MCID: SPN191
MIFTS: 25

Spinal Muscular Atrophy, Distal, Autosomal Recessive, 4

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

Aliases & Classifications for Spinal Muscular Atrophy, Distal, Autosomal Recessive, 4

MalaCards integrated aliases for Spinal Muscular Atrophy, Distal, Autosomal Recessive, 4:

Name: Spinal Muscular Atrophy, Distal, Autosomal Recessive, 4 57 13 73
Dsma4 57 59 75
Distal Spinal Muscular Atrophy, Autosomal Recessive 4 29 6
Autosomal Recessive Lower Motor Neuron Disease with Childhood Onset 59
Atrophy, Muscular, Spinal, Distal, Autosomal Recessive, Type 4 40
Autosomal Recessive Distal Spinal Muscular Atrophy Type 4 59
Distal Spinal Muscular Atrophy, Autosomal Recessive, 4 75
Distal Spinal Muscular Atrophy Type 4 59

Characteristics:

Orphanet epidemiological data:

59
autosomal recessive lower motor neuron disease with childhood onset
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
rapidly progressive
onset in early childhood
patients may become ventilator-dependent


HPO:

32
spinal muscular atrophy, distal, autosomal recessive, 4:
Onset and clinical course rapidly progressive childhood onset
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 59  
Rare neurological diseases


External Ids:

OMIM 57 611067
Orphanet 59 ORPHA206580
ICD10 via Orphanet 34 G12.2
UMLS via Orphanet 74 C1970211
MedGen 42 C1970211
MeSH 44 D009134
UMLS 73 C1970211

Summaries for Spinal Muscular Atrophy, Distal, Autosomal Recessive, 4

UniProtKB/Swiss-Prot : 75 Distal spinal muscular atrophy, autosomal recessive, 4: A neuromuscular disorder. Distal spinal muscular atrophy, also known as distal hereditary motor neuronopathy, represents a heterogeneous group of neuromuscular disorders caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs. DSMA4 is characterized by childhood onset, generalized muscle weakness and atrophy with denervation and normal sensation. Bulbar symptoms and pyramidal signs are absent.

MalaCards based summary : Spinal Muscular Atrophy, Distal, Autosomal Recessive, 4, also known as dsma4, is related to motor neuron disease and neuronitis, and has symptoms including waddling gait An important gene associated with Spinal Muscular Atrophy, Distal, Autosomal Recessive, 4 is PLEKHG5 (Pleckstrin Homology And RhoGEF Domain Containing G5). Affiliated tissues include spinal cord, and related phenotypes are areflexia and talipes equinovarus

Description from OMIM: 611067

Related Diseases for Spinal Muscular Atrophy, Distal, Autosomal Recessive, 4

Diseases in the Spinal Muscular Atrophy, Distal, Autosomal Recessive, 1 family:

Spinal Muscular Atrophy, Distal, Autosomal Recessive, 2 Spinal Muscular Atrophy, Distal, Autosomal Recessive, 3
Spinal Muscular Atrophy, Distal, Autosomal Recessive, 4 Spinal Muscular Atrophy, Distal, Autosomal Recessive, 5

Diseases related to Spinal Muscular Atrophy, Distal, Autosomal Recessive, 4 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 motor neuron disease 10.2
2 neuronitis 10.2

Symptoms & Phenotypes for Spinal Muscular Atrophy, Distal, Autosomal Recessive, 4

Symptoms via clinical synopsis from OMIM:

57
Skeletal Spine:
scoliosis
hyperlordosis

Neurologic Peripheral Nervous System:
areflexia
normal sensation
sural nerve biopsy shows normal findings

Respiratory:
decreased respiratory function due to muscle weakness

Muscle Soft Tissue:
distal muscle atrophy due to denervation
scapuloperoneal muscular atrophy due to denervation

Skeletal Feet:
talipes equinovarus

Neurologic Central Nervous System:
proximal muscle weakness
waddling gait
normal mental development
lower motor neuron disease
distal muscle weakness and atrophy due to motor neuronopathy
more
Skeletal Hands:
contractures, hand and finger muscles


Clinical features from OMIM:

611067

Human phenotypes related to Spinal Muscular Atrophy, Distal, Autosomal Recessive, 4:

32 (show all 16)
# Description HPO Frequency HPO Source Accession
1 areflexia 32 HP:0001284
2 talipes equinovarus 32 HP:0001762
3 difficulty walking 32 HP:0002355
4 abnormal lower motor neuron morphology 32 HP:0002366
5 distal muscle weakness 32 HP:0002460
6 waddling gait 32 HP:0002515
7 scoliosis 32 HP:0002650
8 respiratory insufficiency due to muscle weakness 32 HP:0002747
9 hyperlordosis 32 HP:0003307
10 emg 32 HP:0003445
11 difficulty climbing stairs 32 HP:0003551
12 distal amyotrophy 32 HP:0003693
13 scapuloperoneal amyotrophy 32 HP:0003697
14 proximal muscle weakness 32 HP:0003701
15 spinal muscular atrophy 32 HP:0007269
16 joint contracture of the hand 32 HP:0009473

UMLS symptoms related to Spinal Muscular Atrophy, Distal, Autosomal Recessive, 4:


waddling gait

Drugs & Therapeutics for Spinal Muscular Atrophy, Distal, Autosomal Recessive, 4

Search Clinical Trials , NIH Clinical Center for Spinal Muscular Atrophy, Distal, Autosomal Recessive, 4

Genetic Tests for Spinal Muscular Atrophy, Distal, Autosomal Recessive, 4

Genetic tests related to Spinal Muscular Atrophy, Distal, Autosomal Recessive, 4:

# Genetic test Affiliating Genes
1 Distal Spinal Muscular Atrophy, Autosomal Recessive 4 29 PLEKHG5

Anatomical Context for Spinal Muscular Atrophy, Distal, Autosomal Recessive, 4

MalaCards organs/tissues related to Spinal Muscular Atrophy, Distal, Autosomal Recessive, 4:

41
Spinal Cord

Publications for Spinal Muscular Atrophy, Distal, Autosomal Recessive, 4

Articles related to Spinal Muscular Atrophy, Distal, Autosomal Recessive, 4:

# Title Authors Year
1
The nuclear factor kappaB-activator gene PLEKHG5 is mutated in a form of autosomal recessive lower motor neuron disease with childhood onset. ( 17564964 )
2007
2
A gene for an autosomal recessive lower motor neuron disease with childhood onset maps to 1p36. ( 16728649 )
2006

Variations for Spinal Muscular Atrophy, Distal, Autosomal Recessive, 4

UniProtKB/Swiss-Prot genetic disease variations for Spinal Muscular Atrophy, Distal, Autosomal Recessive, 4:

75
# Symbol AA change Variation ID SNP ID
1 PLEKHG5 p.Phe703Ser VAR_035357 rs63750315

ClinVar genetic disease variations for Spinal Muscular Atrophy, Distal, Autosomal Recessive, 4:

6
(show top 50) (show all 244)
# Gene Variation Type Significance SNP ID Assembly Location
1 PLEKHG5 NM_020631.4(PLEKHG5): c.1940T> C (p.Phe647Ser) single nucleotide variant Pathogenic rs63750315 GRCh37 Chromosome 1, 6529504: 6529504
2 PLEKHG5 NM_020631.4(PLEKHG5): c.1940T> C (p.Phe647Ser) single nucleotide variant Pathogenic rs63750315 GRCh38 Chromosome 1, 6469444: 6469444
3 PLEKHG5 NM_020631.4(PLEKHG5): c.1616C> T (p.Ala539Val) single nucleotide variant Uncertain significance rs370515061 GRCh37 Chromosome 1, 6530630: 6530630
4 PLEKHG5 NM_020631.4(PLEKHG5): c.1616C> T (p.Ala539Val) single nucleotide variant Uncertain significance rs370515061 GRCh38 Chromosome 1, 6470570: 6470570
5 PLEKHG5 NM_020631.4(PLEKHG5): c.1729G> A (p.Ala577Thr) single nucleotide variant Uncertain significance rs143545780 GRCh37 Chromosome 1, 6530367: 6530367
6 PLEKHG5 NM_020631.4(PLEKHG5): c.1729G> A (p.Ala577Thr) single nucleotide variant Uncertain significance rs143545780 GRCh38 Chromosome 1, 6470307: 6470307
7 PLEKHG5 NM_020631.4(PLEKHG5): c.1932T> C (p.Pro644=) single nucleotide variant Conflicting interpretations of pathogenicity rs150807400 GRCh37 Chromosome 1, 6529605: 6529605
8 PLEKHG5 NM_020631.4(PLEKHG5): c.1932T> C (p.Pro644=) single nucleotide variant Conflicting interpretations of pathogenicity rs150807400 GRCh38 Chromosome 1, 6469545: 6469545
9 PLEKHG5 NM_020631.4(PLEKHG5): c.2163_2168delGGAGGA (p.Glu722_Glu723del) deletion Benign rs748573566 GRCh37 Chromosome 1, 6529183: 6529188
10 PLEKHG5 NM_020631.4(PLEKHG5): c.2163_2168delGGAGGA (p.Glu722_Glu723del) deletion Benign rs748573566 GRCh38 Chromosome 1, 6469123: 6469128
11 PLEKHG5 NM_020631.4(PLEKHG5): c.2564C> T (p.Ser855Leu) single nucleotide variant Uncertain significance rs768995193 GRCh37 Chromosome 1, 6528332: 6528332
12 PLEKHG5 NM_020631.4(PLEKHG5): c.2564C> T (p.Ser855Leu) single nucleotide variant Uncertain significance rs768995193 GRCh38 Chromosome 1, 6468272: 6468272
13 PLEKHG5 NM_020631.4(PLEKHG5): c.73C> T (p.Arg25Trp) single nucleotide variant Uncertain significance rs377503203 GRCh37 Chromosome 1, 6536067: 6536067
14 PLEKHG5 NM_020631.4(PLEKHG5): c.73C> T (p.Arg25Trp) single nucleotide variant Uncertain significance rs377503203 GRCh38 Chromosome 1, 6476007: 6476007
15 PLEKHG5 NM_020631.4(PLEKHG5): c.518G> A (p.Arg173Gln) single nucleotide variant Uncertain significance rs142378760 GRCh37 Chromosome 1, 6534146: 6534146
16 PLEKHG5 NM_020631.4(PLEKHG5): c.518G> A (p.Arg173Gln) single nucleotide variant Uncertain significance rs142378760 GRCh38 Chromosome 1, 6474086: 6474086
17 PLEKHG5 NM_020631.4(PLEKHG5): c.719A> G (p.Asp240Gly) single nucleotide variant Uncertain significance rs199794578 GRCh37 Chromosome 1, 6533387: 6533387
18 PLEKHG5 NM_020631.4(PLEKHG5): c.719A> G (p.Asp240Gly) single nucleotide variant Uncertain significance rs199794578 GRCh38 Chromosome 1, 6473327: 6473327
19 PLEKHG5 NM_020631.4(PLEKHG5): c.691G> A (p.Gly231Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs146651455 GRCh37 Chromosome 1, 6533415: 6533415
20 PLEKHG5 NM_020631.4(PLEKHG5): c.691G> A (p.Gly231Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs146651455 GRCh38 Chromosome 1, 6473355: 6473355
21 PLEKHG5 NM_020631.4(PLEKHG5): c.2458G> A (p.Gly820Ser) single nucleotide variant Benign/Likely benign rs202191898 GRCh38 Chromosome 1, 6468378: 6468378
22 PLEKHG5 NM_020631.4(PLEKHG5): c.2458G> A (p.Gly820Ser) single nucleotide variant Benign/Likely benign rs202191898 GRCh37 Chromosome 1, 6528438: 6528438
23 PLEKHG5 NM_020631.4(PLEKHG5): c.2594A> G (p.Gln865Arg) single nucleotide variant Benign/Likely benign rs3007419 GRCh37 Chromosome 1, 6528302: 6528302
24 PLEKHG5 NM_020631.4(PLEKHG5): c.2594A> G (p.Gln865Arg) single nucleotide variant Benign/Likely benign rs3007419 GRCh38 Chromosome 1, 6468242: 6468242
25 PLEKHG5 NM_020631.4(PLEKHG5): c.2525G> A (p.Arg842Gln) single nucleotide variant Uncertain significance rs149682441 GRCh37 Chromosome 1, 6528371: 6528371
26 PLEKHG5 NM_020631.4(PLEKHG5): c.2525G> A (p.Arg842Gln) single nucleotide variant Uncertain significance rs149682441 GRCh38 Chromosome 1, 6468311: 6468311
