SPG1
MCID: MSS001
MIFTS: 47

Masa Syndrome (SPG1)

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

Aliases & Classifications for Masa Syndrome

MalaCards integrated aliases for Masa Syndrome:

Name: Masa Syndrome 57 12 76 59 75 37 55 15 73
L1 Syndrome 12 24 53 25 59 37 29
Crash Syndrome 57 12 53 25 59 13
X-Linked Hydrocephalus Syndrome 25 29 6 73
Spg1 57 12 75
Corpus Callosum Hypoplasia-Retardation-Adducted Thumbs-Spasticity-Hydrocephalus Syndrome 53 59
Adducted Thumb with Mental Retardation 57 75
Clasped Thumb and Mental Retardation 57 75
Spastic Paraplegia 1, X-Linked 57 75
Gareis-Mason Syndrome 57 12
L1cam Syndrome 53 59
Corpus Callosum Hypoplasia, Mental Retardation, Adducted Thumbs, Spastic Paraplegia, Hydrocephalus Syndrome 25
Corpus Callosum Hypoplasia-Psychomotor Retardation, Adducted Thumbs-Spastic Paraparesis-Hydrocephalus 75
Mental Retardation, Aphasia, Shuffling Gait, and Adducted Thumbs Syndrome 75
Intellectual Disability-Aphasia-Shuffling Gait-Adducted Thumbs Syndrome 59
Mental Retardation, Aphasia, Shuffling Gait, and Adducted Thumbs 57
X-Linked Complicated Hereditary Spastic Paraplegia Type 1 12
Thumb, Congenital Clasped, with Mental Retardation 57
Adducted Thumbs-Mental Retardation Syndrome 25
Mental Retardation-Clasped Thumb Syndrome 25
Spastic Paraplegia 1, X-Linked; Spg1 57
Spastic Paraplegia Type 1, X-Linked 76
X-Linked Corpus Callosum Agenesis 12
Hereditary Spastic Paraplegia 1 12
X-Linked Spastic Paraplegia 1 12
Spastic Paraplegia 1 75
Masa Syndrome ) 40
Masa Syndrome 44
L1 Spectrum 24
L1 Disease 24
Crash 75
Masa 75

Characteristics:

Orphanet epidemiological data:

59
masa syndrome
Inheritance: X-linked recessive; Age of onset: Neonatal;
l1 syndrome
Inheritance: X-linked recessive; Age of onset: Infancy,Neonatal; Age of death: early childhood;

OMIM:

57
Inheritance:
x-linked recessive

Miscellaneous:
masa is an acronym - mental retardation, adducted thumbs, shuffling gait, and aphasia
crash is an acronym for corpus callosum hypoplasia, retardation, adducted thumbs, spastic paraplegia, and hydrocephalus which encompasses all l1cam diseases


HPO:

32
masa syndrome:
Inheritance x-linked recessive inheritance


Classifications:



Summaries for Masa Syndrome

OMIM : 57 The hereditary spastic paraplegias (SPG) are a group of clinically and genetically diverse disorders characterized by progressive, usually severe, lower extremity spasticity; see reviews of Fink et al. (1996) and Fink (1997). Some forms of SPG are considered 'uncomplicated,' i.e., progressive spasticity occurs in isolation; others are considered 'complicated,' i.e., progressive spasticity occurs with other neurologic features. X-linked, autosomal dominant (see 182600), and autosomal recessive (see 270800) forms of SPG have been described. Spastic paraplegia-1 is usually called MASA syndrome, the designation originally suggested by Bianchine and Lewis (1974), because the main clinical features are summarized by the acronym MASA (mental retardation, aphasia, shuffling gait, and adducted thumbs). The shuffling gait is probably caused by spasticity of the lower limbs, and all affected males have been reported to have increased reflexes. The adducted thumbs are thought to be caused by hypoplastic or absent extensor pollicis longus or brevis muscles. In affected males, the onset of speech is delayed (Winter et al., 1989). See 314100 for isolated X-linked congenital clasped thumb and 201550 for an autosomal adducted thumbs syndrome. (303350)

MalaCards based summary : Masa Syndrome, also known as l1 syndrome, is related to spastic paraplegia 3, autosomal dominant and spastic paraparesis, and has symptoms including muscle spasticity An important gene associated with Masa Syndrome is L1CAM (L1 Cell Adhesion Molecule), and among its related pathways/superpathways are Axon guidance and Cell adhesion molecules (CAMs). Affiliated tissues include testes, brain and skeletal muscle, and related phenotypes are agenesis of corpus callosum and hydrocephalus

Disease Ontology : 12 A hereditary spastic paraplegia that is characterized by hydrocephalus, spasticity of the lower limbs, adducted thumbs, aphasia, seizures, agenesis of the corpus callosum and intellectual disability in the mild to moderate range.

