Spastic Paraplegia 2, X-Linked (SPG2)

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Disease Ontology 12 DOID:0110773 OMIM® 57 312920 OMIM Phenotypic Series 57 PS303350 MeSH 44 D015419 ICD10 32 G11.4 MESH via Orphanet 45 C536857

ICD10 via Orphanet 33 G11.4 UMLS via Orphanet 72 C1839264 Orphanet 58 ORPHA99015 MedGen 41 C1839264 SNOMED-CT via HPO 68 192967009 203598005 205091006 228156007 246586009 247578003 249945007 26544005 312444006 32566006 366575004 385522000 394679006 43378000 55033002 563001 57048009 59282003 72042002 74035001 76349003 76976005 7890003 8011004 85102008 86854008 88565003 91138005 9447003 95662005 more UMLS 71 C0751604 C1839264

GARD : ²⁰ The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 99015DefinitionA rare, 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 (<5 years) but may be delayed until early adulthood. It presents with weakness, hyperreflexia, Babinski sign and spastic gait due to spastic paraparesis. Autonomic dysfunction (spastic urinary bladder and possibly bowel, with increased urinary and fecal frequency and incontinence) is frequent. Patients are able to walk and their speech is normal. There is no CNS involvement and no cognitive decline. Complicated SPG2 shares the same features as SPG2 but also shows additional CNS involvement like nystagmus, and ataxia that present in the first years of life. Optic atrophy may be present. Patients can also show a mild intellectual deficit.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.

MalaCards based summary : Spastic Paraplegia 2, X-Linked, also known as spg2, is related to pelizaeus-merzbacher disease and spastic quadriplegia, and has symptoms including ataxia and cerebellar signs. An important gene associated with Spastic Paraplegia 2, X-Linked is PLP1 (Proteolipid Protein 1), and among its related pathways/superpathways are Endocytosis and Glial Cell Differentiation. Affiliated tissues include brain, spinal cord and eye, and related phenotypes are hyperreflexia and muscle weakness

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

MedlinePlus Genetics : ⁴³ 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.People with the pure form of spastic paraplegia type 2 experience spasticity in the lower limbs, usually without any additional features. People with the complex form of spastic paraplegia type 2 have lower limb spasticity and can also experience problems with movement and balance (ataxia); involuntary movements of the eyes (nystagmus); mild intellectual disability; involuntary, rhythmic shaking (tremor); and degeneration (atrophy) of the optic nerves, which carry information from the eyes to the brain. Symptoms usually become apparent between the ages of 1 and 5 years; those affected are typically able to walk and have a normal lifespan.

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. For discussion of genetic heterogeneity of X-linked SPG, see 303350. (312920) (Updated 05-Mar-2021)

UniProtKB/Swiss-Prot : ⁷³ 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.

Wikipedia : ⁷⁴ Hereditary spastic paraplegia (HSP) is a group of inherited diseases whose main feature is a progressive... more...

Clinical features from OMIM®:

312920 (Updated 05-Mar-2021)

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

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