Autosomal dominant distal hereditary motor neuronopathy-6 (HMND6) is a neurologic disorder characterized by onset of slowly progressive distal lower limb weakness and atrophy between the second and fourth decades of life. Weakness usually begins in the calf muscles and later involves more proximal muscles. The severity is variable, and some patients have difficulty walking or running. Most also have upper limb involvement, particularly of the triceps and intrinsic hand muscles. Some patients may lose independent ambulation later in the disease course. Sensory impairment is typically not present, and cognition and bulbar function are normal (summary by Sumner et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal dominant distal HMN (dHMN), see HMND1 (182960).

Axonal Charcot-Marie-Tooth disease type 2HH (CMT2HH) is an autosomal dominant peripheral neuropathy characterized predominantly by onset of vocal cord weakness resulting in stridor in infancy or early childhood. The vocal cord paresis remains throughout life and may be severe enough to require tracheostomy. Additional features of the disorder usually include pes cavus and scoliosis. Some patients have mild distal muscle weakness and atrophy primarily affecting the lower limbs, although the upper limbs may also be involved, and distal sensory impairment, often with hyporeflexia (Sullivan et al., 2020). For a discussion of genetic heterogeneity of axonal CMT, see CMT2A1 (118210).