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Spastic ataxia 4(SPAX4)

MedGen UID:
462275
Concept ID:
C3150925
Disease or Syndrome
Synonym: Ataxia, spastic, 4, autosomal recessive
SNOMED CT: Autosomal recessive spastic ataxia type 4 (784347002); Autosomal recessive spastic ataxia, optic atrophy, dysarthria syndrome (784347002); SPAX 4 - autosomal recessive spastic ataxia type 4 (784347002)
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).
 
Gene (location): MTPAP (10p11.23)
 
Monarch Initiative: MONDO:0013354
OMIM®: 613672
Orphanet: ORPHA254343

Definition

A rare genetic autosomal recessive spastic ataxia disease with characteristics of the onset in early childhood of spastic paraparesis, cerebellar ataxia, dysarthria and optic atrophy. Caused by homozygous mutation in the MTPAP gene on chromosome 10p11. [from SNOMEDCT_US]

Clinical features

From HPO
Decreased Achilles reflex
MedGen UID:
324765
Concept ID:
C1837323
Finding
Decreased intensity of the Achilles reflex (also known as the ankle jerk reflex), which can be elicited by tapping the tendon is tapped while the foot is dorsiflexed.
Lower limb hypertonia
MedGen UID:
375612
Concept ID:
C1845245
Finding
Upper limb hypertonia
MedGen UID:
867515
Concept ID:
C4021898
Anatomical Abnormality
Increased muscle tone observed in the arms of the affected person.
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
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.
Spastic paraparesis
MedGen UID:
52432
Concept ID:
C0037771
Sign or Symptom
Mild or moderate loss of motor function accompanied by spasticity in the lower extremities. This condition is a manifestation of CENTRAL NERVOUS SYSTEM DISEASES that cause injury to the motor cortex or descending motor pathways.
Emotional lability
MedGen UID:
39319
Concept ID:
C0085633
Mental or Behavioral Dysfunction
Unstable emotional experiences and frequent mood changes; emotions that are easily aroused, intense, and/or disproportionate to events and circumstances.
Hyperactive patellar reflex
MedGen UID:
66003
Concept ID:
C0240116
Finding
Delayed ability to walk
MedGen UID:
66034
Concept ID:
C0241726
Finding
A failure to achieve the ability to walk at an appropriate developmental stage. Most children learn to walk in a series of stages, and learn to walk short distances independently between 12 and 15 months.
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
Limb ataxia
MedGen UID:
196692
Concept ID:
C0750937
Finding
A kind of ataxia that affects movements of the extremities.
Gait ataxia
MedGen UID:
155642
Concept ID:
C0751837
Sign or Symptom
A type of ataxia characterized by the impairment of the ability to coordinate the movements required for normal walking. Gait ataxia is characteirzed by a wide-based staggering gait with a tendency to fall.
Spastic ataxia
MedGen UID:
376528
Concept ID:
C1849156
Disease or Syndrome
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.
Optic atrophy
MedGen UID:
18180
Concept ID:
C0029124
Disease or Syndrome
Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVSpastic ataxia 4
Follow this link to review classifications for Spastic ataxia 4 in Orphanet.

Professional guidelines

PubMed

Méreaux JL, Firanescu C, Coarelli G, Kvarnung M, Rodrigues R, Pegoraro E, Tazir M, Taithe F, Valter R, Huin V, Lidström K, Banneau G, Morais S, Parodi L, Coutelier M, Papin M, Svenningsson P, Azulay JP, Alonso I, Nilsson D, Brice A, Le Guern E, Press R, Vazza G, Loureiro JL, Goizet C, Durr A, Paucar M, Stevanin G
Neurogenetics 2021 Mar;22(1):71-79. Epub 2021 Jan 23 doi: 10.1007/s10048-020-00633-2. PMID: 33486633Free PMC Article
Vogel AP, Stoll LH, Oettinger A, Rommel N, Kraus EM, Timmann D, Scott D, Atay C, Storey E, Schöls L, Synofzik M
J Neurol 2019 May;266(5):1260-1266. Epub 2019 Mar 6 doi: 10.1007/s00415-019-09258-4. PMID: 30840144
van de Warrenburg BP, van Gaalen J, Boesch S, Burgunder JM, Dürr A, Giunti P, Klockgether T, Mariotti C, Pandolfo M, Riess O
Eur J Neurol 2014 Apr;21(4):552-62. Epub 2014 Jan 13 doi: 10.1111/ene.12341. PMID: 24418350

Recent clinical studies

Etiology

Azeem A, Ahmed AN, Khan N, Voutsina N, Ullah I, Ubeyratna N, Yasin M, Baple EL, Crosby AH, Rawlins LE, Saleha S
BMC Neurol 2024 Sep 20;24(1):354. doi: 10.1186/s12883-024-03855-1. PMID: 39304850Free PMC Article
Lessard I, Côté I, St-Gelais R, Hébert LJ, Brais B, Mathieu J, Rodrigue X, Gagnon C
Cerebellum 2024 Apr;23(2):489-501. Epub 2023 Apr 27 doi: 10.1007/s12311-023-01558-w. PMID: 37101017
Rezk M, Pittock SJ, Kapadia RK, Knight AM, Guo Y, Gupta P, LaFrance-Corey RG, Zekeridou A, McKeon A, Dasari S, Mills JR, Dubey D
Front Immunol 2023;14:1243946. Epub 2023 Sep 18 doi: 10.3389/fimmu.2023.1243946. PMID: 37795104Free PMC Article
Wang M, Yang H, Lin Z, Li X, Liu L, Huang S, Zhao H, Zhu X, Xiao Q, Duan R, Wang J, Zuchner S, Tang B, Zhang R
J Neurol 2023 Oct;270(10):4959-4967. Epub 2023 Jun 26 doi: 10.1007/s00415-023-11821-z. PMID: 37365282
Finsterer J
Can J Neurol Sci 2009 Jul;36(4):409-28. doi: 10.1017/s0317167100007733. PMID: 19650351