Genetics Home Reference : 25 L1 syndrome describes a group of conditions that primarily affect the nervous system and occur almost exclusively in males. These conditions vary in severity and include, from most severe to least, X-linked hydrocephalus with stenosis of the aqueduct of Sylvius (HSAS), MASA syndrome, spastic paraplegia type 1, and X-linked complicated corpus callosum agenesis.

NIH Rare Diseases : 53 L1 syndrome is a mild to severe congenital disorder with hydrocephalus of varying degrees of severity, intellectual disability, spasticity of the legs, and adducted thumbs. It includes several conditions, some more severe than others: X-linked hydrocephalus with stenosis of the aqueduct of Sylvius (HSAS) - the most severe of all; MASA syndrome (intellectual disability, aphasia (delayed speech), spastic paraplegia (shuffling gait), adducted thumbs); SPG1 (X-linked complicated hereditary spastic paraplegia type 1) X-linked complicated corpus callosum agenesis. It is inherited in an X-linked manner; therefore, it only affects males. It is caused by alterations (mutations) in L1CAM gene. The diagnosis is made in males who have the clinical and neurologic findings and a family history consistent with X-linked inheritance and is confirmed by a genetic test showing the L1CAM gene mutation. The treatment involves doing a surgery for the hydrocephalus.

UniProtKB/Swiss-Prot : 75 Mental retardation, aphasia, shuffling gait, and adducted thumbs syndrome: An X-linked recessive syndrome with a highly variable clinical spectrum. Main clinical features include spasticity and hyperreflexia of lower limbs, shuffling gait, mental retardation, aphasia and adducted thumbs. The features of spasticity have been referred to as complicated spastic paraplegia type 1 (SPG1). Some patients manifest corpus callosum hypoplasia and hydrocephalus. Inter- and intrafamilial variability is very wide, such that patients with hydrocephalus, MASA, SPG1, and agenesis of corpus callosum can be present within the same family. Spastic paraplegia 1, X-linked: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body.

Wikipedia : 76 MASA syndrome, also called CRASH syndrome, Gareis-Mason syndrome, L1 syndrome, spastic paraplegia 1 is a... more...

GeneReviews: NBK1484

Related Diseases for Masa Syndrome

Diseases related to Masa Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 76)
# Related Disease Score Top Affiliating Genes
1 spastic paraplegia 3, autosomal dominant 31.0 ATL1 NIPA1 REEP1 SPAST SPG11
2 spastic paraparesis 29.5 L1CAM SPAST SPG11
3 paraplegia 29.0 AP5Z1 ATL1 L1CAM NIPA1 REEP1 SPART
4 spastic paraplegia 1 11.6
5 x-linked complicated spastic paraplegia type 1 11.5
6 sleep apnea 11.4
7 telogen effluvium 11.4
8 hydrocephalus with stenosis of the aqueduct of sylvius 11.3
9 hydrocephalus due to congenital stenosis of aqueduct of sylvius 11.2
10 chronic fatigue syndrome 11.1
11 carney complex, type 1 10.5
12 caronte 10.5
13 hydrocephalus 10.5
14 head injury 10.4
15 whiplash 10.3
16 brain injury 10.2
17 traumatic brain injury 10.2
18 eosinophilia-myalgia syndrome 10.2
19 anxiety 10.2
20 spinal cord injury 10.2
21 esterase c 10.1
22 alcohol abuse 10.1
23 spastic paraplegia 32, autosomal recessive 10.1 ATL1 SPG11
24 attention deficit-hyperactivity disorder 10.1
25 spastic paraplegia 47, autosomal recessive 10.0 AP5Z1 REEP1
26 spastic paraplegia 39, autosomal recessive 10.0 AP5Z1 REEP1
27 neural tube defects 10.0
28 arts syndrome 10.0
29 neural tube defects, folate-sensitive 10.0
30 aging 10.0
31 cataract 10.0
32 pulmonary edema 10.0
33 epilepsy 10.0
34 post-traumatic stress disorder 10.0
35 heparin-induced thrombocytopenia 10.0
36 syncope 10.0
37 moderate and severe traumatic brain injury 10.0
38 spastic paraplegia 48, autosomal recessive 10.0 AP5Z1 SPG11
39 spastic paraplegia 30, autosomal recessive 10.0 AP5Z1 REEP1
40 spastic paraplegia 2, x-linked 9.9 AP5Z1 ATL1 REEP1
41 spastic paraplegia 15, autosomal recessive 9.9 AP5Z1 SPG11
42 spastic paraplegia 18, autosomal recessive 9.9 AP5Z1 NIPA1 REEP1
43 spastic paraplegia 42, autosomal dominant 9.9 AP5Z1 NIPA1 REEP1
44 spastic paraplegia 61, autosomal recessive 9.8 ATL1 REEP1 SPAST
45 spastic paraplegia 35, autosomal recessive 9.8 AP5Z1 SPG11
46 parkinson disease, late-onset 9.8
47 pulmonary hypertension, primary, 1 9.8
48 multiple acyl-coa dehydrogenase deficiency 9.8
49 hydrocephalus, normal-pressure 9.8
50 late-onset retinal degeneration 9.8

