Distal myopathies are rare inherited muscle disorders which may be caused by autosomal dominant (AD) or recessive (AR) mutations in a number of different genes. Until recently, myopathies caused by mutations in the nebulin gene (NEB) were all thought to be AR. However, a large deletion in NEB was recently reported in a family with AD distal myopathy (Kiiski et al., Neuromuscular Disorders 29:97-107, 2019).

Here, we describe a second family with an AD NEB-related distal-onset myopathy. Four members of the family, 3 of whom were symptomatic, were clinically evaluated. Sequence analysis and deletion/duplication testing of 53 genes associated with inherited myopathy were performed on the index patient.

The index case was a 39-year-old mobile woman with childhood-onset distal lower limb weakness leading to bilateral foot drop. Weakness progressed to the proximal lower limbs as well as the upper limbs, and predominantly affected ankle dorsiflexors and neck flexors. Mild facial weakness was present. Creatine kinase was normal (124 U/L). Histological analysis of a vastus lateralis muscle biopsy only showed mild atrophy of both fiber types. Ten of the eighteen-member three-generation family were reported to be affected, some of whom were wheelchair-bound by the seventh or eighth decade. With the exception of the index case, age of onset was in the fourth or fifth decade. Analysis of NEB was performed in five family members (including the index case), three of whom were symptomatic. An in-frame heterozygous deletion of exons 14-77 was identified in all three affected individuals, as well as in one 36-year-old unaffected relative.