NMAN
MCID: NRM016
MIFTS: 33

Neuromyotonia and Axonal Neuropathy, Autosomal Recessive (NMAN)

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

Aliases & Classifications for Neuromyotonia and Axonal Neuropathy, Autosomal Recessive

MalaCards integrated aliases for Neuromyotonia and Axonal Neuropathy, Autosomal Recessive:

Name: Neuromyotonia and Axonal Neuropathy, Autosomal Recessive 58 76 13 41
Gamstorp-Wohlfart Syndrome 58 12 54 26 76 15
Autosomal Recessive Axonal Neuropathy with Neuromyotonia 54 26 60 30 6
Nman 58 54 26 76
Autosomal Recessive Charcot-Marie-Tooth Disease Type 2 with Neuromyotonia 54 26 60
Myokymia, Myotonia, and Muscle Wasting 58 54 26
Aran-Nm 54 26 60
Autosomal Recessive Neuromyotonia and Axonal Neuropathy 12 26
Arcmt2-Nm 54 60
Myokymia, Myotonia and Muscle Wasting 12
Myokymia Myotonia and Muscle Wasting 76
Isaacs Syndrome 74

Characteristics:

Orphanet epidemiological data:

60
autosomal recessive axonal neuropathy with neuromyotonia
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
progressive disorder
onset in first or second decade
most patients retain ambulation with aids
motor neuropathy more prominent than sensory neuropathy


HPO:

33
neuromyotonia and axonal neuropathy, autosomal recessive:
Onset and clinical course progressive
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 60  
Rare neurological diseases


Summaries for Neuromyotonia and Axonal Neuropathy, Autosomal Recessive

NIH Rare Diseases : 54 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 324442Disease definitionAutosomal recessive axonal neuropathy with neuromyotonia is a rare peripheral neuropathy characterized by slowly progressive axonal, motor greater than sensory polyneuropathy combined with neuromytonia (including spontaneous muscular activity at rest (myokymia), impaired muscle relaxation (pseudomyotonia), and contractures of hands and feet) and neuromyotonic or myokymic discharges on needle EMG. It presents with distal lower limb weakness with gait impairment, muscle stiffness, fasciculations and cramps in hands and legs worsened by cold, decreased to absent tendon reflexes, intrinsic hand muscle atrophy and, variably, mild distal sensory impairment.Visit the Orphanet disease page for more resources.

MalaCards based summary : Neuromyotonia and Axonal Neuropathy, Autosomal Recessive, also known as gamstorp-wohlfart syndrome, is related to axonal neuropathy and neuropathy, and has symptoms including muscle weakness, myalgia and myokymia. An important gene associated with Neuromyotonia and Axonal Neuropathy, Autosomal Recessive is HINT1 (Histidine Triad Nucleotide Binding Protein 1). Affiliated tissues include brain, spinal cord and tongue, and related phenotypes are distal lower limb muscle weakness and emg: myokymic discharges

Disease Ontology : 12 A syndrome characterized by progressive weakness and atrophy of muscles in feet, legs and hands. In some patients the syndrome also causes decreased sensitivity to touch, heat or cold, particularly in the lower arms or legs.

Genetics Home Reference : 26 Autosomal recessive axonal neuropathy with neuromyotonia is a disorder that affects the peripheral nerves. Peripheral nerves connect the brain and spinal cord to muscles and to sensory cells that detect sensations such as touch, pain, heat, and sound.

OMIM : 58 NMAN is an autosomal recessive neurologic disorder characterized by onset in the first or second decade of a peripheral axonal neuropathy predominantly affecting motor more than sensory nerves. The axonal neuropathy is reminiscent of Charcot-Marie-Tooth disease type 2 (see, e.g., CMT2A1, 118210) and distal hereditary motor neuropathy (see, e.g., HMN1, 182960). Individuals with NMAN also have delayed muscle relaxation and action myotonia associated with neuromyotonic discharges on needle EMG resulting from hyperexcitability of the peripheral nerves (summary by Zimon et al., 2012). (137200)

UniProtKB/Swiss-Prot : 76 Neuromyotonia and axonal neuropathy, autosomal recessive: An autosomal recessive neurologic disorder characterized by onset in the first or second decade of a peripheral axonal neuropathy predominantly affecting motor more than sensory nerves. The axonal neuropathy is reminiscent of Charcot-Marie-Tooth disease type 2 and distal hereditary motor neuropathy. Individuals with NMAN also have delayed muscle relaxation and action myotonia associated with neuromyotonic discharges on needle EMG resulting from hyperexcitability of the peripheral nerves.

