HMN8
MCID: NRN036
MIFTS: 34

Neuronopathy, Distal Hereditary Motor, Type Viii (HMN8)

Categories: Genetic diseases, Muscle diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Neuronopathy, Distal Hereditary Motor, Type Viii

MalaCards integrated aliases for Neuronopathy, Distal Hereditary Motor, Type Viii:

Name: Neuronopathy, Distal Hereditary Motor, Type Viii 57
Dhmn8 57 12 72
Hmn8 57 12 72
Autosomal Dominant Congenital Benign Spinal Muscular Atrophy 12 58
Congenital Benign Spinal Muscular Atrophy with Contractures 12 58
Spinal Muscular Atrophy, Distal, Congenital Nonprogressive 57 13
Distal Spinal Muscular Atrophy, Congenital Nonprogressive 29 6
Autosomal Dominant Benign Distal Spinal Muscular Atrophy 12 58
Congenital Nonprogressive Spinal Muscular Atrophy 12 58
Neuropathy, Distal Hereditary Motor, Type Viii 57 72
Distal Hereditary Motor Neuronopathy Type 8 12 15
Spinal Muscular Atrophy, Congenital Benign, with Contractures 57
Atrophy, Muscular, Spinal, Distal, Congenital Nonprogressive 39
Spinal Muscular Atrophy Congenital Benign with Contractures 72
Distal Spinal Muscular Atrophy, Congenital Non-Progressive 72
Neuropathy, Distal Hereditary Motor, Type Viii; Dhmn8 57
Distal Hereditary Motor Neuropathy Type Viii 12
Neuronopathy, Distal Hereditary Motor, 8 72

Characteristics:

Orphanet epidemiological data:

58

OMIM®:

57 (Updated 20-May-2021)
Miscellaneous:
incomplete penetrance
variable severity
nonprogressive disorder
onset prenatally or at birth

Inheritance:
autosomal dominant


HPO:

31
neuronopathy, distal hereditary motor, type viii:
Inheritance autosomal dominant inheritance
Onset and clinical course variable expressivity incomplete penetrance nonprogressive


Classifications:

Orphanet: 58  
Rare neurological diseases


Summaries for Neuronopathy, Distal Hereditary Motor, Type Viii

UniProtKB/Swiss-Prot : 72 Neuronopathy, distal hereditary motor, 8: A clinically variable, neuromuscular disorder characterized by congenital lower motor neuron disorder restricted to the lower part of the body. Clinical manifestations include non-progressive muscular atrophy, thigh muscle atrophy, weak thigh adductors, weak knee and foot extensors, minimal jaw muscle and neck flexor weakness, flexion contractures of knees and pes equinovarus. Tendon reflexes are normal.

MalaCards based summary : Neuronopathy, Distal Hereditary Motor, Type Viii, is also known as dhmn8. An important gene associated with Neuronopathy, Distal Hereditary Motor, Type Viii is TRPV4 (Transient Receptor Potential Cation Channel Subfamily V Member 4). Related phenotypes are joint stiffness and cachexia

Disease Ontology : 12 A autosomal dominant distal hereditary motor neuronopathy characterized by congenital, non-progressive, predominantly distal, lower limb muscle weakness and atrophy with variable serverity that has material basis in heterozygous mutation in TRPV4 on 12q24.11.

More information from OMIM: 600175

Symptoms & Phenotypes for Neuronopathy, Distal Hereditary Motor, Type Viii

Human phenotypes related to Neuronopathy, Distal Hereditary Motor, Type Viii:

58 31 (show all 22)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 joint stiffness 58 31 hallmark (90%) Very frequent (99-80%) HP:0001387
2 cachexia 58 31 hallmark (90%) Very frequent (99-80%) HP:0004326
3 distal amyotrophy 58 31 hallmark (90%) Very frequent (99-80%) HP:0003693
4 nonprogressive muscular atrophy 58 31 hallmark (90%) Very frequent (99-80%) HP:0008964
5 hypotonia 31 hallmark (90%) HP:0001252
6 scoliosis 31 HP:0002650
7 kyphosis 31 HP:0002808
8 muscular hypotonia 58 Very frequent (99-80%)
9 hyperlordosis 31 HP:0003307
10 pes planus 31 HP:0001763
11 elevated serum creatine kinase 31 HP:0003236
12 elbow flexion contracture 31 HP:0002987
13 proximal lower limb amyotrophy 31 HP:0008956
14 talipes equinovarus 31 HP:0001762
15 areflexia 31 HP:0001284
16 decreased fetal movement 31 HP:0001558
17 hyporeflexia 31 HP:0001265
18 arthrogryposis multiplex congenita 31 HP:0002804
19 hip contracture 31 HP:0003273
20 knee flexion contracture 31 HP:0006380
21 distal muscle weakness 31 HP:0002460
22 spinal muscular atrophy 31 HP:0007269

