SMAX2
MCID: SPN402
MIFTS: 32

Spinal Muscular Atrophy, X-Linked 2 (SMAX2)

Categories: Bone diseases, Fetal diseases, Genetic diseases, Muscle diseases, Neuronal diseases, Rare 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 58 26 30 6
Arthrogryposis Multiplex Congenita, Distal, X-Linked 58 77 54 26 74
Smax2 58 26 60 76
Xlsma 58 26 76
Amcx1 58 26 76
Spinal Muscular Atrophy, X-Linked Lethal Infantile 58 26
Spinal Muscular Atrophy, X-Linked 2, Infantile 58 13
Spinal Muscular Atrophy, Infantile X-Linked 58 26
Amc, Distal, X-Linked 58 54
Xl-Sma 25 26
Atrophy, Muscular, Spinal, X-Linked, Type 2, Infantile 41
Spinal Muscular Atrophy, Infantile X-Linked; Xlsma 58
X-Linked Distal Arthrogryposis Multiplex Congenita 60
Arthrogryposis Multiplex Congenita Distal X-Linked 76
Spinal Muscular Atrophy X-Linked Lethal Infantile 76
Infantile-Onset X-Linked Spinal Muscular Atrophy 60
Spinal Muscular Atrophy, X-Linked Infantile 25
X-Linked Arthrogryposis Multiplex Congenita 26
Spinal Muscular Atrophy with Arthrogryposis 60
X-Linked Infantile Spinal Muscular Atrophy 26
Spinal Muscular Atrophy Infantile X-Linked 76
Arthrogryposis, X-Linked, Type I; Amcx1 58
X-Linked Spinal Muscular Atrophy Type 2 60
Spinal Muscular Atrophy X-Linked 2 76
Arthrogryposis, X-Linked, Type I 58
Arthrogryposis, X-Lined, Type I 26
X-Linked Arthrogryposis Type I 26
Arthrogryposis X-Linked Type I 76
X-Linked Lethal Infantile Sma 26
Infantile X-Linked Sma 26
Distal X-Linked Amc 26
Amc Distal X-Linked 76

Characteristics:

Orphanet epidemiological data:

60
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:

58
Inheritance:
x-linked recessive

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


HPO:

33
spinal muscular atrophy, x-linked 2:
Inheritance x-linked recessive inheritance


GeneReviews:

25
Penetrance Evidence suggests that the disorder is fully penetrant in hemizygous males...

Classifications:



Summaries for Spinal Muscular Atrophy, X-Linked 2

OMIM : 58 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 gait disturbance and joint stiffness

Genetics Home Reference : 26 X-linked infantile spinal muscular atrophy is a condition that affects only boys and is characterized by severe muscle weakness and absent reflexes (areflexia). Affected children often have multiple joint deformities (contractures) from birth that cause joint stiffness (arthrogryposis) and impair movement. In severe cases, affected infants are born with broken bones. The muscle weakness worsens over time; affected children reach some early motor developmental milestones, such as sitting unassisted, but these skills are often lost (developmental regression).

NIH Rare Diseases : 54 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.

UniProtKB/Swiss-Prot : 76 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.

Wikipedia : 77 Arthrogryposis multiplex congenita (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 10.3
2 muscular atrophy 10.3
3 alkuraya-kucinskas syndrome 10.2
4 proximal spinal muscular atrophy 10.1

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

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

60 33 (show all 46)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 gait disturbance 60 33 hallmark (90%) Very frequent (99-80%) HP:0001288
2 joint stiffness 60 33 hallmark (90%) Very frequent (99-80%) HP:0001387
3 camptodactyly of finger 60 33 hallmark (90%) Very frequent (99-80%) HP:0100490
4 short neck 60 33 frequent (33%) Frequent (79-30%) HP:0000470
5 muscular hypotonia 60 33 frequent (33%) Frequent (79-30%) HP:0001252
6 scoliosis 60 33 frequent (33%) Frequent (79-30%) HP:0002650
7 kyphosis 60 33 frequent (33%) Frequent (79-30%) HP:0002808
8 wide nasal bridge 60 33 frequent (33%) Frequent (79-30%) HP:0000431
9 short nose 60 33 frequent (33%) Frequent (79-30%) HP:0003196
10 cognitive impairment 60 33 frequent (33%) Frequent (79-30%) HP:0100543
11 long philtrum 60 33 frequent (33%) Frequent (79-30%) HP:0000343
12 micrognathia 60 33 frequent (33%) Frequent (79-30%) HP:0000347
13 narrow chest 60 33 frequent (33%) Frequent (79-30%) HP:0000774
14 dolichocephaly 60 33 frequent (33%) Frequent (79-30%) HP:0000268
15 cryptorchidism 60 33 frequent (33%) Frequent (79-30%) HP:0000028
16 failure to thrive in infancy 60 33 frequent (33%) Frequent (79-30%) HP:0001531
17 bilateral single transverse palmar creases 60 33 frequent (33%) Frequent (79-30%) HP:0007598
18 adducted thumb 60 33 frequent (33%) Frequent (79-30%) HP:0001181
19 proximal placement of thumb 60 33 frequent (33%) Frequent (79-30%) HP:0009623
20 ptosis 60 33 occasional (7.5%) Occasional (29-5%) HP:0000508
21 seizures 60 33 occasional (7.5%) Occasional (29-5%) HP:0001250
22 macrotia 60 33 occasional (7.5%) Occasional (29-5%) HP:0000400
23 strabismus 60 33 occasional (7.5%) Occasional (29-5%) HP:0000486
24 wide intermamillary distance 60 33 occasional (7.5%) Occasional (29-5%) HP:0006610
25 thickened nuchal skin fold 60 33 occasional (7.5%) Occasional (29-5%) HP:0000474
26 abnormality of the fingernails 60 33 occasional (7.5%) Occasional (29-5%) HP:0001231
27 open mouth 60 33 occasional (7.5%) Occasional (29-5%) HP:0000194
28 hypoplasia of penis 60 33 occasional (7.5%) Occasional (29-5%) HP:0008736
29 skin dimples 60 33 occasional (7.5%) Occasional (29-5%) HP:0010781
30 respiratory insufficiency 33 HP:0002093
31 facial palsy 33 HP:0010628
32 inguinal hernia 33 HP:0000023
33 myopathy 33 HP:0003198
34 abnormality of metabolism/homeostasis 33 HP:0001939
35 respiratory insufficiency due to muscle weakness 33 HP:0002747
36 arthrogryposis multiplex congenita 33 HP:0002804
37 multiple joint contractures 33 HP:0002828
38 hypospadias 33 HP:0000047
39 areflexia 33 HP:0001284
40 decreased fetal movement 33 HP:0001558
41 myopathic facies 33 HP:0002058
42 severe muscular hypotonia 33 HP:0006829
43 micropenis 33 HP:0000054
44 spinal muscular atrophy 33 HP:0007269
45 tongue fasciculations 33 HP:0001308
46 degeneration of anterior horn cells 33 HP:0002398

Symptoms via clinical synopsis from OMIM:

58
Respiratory:
respiratory insufficiency due to muscle weakness

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

Neurologic Peripheral Nervous System:
areflexia

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

Genitourinary Internal Genitalia Male:
cryptorchidism

Genitourinary External Genitalia Male:
hypospadias

Head And Neck Face:
myopathic facies
facial weakness

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

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 Spinal Muscular Atrophy, X-Linked 2 30 UBA1

Anatomical Context for Spinal Muscular Atrophy, X-Linked 2

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

42
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:

76
# 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 118)
# 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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