Related Diseases for Neuromyotonia and Axonal Neuropathy, Autosomal Recessive

Diseases related to Neuromyotonia and Axonal Neuropathy, Autosomal Recessive via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 axonal neuropathy 10.6
2 neuropathy 10.6

Symptoms & Phenotypes for Neuromyotonia and Axonal Neuropathy, Autosomal Recessive

Human phenotypes related to Neuromyotonia and Axonal Neuropathy, Autosomal Recessive:

60 33 (show top 50) (show all 52)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 distal lower limb muscle weakness 60 33 hallmark (90%) Very frequent (99-80%) HP:0009053
2 emg: myokymic discharges 60 33 hallmark (90%) Very frequent (99-80%) HP:0100288
3 emg: chronic denervation signs 60 33 hallmark (90%) Very frequent (99-80%) HP:0003444
4 handgrip myotonia 60 33 frequent (33%) Frequent (79-30%) HP:0012899
5 fatigable weakness of distal limb muscles 60 33 frequent (33%) Frequent (79-30%) HP:0030198
6 exercise intolerance 60 33 frequent (33%) Frequent (79-30%) HP:0003546
7 frequent falls 60 33 frequent (33%) Frequent (79-30%) HP:0002359
8 absent achilles reflex 60 33 frequent (33%) Frequent (79-30%) HP:0003438
9 limb fasciculations 60 33 frequent (33%) Frequent (79-30%) HP:0007289
10 motor axonal neuropathy 60 33 frequent (33%) Frequent (79-30%) HP:0007002
11 motor polyneuropathy 60 33 frequent (33%) Frequent (79-30%) HP:0007178
12 elevated serum creatine kinase 33 frequent (33%) HP:0003236
13 pes cavus 60 33 occasional (7.5%) Occasional (29-5%) HP:0001761
14 sensory axonal neuropathy 60 33 occasional (7.5%) Occasional (29-5%) HP:0003390
15 achilles tendon contracture 60 33 occasional (7.5%) Occasional (29-5%) HP:0001771
16 paresthesia 60 33 occasional (7.5%) Occasional (29-5%) HP:0003401
17 muscle stiffness 60 33 occasional (7.5%) Occasional (29-5%) HP:0003552
18 writer's cramp 60 33 occasional (7.5%) Occasional (29-5%) HP:0002356
19 foot dorsiflexor weakness 60 33 occasional (7.5%) Occasional (29-5%) HP:0009027
20 impaired vibration sensation in the lower limbs 60 33 occasional (7.5%) Occasional (29-5%) HP:0002166
21 peroneal muscle atrophy 60 33 occasional (7.5%) Occasional (29-5%) HP:0009049
22 steppage gait 60 33 occasional (7.5%) Occasional (29-5%) HP:0003376
23 intrinsic hand muscle atrophy 60 33 occasional (7.5%) Occasional (29-5%) HP:0008954
24 weakness of the intrinsic hand muscles 60 33 occasional (7.5%) Occasional (29-5%) HP:0009005
25 tetraparesis 60 33 occasional (7.5%) Occasional (29-5%) HP:0002273
26 distal lower limb amyotrophy 60 33 occasional (7.5%) Occasional (29-5%) HP:0008944
27 progressive inability to walk 60 33 occasional (7.5%) Occasional (29-5%) HP:0002505
28 distal sensory impairment of all modalities 60 33 occasional (7.5%) Occasional (29-5%) HP:0003409
29 percussion-induced rapid rolling muscle contractions 60 33 occasional (7.5%) Occasional (29-5%) HP:0003760
30 exercise-induced leg cramps 60 33 occasional (7.5%) Occasional (29-5%) HP:0008991
31 weakness of long finger extensor muscles 60 33 occasional (7.5%) Occasional (29-5%) HP:0009077
32 hyperhidrosis 60 33 very rare (1%) Very rare (<4-1%) HP:0000975
33 intellectual disability, mild 60 33 very rare (1%) Very rare (<4-1%) HP:0001256
34 specific learning disability 60 33 very rare (1%) Very rare (<4-1%) HP:0001328
35 split hand 60 33 very rare (1%) Very rare (<4-1%) HP:0001171
36 camptodactyly of finger 60 33 very rare (1%) Very rare (<4-1%) HP:0100490
37 thoracic scoliosis 60 33 very rare (1%) Very rare (<4-1%) HP:0002943
38 short third metatarsal 60 33 very rare (1%) Very rare (<4-1%) HP:0004686
39 myotonia 60 33 Very frequent (99-80%) HP:0002486
40 abnormality of the foot 60 33 Frequent (79-30%) HP:0001760
41 myokymia 60 33 Very frequent (99-80%) HP:0002411
42 gait disturbance 60 Frequent (79-30%)
43 flexion contracture 60 Occasional (29-5%)
44 elevated serum creatine phosphokinase 60 Frequent (79-30%)
45 skeletal muscle atrophy 33 HP:0003202
46 hand muscle atrophy 60 Occasional (29-5%)
47 reduced tendon reflexes 60 Frequent (79-30%)
48 areflexia 60 Occasional (29-5%)
49 fasciculations 33 HP:0002380
50 distal sensory impairment 33 HP:0002936

