Distal hereditary motor neuronopathies (distal HMN, dHMN), sometimes also called distal hereditary motor neuropathies, 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.
Another common system of classification groups many of DHMNs under the heading of spinal muscular atrophies.__TOC__
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 | OMIM | Gene | Locus | Inheritance | Common names and characteristics | |
|---|---|---|---|---|---|---|
| DHMN1 | ? | 7q34–q36 | Autosomal dominant | Autosomal dominant juvenile distal spinal muscular atrophy Juvenile onset | ||
| DHMN2A | HSPB8 | 12q24.23 | Autosomal dominant | Autosomal dominant distal spinal muscular atrophy Adult onset. Allelic with Charcot–Marie–Tooth disease type 2F | ||
| DHMN2B | HSPB1 | 7q11.23 | Autosomal dominant | Adult onset | ||
| DHMN2C | HSPB3 | 5q11.2 | Autosomal dominant | |||
| DHMN2D | FBXO38 | 5q32 | Autosomal dominant | Distal spinal muscular atrophy with calf predominance Juvenile or adult onset, slowly progressive, affects both proximal and distal muscles, initially manifests with calf weakness which progresses to hands | ||
| DHMN3 DHMN4 | ? | 11q13 | Autosomal recessive | Distal spinal muscular atrophy type 3 DHMN3 – benign form: early adult onset, slowly progressive, no diaphragmatic paralysis DHMN4 – severe form: juvenile onset with diaphragmatic paralysis | ||
| DHMN5A | GARS | 7p14.3 | Autosomal dominant | Distal spinal muscular atrophy type VA Upper limb predominance with spasticity of lower limbs | ||
| DHMN5B | REEP1 | 2p11.2 | Autosomal dominant | Distal spinal muscular atrophy type VB Locus and phenotype overlapping with SPG-31 | ||
| DHMN6 | IGHMBP2 | 11q13.3 | Autosomal recessive | Distal spinal muscular atrophy type 1 (DSMA1); spinal muscular atrophy with respiratory distress type 1 (SMARD1) Infant onset, severe, with diaphragmatic failure | ||
| DHMN7A | SLC5A7 | 2q12.3 | Autosomal dominant | Spinal muscular atrophy with vocal cord paralysis
| ||
| DHMN7B | DCTN1 | 2p13.1 | Autosomal dominant | Adult onset with vocal cord paralysis and facial weakness | ||
| DHMN8 | TRPV4 | 12q24.11 | Autosomal dominant | Congenital distal spinal muscular atrophy Affects primarily distal muscles of lower limbs, non-progressive, rare | ||
| DHMNJ | SIGMAR1 | 9p13.3 | Autosomal recessive | Distal spinal muscular atrophy type 2
|
Note: Acronym HMN is also used interchangeably with DHMN.