MCID: SPS133
MIFTS: 41

Spastic Paraplegia 2, X-Linked

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Eye diseases

Aliases & Classifications for Spastic Paraplegia 2, X-Linked

MalaCards integrated aliases for Spastic Paraplegia 2, X-Linked:

Name: Spastic Paraplegia 2, X-Linked 53 71 13 69
Spg2 53 12 49 55 71
Spastic Paraplegia 2 49 24 71 28
Spastic Paraplegia Type 2 12 24 55
Sppx2 53 49 71
Hereditary X-Linked Recessive Spastic Paraplegia 24 69
Hereditary Spastic Paraplegia 2 12 14
X Linked Recessive Hereditary Spastic Paraplegia 24
Spastic Paraplegia Type 2, X-Linked 72
X-Linked Spastic Paraplegia Type 2 55
X-Linked Spastic Paraplegia 2 12
Spastic Paraparesis Type 2 55
Spastic Gait Type 2 55

Characteristics:

Orphanet epidemiological data:

55
spastic paraplegia type 2
Inheritance: X-linked recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood; Age of death: adult;

OMIM:

53
Miscellaneous:
highly variable phenotype
onset in childhood
pelizaeus-merzbacher disease (pmd, ) is an allelic disorder

Inheritance:
x-linked recessive


HPO:

31
spastic paraplegia 2, x-linked:
Onset and clinical course phenotypic variability juvenile onset
Inheritance x-linked recessive inheritance


Classifications:



Summaries for Spastic Paraplegia 2, X-Linked

NIH Rare Diseases : 49 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 99015Disease definitionSpastic paraplegia type 2 (SPG2) is an X-linked leukodystrophy characterized primarily by spastic gait and autonomic dysfunction. When additional central nervous system (CNS) signs, such as intellectual deficit, ataxia, or extrapyramidal signs, are present, the syndrome is referred to as complicated SPG.EpidemiologyThe prevalence and incidence of SPG2 have not been reported, but as part of the Pelizaeus-Merzbacher (PMD; see this term) spectrum, SPG2 roughly accounts for about 20 % of cases. There have been approximately 20 cases published on SPG2. SPG2 affects males but some female heterozygotes presenting in adulthood with a milder phenotype have also been reported.Clinical descriptionSPG2 spans a continuum of phenotypes that goes from pure to complicated SPG2. Pure SPG2 manifests as early as infancy or early childhood (EtiologySPG2 is due to missense substitutions affecting the PLP1 gene. PLP1 encodes the proteolipid protein (PLP), the most abundant protein of the myelin sheath in the central nervous system, and its alternatively spliced isoform (DM20). SPG2 is allelic to Pelizaeus-Merzbacher disease (PMD; see this term) that is also due to PLP1 mutations.Diagnostic methodsDiagnosis is based on clinical, electrophysiologic, and neuroradiological findings. White matter N-acetyl aspartate levels are reduced. Brain magnetic resonance imaging (MRI) reveals patchy or diffuse hypomyelination on T2-weighted images. Patients with pure SPG2 can have very subtle T2 hyperintensity. Other MR techniques, including MR spectroscopy and diffusion tensor imaging are useful in the diagnosis of the disease. Molecular genetic testing of PLP1 confirms the diagnosis.Differential diagnosisDifferential diagnosis includes other forms of hereditary spastic paraplegia (see this tem). Complicated SPG2 is not clearly distinguishable from mild Pelizaeus-Merzbacher disease (PMD) and null syndrome (see these terms).Antenatal diagnosisPrenatal genetic testing is possible when a family's underlying PLP1 mutation has been identified.Genetic counselingTransmission is X-linked recessive.Management and treatmentA son born to a female carrier has a 50% risk of inheriting the mutation and developing the disease, while a daughter has a 50% risk of being a carrier. All daughters of an affected male will be carriers but none of his sons will be affected. Management is multidisciplinary and involves neurologists, physical therapists, and orthopedic doctors. Treatment may include antiepileptic drugs for seizures, and physical therapy with antispasticity drugs (baclofen, diazepam, tizanidine, botulinum toxin, dantrolene) for spasticity. Regular surveillance is necessary.PrognosisPure SPG2 patients show a normal life expectancy. In complicated SPG2 cases, patients deteriorate neurologically leading to a shorter life expectancy (between the fourth and seventh decade) typically from aspiration pneumonia, pulmonary embolism and other complications of generalized weakness.Visit the Orphanet disease page for more resources. Last updated: 10/10/2011

MalaCards based summary : Spastic Paraplegia 2, X-Linked, also known as spg2, is related to pelizaeus-merzbacher disease and paraplegia, and has symptoms including ataxia, abnormality of extrapyramidal motor function and muscle weakness. An important gene associated with Spastic Paraplegia 2, X-Linked is PLP1 (Proteolipid Protein 1). Affiliated tissues include brain, spinal cord and testes.