Symptoms via clinical synopsis from OMIM:

58
Muscle Soft Tissue:
muscle stiffness
muscle cramps
fasciculations
foot drop
distal muscle weakness and atrophy, upper and lower limbs
more
Skeletal Feet:
foot deformities

Neurologic Central Nervous System:
impaired gait due to peripheral neuropathy

Neurologic Peripheral Nervous System:
myokymia
axonal motor neuropathy
axonal sensory neuropathy
neuromyotonia
action myotonia
more
Head And Neck Mouth:
percussion contraction of the tongue (1 family)

Laboratory Abnormalities:
increased serum creatine kinase

Clinical features from OMIM:

137200

UMLS symptoms related to Neuromyotonia and Axonal Neuropathy, Autosomal Recessive:


muscle weakness, myalgia, myokymia, muscular fasciculation, muscle cramp, muscle rigidity, muscle spasticity, neuralgia, muscular stiffness

Drugs & Therapeutics for Neuromyotonia and Axonal Neuropathy, Autosomal Recessive

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Inherited Myokymia: A Clinical and Genetic Study of a Family Unknown status NCT01250704
2 Screening and Natural History: Primary Lateral Sclerosis and Related Disorders Completed NCT00015444

Search NIH Clinical Center for Neuromyotonia and Axonal Neuropathy, Autosomal Recessive

Genetic Tests for Neuromyotonia and Axonal Neuropathy, Autosomal Recessive

Genetic tests related to Neuromyotonia and Axonal Neuropathy, Autosomal Recessive:

# Genetic test Affiliating Genes
1 Autosomal Recessive Axonal Neuropathy with Neuromyotonia 30 HINT1

Anatomical Context for Neuromyotonia and Axonal Neuropathy, Autosomal Recessive

MalaCards organs/tissues related to Neuromyotonia and Axonal Neuropathy, Autosomal Recessive:

42
Brain, Spinal Cord, Tongue, Skeletal Muscle

Publications for Neuromyotonia and Axonal Neuropathy, Autosomal Recessive

Articles related to Neuromyotonia and Axonal Neuropathy, Autosomal Recessive:

# Title Authors Year
1
Novel mutations in HINT1 gene cause the autosomal recessive axonal neuropathy with neuromyotonia. ( 30006059 )
2019
2
Novel mutations in HINT1 gene cause autosomal recessive axonal neuropathy with neuromyotonia in two cases of sensorimotor neuropathy and one case of motor neuropathy. ( 30001929 )
2018
3
A Novel Variant in the HINT1 Gene in a Girl with Autosomal Recessive Axonal Neuropathy with Neuromyotonia: Thorough Neurological Examination Gives the Clue. ( 26760849 )
2016
4
Autosomal recessive axonal neuropathy with neuromyotonia: a rare entity. ( 24131582 )
2014
5
HINT1 mutations define a novel disease entity - autosomal recessive axonal neuropathy with neuromyotonia. ( 23043279 )
2013
6
Loss-of-function mutations in HINT1 cause axonal neuropathy with neuromyotonia. ( 22961002 )
2012
7
Neuromyotonia in hereditary motor neuropathy. ( 1851512 )
1991

