Distal hereditary motor neuronopathies (distal HMNs, DHMNs, or dHMNs; 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__
Classification 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:
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 DHMN3DHMN4 ? 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 Locus and phenotype overlapping with CMT-2D and SPG-17 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; Harper–Young myopathy Infant onset 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; Jerash type spinal muscular atrophy Juvenile onset with pyramidal features
Note: Acronym HMN is also used interchangeably with DHMN.
See also Motor neuron disease Hereditary motor and sensory neuropathies Spinal muscular atrophies Charcot–Marie–Tooth disease Hereditary spastic paraplegia
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