U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Hereditary spastic paraplegia 23(SPG23)

MedGen UID:
167094
•Concept ID:
C0796019
•
Disease or Syndrome
Synonyms: Autosomal recessive spastic paraplegia type 23; Lison syndrome; SPASTIC PARAPARESIS, VITILIGO, PREMATURE GRAYING, CHARACTERISTIC FACIES; Spastic paraplegia 23; Spastic paraplegia and pigmentary abnormalities; Spastic paraplegia vitiligo premature graying and characteristic facies; SPASTIC PARAPLEGIA WITH PIGMENTARY ABNORMALITIES; SPG 23
SNOMED CT: Autosomal recessive spastic paraplegia type 23 (726608002); Lison syndrome (726608002); Spastic paraparesis, vitiligo, premature graying, characteristic facies syndrome (726608002)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
•Concept ID:
C0441748
•
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (Orphanet)
 
Gene (location): DSTYK (1q32.1)
 
Monarch Initiative: MONDO:0010046
OMIM®: 270750
Orphanet: ORPHA101003

Definition

Spastic paraplegia-23 (SPG23) is an autosomal recessive neurologic disorder characterized by childhood-onset spastic paraplegia resulting in gait difficulties and associated with pigmentary abnormalities, including premature graying of the hair and vitiligo-like or hyperpigmented skin lesions. Some patients may also have a peripheral neuropathy (summary by Lee et al., 2017). [from OMIM]

Clinical features

From HPO
Scapular winging
MedGen UID:
66822
•Concept ID:
C0240953
•
Anatomical Abnormality
Abnormal protrusion of the scapula away from the surface of the back.
See: Feature record | Search on this feature
Lower limb muscle weakness
MedGen UID:
324478
•Concept ID:
C1836296
•
Finding
Weakness of the muscles of the legs.
See: Feature record | Search on this feature
Intellectual disability, mild
MedGen UID:
10044
•Concept ID:
C0026106
•
Mental or Behavioral Dysfunction
Mild intellectual disability is defined as an intelligence quotient (IQ) in the range of 50-69.
See: Feature record | Search on this feature
Peripheral neuropathy
MedGen UID:
18386
•Concept ID:
C0031117
•
Disease or Syndrome
Peripheral neuropathy is a general term for any disorder of the peripheral nervous system. The main clinical features used to classify peripheral neuropathy are distribution, type (mainly demyelinating versus mainly axonal), duration, and course.
See: Feature record | Search on this feature
Babinski sign
MedGen UID:
19708
•Concept ID:
C0034935
•
Finding
Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract.
See: Feature record | Search on this feature
Spastic paraplegia
MedGen UID:
20882
•Concept ID:
C0037772
•
Disease or Syndrome
Spasticity and weakness of the leg and hip muscles.
See: Feature record | Search on this feature
Hyperreflexia
MedGen UID:
57738
•Concept ID:
C0151889
•
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
See: Feature record | Search on this feature
Loss of ambulation
MedGen UID:
332305
•Concept ID:
C1836843
•
Finding
Inability to walk in a person who previous had the ability to walk.
See: Feature record | Search on this feature
Micrognathia
MedGen UID:
44428
•Concept ID:
C0025990
•
Congenital Abnormality
Developmental hypoplasia of the mandible.
See: Feature record | Search on this feature
Retrognathia
MedGen UID:
19766
•Concept ID:
C0035353
•
Congenital Abnormality
An abnormality in which the mandible is mislocalised posteriorly.
See: Feature record | Search on this feature
Scoliosis
MedGen UID:
11348
•Concept ID:
C0036439
•
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
See: Feature record | Search on this feature
Microcephaly
MedGen UID:
1644158
•Concept ID:
C4551563
•
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
See: Feature record | Search on this feature
Narrow face
MedGen UID:
373334
•Concept ID:
C1837463
•
Finding
Bizygomatic (upper face) and bigonial (lower face) width are both more than 2 standard deviations below the mean (objective); or, an apparent reduction in the width of the upper and lower face (subjective).
See: Feature record | Search on this feature
Vitiligo
MedGen UID:
22677
•Concept ID:
C0042900
•
Disease or Syndrome
Generalized well circumscribed patches of leukoderma that are generally distributed over symmetric body locations and is due to autoimmune destruction of melanocytes.
See: Feature record | Search on this feature
Multiple lentigines
MedGen UID:
272242
•Concept ID:
C1328931
•
Disease or Syndrome
Presence of an unusually high number of lentigines (singular
See: Feature record | Search on this feature
Premature graying of body hair
MedGen UID:
341386
•Concept ID:
C1849125
•
Finding
See: Feature record | Search on this feature
Hyperpigmentation in sun-exposed areas
MedGen UID:
812207
•Concept ID:
C3805877
•
Finding
See: Feature record | Search on this feature
Show allHide all

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHereditary spastic paraplegia 23
Follow this link to review classifications for Hereditary spastic paraplegia 23 in Orphanet.