Variations for Neuromyotonia and Axonal Neuropathy, Autosomal Recessive

UniProtKB/Swiss-Prot genetic disease variations for Neuromyotonia and Axonal Neuropathy, Autosomal Recessive:

76
# Symbol AA change Variation ID SNP ID
1 HINT1 p.Arg37Pro VAR_069212 rs149782619
2 HINT1 p.His51Arg VAR_069213 rs397514491
3 HINT1 p.Cys84Arg VAR_069214 rs397514489
4 HINT1 p.Gly89Val VAR_069215 rs397514490
5 HINT1 p.Gly93Asp VAR_069216 rs397514493
6 HINT1 p.His112Asn VAR_069217 rs373849532

ClinVar genetic disease variations for Neuromyotonia and Axonal Neuropathy, Autosomal Recessive:

6 (show all 36)
# Gene Variation Type Significance SNP ID Assembly Location
1 HINT1 NM_005340.6(HINT1): c.110G> C (p.Arg37Pro) single nucleotide variant Pathogenic rs149782619 GRCh37 Chromosome 5, 130500789: 130500789
2 HINT1 NM_005340.6(HINT1): c.110G> C (p.Arg37Pro) single nucleotide variant Pathogenic rs149782619 GRCh38 Chromosome 5, 131165096: 131165096
3 HINT1 NM_005340.6(HINT1): c.250T> C (p.Cys84Arg) single nucleotide variant Pathogenic rs397514489 GRCh37 Chromosome 5, 130495271: 130495271
4 HINT1 NM_005340.6(HINT1): c.250T> C (p.Cys84Arg) single nucleotide variant Pathogenic rs397514489 GRCh38 Chromosome 5, 131159578: 131159578
5 HINT1 NM_005340.6(HINT1): c.266G> T (p.Gly89Val) single nucleotide variant Pathogenic rs397514490 GRCh37 Chromosome 5, 130495255: 130495255
6 HINT1 NM_005340.6(HINT1): c.266G> T (p.Gly89Val) single nucleotide variant Pathogenic rs397514490 GRCh38 Chromosome 5, 131159562: 131159562
7 HINT1 NM_005340.6(HINT1): c.334C> A (p.His112Asn) single nucleotide variant Pathogenic rs373849532 GRCh37 Chromosome 5, 130495187: 130495187
8 HINT1 NM_005340.6(HINT1): c.334C> A (p.His112Asn) single nucleotide variant Pathogenic rs373849532 GRCh38 Chromosome 5, 131159494: 131159494
9 HINT1 NM_005340.6(HINT1): c.152A> G (p.His51Arg) single nucleotide variant Pathogenic rs397514491 GRCh37 Chromosome 5, 130498329: 130498329
10 HINT1 NM_005340.6(HINT1): c.152A> G (p.His51Arg) single nucleotide variant Pathogenic rs397514491 GRCh38 Chromosome 5, 131162636: 131162636
11 HINT1 NM_005340.6(HINT1): c.184C> T (p.Gln62Ter) single nucleotide variant Pathogenic rs397514492 GRCh37 Chromosome 5, 130498297: 130498297
12 HINT1 NM_005340.6(HINT1): c.184C> T (p.Gln62Ter) single nucleotide variant Pathogenic rs397514492 GRCh38 Chromosome 5, 131162604: 131162604
13 HINT1 NM_005340.6(HINT1): c.278G> A (p.Gly93Asp) single nucleotide variant Pathogenic rs397514493 GRCh37 Chromosome 5, 130495243: 130495243
14 HINT1 NM_005340.6(HINT1): c.278G> A (p.Gly93Asp) single nucleotide variant Pathogenic rs397514493 GRCh38 Chromosome 5, 131159550: 131159550
15 HINT1 NM_005340.6(HINT1): c.203A> T (p.Asp68Val) single nucleotide variant Uncertain significance rs371048016 GRCh37 Chromosome 5, 130498278: 130498278
16 HINT1 NM_005340.6(HINT1): c.203A> T (p.Asp68Val) single nucleotide variant Uncertain significance rs371048016 GRCh38 Chromosome 5, 131162585: 131162585
17 HINT1 NM_005340.6(HINT1): c.111+6_111+7insC insertion Likely benign rs770851222 GRCh38 Chromosome 5, 131165088: 131165089