Graphical network of the top 20 diseases related to Masa Syndrome:



Diseases related to Masa Syndrome

Symptoms & Phenotypes for Masa Syndrome

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Head:
macrocephaly
microcephaly

Skeletal Spine:
kyphosis
lordosis

Skeletal Feet:
pes cavus
talipes equinovarus

Growth Height:
short stature (<5-15th percentile)

Neurologic Central Nervous System:
hydrocephalus
aphasia
lower limb spasticity
shuffling gait
agenesis of the corpus callosum
more
Head And Neck Eyes:
strabismus

Skeletal Hands:
adducted thumbs


Clinical features from OMIM:

303350

Human phenotypes related to Masa Syndrome:

59 32 (show all 33)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 agenesis of corpus callosum 59 32 occasional (7.5%) Occasional (29-5%) HP:0001274
2 hydrocephalus 59 32 hallmark (90%) Very frequent (99-80%) HP:0000238
3 depressivity 59 32 hallmark (90%) Very frequent (99-80%) HP:0000716
4 intellectual disability 59 32 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0001249
5 seizures 59 32 occasional (7.5%) Occasional (29-5%) HP:0001250
6 spasticity 59 32 hallmark (90%) Very frequent (99-80%) HP:0001257
7 gait disturbance 59 32 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0001288
8 hyperreflexia 59 32 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0001347
9 nausea and vomiting 59 32 hallmark (90%) Very frequent (99-80%) HP:0002017
10 aqueductal stenosis 59 32 hallmark (90%) Very frequent (99-80%) HP:0002410
11 global developmental delay 59 32 hallmark (90%) Very frequent (99-80%) HP:0001263
12 delayed speech and language development 59 32 hallmark (90%) Very frequent (99-80%) HP:0000750
13 short stature 59 32 hallmark (90%) Very frequent (99-80%) HP:0004322
14 skeletal muscle atrophy 59 32 occasional (7.5%) Occasional (29-5%) HP:0003202
15 hemiplegia/hemiparesis 59 32 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0004374
16 ventriculomegaly 59 32 occasional (7.5%) Occasional (29-5%) HP:0002119
17 aphasia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002381
18 aganglionic megacolon 59 32 occasional (7.5%) Occasional (29-5%) HP:0002251
19 clinodactyly of the 5th finger 59 32 frequent (33%) Frequent (79-30%) HP:0004209
20 adducted thumb 59 32 frequent (33%) Frequent (79-30%) HP:0001181
21 headache 59 32 hallmark (90%) Very frequent (99-80%) HP:0002315
22 spastic paraplegia 59 32 hallmark (90%) Very frequent (99-80%) HP:0001258
23 camptodactyly of finger 59 32 frequent (33%) Frequent (79-30%) HP:0100490
24 hand clenching 59 32 hallmark (90%) Very frequent (99-80%) HP:0001188
25 language impairment 59 32 hallmark (90%) Very frequent (99-80%) HP:0002463
26 macrocephaly 32 HP:0000256
27 kyphosis 32 HP:0002808
28 hyperlordosis 32 HP:0003307
29 microcephaly 32 HP:0000252
30 strabismus 32 HP:0000486
31 pes cavus 32 HP:0001761
32 talipes equinovarus 32 HP:0001762
33 shuffling gait 32 HP:0002362

UMLS symptoms related to Masa Syndrome:


muscle spasticity

Drugs & Therapeutics for Masa Syndrome

Search Clinical Trials , NIH Clinical Center for Masa Syndrome

Cochrane evidence based reviews: masa syndrome

Genetic Tests for Masa Syndrome

Genetic tests related to Masa Syndrome:

# Genetic test Affiliating Genes
1 L1 Syndrome 29
2 X-Linked Hydrocephalus Syndrome 29 L1CAM

Anatomical Context for Masa Syndrome

MalaCards organs/tissues related to Masa Syndrome:

41
Testes, Brain, Skeletal Muscle, Spinal Cord

Publications for Masa Syndrome

Articles related to Masa Syndrome:

(show all 26)
# Title Authors Year
1
Clinical and genetic features of L1 syndrome patients: Definition of two novel mutations. ( 29960101 )
2018
2
Induced knockouts provide insights into human L1 syndrome. ( 27045055 )
2016
3
Genotype-phenotype correlations in L1 syndrome: a guide for genetic counselling and mutation analysis. ( 19846429 )
2010
4
First case of L1CAM gene mutation identified in MASA syndrome in Asia. ( 15904436 )
2005
5
MASA syndrome: ultrasonographic evidence in a male fetus. ( 11113917 )
2000
6
Differential effects of two hydrocephalus/MASA syndrome-related mutations on the homophilic binding and neuritogenic activities of the cell adhesion molecule L1. ( 8636066 )
1996
7
X linked hydrocephalus and MASA syndrome. ( 8825051 )
1996
8
Mutations in L1-CAM in two families with X linked complicated spastic paraplegia, MASA syndrome, and HSAS. ( 7562969 )
1995
9
Spectrum of X-linked hydrocephalus (HSAS), MASA syndrome, and complicated spastic paraplegia (SPG1): Clinical review with six additional families. ( 7645588 )
1995
10
New domains of neural cell-adhesion molecule L1 implicated in X- linked hydrocephalus and MASA syndrome. ( 7762552 )
1995
11
MASA syndrome is due to mutations in the neural cell adhesion gene L1CAM. ( 7920660 )
1994
12
Clinical aspects of the MASA syndrome in a large family, including expressing females. ( 8062435 )
1994
13
X-linked hydrocephalus and MASA syndrome present in one family are due to a single missense mutation in exon 28 of the L1CAM gene. ( 7881431 )
1994
14
X-linked spastic paraplegia (SPG1), MASA syndrome and X-linked hydrocephalus result from mutations in the L1 gene. ( 7920659 )
1994
15
The spectrum of &amp;quot;complicated spastic paraplegia, MASA syndrome and X-linked hydrocephalus&amp;quot;. Contribution of DNA linkage analysis in genetic counseling of individual families. ( 8031529 )
1994
16
Fine mapping of X-linked clasped thumb and mental retardation (MASA syndrome) in Xq28. ( 8062432 )
1994
17
Agenesis of the corpus callosum associated with MASA syndrome. ( 8305964 )
1993
18
MASA syndrome (a form of complicated spastic paraplegia) and X linked hydrocephalus: variable expression of the same mutation at Xq28? Call for families. ( 1552562 )
1992
19
MASA syndrome: delineation of the clinical spectrum at prepubertal age. ( 1605218 )
1992
20
MASA syndrome. ( 1424231 )
1992
21
Clasped-thumb mental retardation (MASA) syndrome: confirmation of linkage to Xq28. ( 1605219 )
1992
22
X linked complicated spastic paraplegia, MASA syndrome, and X linked hydrocephalus owing to congenital stenosis of the aqueduct of Sylvius: variable expression of the same mutation at Xq28. ( 1870106 )
1991
23
MASA syndrome: clinical variability and linkage analysis. ( 1951449 )
1991
24
MASA syndrome: new clinical features and linkage analysis using DNA probes. ( 2277384 )
1990
25
MASA syndrome: further clinical delineation and chromosomal localisation. ( 2737668 )
1989
26
The MASA syndrome: a new heritable mental retardation syndrome. ( 4855169 )
1974

Variations for Masa Syndrome

UniProtKB/Swiss-Prot genetic disease variations for Masa Syndrome:

75 (show all 19)
# Symbol AA change Variation ID SNP ID
1 L1CAM p.Ile179Ser VAR_003923 rs137852523
2 L1CAM p.His210Gln VAR_003926 rs28933683
3 L1CAM p.Glu309Lys VAR_003930 rs367665974
4 L1CAM p.Trp335Arg VAR_003931
5 L1CAM p.Gly370Arg VAR_003932 rs137852524
6 L1CAM p.Arg473Cys VAR_003936 rs886039408
7 L1CAM p.Asp598Asn VAR_003937 rs137852519
8 L1CAM p.Arg632Pro VAR_003938
9 L1CAM p.Ala691Asp VAR_003939
10 L1CAM p.Gly698Arg VAR_003940 rs886039409
11 L1CAM p.Pro941Leu VAR_003945
12 L1CAM p.Ser1194Leu VAR_003947 rs137852522
13 L1CAM p.Val752Met VAR_014421 rs137852525
14 L1CAM p.Ser674Cys VAR_027513
15 L1CAM p.Asp770Asn VAR_027514 rs148516831
16 L1CAM p.Asp202Tyr VAR_030405
17 L1CAM p.Gly268Asp VAR_030406
18 L1CAM p.Ala426Asp VAR_030410
19 L1CAM p.Leu482Pro VAR_030411 rs106479424