OMIM : 53 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. For discussion of genetic heterogeneity of X-linked SPG, see 303350. (312920)

UniProtKB/Swiss-Prot : 71 Spastic paraplegia 2, 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. SPG2 is characterized by spastic gait and hyperreflexia. In some patients, complicating features include nystagmus, dysarthria, sensory disturbance, mental retardation, optic atrophy.

Genetics Home Reference : 24 Spastic paraplegia type 2 is part of a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by progressive muscle stiffness (spasticity) and the development of paralysis of the lower limbs (paraplegia). Hereditary spastic paraplegias are divided into two types: pure and complex. The pure types involve the lower limbs. The complex types involve the lower limbs and can also affect the upper limbs to a lesser degree; the structure or functioning of the brain; and the nerves connecting the brain and spinal cord to muscles and sensory cells that detect sensations such as touch, pain, heat, and sound (the peripheral nervous system). Spastic paraplegia type 2 can occur in either the pure or complex form.

Disease Ontology : 12 A hereditary spastic paraplegia that has material basis in mutation in the PLP1 gene on chromosome Xq22.2.

Wikipedia : 72 Hereditary spastic paraplegia (HSP) is a group of inherited diseases whose main feature is a progressive... more...

Related Diseases for Spastic Paraplegia 2, X-Linked

Diseases in the Spastic Paraplegia 2, X-Linked family:

Spastic Paraplegia 16, X-Linked Spastic Paraplegia 34, X-Linked

Diseases related to Spastic Paraplegia 2, X-Linked via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 36)
# Related Disease Score Top Affiliating Genes
1 pelizaeus-merzbacher disease 32.6 GJC2 PLP1
2 paraplegia 28.3 ATL1 PLP1 REEP1 RTN2 ZFYVE27
3 leukodystrophy, hypomyelinating, 4 10.3 GJC2 PLP1
4 pelizaeus-merzbacher-like disease 10.3 GJC2 PLP1
5 hypomyelinating leukoencephalopathy 10.2 GJC2 PLP1
6 leukodystrophy, hypomyelinating, 2 10.2 GJC2 PLP1
7 hereditary spastic paraplegia 51 10.1 AP5Z1 RTN2
8 spastic paraplegia 52, autosomal recessive 10.1 AP5Z1 RTN2
9 spastic paraplegia 28, autosomal recessive 10.1 AP5Z1 RTN2
10 hypomyelinating leukodystrophy 10.1 GJC2 PLP1
11 spastic paraplegia 50, autosomal recessive 10.1 AP5Z1 RTN2
12 spastic paraplegia 54, autosomal recessive 10.1 AP5Z1 RTN2
13 spastic paraplegia 18, autosomal recessive 10.1 AP5Z1 ERLIN2
14 cerebral degeneration 10.1 GJC2 PLP1
15 spastic paraplegia 48, autosomal recessive 10.0 AP5Z1 ERLIN2
16 spastic paraplegia 39, autosomal recessive 10.0 AP5Z1 ERLIN2
17 spastic paraplegia 30, autosomal recessive 10.0 AP5Z1 ERLIN2
18 spasticity 10.0
19 spastic paraplegia 35, autosomal recessive 9.9 AP5Z1 ERLIN2
20 leukodystrophy 9.8 GJC2 PLP1
21 cerebral palsy 9.6 ATL1 PLP1
22 spastic paraplegia 47, autosomal recessive 9.6 AP5Z1 ERLIN2 REEP1
23 spastic paraplegia 42, autosomal dominant 9.6 AP5Z1 ERLIN2 REEP1
24 spastic paraplegia 44, autosomal recessive 9.5 AP5Z1 ERLIN2 GJC2 ZFYVE27
25 spastic paraplegia 61, autosomal recessive 9.5 ATL1 REEP1 RTN2
26 spastic paraplegia 33, autosomal dominant 9.4 AP5Z1 REEP1 RTN2 ZFYVE27
27 spastic paraplegia 13, autosomal dominant 9.2 AP5Z1 ATL1 ERLIN2 GJC2
28 spastic paraplegia 4, autosomal dominant 9.1 ATL1 REEP1 RTN2 ZFYVE27
29 spastic paraplegia 3, autosomal dominant 9.1 ATL1 REEP1 RTN2 ZFYVE27
30 spastic paraplegia 6, autosomal dominant 9.0 AP5Z1 ATL1 ERLIN2 REEP1
31 spastic paraplegia 8, autosomal dominant 9.0 AP5Z1 ATL1 ERLIN2 REEP1
32 masa syndrome 9.0 AP5Z1 ATL1 ERLIN2 REEP1
33 spastic paraplegia 31, autosomal dominant 8.8 AP5Z1 ATL1 REEP1 RTN2 ZFYVE27
34 spastic paraplegia 10, autosomal dominant 8.8 AP5Z1 ATL1 REEP1 RTN2 ZFYVE27
35 spastic paraplegia 12, autosomal dominant 8.4 AP5Z1 ATL1 ERLIN2 REEP1 RTN2 ZFYVE27
36 hereditary spastic paraplegia 7.9 AP5Z1 ATL1 ERLIN2 GJC2 PLP1 REEP1