Professional guidelines

PubMed

The Puzzle of Hereditary Spastic Paraplegia: From Epidemiology to Treatment.
Meyyazhagan A, Kuchi Bhotla H, Pappuswamy M, Orlacchio A
Int J Mol Sci 2022 Jul 11;23(14) doi: 10.3390/ijms23147665. PMID: 35887006Free PMC Article
How are genetic test results being used by Australian life insurers?
Barlow-Stewart K, Liepins M, Doble A, Otlowski M
Eur J Hum Genet 2018 Sep;26(9):1248-1256. Epub 2018 Jun 11 doi: 10.1038/s41431-018-0198-z. PMID: 29891881Free PMC Article
Prenatal diagnosis of hereditary spastic paraplegia.
Hedera P, Williamson JA, Rainier S, Alvarado D, Tukel T, Apak M, Fink JK
Prenat Diagn 2001 Mar;21(3):202-6. doi: 10.1002/1097-0223(200103)21:3<202::aid-pd4>3.0.co;2-u. PMID: 11260609

Recent clinical studies

Etiology

Expanding SPTAN1 monoallelic variant associated disorders: From epileptic encephalopathy to pure spastic paraplegia and ataxia.
Morsy H, Benkirane M, Cali E, Rocca C, Zhelcheska K, Cipriani V, Galanaki E, Maroofian R, Efthymiou S, Murphy D, O'Driscoll M, Suri M, Banka S, Clayton-Smith J, Wright T, Redman M, Bassetti JA, Nizon M, Cogne B, Jamra RA, Bartolomaeus T, Heruth M, Krey I, Gburek-Augustat J, Wieczorek D, Gattermann F, Mcentagart M, Goldenberg A, Guyant-Marechal L, Garcia-Moreno H, Giunti P, Chabrol B, Bacrot S, Buissonnière R, Magry V, Gowda VK, Srinivasan VM, Melegh B, Szabó A, Sümegi K, Cossée M, Ziff M, Butterfield R, Hunt D, Bird-Lieberman G, Hanna M, Koenig M, Stankewich M, Vandrovcova J, Houlden H; Genomics England Research Consortium
Genet Med 2023 Jan;25(1):76-89. Epub 2022 Nov 4 doi: 10.1016/j.gim.2022.09.013. PMID: 36331550
Inherited metabolic diseases mimicking hereditary spastic paraplegia (HSP): a chance for treatment.
Teive HAG, Camargo CHF, Pereira ER, Coutinho L, Munhoz RP
Neurogenetics 2022 Jul;23(3):167-177. Epub 2022 Apr 9 doi: 10.1007/s10048-022-00688-3. PMID: 35397036
Genetic mutation analysis of hereditary spastic paraplegia: A retrospective study.
Cui F, Sun L, Qiao J, Li J, Li M, Chen S, Sun B, Huang X
Medicine (Baltimore) 2020 Jun 5;99(23):e20193. doi: 10.1097/MD.0000000000020193. PMID: 32501971Free PMC Article
Hereditary spastic paraplegia: a clinical and epidemiological study of a Brazilian pediatric population.
Ortega RPM, Rosemberg S
Arq Neuropsiquiatr 2019 Jan;77(1):10-18. doi: 10.1590/0004-282X20180153. PMID: 30758437
Hereditary spastic paraplegia type 5: natural history, biomarkers and a randomized controlled trial.
Schöls L, Rattay TW, Martus P, Meisner C, Baets J, Fischer I, Jägle C, Fraidakis MJ, Martinuzzi A, Saute JA, Scarlato M, Antenora A, Stendel C, Höflinger P, Lourenco CM, Abreu L, Smets K, Paucar M, Deconinck T, Bis DM, Wiethoff S, Bauer P, Arnoldi A, Marques W, Jardim LB, Hauser S, Criscuolo C, Filla A, Züchner S, Bassi MT, Klopstock T, De Jonghe P, Björkhem I, Schüle R
Brain 2017 Dec 1;140(12):3112-3127. doi: 10.1093/brain/awx273. PMID: 29126212Free PMC Article

