise in her mother. Consecutive muscle biopsy findings were first attributed to a mild congenital myopathy and later on interpreted as neurogenic changes without clear signs of a myopathy. Molecular genetic analysis was performed because of the clinical impression of a distal myopathy combined with dominant inheritance. The heterozygous mutation c.349G>A (p.D117N) in the ZASP gene could be found. This mutation had been previously associated with an adult-onset, isolated, dilated left ventricular non-compaction cardiomyopathy (OMIM*605906.0007), which was not present in our patients. Our data show that this mutation can be associated with an isolated skeletal muscle phenotype. Second, mutation analysis of the ZASP gene is suggested for distal myopathies of any age, even in cases of uncharacteristic muscle biopsy findings on routine analysis.