ClinVar genetic disease variations for Masa Syndrome:

6 (show all 14)
# Gene Variation Type Significance SNP ID Assembly Location
1 L1CAM NM_000425.4(L1CAM): c.630C> A (p.His210Gln) single nucleotide variant Pathogenic rs28933683 GRCh37 Chromosome X, 153136309: 153136309
2 L1CAM NM_000425.4(L1CAM): c.630C> A (p.His210Gln) single nucleotide variant Pathogenic rs28933683 GRCh38 Chromosome X, 153870854: 153870854
3 L1CAM NM_000425.4(L1CAM): c.1792G> A (p.Asp598Asn) single nucleotide variant Pathogenic rs137852519 GRCh37 Chromosome X, 153133489: 153133489
4 L1CAM NM_000425.4(L1CAM): c.1792G> A (p.Asp598Asn) single nucleotide variant Pathogenic rs137852519 GRCh38 Chromosome X, 153868034: 153868034
5 L1CAM NM_000425.4(L1CAM): c.3489_3490delTG (p.Glu1164Glyfs) deletion Pathogenic rs879253714 GRCh37 Chromosome X, 153128972: 153128973
6 L1CAM NM_000425.4(L1CAM): c.3489_3490delTG (p.Glu1164Glyfs) deletion Pathogenic rs879253714 GRCh38 Chromosome X, 153863517: 153863518
7 L1CAM NM_000425.4(L1CAM): c.3581C> T (p.Ser1194Leu) single nucleotide variant Pathogenic rs137852522 GRCh37 Chromosome X, 153128311: 153128311
8 L1CAM NM_000425.4(L1CAM): c.3581C> T (p.Ser1194Leu) single nucleotide variant Pathogenic rs137852522 GRCh38 Chromosome X, 153862856: 153862856
9 L1CAM NM_000425.4(L1CAM): c.536T> G (p.Ile179Ser) single nucleotide variant Pathogenic rs137852523 GRCh37 Chromosome X, 153136403: 153136403
10 L1CAM NM_000425.4(L1CAM): c.536T> G (p.Ile179Ser) single nucleotide variant Pathogenic rs137852523 GRCh38 Chromosome X, 153870948: 153870948
11 L1CAM NM_000425.4(L1CAM): c.1108G> A (p.Gly370Arg) single nucleotide variant Pathogenic rs137852524 GRCh37 Chromosome X, 153135273: 153135273
12 L1CAM NM_000425.4(L1CAM): c.1108G> A (p.Gly370Arg) single nucleotide variant Pathogenic rs137852524 GRCh38 Chromosome X, 153869818: 153869818
13 L1CAM NM_000425.4(L1CAM): c.3654G> C (p.Gln1218His) single nucleotide variant Uncertain significance GRCh37 Chromosome X, 153128238: 153128238
14 L1CAM NM_000425.4(L1CAM): c.3654G> C (p.Gln1218His) single nucleotide variant Uncertain significance GRCh38 Chromosome X, 153862783: 153862783

Expression for Masa Syndrome

Search GEO for disease gene expression data for Masa Syndrome.

Pathways for Masa Syndrome

Pathways related to Masa Syndrome according to KEGG:

37
# Name Kegg Source Accession
1 Axon guidance hsa04360
2 Cell adhesion molecules (CAMs) hsa04514

GO Terms for Masa Syndrome

Cellular components related to Masa Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 lipid droplet GO:0005811 9.16 SPART SPAST
2 axon GO:0030424 9.13 ATL1 L1CAM SPG11
3 endoplasmic reticulum tubular network GO:0071782 8.62 ATL1 REEP1

Biological processes related to Masa Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 axonogenesis GO:0007409 8.62 ATL1 SPAST

Sources for Masa Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
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36 IUPHAR
37 KEGG
38 LifeMap
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42 MedGen
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45 MESH via Orphanet
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49 NCI
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54 NINDS
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57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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