MCID: SPN402
MIFTS: 31

Spinal Muscular Atrophy, X-Linked 2

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

Aliases & Classifications for Spinal Muscular Atrophy, X-Linked 2

MalaCards integrated aliases for Spinal Muscular Atrophy, X-Linked 2:

Name: Spinal Muscular Atrophy, X-Linked 2 57
Arthrogryposis Multiplex Congenita, Distal, X-Linked 57 76 53 29 6 73
Smax2 57 59 75
Spinal Muscular Atrophy, X-Linked 2, Infantile 57 13
Amc, Distal, X-Linked 57 53
Xlsma 57 75
Amcx1 57 75
Atrophy, Muscular, Spinal, X-Linked, Type 2, Infantile 40
Spinal Muscular Atrophy, X-Linked Lethal Infantile 57
Spinal Muscular Atrophy, Infantile X-Linked; Xlsma 57
X-Linked Distal Arthrogryposis Multiplex Congenita 59
Arthrogryposis Multiplex Congenita Distal X-Linked 75
Spinal Muscular Atrophy X-Linked Lethal Infantile 75
Infantile-Onset X-Linked Spinal Muscular Atrophy 59
Spinal Muscular Atrophy, Infantile X-Linked 57
Spinal Muscular Atrophy, X-Linked Infantile 24
Spinal Muscular Atrophy with Arthrogryposis 59
Spinal Muscular Atrophy Infantile X-Linked 75
Arthrogryposis, X-Linked, Type I; Amcx1 57
X-Linked Spinal Muscular Atrophy Type 2 59
Spinal Muscular Atrophy X-Linked 2 75
Arthrogryposis, X-Linked, Type I 57
Arthrogryposis X-Linked Type I 75
Amc Distal X-Linked 75
Xl-Sma 24

Characteristics:

Orphanet epidemiological data:

59
infantile-onset x-linked spinal muscular atrophy
Inheritance: X-linked recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Neonatal; Age of death: adolescent,early childhood,infantile,late childhood;

OMIM:

57
Inheritance:
x-linked recessive

Miscellaneous:
death usually in infancy due to respiratory failure
increased spontaneous abortions in carrier mothers


HPO:

32
spinal muscular atrophy, x-linked 2:
Inheritance x-linked recessive inheritance


GeneReviews:

24
Penetrance Evidence suggests that the disorder is fully penetrant in hemizygous males...

Classifications:



Summaries for Spinal Muscular Atrophy, X-Linked 2

OMIM : 57 X-linked infantile spinal muscular atrophy (XL-SMA) is characterized by neonatal onset of severe hypotonia, areflexia, and multiple congenital contractures, known as arthrogryposis, associated with loss of anterior horn cells and infantile death (summary by Ramser et al., 2008). Historically, Hall et al. (1982) distinguished at least 3 clinical varieties of X-linked arthrogryposis. (1) One family had a severe lethal form with severe contractures, scoliosis, chest deformities, hypotonia, micrognathia, and death from respiratory insufficiency by age 3 months. Apparently progressive loss of anterior horn cells was the cause. (2) Two families had moderately severe AMC associated with ptosis, microphallus, cryptorchidism, inguinal hernias, and normal intelligence. Nonprogressive intrauterine myopathy appeared to be the 'cause'. (3) In 2 families and a sporadic case, the disorder took the form of a resolving AMC, with mild to moderate contractures improving dramatically with time, normal intelligence, and no other anomalies; tight connective tissues on misplaced tendons was postulated. (301830)

MalaCards based summary : Spinal Muscular Atrophy, X-Linked 2, also known as arthrogryposis multiplex congenita, distal, x-linked, is related to spinal muscular atrophy and muscular atrophy, and has symptoms including facial paresis An important gene associated with Spinal Muscular Atrophy, X-Linked 2 is UBA1 (Ubiquitin Like Modifier Activating Enzyme 1). Affiliated tissues include bone, spinal cord and skin, and related phenotypes are cryptorchidism and open mouth

UniProtKB/Swiss-Prot : 75 Spinal muscular atrophy X-linked 2: A lethal infantile form of spinal muscular atrophy, a neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. Clinical features include hypotonia, areflexia, and multiple congenital contractures.