Diagnosis

The clinical and molecular spectrum of ZFYVE26-associated hereditary spastic paraplegia: SPG15.
Saffari A, Kellner M, Jordan C, Rosengarten H, Mo A, Zhang B, Strelko O, Neuser S, Davis MY, Yoshikura N, Futamura N, Takeuchi T, Nabatame S, Ishiura H, Tsuji S, Aldeen HS, Cali E, Rocca C, Houlden H, Efthymiou S, Assmann B, Yoon G, Trombetta BA, Kivisäkk P, Eichler F, Nan H, Takiyama Y, Tessa A, Santorelli FM, Sahin M, Blackstone C, Yang E, Schüle R, Ebrahimi-Fakhari D
Brain 2023 May 2;146(5):2003-2015. doi: 10.1093/brain/awac391. PMID: 36315648Free PMC Article
Specific Gait Changes in Prodromal Hereditary Spastic Paraplegia Type 4: preSPG4 Study.
Laßmann C, Ilg W, Schneider M, Völker M, Haeufle DFB, Schüle R, Giese M, Synofzik M, Schöls L, Rattay TW
Mov Disord 2022 Dec;37(12):2417-2426. Epub 2022 Aug 29 doi: 10.1002/mds.29199. PMID: 36054444
Inherited metabolic diseases mimicking hereditary spastic paraplegia (HSP): a chance for treatment.
Teive HAG, Camargo CHF, Pereira ER, Coutinho L, Munhoz RP
Neurogenetics 2022 Jul;23(3):167-177. Epub 2022 Apr 9 doi: 10.1007/s10048-022-00688-3. PMID: 35397036
Hereditary Spastic Paraplegia: An Update.
Meyyazhagan A, Orlacchio A
Int J Mol Sci 2022 Feb 1;23(3) doi: 10.3390/ijms23031697. PMID: 35163618Free PMC Article
Genetic and Epidemiological Study of Adult Ataxia and Spastic Paraplegia in Eastern Quebec.
Haj Salem I, Beaudin M, Stumpf M, Estiar MA, Côté PO, Brunet F, Gamache PL, Rouleau GA, Mourabit-Amari K, Gan-Or Z, Dupré N
Can J Neurol Sci 2021 Sep;48(5):655-665. Epub 2021 Jan 5 doi: 10.1017/cjn.2020.277. PMID: 33397523

Therapy

The clinical and molecular spectrum of ZFYVE26-associated hereditary spastic paraplegia: SPG15.
Saffari A, Kellner M, Jordan C, Rosengarten H, Mo A, Zhang B, Strelko O, Neuser S, Davis MY, Yoshikura N, Futamura N, Takeuchi T, Nabatame S, Ishiura H, Tsuji S, Aldeen HS, Cali E, Rocca C, Houlden H, Efthymiou S, Assmann B, Yoon G, Trombetta BA, Kivisäkk P, Eichler F, Nan H, Takiyama Y, Tessa A, Santorelli FM, Sahin M, Blackstone C, Yang E, Schüle R, Ebrahimi-Fakhari D
Brain 2023 May 2;146(5):2003-2015. doi: 10.1093/brain/awac391. PMID: 36315648Free PMC Article
The Puzzle of Hereditary Spastic Paraplegia: From Epidemiology to Treatment.
Meyyazhagan A, Kuchi Bhotla H, Pappuswamy M, Orlacchio A
Int J Mol Sci 2022 Jul 11;23(14) doi: 10.3390/ijms23147665. PMID: 35887006Free PMC Article
Successful treatment of infantile oxysterol 7α-hydroxylase deficiency with oral chenodeoxycholic acid.
Tang YP, Gong JY, Setchell KDR, Zhang W, Zhao J, Wang JS
BMC Gastroenterol 2021 Apr 13;21(1):163. doi: 10.1186/s12876-021-01749-x. PMID: 33849447Free PMC Article
Improving gait adaptability in patients with hereditary spastic paraplegia (Move-HSP): study protocol for a randomized controlled trial.
van de Venis L, van de Warrenburg BPC, Weerdesteyn V, van Lith BJH, Geurts ACH, Nonnekes J
Trials 2021 Jan 7;22(1):32. doi: 10.1186/s13063-020-04932-9. PMID: 33413555Free PMC Article
Hereditary spastic paraplegia type 5: natural history, biomarkers and a randomized controlled trial.
Schöls L, Rattay TW, Martus P, Meisner C, Baets J, Fischer I, Jägle C, Fraidakis MJ, Martinuzzi A, Saute JA, Scarlato M, Antenora A, Stendel C, Höflinger P, Lourenco CM, Abreu L, Smets K, Paucar M, Deconinck T, Bis DM, Wiethoff S, Bauer P, Arnoldi A, Marques W, Jardim LB, Hauser S, Criscuolo C, Filla A, Züchner S, Bassi MT, Klopstock T, De Jonghe P, Björkhem I, Schüle R
Brain 2017 Dec 1;140(12):3112-3127. doi: 10.1093/brain/awx273. PMID: 29126212Free PMC Article