18 HINT1 NM_005340.6(HINT1): c.111+6_111+7insC insertion Likely benign rs770851222 GRCh37 Chromosome 5, 130500781: 130500782
19 HINT1 NM_005340.6(HINT1): c.330C> T (p.His110=) single nucleotide variant Benign/Likely benign rs139624223 GRCh38 Chromosome 5, 131159498: 131159498
20 HINT1 NM_005340.6(HINT1): c.330C> T (p.His110=) single nucleotide variant Benign/Likely benign rs139624223 GRCh37 Chromosome 5, 130495191: 130495191
21 HINT1 NC_000005.10: g.(?_131159427)_(131165225_?)del deletion Pathogenic GRCh37 Chromosome 5, 130495120: 130500918
22 HINT1 NC_000005.10: g.(?_131159427)_(131165225_?)del deletion Pathogenic GRCh38 Chromosome 5, 131159427: 131165225
23 HINT1 NM_005340.6(HINT1): c.243C> T (p.Gly81=) single nucleotide variant Uncertain significance rs1426690264 GRCh37 Chromosome 5, 130495278: 130495278
24 HINT1 NM_005340.6(HINT1): c.243C> T (p.Gly81=) single nucleotide variant Uncertain significance rs1426690264 GRCh38 Chromosome 5, 131159585: 131159585
25 HINT1 NM_005340.6(HINT1): c.289G> A (p.Val97Met) single nucleotide variant Likely pathogenic rs1554088064 GRCh37 Chromosome 5, 130495232: 130495232
26 HINT1 NM_005340.6(HINT1): c.289G> A (p.Val97Met) single nucleotide variant Likely pathogenic rs1554088064 GRCh38 Chromosome 5, 131159539: 131159539
27 HINT1 NM_005340.6(HINT1): c.112T> C (p.Cys38Arg) single nucleotide variant Likely pathogenic rs762701283 GRCh37 Chromosome 5, 130498369: 130498369
28 HINT1 NM_005340.6(HINT1): c.112T> C (p.Cys38Arg) single nucleotide variant Likely pathogenic rs762701283 GRCh38 Chromosome 5, 131162676: 131162676
29 HINT1 NM_005340.6(HINT1): c.237T> A (p.Ile79=) single nucleotide variant Uncertain significance GRCh38 Chromosome 5, 131159591: 131159591
30 HINT1 NM_005340.6(HINT1): c.237T> A (p.Ile79=) single nucleotide variant Uncertain significance GRCh37 Chromosome 5, 130495284: 130495284
31 HINT1 NM_005340.6(HINT1): c.81A> G (p.Ile27Met) single nucleotide variant Uncertain significance GRCh37 Chromosome 5, 130500818: 130500818
32 HINT1 NM_005340.6(HINT1): c.81A> G (p.Ile27Met) single nucleotide variant Uncertain significance GRCh38 Chromosome 5, 131165125: 131165125
33 HINT1 NM_005340.6(HINT1): c.277G> T (p.Gly93Cys) single nucleotide variant Uncertain significance GRCh37 Chromosome 5, 130495244: 130495244
34 HINT1 NM_005340.6(HINT1): c.277G> T (p.Gly93Cys) single nucleotide variant Uncertain significance GRCh38 Chromosome 5, 131159551: 131159551
35 HINT1 NM_005340.6(HINT1): c.117T> C (p.Leu39=) single nucleotide variant Benign rs78949626 GRCh38 Chromosome 5, 131162671: 131162671
36 HINT1 NM_005340.6(HINT1): c.117T> C (p.Leu39=) single nucleotide variant Benign rs78949626 GRCh37 Chromosome 5, 130498364: 130498364

Expression for Neuromyotonia and Axonal Neuropathy, Autosomal Recessive

Search GEO for disease gene expression data for Neuromyotonia and Axonal Neuropathy, Autosomal Recessive.

Pathways for Neuromyotonia and Axonal Neuropathy, Autosomal Recessive

GO Terms for Neuromyotonia and Axonal Neuropathy, Autosomal Recessive

Sources for Neuromyotonia and Axonal Neuropathy, Autosomal Recessive

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