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 1145Disease definitionX-linked distal arthrogryposis multiplex congenital (SMAX2) is a rare form of spinal muscular atrophy characterized by the neonatal onset of severe hypotonia, areflexia, profound weakness, multiple congenital contractures, facial dysmorphic features (myopathic face with open, tent-shaped mouth), cryptorchidism, and mild skeletal abnormalities (i.e. kyphosis, scoliosis), that is often preceded by polyhydramnios and reduced fetal movements in utero and followed by bone fractures shortly after birth. SMAX2 patients often have a limited life span, often succumbing to the disease within 2 years, as muscle weakness is progressive and chest muscle involvement eventually leads to ventilatory insufficiency and respiratory failure.Visit the Orphanet disease page for more resources.

Wikipedia : 76 Arthrogryposis multiplex congenital (AMC), or simply arthrogryposis, describes congenital joint... more...

GeneReviews: NBK2594

Related Diseases for Spinal Muscular Atrophy, X-Linked 2

Diseases related to Spinal Muscular Atrophy, X-Linked 2 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 spinal muscular atrophy 9.9
2 muscular atrophy 9.9

Symptoms & Phenotypes for Spinal Muscular Atrophy, X-Linked 2

Symptoms via clinical synopsis from OMIM:

57
Respiratory:
respiratory insufficiency due to muscle weakness

Genitourinary External Genitalia Male:
hypospadias

Head And Neck Face:
myopathic facies
facial weakness

Head And Neck Mouth:
tongue fasciculations

Muscle Soft Tissue:
hypotonia, severe
muscle biopsy shows neurogenic atrophy affecting both fibers types
denervation of skeletal muscles

Chest External Features:
chest deformities

Skeletal Skull:
dysmorphic skull

GenitourinaryInternal GenitaliaMale:
cryptorchidism

Neurologic Peripheral Nervous System:
areflexia

Skeletal:
multiple joint contractures
arthrogryposis
bone fractures (at birth and postnatal)

Skeletal Hands:
digital contractures

Neurologic Central Nervous System:
hypotonia, severe
loss of anterior horn cells

Prenatal Manifestations Movement:
decreased fetal movements


Clinical features from OMIM:

301830

Human phenotypes related to Spinal Muscular Atrophy, X-Linked 2:

59 32 (show all 46)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 cryptorchidism 59 32 frequent (33%) Frequent (79-30%) HP:0000028
2 open mouth 59 32 occasional (7.5%) Occasional (29-5%) HP:0000194
3 dolichocephaly 59 32 frequent (33%) Frequent (79-30%) HP:0000268
4 long philtrum 59 32 frequent (33%) Frequent (79-30%) HP:0000343
5 micrognathia 59 32 frequent (33%) Frequent (79-30%) HP:0000347
6 macrotia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000400
7 wide nasal bridge 59 32 frequent (33%) Frequent (79-30%) HP:0000431
8 short neck 59 32 frequent (33%) Frequent (79-30%) HP:0000470
9 thickened nuchal skin fold 59 32 occasional (7.5%) Occasional (29-5%) HP:0000474
10 strabismus 59 32 occasional (7.5%) Occasional (29-5%) HP:0000486
11 ptosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0000508
12 narrow chest 59 32 frequent (33%) Frequent (79-30%) HP:0000774
13 adducted thumb 59 32 frequent (33%) Frequent (79-30%) HP:0001181
14 abnormality of the fingernails 59 32 occasional (7.5%) Occasional (29-5%) HP:0001231
15 seizures 59 32 occasional (7.5%) Occasional (29-5%) HP:0001250
16 muscular hypotonia 59 32 frequent (33%) Frequent (79-30%) HP:0001252
17 gait disturbance 59 32 hallmark (90%) Very frequent (99-80%) HP:0001288
18 joint stiffness 59 32 hallmark (90%) Very frequent (99-80%) HP:0001387
19 failure to thrive in infancy 59 32 frequent (33%) Frequent (79-30%) HP:0001531
20 scoliosis 59 32 frequent (33%) Frequent (79-30%) HP:0002650
21 kyphosis 59 32 frequent (33%) Frequent (79-30%) HP:0002808
22 short nose 59 32 frequent (33%) Frequent (79-30%) HP:0003196
23 wide intermamillary distance 59 32 occasional (7.5%) Occasional (29-5%) HP:0006610
24 bilateral single transverse palmar creases 59 32 frequent (33%) Frequent (79-30%) HP:0007598
25 hypoplasia of penis 59 32 occasional (7.5%) Occasional (29-5%) HP:0008736
26 proximal placement of thumb 59 32 frequent (33%) Frequent (79-30%) HP:0009623
27 skin dimples 59 32 occasional (7.5%) Occasional (29-5%) HP:0010781
28 camptodactyly of finger 59 32 hallmark (90%) Very frequent (99-80%) HP:0100490
29 cognitive impairment 59 32 frequent (33%) Frequent (79-30%) HP:0100543
30 inguinal hernia 32 HP:0000023
31 hypospadias 32 HP:0000047
32 micropenis 32 HP:0000054
33 areflexia 32 HP:0001284
34 tongue fasciculations 32 HP:0001308
35 decreased fetal movement 32 HP:0001558
36 abnormality of metabolism/homeostasis 32 HP:0001939
37 myopathic facies 32 HP:0002058
38 respiratory insufficiency 32 HP:0002093
39 degeneration of anterior horn cells 32 HP:0002398
40 respiratory insufficiency due to muscle weakness 32 HP:0002747
41 arthrogryposis multiplex congenita 32 HP:0002804
42 multiple joint contractures 32 HP:0002828
43 myopathy 32 HP:0003198
44 severe muscular hypotonia 32 HP:0006829
45 spinal muscular atrophy 32 HP:0007269
46 facial palsy 32 HP:0010628

