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Distal hereditary motor neuropathies

Distal hereditary motor neuropathies (distal HMN, dHMN) are a genetically and clinically heterogeneous group of motor neuron diseases that result from genetic mutations in various genes and are characterized by degeneration and loss of motor neuron cells in the anterior horn of the spinal cord and subsequent muscle atrophy.

Although they can hardly be distinguished from hereditary motor and sensory neuropathies on the clinical level, dHMNs are considered a separate class of disorders.


In 1993, A. E. Hardnig proposed to classify hereditary motor neuropathies into seven groups based on age at onset, mode of inheritance, and presence of additional features. This initial classification has since been widely adopted and expanded and currently looks as follows:[1][2]

Type Common name
Alternate names
OMIM Gene Locus Inheritance Characteristics
HMN1 Autosomal dominant juvenile distal spinal muscular atrophy 182960  ? 7q34–q36 Autosomal dominant Juvenile-onset
HMN2A Autosomal dominant distal spinal muscular atrophy 158590 HSPB8 12q24.23 Autosomal dominant Adult-onset. Allelic with Charcot–Marie–Tooth disease type 2F
HMN2B 608634 HSPB1 7q11.23 Autosomal dominant Adult-onset
HMN2C 613376 HSPB3 5q11.2 Autosomal dominant
HMN2D Distal spinal muscular atrophy with calf predominance 615575 FBXO38 5q32 Autosomal dominant Juvenile- or adult-onset, slowly progressive, affects both proximal and distal muscles, initially manifests with calf weakness which progresses to hands
Distal spinal muscular atrophy type 3 607088  ? 11q13 Autosomal recessive HMN3 – benign form: early adult onset, slowly progressive, no diaphragmatic paralysis
HMN4 – severe form: juvenile-onset with diaphragmatic paralysis
HMN5A Distal spinal muscular atrophy type VA 600794 GARS 7p14.3 Autosomal dominant Upper limb predominance with spasticity of lower limbs
Locus and phenotype overlapping with CMT-2D and SPG-17
HMN5B Distal spinal muscular atrophy type VB 614751 REEP1 2p11.2 Autosomal dominant Locus and phenotype overlapping with SPG-31
HMN6 Distal spinal muscular atrophy type 1

Spinal muscular atrophy with respiratory distress type 1

604320 IGHMBP2 11q13.3 Autosomal recessive Infant-onset, severe, with diaphragmatic failure
HMN7A Spinal muscular atrophy with vocal cord paralysis

Harper–Young myopathy

158580 SLC5A7 2q12.3 Autosomal dominant Infant-onset with vocal cord paralysis
HMN7B 607641 DCTN1 2p13.1 Autosomal dominant Adult-onset with vocal cord paralysis and facial weakness
HMN-J Distal spinal muscular atrophy type 2

Jerash type spinal muscular atrophy

605726  ? 9p21.1–p12 Autosomal recessive Juvenile-onset with pyramidal features

See also


  1. Irobi, J; De Jonghe, P; Timmerman, V (2004). "Molecular genetics of distal hereditary motor neuropathies". Human Molecular Genetics 13 (suppl 2): R195–R202. PMID 15358725. doi:10.1093/hmg/ddh226. 
  2. Scherer, SS (2006). "Finding the causes of inherited neuropathies". Archives of Neurology 63 (6): 812. PMID 16769861. doi:10.1001/archneur.63.6.812.