Distal hereditary motor neuronopathy (dHMN or HMN) is a heterogeneous group of neuromuscular disorders caused by anterior horn cell degeneration and characterized by progressive distal motor weakness and muscular atrophy of the peripheral nervous system without sensory impairment. ... Distal hereditary motor neuronopathy (dHMN or HMN) is a heterogeneous group of neuromuscular disorders caused by anterior horn cell degeneration and characterized by progressive distal motor weakness and muscular atrophy of the peripheral nervous system without sensory impairment. Distal HMN is also referred to as spinal Charcot-Marie-Tooth disease (spinal CMT). Distal HMN is often referred to as a 'neuronopathy' instead of a 'neuropathy' based on the hypothesis that the primary pathologic process resides in the neuron cell body and not in the axons (Irobi et al., 2006). - Genetic Heterogeneity of Autosomal Dominant Distal Hereditary Motor Neuronopathy Harding (1993) proposed a classification of distal HMN into 7 phenotypic subtypes according to age at onset, mode of inheritance, and presence of additional features. Those that show autosomal dominant inheritance include distal HMN type I, and II (HMN2A, 158590 and HMN2B, 608634), characterized by juvenile and adult onset, respectively; HMN type V (HMN5A, 600794 and HMN5B, 614751), characterized by upper limb involvement; and HMN VII (HMN7A, 158580 and HMN7B, 607641), with vocal cord paralysis. HMN2A is caused by mutation in the HSPB8 gene (608014), HMN2B by mutation in the HSPB1 gene (602195), HMN2C (613376) by mutation in the HSPB3 gene (604624), and HMN2D (615575) by mutation in the FBXO38 gene (608533). HMN5A is caused by mutation in the GARS gene (600287) and HMN5B is caused by mutation in the REEP1 gene (609139). HMN7A is caused by mutation in the SLC5A7 gene (608761). HMN7B is caused by mutation in the DCTN1 gene (601143). See also autosomal dominant ALS4 (602433) and congenital autosomal dominant distal SMA (600175). - Genetic Heterogeneity of Autosomal Recessive Distal Hereditary Motor Neuronopathy (Distal Spinal Muscular Atrophy) Harding (1993) classified autosomal recessive distal hereditary motor neuronopathy as dHMN IV (HMN4) and dHMN III (HMN3) (see DSMA3; 607088). HMN has also been referred to as distal spinal muscular atrophy (DSMA). 'Distal' SMA is distinguished from 'proximal' autosomal recessive spinal muscular atrophy (SMA, 253300) by the primary muscles involved. DSMA here refers to the autosomal recessive forms of HMN. See DSMA1 (SMARD1; 604320), caused by mutation in the IGHMBP2 gene (600502); DSMA2 (605726), which maps to chromosome 9p; DSMA3 (607088), encompassing HMN types III and IV, which maps to chromosome 11q13; DSMA4 (611067), caused by mutation in the PLEKHG5 gene (611101); and DSMA5 (614881), caused by mutation in the DNAJB2 gene (604139). See also X-linked SMAX3 (300489).
Davis et al. (1978) reported autosomal dominant distal motor neuronopathy without sensory impairment. Motor nerve conduction velocities were normal. Onset was usually in the first decade.
Harding and Thomas (1980) reported 4 families with autosomal dominant ... Davis et al. (1978) reported autosomal dominant distal motor neuronopathy without sensory impairment. Motor nerve conduction velocities were normal. Onset was usually in the first decade. Harding and Thomas (1980) reported 4 families with autosomal dominant inheritance of dHMN. All patients developed symptoms before age 20 years, and most in the first decade. All had distal lower limb weakness and some had pes cavus. Irobi et al. (2006) noted that descriptions of HMN type I are based on a small series of patients; no large pedigrees had been reported. Patients typically have juvenile onset of classic lower limb muscle weakness and atrophy which progresses throughout adulthood. Life expectancy is normal. Gopinath et al. (2007) reported a family in which 10 members had autosomal dominant distal HMN type I. The family had previously been reported as having juvenile ALS (602433) as a part of larger studies by De Jonghe et al. (2002) and Chen et al. (2004). Age at onset was usually in the first or second decade (median 10 years), but 1 individual had onset at age 40 years. The presenting features were difficulty with walking and running due to lower limb weakness. All patients had pes cavus and most had hammertoes. Muscle tone was increased in 6 patients, but power was reduced in the ankle extensors and intrinsic feet muscles in all but 1 patient. Plantar responses were extensor in 5 patients. There were no sensory abnormalities except for reduced vibration in the feet of 4 patients. Sural nerve biopsy in 1 patient at age 43 years showed chronic axonal neuropathy.