UMLS symptoms related to Spinal Muscular Atrophy, X-Linked 2:


facial paresis

Drugs & Therapeutics for Spinal Muscular Atrophy, X-Linked 2

Search Clinical Trials , NIH Clinical Center for Spinal Muscular Atrophy, X-Linked 2

Genetic Tests for Spinal Muscular Atrophy, X-Linked 2

Genetic tests related to Spinal Muscular Atrophy, X-Linked 2:

# Genetic test Affiliating Genes
1 Arthrogryposis Multiplex Congenita, Distal, X-Linked 29 UBA1

Anatomical Context for Spinal Muscular Atrophy, X-Linked 2

MalaCards organs/tissues related to Spinal Muscular Atrophy, X-Linked 2:

41
Bone, Spinal Cord, Skin, Tongue, Skeletal Muscle

Publications for Spinal Muscular Atrophy, X-Linked 2

Articles related to Spinal Muscular Atrophy, X-Linked 2:

# Title Authors Year
1
Spinal Muscular Atrophy, X-Linked Infantile ( 20301739 )
1993

Variations for Spinal Muscular Atrophy, X-Linked 2

UniProtKB/Swiss-Prot genetic disease variations for Spinal Muscular Atrophy, X-Linked 2:

75
# Symbol AA change Variation ID SNP ID
1 UBA1 p.Met539Ile VAR_043501 rs80356545
2 UBA1 p.Ser547Gly VAR_043502 rs80356546
3 UBA1 p.Glu557Val VAR_071121

ClinVar genetic disease variations for Spinal Muscular Atrophy, X-Linked 2:

6
(show top 50) (show all 102)
# Gene Variation Type Significance SNP ID Assembly Location
1 UBA1 NM_003334.3(UBA1): c.1617G> T (p.Met539Ile) single nucleotide variant Pathogenic rs80356545 GRCh37 Chromosome X, 47065388: 47065388
2 UBA1 NM_003334.3(UBA1): c.1617G> T (p.Met539Ile) single nucleotide variant Pathogenic rs80356545 GRCh38 Chromosome X, 47205989: 47205989
3 UBA1 NM_003334.3(UBA1): c.1639A> G (p.Ser547Gly) single nucleotide variant Pathogenic rs80356546 GRCh37 Chromosome X, 47065410: 47065410
4 UBA1 NM_003334.3(UBA1): c.1639A> G (p.Ser547Gly) single nucleotide variant Pathogenic rs80356546 GRCh38 Chromosome X, 47206011: 47206011
5 UBA1 NM_003334.3(UBA1): c.1731C> T (p.Asn577=) single nucleotide variant Pathogenic rs80356547 GRCh37 Chromosome X, 47065502: 47065502
6 UBA1 NM_003334.3(UBA1): c.1731C> T (p.Asn577=) single nucleotide variant Pathogenic rs80356547 GRCh38 Chromosome X, 47206103: 47206103
7 UBA1 NM_003334.3(UBA1): c.1296C> T (p.Leu432=) single nucleotide variant Benign/Likely benign rs147825775 GRCh38 Chromosome X, 47203005: 47203005
8 UBA1 NM_003334.3(UBA1): c.1296C> T (p.Leu432=) single nucleotide variant Benign/Likely benign rs147825775 GRCh37 Chromosome X, 47062404: 47062404
9 UBA1 NM_003334.3(UBA1): c.1543C> A (p.Arg515=) single nucleotide variant Uncertain significance rs150198324 GRCh38 Chromosome X, 47203664: 47203664
10 UBA1 NM_003334.3(UBA1): c.1543C> A (p.Arg515=) single nucleotide variant Uncertain significance rs150198324 GRCh37 Chromosome X, 47063063: 47063063
11 UBA1 NM_003334.3(UBA1): c.1742-11G> C single nucleotide variant Benign rs5953010 GRCh38 Chromosome X, 47206237: 47206237
12 UBA1 NM_003334.3(UBA1): c.1742-11G> C single nucleotide variant Benign rs5953010 GRCh37 Chromosome X, 47065636: 47065636
13 UBA1 NM_003334.3(UBA1): c.2838+8C> T single nucleotide variant Uncertain significance rs782075261 GRCh37 Chromosome X, 47072588: 47072588
14 UBA1 NM_003334.3(UBA1): c.2838+8C> T single nucleotide variant Uncertain significance rs782075261 GRCh38 Chromosome X, 47213189: 47213189
15 UBA1 NM_003334.3(UBA1): c.2839-7C> T single nucleotide variant Uncertain significance rs199797125 GRCh37 Chromosome X, 47073719: 47073719
16 UBA1 NM_003334.3(UBA1): c.2839-7C> T single nucleotide variant Uncertain significance rs199797125 GRCh38 Chromosome X, 47214320: 47214320
17 UBA1 NM_003334.3(UBA1): c.1137C> T (p.Asp379=) single nucleotide variant Benign/Likely benign rs143935711 GRCh38 Chromosome X, 47202718: 47202718
18 UBA1 NM_003334.3(UBA1): c.1137C> T (p.Asp379=) single nucleotide variant Benign/Likely benign rs143935711 GRCh37 Chromosome X, 47062117: 47062117
19 UBA1 NM_003334.3(UBA1): c.1242C> T (p.Ser414=) single nucleotide variant Benign/Likely benign rs369843264 GRCh38 Chromosome X, 47202951: 47202951
20 UBA1 NM_003334.3(UBA1): c.1242C> T (p.Ser414=) single nucleotide variant Benign/Likely benign rs369843264 GRCh37 Chromosome X, 47062350: 47062350
21 UBA1 NM_003334.3(UBA1): c.1340G> A (p.Arg447His) single nucleotide variant Benign rs2070169 GRCh38 Chromosome X, 47203135: 47203135
22 UBA1 NM_003334.3(UBA1): c.1340G> A (p.Arg447His) single nucleotide variant Benign rs2070169 GRCh37 Chromosome X, 47062534: 47062534
23 UBA1 NM_003334.3(UBA1): c.1486G> A (p.Glu496Lys) single nucleotide variant Conflicting interpretations of pathogenicity rs140950898 GRCh38 Chromosome X, 47203607: 47203607
24 UBA1 NM_003334.3(UBA1): c.1486G> A (p.Glu496Lys) single nucleotide variant Conflicting interpretations of pathogenicity rs140950898 GRCh37 Chromosome X, 47063006: 47063006
25 UBA1 NM_003334.3(UBA1): c.1702C> G (p.Leu568Val) single nucleotide variant Benign rs150574055 GRCh38 Chromosome X, 47206074: 47206074
