MCID: SPN205
MIFTS: 32

Spinal Muscular Atrophy, X-Linked 2, Infantile

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

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

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

Name: Spinal Muscular Atrophy, X-Linked 2, Infantile 54 13
Arthrogryposis Multiplex Congenita, Distal, X-Linked 50 29 69
Spinal Muscular Atrophy, X-Linked Infantile 23 24
Xl-Sma 23 24
Smax2 56 71
X-Linked Distal Arthrogryposis Multiplex Congenita 56
Arthrogryposis Multiplex Congenita Distal X-Linked 71
Spinal Muscular Atrophy X-Linked Lethal Infantile 71
Infantile-Onset X-Linked Spinal Muscular Atrophy 56
Spinal Muscular Atrophy with Arthrogryposis 56
Spinal Muscular Atrophy Infantile X-Linked 71
X-Linked Spinal Muscular Atrophy Type 2 56
Spinal Muscular Atrophy X-Linked 2 71
Arthrogryposis X-Linked Type I 71
Amc, Distal, X-Linked 50
Amc Distal X-Linked 71
Amcx1 71
Xlsma 71

Characteristics:

Orphanet epidemiological data:

56
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:

54
Miscellaneous:
death usually in infancy due to respiratory failure
increased spontaneous abortions in carrier mothers

Inheritance:
x-linked recessive


HPO:

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


GeneReviews:

23
Penetrance Evidence suggests that the disorder is fully penetrant in hemizygous males...

Classifications:



Summaries for Spinal Muscular Atrophy, X-Linked 2, Infantile

OMIM : 54
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, Infantile, also known as arthrogryposis multiplex congenita, distal, x-linked, is related to spinal muscular atrophy and muscular atrophy, and has symptoms including scoliosis, strabismus and cognitive impairment. An important gene associated with Spinal Muscular Atrophy, X-Linked 2, Infantile is UBA1 (Ubiquitin Like Modifier Activating Enzyme 1). Affiliated tissues include bone, spinal cord and skin.

NIH Rare Diseases : 50 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. last updated: 9/29/2015

UniProtKB/Swiss-Prot : 71 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.

GeneReviews: NBK2594

Related Diseases for Spinal Muscular Atrophy, X-Linked 2, Infantile

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

id Related Disease Score Top Affiliating Genes
1 spinal muscular atrophy 10.0
2 muscular atrophy 10.0

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

Symptoms via clinical synopsis from OMIM:

54

Head And Neck- Face:
facial weakness
myopathic facies

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

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

Neurologic- Peripheral Nervous System:
areflexia

Respiratory:
respiratory insufficiency due to muscle weakness

Head And Neck- Mouth:
tongue fasciculations

Skeletal- Hands:
digital contractures

Genitourinary- External Genitalia Male:
hypospadias

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

Genitourinary- Internal Genitalia Male:
cryptorchidism

Prenatal Manifestations- Movement:
decreased fetal movements

Chest- External Features:
chest deformities

Skeletal- Skull:
dysmorphic skull


Clinical features from OMIM:

301830

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

56 32 (show all 46)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 scoliosis 56 32 frequent (33%) Frequent (79-30%) HP:0002650
2 strabismus 56 32 occasional (7.5%) Occasional (29-5%) HP:0000486
3 cognitive impairment 56 32 frequent (33%) Frequent (79-30%) HP:0100543
4 seizures 56 32 occasional (7.5%) Occasional (29-5%) HP:0001250
5 ptosis 56 32 occasional (7.5%) Occasional (29-5%) HP:0000508
6 micrognathia 56 32 frequent (33%) Frequent (79-30%) HP:0000347
7 kyphosis 56 32 frequent (33%) Frequent (79-30%) HP:0002808
8 short nose 56 32 frequent (33%) Frequent (79-30%) HP:0003196
9 cryptorchidism 56 32 frequent (33%) Frequent (79-30%) HP:0000028
10 short neck 56 32 frequent (33%) Frequent (79-30%) HP:0000470
11 narrow chest 56 32 frequent (33%) Frequent (79-30%) HP:0000774
12 long philtrum 56 32 frequent (33%) Frequent (79-30%) HP:0000343
13 wide nasal bridge 56 32 frequent (33%) Frequent (79-30%) HP:0000431
14 open mouth 56 32 occasional (7.5%) Occasional (29-5%) HP:0000194
15 joint stiffness 56 32 hallmark (90%) Very frequent (99-80%) HP:0001387
16 dolichocephaly 56 32 frequent (33%) Frequent (79-30%) HP:0000268
17 muscular hypotonia 56 32 frequent (33%) Frequent (79-30%) HP:0001252
18 gait disturbance 56 32 hallmark (90%) Very frequent (99-80%) HP:0001288
19 macrotia 56 32 occasional (7.5%) Occasional (29-5%) HP:0000400
20 failure to thrive in infancy 56 32 frequent (33%) Frequent (79-30%) HP:0001531
21 hypoplasia of penis 56 32 occasional (7.5%) Occasional (29-5%) HP:0008736
22 bilateral single transverse palmar creases 56 32 frequent (33%) Frequent (79-30%) HP:0007598
23 adducted thumb 56 32 frequent (33%) Frequent (79-30%) HP:0001181
24 wide intermamillary distance 56 32 occasional (7.5%) Occasional (29-5%) HP:0006610
25 thickened nuchal skin fold 56 32 occasional (7.5%) Occasional (29-5%) HP:0000474
26 abnormality of the fingernails 56 32 occasional (7.5%) Occasional (29-5%) HP:0001231
27 skin dimples 56 32 occasional (7.5%) Occasional (29-5%) HP:0010781
28 camptodactyly of finger 56 32 hallmark (90%) Very frequent (99-80%) HP:0100490
29 proximal placement of thumb 56 32 frequent (33%) Frequent (79-30%) HP:0009623
30 micropenis 32 HP:0000054
31 hypospadias 32 HP:0000047
32 myopathic facies 32 HP:0002058
33 arthrogryposis multiplex congenita 32 HP:0002804
34 inguinal hernia 32 HP:0000023
35 areflexia 32 HP:0001284
36 myopathy 32 HP:0003198
37 respiratory insufficiency due to muscle weakness 32 HP:0002747
38 spinal muscular atrophy 32 HP:0007269
39 decreased fetal movement 32 HP:0001558
40 facial palsy 32 HP:0010628
41 degeneration of anterior horn cells 32 HP:0002398
42 tongue fasciculations 32 HP:0001308
43 multiple joint contractures 32 HP:0002828
44 flexion contracture 32 HP:0001371
45 abnormality of metabolism/homeostasis 32 HP:0001939
46 severe muscular hypotonia 32 HP:0006829

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


facial paresis

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

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford Recruiting NCT01793168

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

Genetic Tests for Spinal Muscular Atrophy, X-Linked 2, Infantile

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

id Genetic test Affiliating Genes
1 Arthrogryposis Multiplex Congenita, Distal, X-Linked 29
2 Spinal Muscular Atrophy, X-Linked Infantile 24 UBA1

Anatomical Context for Spinal Muscular Atrophy, X-Linked 2, Infantile

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

39
Bone, Spinal Cord, Skin, Skeletal Muscle, Tongue

Publications for Spinal Muscular Atrophy, X-Linked 2, Infantile

Variations for Spinal Muscular Atrophy, X-Linked 2, Infantile

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

71
id 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, Infantile:

6
id 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.1639A> G (p.Ser547Gly) single nucleotide variant Pathogenic rs80356546 GRCh37 Chromosome X, 47065410: 47065410
3 UBA1 NM_003334.3(UBA1): c.1731C> T (p.Asn577=) single nucleotide variant Pathogenic rs80356547 GRCh37 Chromosome X, 47065502: 47065502

Expression for Spinal Muscular Atrophy, X-Linked 2, Infantile

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

Pathways for Spinal Muscular Atrophy, X-Linked 2, Infantile

GO Terms for Spinal Muscular Atrophy, X-Linked 2, Infantile

Sources for Spinal Muscular Atrophy, X-Linked 2, Infantile

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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