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Skeletal Spine:
scoliosis
kyphosis
lordosis

Neurologic Peripheral Nervous System:
areflexia
hyporeflexia

Skeletal Limbs:
knee contractures
elbow contractures

Skeletal Pelvis:
hip contractures

Skeletal Feet:
pes planus
club feet
pes equinovarus

Prenatal Manifestations Movement:
decreased fetal movement

Skeletal:
arthrogryposis

Muscle Soft Tissue:
muscle atrophy, distal
muscle weakness, distal, restricted to the lower limbs
muscle weakness, proximal, pelvic girdle (in severe cases)
trunk muscle weakness
muscle biopsy shows groups of small angulated fibers consistent with denervation
more

Clinical features from OMIM®:

600175 (Updated 20-May-2021)

MGI Mouse Phenotypes related to Neuronopathy, Distal Hereditary Motor, Type Viii:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 liver/biliary system MP:0005370 8.92 DPH1 FAF2 RPL12 SNRK

Drugs & Therapeutics for Neuronopathy, Distal Hereditary Motor, Type Viii

Search Clinical Trials , NIH Clinical Center for Neuronopathy, Distal Hereditary Motor, Type Viii

Genetic Tests for Neuronopathy, Distal Hereditary Motor, Type Viii

Genetic tests related to Neuronopathy, Distal Hereditary Motor, Type Viii:

# Genetic test Affiliating Genes
1 Distal Spinal Muscular Atrophy, Congenital Nonprogressive 29 TRPV4

Anatomical Context for Neuronopathy, Distal Hereditary Motor, Type Viii

Publications for Neuronopathy, Distal Hereditary Motor, Type Viii

Articles related to Neuronopathy, Distal Hereditary Motor, Type Viii:

(show all 17)
# Title Authors PMID Year
1
Phenotypic spectrum and incidence of TRPV4 mutations in patients with inherited axonal neuropathy. 6 57
24789864 2014
2
Muscle MRI in TRPV4-related congenital distal SMA. 6 57
22291064 2012
3
Reduced penetrance in hereditary motor neuropathy caused by TRPV4 Arg269Cys mutation. 57 6
21336783 2011
4
Alterations in the ankyrin domain of TRPV4 cause congenital distal SMA, scapuloperoneal SMA and HMSN2C. 6 57
20037588 2010
5
A dominantly inherited lower motor neuron disorder presenting at birth with associated arthrogryposis. 6 57
4056805 1985
6
Exome sequencing identifies a novel TRPV4 mutation in a CMT2C family. 6
22675077 2012
7
Striking phenotypic variability in familial TRPV4-axonal neuropathy spectrum disorder. 6
22065612 2011
8
TRPV4 mutations and cytotoxic hypercalcemia in axonal Charcot-Marie-Tooth neuropathies. 6
21288981 2011
9
CMT2C with vocal cord paresis associated with short stature and mutations in the TRPV4 gene. 6
21115951 2010
10
Mutations in TRPV4 cause Charcot-Marie-Tooth disease type 2C. 6
20037586 2010
11
Scapuloperoneal spinal muscular atrophy and CMT2C are allelic disorders caused by alterations in TRPV4. 6
20037587 2010
12
Channelopathies converge on TRPV4. 6
20104247 2010
13
Autosomal dominant congenital spinal muscular atrophy--a possible developmental deficiency of motor neurones? 57
18579380 2008
14
Confirmation of a hereditary motor and sensory neuropathy IIC locus at chromosome 12q23-q24. 6
15668982 2005
15
Varying occurrence of vocal cord paralysis in a family with autosomal dominant hereditary motor and sensory neuropathy. 6
10463355 1999
16
Localisation of the gene for a dominant congenital spinal muscular atrophy predominantly affecting the lower limbs to chromosome 12q23-q24. 57
9781046 1998
17
Hereditary motor and sensory neuropathy with diaphragm and vocal cord paresis. 6
8179305 1994