Prognosis

A novel homozygous mutation in ERLIN1 gene causing spastic paraplegia 62 and literature review.
Zhu ZY, Li ZY, Zhang C, Liu XL, Tian WT, Cao L
Eur J Med Genet 2022 Nov;65(11):104608. Epub 2022 Sep 12 doi: 10.1016/j.ejmg.2022.104608. PMID: 36100157
A review of the genetic spectrum of hereditary spastic paraplegias, inherited neuropathies and spinal muscular atrophies in Africans.
Mahungu AC, Monnakgotla N, Nel M, Heckmann JM
Orphanet J Rare Dis 2022 Mar 24;17(1):133. doi: 10.1186/s13023-022-02280-2. PMID: 35331287Free PMC Article
Successful treatment of infantile oxysterol 7α-hydroxylase deficiency with oral chenodeoxycholic acid.
Tang YP, Gong JY, Setchell KDR, Zhang W, Zhao J, Wang JS
BMC Gastroenterol 2021 Apr 13;21(1):163. doi: 10.1186/s12876-021-01749-x. PMID: 33849447Free PMC Article
Autosomal recessive hereditary spastic paraplegia with thin corpus callosum among Saudis.
Wakil SM, Murad HN, Baz BM, Hagos ST, Al-Amr RA, Al-Yamani SA, Al-Wadaee SM, Meyer BF, Bohlega SA
Neurosciences (Riyadh) 2012 Jan;17(1):48-52. PMID: 22246010
'Pure' and 'complicated' forms of hereditary spastic paraplegia presenting in childhood.
Appleton RE, Farrell K, Dunn HG
Dev Med Child Neurol 1991 Apr;33(4):304-12. doi: 10.1111/j.1469-8749.1991.tb14881.x. PMID: 2044852

Clinical prediction guides

The clinical and molecular spectrum of ZFYVE26-associated hereditary spastic paraplegia: SPG15.
Saffari A, Kellner M, Jordan C, Rosengarten H, Mo A, Zhang B, Strelko O, Neuser S, Davis MY, Yoshikura N, Futamura N, Takeuchi T, Nabatame S, Ishiura H, Tsuji S, Aldeen HS, Cali E, Rocca C, Houlden H, Efthymiou S, Assmann B, Yoon G, Trombetta BA, Kivisäkk P, Eichler F, Nan H, Takiyama Y, Tessa A, Santorelli FM, Sahin M, Blackstone C, Yang E, Schüle R, Ebrahimi-Fakhari D
Brain 2023 May 2;146(5):2003-2015. doi: 10.1093/brain/awac391. PMID: 36315648Free PMC Article
Specific Gait Changes in Prodromal Hereditary Spastic Paraplegia Type 4: preSPG4 Study.
Laßmann C, Ilg W, Schneider M, Völker M, Haeufle DFB, Schüle R, Giese M, Synofzik M, Schöls L, Rattay TW
Mov Disord 2022 Dec;37(12):2417-2426. Epub 2022 Aug 29 doi: 10.1002/mds.29199. PMID: 36054444
The Puzzle of Hereditary Spastic Paraplegia: From Epidemiology to Treatment.
Meyyazhagan A, Kuchi Bhotla H, Pappuswamy M, Orlacchio A
Int J Mol Sci 2022 Jul 11;23(14) doi: 10.3390/ijms23147665. PMID: 35887006Free PMC Article
Hereditary Spastic Paraplegia: An Update.
Meyyazhagan A, Orlacchio A
Int J Mol Sci 2022 Feb 1;23(3) doi: 10.3390/ijms23031697. PMID: 35163618Free PMC Article
Disc degeneration-related clinical phenotypes.
Battié MC, Lazáry A, Fairbank J, Eisenstein S, Heywood C, Brayda-Bruno M, Varga PP, McCall I
Eur Spine J 2014 Jun;23 Suppl 3:S305-14. Epub 2013 Jul 25 doi: 10.1007/s00586-013-2903-5. PMID: 23884550

Recent systematic reviews

Movement disorders in hereditary spastic paraplegia (HSP): a systematic review and individual participant data meta-analysis.
Fereshtehnejad SM, Saleh PA, Oliveira LM, Patel N, Bhowmick S, Saranza G, Kalia LV
Neurol Sci 2023 Mar;44(3):947-959. Epub 2022 Nov 28 doi: 10.1007/s10072-022-06516-8. PMID: 36441344Free PMC Article

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Reviews

    Related information

    • ClinVar
      Related medical variations
    • Gene
      Related information in NCBI Gene
    • GTR
      Related information in GTR
    • GTR(Clinical)
      Clinical tests in GTR
    • MeSH
      Related Medical Subject Headings
    • OMIM
      Related records in OMIM
    • OMIM(Genes)
      OMIM records containing genes associated with phenotypes registered in MedGen
    • PMC Articles
      Related information in PubMed Central Links
    • PubMed
      Related literature resources in PubMed
    • PubMed (OMIM)
      Related literature resources in PubMed

    Recent activity

    Clear Turn Off Turn On

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...