26 UBA1 NM_003334.3(UBA1): c.1702C> G (p.Leu568Val) single nucleotide variant Benign rs150574055 GRCh37 Chromosome X, 47065473: 47065473
27 UBA1 NM_003334.3(UBA1): c.2004-13C> T single nucleotide variant Likely benign rs201794720 GRCh38 Chromosome X, 47209915: 47209915
28 UBA1 NM_003334.3(UBA1): c.2004-13C> T single nucleotide variant Likely benign rs201794720 GRCh37 Chromosome X, 47069314: 47069314
29 UBA1 NM_003334.3(UBA1): c.2220G> A (p.Pro740=) single nucleotide variant Benign rs2230147 GRCh38 Chromosome X, 47210862: 47210862
30 UBA1 NM_003334.3(UBA1): c.2220G> A (p.Pro740=) single nucleotide variant Benign rs2230147 GRCh37 Chromosome X, 47070261: 47070261
31 UBA1 NM_003334.3(UBA1): c.2308A> C (p.Asn770His) single nucleotide variant Benign/Likely benign rs143044923 GRCh37 Chromosome X, 47070468: 47070468
32 UBA1 NM_003334.3(UBA1): c.2308A> C (p.Asn770His) single nucleotide variant Benign/Likely benign rs143044923 GRCh38 Chromosome X, 47211069: 47211069
33 UBA1 NM_003334.3(UBA1): c.2838+7delG deletion Uncertain significance rs1057515899 GRCh37 Chromosome X, 47072587: 47072587
34 UBA1 NM_003334.3(UBA1): c.2838+7delG deletion Uncertain significance rs1057515899 GRCh38 Chromosome X, 47213188: 47213188
35 UBA1 NM_003334.3(UBA1): c.-178G> A single nucleotide variant Uncertain significance rs1057515898 GRCh38 Chromosome X, 47193847: 47193847
36 UBA1 NM_003334.3(UBA1): c.-178G> A single nucleotide variant Uncertain significance rs1057515898 GRCh37 Chromosome X, 47053246: 47053246
37 UBA1 NM_003334.3(UBA1): c.351C> T (p.Tyr117=) single nucleotide variant Likely benign rs782799228 GRCh38 Chromosome X, 47199485: 47199485
38 UBA1 NM_003334.3(UBA1): c.351C> T (p.Tyr117=) single nucleotide variant Likely benign rs782799228 GRCh37 Chromosome X, 47058884: 47058884
39 UBA1 NM_003334.3(UBA1): c.430G> A (p.Val144Ile) single nucleotide variant Likely benign rs781887272 GRCh38 Chromosome X, 47199564: 47199564
40 UBA1 NM_003334.3(UBA1): c.430G> A (p.Val144Ile) single nucleotide variant Likely benign rs781887272 GRCh37 Chromosome X, 47058963: 47058963
41 UBA1 NM_003334.3(UBA1): c.811+9C> G single nucleotide variant Benign rs4239964 GRCh38 Chromosome X, 47201619: 47201619
42 UBA1 NM_003334.3(UBA1): c.811+9C> G single nucleotide variant Benign rs4239964 GRCh37 Chromosome X, 47061018: 47061018
43 UBA1 NM_003334.3(UBA1): c.2928C> T (p.Leu976=) single nucleotide variant Likely benign rs782070102 GRCh37 Chromosome X, 47073815: 47073815
44 UBA1 NM_003334.3(UBA1): c.2928C> T (p.Leu976=) single nucleotide variant Likely benign rs782070102 GRCh38 Chromosome X, 47214416: 47214416
45 UBA1 NM_003334.3(UBA1): c.*123C> T single nucleotide variant Uncertain significance rs1057515900 GRCh37 Chromosome X, 47074451: 47074451
46 UBA1 NM_003334.3(UBA1): c.*123C> T single nucleotide variant Uncertain significance rs1057515900 GRCh38 Chromosome X, 47215052: 47215052
47 UBA1 NM_003334.3(UBA1): c.720C> T (p.His240=) single nucleotide variant Likely benign rs193168226 GRCh38 Chromosome X, 47201519: 47201519
48 UBA1 NM_003334.3(UBA1): c.720C> T (p.His240=) single nucleotide variant Likely benign rs193168226 GRCh37 Chromosome X, 47060918: 47060918
49 UBA1 NM_003334.3(UBA1): c.909+12G> A single nucleotide variant Likely benign rs367556596 GRCh38 Chromosome X, 47202265: 47202265
50 UBA1 NM_003334.3(UBA1): c.909+12G> A single nucleotide variant Likely benign rs367556596 GRCh37 Chromosome X, 47061664: 47061664

Expression for Spinal Muscular Atrophy, X-Linked 2

Search GEO for disease gene expression data for Spinal Muscular Atrophy, X-Linked 2.

Pathways for Spinal Muscular Atrophy, X-Linked 2

GO Terms for Spinal Muscular Atrophy, X-Linked 2

Sources for Spinal Muscular Atrophy, X-Linked 2

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