Variations for Neuronopathy, Distal Hereditary Motor, Type Viii

ClinVar genetic disease variations for Neuronopathy, Distal Hereditary Motor, Type Viii:

6 (show top 50) (show all 117)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 TRPV4 NM_021625.4(TRPV4):c.806G>A (p.Arg269His) SNV Pathogenic 5000 rs267607144 GRCh37: 12:110238470-110238470
GRCh38: 12:109800665-109800665
2 TRPV4 NM_021625.4(TRPV4):c.557G>A (p.Arg186Gln) SNV Pathogenic 39419 rs397514494 GRCh37: 12:110246103-110246103
GRCh38: 12:109808298-109808298
3 TRPV4 NM_021625.4(TRPV4):c.694C>T (p.Arg232Cys) SNV Pathogenic 30472 rs387906904 GRCh37: 12:110240814-110240814
GRCh38: 12:109803009-109803009
4 TRPV4 NM_021625.4(TRPV4):c.805C>T (p.Arg269Cys) SNV Pathogenic 5002 rs267607146 GRCh37: 12:110238471-110238471
GRCh38: 12:109800666-109800666
5 TRPV4 NM_021625.4(TRPV4):c.943C>T (p.Arg315Trp) SNV Pathogenic 4999 rs267607143 GRCh37: 12:110236628-110236628
GRCh38: 12:109798823-109798823
6 TRPV4 NM_021625.4(TRPV4):c.806G>A (p.Arg269His) SNV Conflicting interpretations of pathogenicity 5000 rs267607144 GRCh37: 12:110238470-110238470
GRCh38: 12:109800665-109800665
7 TRPV4 NM_021625.4(TRPV4):c.2560G>A (p.Asp854Asn) SNV Uncertain significance 246571 rs368963822 GRCh37: 12:110221482-110221482
GRCh38: 12:109783677-109783677
8 TRPV4 NM_021625.4(TRPV4):c.171T>C (p.Pro57=) SNV Uncertain significance 307144 rs886048941 GRCh37: 12:110252431-110252431
GRCh38: 12:109814626-109814626
9 TRPV4 NM_021625.4(TRPV4):c.*51G>A SNV Uncertain significance 307120 rs886048939 GRCh37: 12:110221375-110221375
GRCh38: 12:109783570-109783570
10 TRPV4 NM_021625.4(TRPV4):c.2162C>G (p.Thr721Arg) SNV Uncertain significance 567260 rs1423138633 GRCh37: 12:110226251-110226251
GRCh38: 12:109788446-109788446
11 TRPV4 NM_021625.5(TRPV4):c.*145C>T SNV Uncertain significance 881445 GRCh37: 12:110221281-110221281
GRCh38: 12:109783476-109783476
12 TRPV4 , MIR4497 NC_000012.12:g.109833410C>A SNV Uncertain significance 881447 GRCh37: 12:110271215-110271215
GRCh38: 12:109833410-109833410
13 MIR4497 , TRPV4 NM_021625.5(TRPV4):c.-59C>T SNV Uncertain significance 882983 GRCh37: 12:110271182-110271182
GRCh38: 12:109833377-109833377
14 TRPV4 NM_021625.4(TRPV4):c.37G>T (p.Gly13Trp) SNV Uncertain significance 245716 rs763302555 GRCh37: 12:110252565-110252565
GRCh38: 12:109814760-109814760
15 TRPV4 NM_021625.5(TRPV4):c.*227A>G SNV Uncertain significance 881830 GRCh37: 12:110221199-110221199
GRCh38: 12:109783394-109783394
16 TRPV4 NM_021625.5(TRPV4):c.*500C>T SNV Uncertain significance 881730 GRCh37: 12:110220926-110220926
GRCh38: 12:109783121-109783121
17 TRPV4 NM_021625.5(TRPV4):c.797C>T (p.Ala266Val) SNV Uncertain significance 881124 GRCh37: 12:110238479-110238479
GRCh38: 12:109800674-109800674
18 TRPV4 NM_021625.4(TRPV4):c.184G>A (p.Asp62Asn) SNV Uncertain significance 575960 rs770149544 GRCh37: 12:110252418-110252418
GRCh38: 12:109814613-109814613
