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 54 71 13 69
Spastic Paraplegia 2 50 24 25 71 29
Spg2 12 50 24 56 71
Spastic Paraplegia Type 2 12 25 56
Hereditary X-Linked Recessive Spastic Paraplegia 25 69
Hereditary Spastic Paraplegia 2 12 14
Sppx2 50 71
X Linked Recessive Hereditary Spastic Paraplegia 25
X-Linked Spastic Paraplegia Type 2 56
X-Linked Spastic Paraplegia 2 12
Spastic Paraparesis Type 2 56
Spastic Gait Type 2 56
Spg 2 24
Hsp2 24

Characteristics:

Orphanet epidemiological data:

56
spastic paraplegia type 2
Inheritance: X-linked recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood; Age of death: adult;

OMIM:

54
Miscellaneous:
onset in childhood
highly variable phenotype
pelizaeus-merzbacher disease (pmd, ) is an allelic disorder

Inheritance:
x-linked recessive


HPO:

32
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 : 50 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 spastic paraplegia 2, is related to pelizaeus-merzbacher disease and spastic ataxia 3, autosomal recessive, and has symptoms including optic atrophy, nystagmus and dysarthria. An important gene associated with Spastic Paraplegia 2, X-Linked is PLP1 (Proteolipid Protein 1). Affiliated tissues include brain, testes and spinal cord.

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 : 25 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.

OMIM : 54
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)

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

Related Diseases for Spastic Paraplegia 2, X-Linked

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

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

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

(show all 45)
id Related Disease Score Top Affiliating Genes
1 pelizaeus-merzbacher disease 11.3
2 spastic ataxia 3, autosomal recessive 10.4 GJC2 PLP1
3 pemphigoid gestationis 10.3 GJC2 PLP1
4 cerebellar ataxia, mental retardation and dysequlibrium syndrome 10.3 GJC2 PLP1
5 spasticity 10.3
6 paraplegia 10.3
7 hereditary spastic paraplegia 72 10.3 AP5Z1 RTN2
8 nemaline myopathy 7, autosomal recessive 10.3 AP5Z1 RTN2
9 l-2-hydroxyglutaric aciduria 10.3 AP5Z1 RTN2
10 leukodystrophy, hypomyelinating, 2 10.3 GJC2 PLP1
11 ehlers-danlos syndrome, type viib 10.2 AP5Z1 RTN2
12 basal ganglia calcification, idiopathic, 1 10.2 AP5Z1 RTN2
13 mohr-tranebjaerg syndrome 10.2 GJC2 PLP1
14 b-cell expansion with nfkb and t-cell anergy 10.2 AP5Z1 ERLIN2
15 prieto syndrome 10.1 GJC2 PLP1
16 pre-eclampsia 10.1 GJC2 PLP1
17 sclerosing keratitis 10.0 GJC2 PLP1
18 hirschsprung disease 8 10.0 AP5Z1 ERLIN2
19 hereditary spastic paraplegia 10.0
20 neuropathy 9.8
21 cerebral atrophy 9.8
22 cerebritis 9.8
23 axonal neuropathy 9.8
24 neuronitis 9.8
25 spastic paraplegia 47, autosomal recessive 9.6 AP5Z1 ERLIN2 REEP1
26 immunodeficiency 15 9.6 AP5Z1 ERLIN2 REEP1
27 neuropathy, hereditary sensory, type iic 9.6 AP5Z1 ERLIN2 REEP1
28 boucher-neuhauser syndrome 9.6 AP5Z1 ERLIN2 REEP1
29 congenital cataracts, hearing loss, and neurodegeneration 9.6 AP5Z1 ERLIN2 REEP1
30 charcot-marie-tooth disease 9.4 ATL1 PLP1
31 spastic paraplegia 44, autosomal recessive 9.4 AP5Z1 ERLIN2 GJC2 ZFYVE27
32 epilepsy, rolandic, with paroxysmal exercise-induced dystonia and writer's cramp 9.3 ATL1 REEP1 RTN2
33 cerebral palsy, spastic quadriplegic, 3 9.2 AP5Z1 REEP1 RTN2 ZFYVE27
34 leukodystrophy, hypomyelinating, 4 9.1 AP5Z1 ATL1 ERLIN2 GJC2
35 chromosome 15q11.2 deletion syndrome 8.8 AP5Z1 ATL1 ERLIN2 REEP1
36 hereditary spastic paraplegia 62 8.8 ATL1 REEP1 RTN2 ZFYVE27
37 ritscher-schinzel syndrome 1 8.8 AP5Z1 ATL1 ERLIN2 REEP1
38 major affective disorder 2 8.8 AP5Z1 ATL1 ERLIN2 REEP1
39 human venous malformation 8.5 ATL1 PLP1 REEP1 RTN2 ZFYVE27
40 pediatric ovarian germ cell tumor 8.5 ATL1 PLP1 REEP1 RTN2 ZFYVE27
41 spastic paraplegia 31, autosomal dominant 8.4 AP5Z1 ATL1 REEP1 RTN2 ZFYVE27
42 myoclonus, intractable, neonatal 8.4 AP5Z1 ATL1 REEP1 RTN2 ZFYVE27
43 spastic paraplegia 4, autosomal dominant 8.4 AP5Z1 ATL1 REEP1 RTN2 ZFYVE27
44 ichthyosis, congenital, autosomal recessive 14 7.9 AP5Z1 ATL1 ERLIN2 REEP1 RTN2 ZFYVE27
45 phosphoribosylpyrophosphate synthetase superactivity 7.2 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:

54

Skeletal- Limbs:
joint contractures

Head And Neck- Eyes:
optic atrophy
nystagmus

Muscle Soft Tissue:
atrophy

Neurologic- Central Nervous System:
mental retardation
dysarthria
ataxia
hyperreflexia
extensor plantar responses
more
Skeletal- Feet:
pes cavus


Clinical features from OMIM:

312920

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

56 32 (show all 27)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 optic atrophy 56 32 frequent (33%) Frequent (79-30%) HP:0000648
2 nystagmus 56 32 occasional (7.5%) Occasional (29-5%) HP:0000639
3 dysarthria 56 32 occasional (7.5%) Occasional (29-5%) HP:0001260
4 ataxia 56 32 occasional (7.5%) Occasional (29-5%) HP:0001251
5 recurrent respiratory infections 56 32 occasional (7.5%) Occasional (29-5%) HP:0002205
6 hyperreflexia 56 32 hallmark (90%) Very frequent (99-80%) HP:0001347
7 muscle weakness 56 32 hallmark (90%) Very frequent (99-80%) HP:0001324
8 intellectual disability 56 32 frequent (33%) Frequent (79-30%) HP:0001249
9 pulmonary embolism 56 32 occasional (7.5%) Occasional (29-5%) HP:0002204
10 spastic gait 56 32 hallmark (90%) Very frequent (99-80%) HP:0002064
11 sensory neuropathy 56 32 occasional (7.5%) Occasional (29-5%) HP:0000763
12 babinski sign 56 32 hallmark (90%) Very frequent (99-80%) HP:0003487
13 spastic/hyperactive bladder 56 32 frequent (33%) Frequent (79-30%) HP:0005340
14 bowel incontinence 56 32 frequent (33%) Frequent (79-30%) HP:0002607
15 limitation of joint mobility 56 32 occasional (7.5%) Occasional (29-5%) HP:0001376
16 abnormality of extrapyramidal motor function 56 32 frequent (33%) Frequent (79-30%) HP:0002071
17 spasticity 56 Very frequent (99-80%)
18 spastic paraplegia 32 HP:0001258
19 pes cavus 32 HP:0001761
20 lower limb spasticity 32 HP:0002061
21 spastic paraparesis 32 HP:0002313
22 dysmetria 32 HP:0001310
23 degeneration of the lateral corticospinal tracts 32 HP:0002314
24 spinocerebellar tract degeneration 32 HP:0002503
25 lower limb muscle weakness 32 HP:0007340
26 flexion contracture 32 HP:0001371
27 skeletal muscle atrophy 32 HP:0003202

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


ataxia, lower limb muscle weakness

Drugs & Therapeutics for Spastic Paraplegia 2, X-Linked

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 Spastic Paraplegia 2, X-Linked

Genetic Tests for Spastic Paraplegia 2, X-Linked

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

id Genetic test Affiliating Genes
1 Spastic Paraplegia 2 29 24 PLP1

Anatomical Context for Spastic Paraplegia 2, X-Linked

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

39
Brain, Testes, Spinal Cord, Skeletal Muscle, Eye

Publications for Spastic Paraplegia 2, X-Linked

Variations for Spastic Paraplegia 2, X-Linked

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

71
id 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
id 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:

id 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

3 CDC
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9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
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43 MESH via Orphanet
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70 UMLS via Orphanet
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