Graphical network of the top 20 diseases related to Spastic Paraplegia 2, X-Linked:



Diseases related to Spastic Paraplegia 2, X-Linked

Symptoms & Phenotypes for Spastic Paraplegia 2, X-Linked

Symptoms via clinical synopsis from OMIM:

53
Neurologic Central Nervous System:
ataxia
dysarthria
hyperreflexia
dysmetria
spastic gait
more
Skeletal Feet:
pes cavus

Muscle Soft Tissue:
atrophy

Head And Neck Eyes:
nystagmus
optic atrophy

Skeletal Limbs:
joint contractures


Clinical features from OMIM:

312920

Human phenotypes related to Spastic Paraplegia 2, X-Linked:

55 31 (show all 27)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ataxia 55 31 occasional (7.5%) Occasional (29-5%) HP:0001251
2 abnormality of extrapyramidal motor function 55 31 frequent (33%) Frequent (79-30%) HP:0002071
3 muscle weakness 55 31 hallmark (90%) Very frequent (99-80%) HP:0001324
4 nystagmus 55 31 occasional (7.5%) Occasional (29-5%) HP:0000639
5 intellectual disability 55 31 frequent (33%) Frequent (79-30%) HP:0001249
6 dysarthria 55 31 occasional (7.5%) Occasional (29-5%) HP:0001260
7 hyperreflexia 55 31 hallmark (90%) Very frequent (99-80%) HP:0001347
8 bowel incontinence 55 31 frequent (33%) Frequent (79-30%) HP:0002607
9 recurrent respiratory infections 55 31 occasional (7.5%) Occasional (29-5%) HP:0002205
10 optic atrophy 55 31 frequent (33%) Frequent (79-30%) HP:0000648
11 pulmonary embolism 55 31 occasional (7.5%) Occasional (29-5%) HP:0002204
12 sensory neuropathy 55 31 occasional (7.5%) Occasional (29-5%) HP:0000763
13 limitation of joint mobility 55 31 occasional (7.5%) Occasional (29-5%) HP:0001376
14 babinski sign 55 31 hallmark (90%) Very frequent (99-80%) HP:0003487
15 spastic gait 55 31 hallmark (90%) Very frequent (99-80%) HP:0002064
16 spastic/hyperactive bladder 55 31 frequent (33%) Frequent (79-30%) HP:0005340
17 lower limb muscle weakness 31 HP:0007340
18 spasticity 55 Very frequent (99-80%)
19 flexion contracture 31 HP:0001371
20 skeletal muscle atrophy 31 HP:0003202
21 dysmetria 31 HP:0001310
22 pes cavus 31 HP:0001761
23 spastic paraplegia 31 HP:0001258
24 spastic paraparesis 31 HP:0002313
25 lower limb spasticity 31 HP:0002061
26 spinocerebellar tract degeneration 31 HP:0002503
27 degeneration of the lateral corticospinal tracts 31 HP:0002314

UMLS symptoms related to Spastic Paraplegia 2, X-Linked:


cerebellar signs, ataxia

Drugs & Therapeutics for Spastic Paraplegia 2, X-Linked

Search Clinical Trials , NIH Clinical Center for Spastic Paraplegia 2, X-Linked

Genetic Tests for Spastic Paraplegia 2, X-Linked

Genetic tests related to Spastic Paraplegia 2, X-Linked:

# Genetic test Affiliating Genes
1 Spastic Paraplegia 2 28 PLP1

Anatomical Context for Spastic Paraplegia 2, X-Linked

MalaCards organs/tissues related to Spastic Paraplegia 2, X-Linked:

38
Brain, Spinal Cord, Testes, Eye, Skeletal Muscle

Publications for Spastic Paraplegia 2, X-Linked

Articles related to Spastic Paraplegia 2, X-Linked:

# Title Authors Year
1
Brain magnetic resonance imaging findings and auditory brainstem response in a child with spastic paraplegia 2 due to a PLP1 splice site mutation. ( 24685771 )
2014
2
PLP1 splicing abnormalities identified in Pelizaeus-Merzbacher disease and SPG2 fibroblasts are associated with different types of mutations. ( 18470932 )
2008
3
Cloning and identification of a novel RNF6 transcriptional splice variant Spg2 in human development. ( 18368307 )
2008
4
A case of complicated spastic paraplegia 2 due to a point mutation in the proteolipid protein 1 gene. ( 15450775 )
2004

Variations for Spastic Paraplegia 2, X-Linked

UniProtKB/Swiss-Prot genetic disease variations for Spastic Paraplegia 2, X-Linked:

71
# Symbol AA change Variation ID SNP ID
1 PLP1 p.His140Tyr VAR_004551 rs132630287
2 PLP1 p.Ile187Thr VAR_004556 rs132630288
3 PLP1 p.Phe237Ser VAR_004563 rs132630291
4 PLP1 p.His130Tyr VAR_015024 rs878853076
5 PLP1 p.His148Tyr VAR_015025
6 PLP1 p.Ser170Phe VAR_015029 rs132630294
7 PLP1 p.Ser226Pro VAR_015046
8 PLP1 p.Arg137Trp VAR_046910 rs132630295
9 PLP1 p.Pro216Leu VAR_046914
10 PLP1 p.Ala30Pro VAR_070667

ClinVar genetic disease variations for Spastic Paraplegia 2, X-Linked:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 PLP1 NM_001128834.2(PLP1): c.418C> T (p.His140Tyr) single nucleotide variant Pathogenic rs132630287 GRCh37 Chromosome X, 103041620: 103041620
2 PLP1 NM_001128834.2(PLP1): c.560T> C (p.Ile187Thr) single nucleotide variant Pathogenic rs132630288 GRCh37 Chromosome X, 103042833: 103042833
3 PLP1 NM_001128834.2(PLP1): c.710T> C (p.Phe237Ser) single nucleotide variant Pathogenic rs132630291 GRCh37 Chromosome X, 103044275: 103044275
4 PLP1 NM_001128834.2(PLP1): c.509C> T (p.Ser170Phe) single nucleotide variant Pathogenic rs132630294 GRCh37 Chromosome X, 103042782: 103042782
5 PLP1 NM_001128834.2(PLP1): c.409C> T (p.Arg137Trp) single nucleotide variant Pathogenic rs132630295 GRCh37 Chromosome X, 103041611: 103041611
6 PLP1 NM_000533.4(PLP1): c.2T> C (p.Met1Thr) single nucleotide variant Pathogenic rs864622194 GRCh37 Chromosome X, 103031925: 103031925
7 PLP1 NC_000023.10: g.(?_103031918)_(103045531_?)dup duplication Pathogenic GRCh37 Chromosome X, 103031918: 103045531
8 PLP1 NM_000533.4(PLP1): c.140T> C (p.Ile47Thr) single nucleotide variant Likely pathogenic rs1060500909 GRCh38 Chromosome X, 103785717: 103785717
9 PLP1 NC_000023.10: g.(?_103031754)_(103047548_?)dup duplication Pathogenic GRCh37 Chromosome X, 103031754: 103047548
10 PLP1 NM_001128834.2(PLP1): c.365A> G (p.Lys122Arg) single nucleotide variant Likely pathogenic rs1135401759 GRCh37 Chromosome X, 103041567: 103041567

Expression for Spastic Paraplegia 2, X-Linked

Search GEO for disease gene expression data for Spastic Paraplegia 2, X-Linked.

Pathways for Spastic Paraplegia 2, X-Linked

GO Terms for Spastic Paraplegia 2, X-Linked

Cellular components related to Spastic Paraplegia 2, X-Linked according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 integral component of membrane GO:0016021 9.8 ATL1 ERLIN2 GJC2 PLP1 REEP1 RTN2
2 endoplasmic reticulum GO:0005783 9.55 ATL1 ERLIN2 REEP1 RTN2 ZFYVE27
3 endoplasmic reticulum membrane GO:0005789 9.35 ATL1 ERLIN2 REEP1 RTN2 ZFYVE27
4 integral component of endoplasmic reticulum membrane GO:0030176 9.32 RTN2 ZFYVE27
5 endoplasmic reticulum tubular network GO:0071782 8.8 ATL1 REEP1 ZFYVE27

Sources for Spastic Paraplegia 2, X-Linked

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