19 TRPV4 NM_021625.4(TRPV4):c.569C>T (p.Thr190Met) SNV Uncertain significance 424209 rs1031096826 GRCh37: 12:110240939-110240939
GRCh38: 12:109803134-109803134
20 TRPV4 NM_021625.4(TRPV4):c.1376T>G (p.Leu459Arg) SNV Uncertain significance 521109 rs201132615 GRCh37: 12:110232249-110232249
GRCh38: 12:109794444-109794444
21 TRPV4 NM_021625.4(TRPV4):c.1976C>T (p.Ser659Leu) SNV Uncertain significance 409288 rs779715512 GRCh37: 12:110226437-110226437
GRCh38: 12:109788632-109788632
22 TRPV4 NM_021625.4(TRPV4):c.*99C>T SNV Uncertain significance 307119 rs552478250 GRCh37: 12:110221327-110221327
GRCh38: 12:109783522-109783522
23 TRPV4 NM_021625.4(TRPV4):c.622G>A (p.Asp208Asn) SNV Uncertain significance 307139 rs769445973 GRCh37: 12:110240886-110240886
GRCh38: 12:109803081-109803081
24 TRPV4 NM_021625.4(TRPV4):c.427C>A (p.Pro143Thr) SNV Uncertain significance 307142 rs201642486 GRCh37: 12:110246233-110246233
GRCh38: 12:109808428-109808428
25 MIR4497 , TRPV4 NM_021625.4(TRPV4):c.-74G>A SNV Uncertain significance 307145 rs886048942 GRCh37: 12:110271197-110271197
GRCh38: 12:109833392-109833392
26 TRPV4 NM_021625.4(TRPV4):c.1601T>C (p.Met534Thr) SNV Uncertain significance 307128 rs775011025 GRCh37: 12:110231389-110231389
GRCh38: 12:109793584-109793584
27 TRPV4 NM_021625.4(TRPV4):c.*212G>A SNV Uncertain significance 307118 rs886048938 GRCh37: 12:110221214-110221214
GRCh38: 12:109783409-109783409
28 TRPV4 NM_021625.4(TRPV4):c.2236C>G (p.Arg746Gly) SNV Uncertain significance 307123 rs375189134 GRCh37: 12:110224615-110224615
GRCh38: 12:109786810-109786810
29 TRPV4 NM_021625.4(TRPV4):c.*405G>A SNV Uncertain significance 307114 rs886048937 GRCh37: 12:110221021-110221021
GRCh38: 12:109783216-109783216
30 TRPV4 NM_021625.4(TRPV4):c.1796C>G (p.Thr599Arg) SNV Uncertain significance 307127 rs769225216 GRCh37: 12:110230485-110230485
GRCh38: 12:109792680-109792680
31 TRPV4 NM_021625.4(TRPV4):c.2425G>A (p.Gly809Ser) SNV Uncertain significance 448709 rs375851168 GRCh37: 12:110222154-110222154
GRCh38: 12:109784349-109784349
32 TRPV4 NM_021625.5(TRPV4):c.742C>T (p.Arg248Cys) SNV Uncertain significance 881173 GRCh37: 12:110238534-110238534
GRCh38: 12:109800729-109800729
33 TRPV4 NM_021625.5(TRPV4):c.*421G>A SNV Uncertain significance 881334 GRCh37: 12:110221005-110221005
GRCh38: 12:109783200-109783200
34 TRPV4 NM_021625.5(TRPV4):c.*303G>A SNV Uncertain significance 881386 GRCh37: 12:110221123-110221123
GRCh38: 12:109783318-109783318
35 TRPV4 NM_021625.5(TRPV4):c.*411A>G SNV Uncertain significance 881335 GRCh37: 12:110221015-110221015
GRCh38: 12:109783210-109783210
36 TRPV4 NM_021625.5(TRPV4):c.195A>G (p.Pro65=) SNV Uncertain significance 881336 GRCh37: 12:110252407-110252407
GRCh38: 12:109814602-109814602
37 TRPV4 NM_021625.5(TRPV4):c.*83C>G SNV Uncertain significance 881446 GRCh37: 12:110221343-110221343
GRCh38: 12:109783538-109783538
38 TRPV4 NM_021625.5(TRPV4):c.2433G>A (p.Ser811=) SNV Uncertain significance 882031 GRCh37: 12:110222146-110222146
GRCh38: 12:109784341-109784341