27 PLEKHG5 NM_020631.4(PLEKHG5): c.1738G> A (p.Glu580Lys) single nucleotide variant Uncertain significance rs760122001 GRCh37 Chromosome 1, 6530358: 6530358
28 PLEKHG5 NM_020631.4(PLEKHG5): c.1738G> A (p.Glu580Lys) single nucleotide variant Uncertain significance rs760122001 GRCh38 Chromosome 1, 6470298: 6470298
29 PLEKHG5 NM_020631.4(PLEKHG5): c.1507G> C (p.Glu503Gln) single nucleotide variant Uncertain significance rs868161574 GRCh38 Chromosome 1, 6470770: 6470770
30 PLEKHG5 NM_020631.4(PLEKHG5): c.1507G> C (p.Glu503Gln) single nucleotide variant Uncertain significance rs868161574 GRCh37 Chromosome 1, 6530830: 6530830
31 PLEKHG5 NM_020631.4(PLEKHG5): c.994C> T (p.Arg332Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs140202670 GRCh37 Chromosome 1, 6532673: 6532673
32 PLEKHG5 NM_020631.4(PLEKHG5): c.994C> T (p.Arg332Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs140202670 GRCh38 Chromosome 1, 6472613: 6472613
33 PLEKHG5 NM_020631.4(PLEKHG5): c.638C> T (p.Ala213Val) single nucleotide variant Uncertain significance rs367543633 GRCh37 Chromosome 1, 6533468: 6533468
34 PLEKHG5 NM_020631.4(PLEKHG5): c.638C> T (p.Ala213Val) single nucleotide variant Uncertain significance rs367543633 GRCh38 Chromosome 1, 6473408: 6473408
35 PLEKHG5 NM_020631.4(PLEKHG5): c.482T> C (p.Met161Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs140817021 GRCh37 Chromosome 1, 6534182: 6534182
36 PLEKHG5 NM_020631.4(PLEKHG5): c.482T> C (p.Met161Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs140817021 GRCh38 Chromosome 1, 6474122: 6474122
37 PLEKHG5 NM_020631.4(PLEKHG5): c.307G> A (p.Val103Met) single nucleotide variant Conflicting interpretations of pathogenicity rs141032388 GRCh37 Chromosome 1, 6534643: 6534643
38 PLEKHG5 NM_020631.4(PLEKHG5): c.307G> A (p.Val103Met) single nucleotide variant Conflicting interpretations of pathogenicity rs141032388 GRCh38 Chromosome 1, 6474583: 6474583
39 PLEKHG5 NM_020631.4(PLEKHG5): c.274G> A (p.Val92Ile) single nucleotide variant Uncertain significance rs371516662 GRCh38 Chromosome 1, 6475075: 6475075
40 PLEKHG5 NM_020631.4(PLEKHG5): c.274G> A (p.Val92Ile) single nucleotide variant Uncertain significance rs371516662 GRCh37 Chromosome 1, 6535135: 6535135
41 PLEKHG5 NM_020631.4(PLEKHG5): c.88C> T (p.Arg30Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs111400494 GRCh37 Chromosome 1, 6536052: 6536052
42 PLEKHG5 NM_020631.4(PLEKHG5): c.88C> T (p.Arg30Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs111400494 GRCh38 Chromosome 1, 6475992: 6475992
43 PLEKHG5 NM_020631.4(PLEKHG5): c.83C> T (p.Pro28Leu) single nucleotide variant Uncertain significance rs143585428 GRCh38 Chromosome 1, 6475997: 6475997
44 PLEKHG5 NM_020631.4(PLEKHG5): c.83C> T (p.Pro28Leu) single nucleotide variant Uncertain significance rs143585428 GRCh37 Chromosome 1, 6536057: 6536057
45 PLEKHG5 NM_020631.4(PLEKHG5): c.34C> A (p.Pro12Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs140687324 GRCh38 Chromosome 1, 6477538: 6477538
46 PLEKHG5 NM_020631.4(PLEKHG5): c.34C> A (p.Pro12Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs140687324 GRCh37 Chromosome 1, 6537598: 6537598
47 PLEKHG5 NM_020631.4(PLEKHG5): c.64G> A (p.Val22Met) single nucleotide variant Likely benign rs112530241 GRCh37 Chromosome 1, 6536076: 6536076
48 PLEKHG5 NM_020631.4(PLEKHG5): c.64G> A (p.Val22Met) single nucleotide variant Likely benign rs112530241 GRCh38 Chromosome 1, 6476016: 6476016
49 PLEKHG5 NM_020631.4(PLEKHG5): c.1254C> G (p.Pro418=) single nucleotide variant Conflicting interpretations of pathogenicity rs139904931 GRCh37 Chromosome 1, 6531575: 6531575
50 PLEKHG5 NM_020631.4(PLEKHG5): c.1254C> G (p.Pro418=) single nucleotide variant Conflicting interpretations of pathogenicity rs139904931 GRCh38 Chromosome 1, 6471515: 6471515

Expression for Spinal Muscular Atrophy, Distal, Autosomal Recessive, 4

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Pathways for Spinal Muscular Atrophy, Distal, Autosomal Recessive, 4

GO Terms for Spinal Muscular Atrophy, Distal, Autosomal Recessive, 4

Sources for Spinal Muscular Atrophy, Distal, Autosomal Recessive, 4

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