39 TRPV4 NM_021625.5(TRPV4):c.2258G>A (p.Arg753Lys) SNV Uncertain significance 880695 GRCh37: 12:110224593-110224593
GRCh38: 12:109786788-109786788
40 TRPV4 NM_021625.4(TRPV4):c.1352C>T (p.Ala451Val) SNV Uncertain significance 307131 rs886048940 GRCh37: 12:110232273-110232273
GRCh38: 12:109794468-109794468
41 TRPV4 NM_021625.4(TRPV4):c.1038C>T (p.Tyr346=) SNV Uncertain significance 386671 rs750086412 GRCh37: 12:110236533-110236533
GRCh38: 12:109798728-109798728
42 TRPV4 NM_021625.5(TRPV4):c.425C>T (p.Pro142Leu) SNV Uncertain significance 881731 GRCh37: 12:110246235-110246235
GRCh38: 12:109808430-109808430
43 TRPV4 NM_021625.5(TRPV4):c.*2G>A SNV Uncertain significance 883056 GRCh37: 12:110221424-110221424
GRCh38: 12:109783619-109783619
44 TRPV4 NM_021625.5(TRPV4):c.812G>A (p.Arg271His) SNV Uncertain significance 882712 GRCh37: 12:110238464-110238464
GRCh38: 12:109800659-109800659
45 TRPV4 NM_021625.4(TRPV4):c.651G>A (p.Ala217=) SNV Uncertain significance 517843 rs371280831 GRCh37: 12:110240857-110240857
GRCh38: 12:109803052-109803052
46 TRPV4 NM_021625.4(TRPV4):c.523A>G (p.Thr175Ala) SNV Uncertain significance 448711 rs146304351 GRCh37: 12:110246137-110246137
GRCh38: 12:109808332-109808332
47 TRPV4 NM_021625.5(TRPV4):c.502G>A (p.Gly168Arg) SNV Uncertain significance 881272 GRCh37: 12:110246158-110246158
GRCh38: 12:109808353-109808353
48 TRPV4 NM_021625.4(TRPV4):c.958C>T (p.Arg320Ter) SNV Likely benign 469047 rs142902080 GRCh37: 12:110236613-110236613
GRCh38: 12:109798808-109798808
49 TRPV4 NM_021625.4(TRPV4):c.1700A>T (p.Tyr567Phe) SNV Likely benign 521669 rs763889344 GRCh37: 12:110230581-110230581
GRCh38: 12:109792776-109792776
50 TRPV4 NM_021625.4(TRPV4):c.2439C>T (p.Thr813=) SNV Likely benign 682229 rs545589086 GRCh37: 12:110222140-110222140
GRCh38: 12:109784335-109784335

UniProtKB/Swiss-Prot genetic disease variations for Neuronopathy, Distal Hereditary Motor, Type Viii:

72
# Symbol AA change Variation ID SNP ID
1 TRPV4 p.Arg269His VAR_063529 rs267607144
2 TRPV4 p.Pro97Arg VAR_067989 rs876661124
3 TRPV4 p.Arg232Cys VAR_067990 rs387906904

Expression for Neuronopathy, Distal Hereditary Motor, Type Viii

Search GEO for disease gene expression data for Neuronopathy, Distal Hereditary Motor, Type Viii.

Pathways for Neuronopathy, Distal Hereditary Motor, Type Viii

GO Terms for Neuronopathy, Distal Hereditary Motor, Type Viii

Biological processes related to Neuronopathy, Distal Hereditary Motor, Type Viii according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 translational initiation GO:0006413 9.26 RPS12 RPL12
2 nuclear-transcribed mRNA catabolic process, nonsense-mediated decay GO:0000184 9.16 RPS12 RPL12
3 viral transcription GO:0019083 8.96 RPS12 RPL12
4 SRP-dependent cotranslational protein targeting to membrane GO:0006614 8.62 RPS12 RPL12

Sources for Neuronopathy, Distal Hereditary Motor, Type Viii

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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