Diagnosis

Rezk M, Pittock SJ, Kapadia RK, Knight AM, Guo Y, Gupta P, LaFrance-Corey RG, Zekeridou A, McKeon A, Dasari S, Mills JR, Dubey D
Front Immunol 2023;14:1243946. Epub 2023 Sep 18 doi: 10.3389/fimmu.2023.1243946. PMID: 37795104Free PMC Article
Wang M, Yang H, Lin Z, Li X, Liu L, Huang S, Zhao H, Zhu X, Xiao Q, Duan R, Wang J, Zuchner S, Tang B, Zhang R
J Neurol 2023 Oct;270(10):4959-4967. Epub 2023 Jun 26 doi: 10.1007/s00415-023-11821-z. PMID: 37365282
Pauly MG, Brüggemann N, Efthymiou S, Grözinger A, Diaw SH, Chelban V, Turchetti V, Vona B, Tadic V, Houlden H, Münchau A, Lohmann K
Int J Mol Sci 2023 Jan 18;24(3) doi: 10.3390/ijms24031874. PMID: 36768210Free PMC Article
Parodi L, Coarelli G, Stevanin G, Brice A, Durr A
Curr Opin Neurol 2018 Aug;31(4):462-471. doi: 10.1097/WCO.0000000000000585. PMID: 29847346
Iqbal Z, Rydning SL, Wedding IM, Koht J, Pihlstrøm L, Rengmark AH, Henriksen SP, Tallaksen CM, Toft M
PLoS One 2017;12(3):e0174667. Epub 2017 Mar 31 doi: 10.1371/journal.pone.0174667. PMID: 28362824Free PMC Article

Therapy

Katragadda P, Holla VV, Kamble N, Saini J, Yadav R, Pal PK
Tremor Other Hyperkinet Mov (N Y) 2024;14:10. Epub 2024 Mar 6 doi: 10.5334/tohm.851. PMID: 38476584Free PMC Article
Lessard I, Côté I, St-Gelais R, Hébert LJ, Brais B, Mathieu J, Rodrigue X, Gagnon C
Cerebellum 2024 Apr;23(2):489-501. Epub 2023 Apr 27 doi: 10.1007/s12311-023-01558-w. PMID: 37101017
Bourcier D, Bélanger M, Côté I, Brais B, Synofzik M, Brisson JD, Rodrigue X, Gagnon MM, Mathieu J, Gagnon C
J Neurol Sci 2020 Oct 15;417:117050. Epub 2020 Jul 18 doi: 10.1016/j.jns.2020.117050. PMID: 32736199
Lotti M, Moretto A
Toxicol Rev 2005;24(1):37-49. doi: 10.2165/00139709-200524010-00003. PMID: 16042503
Gagnon C, Mathieu J, Desrosiers J
Can J Neurol Sci 2004 Nov;31(4):484-9. doi: 10.1017/s031716710000367x. PMID: 15595252

Prognosis

Lessard I, Côté I, St-Gelais R, Hébert LJ, Brais B, Mathieu J, Rodrigue X, Gagnon C
Cerebellum 2024 Apr;23(2):489-501. Epub 2023 Apr 27 doi: 10.1007/s12311-023-01558-w. PMID: 37101017
Rezk M, Pittock SJ, Kapadia RK, Knight AM, Guo Y, Gupta P, LaFrance-Corey RG, Zekeridou A, McKeon A, Dasari S, Mills JR, Dubey D
Front Immunol 2023;14:1243946. Epub 2023 Sep 18 doi: 10.3389/fimmu.2023.1243946. PMID: 37795104Free PMC Article
Lessard I, St-Gelais R, Hébert LJ, Côté I, Mathieu J, Brais B, Gagnon C
Orphanet J Rare Dis 2021 Oct 14;16(1):432. doi: 10.1186/s13023-021-02054-2. PMID: 34649570Free PMC Article
Dosi C, Galatolo D, Rubegni A, Doccini S, Pasquariello R, Nesti C, Sicca F, Barghigiani M, Battini R, Tessa A, Santorelli FM
Ann Clin Transl Neurol 2020 Apr;7(4):595-601. Epub 2020 Apr 1 doi: 10.1002/acn3.51024. PMID: 32237276Free PMC Article
van de Warrenburg BP, van Gaalen J, Boesch S, Burgunder JM, Dürr A, Giunti P, Klockgether T, Mariotti C, Pandolfo M, Riess O
Eur J Neurol 2014 Apr;21(4):552-62. Epub 2014 Jan 13 doi: 10.1111/ene.12341. PMID: 24418350

Clinical prediction guides

Lessard I, Côté I, St-Gelais R, Hébert LJ, Brais B, Mathieu J, Rodrigue X, Gagnon C
Cerebellum 2024 Apr;23(2):489-501. Epub 2023 Apr 27 doi: 10.1007/s12311-023-01558-w. PMID: 37101017
Lessard I, St-Gelais R, Hébert LJ, Côté I, Mathieu J, Brais B, Gagnon C
Orphanet J Rare Dis 2021 Oct 14;16(1):432. doi: 10.1186/s13023-021-02054-2. PMID: 34649570Free PMC Article
Nanetti L, Sarto E, Castaldo A, Magri S, Mongelli A, Rossi Sebastiano D, Canafoglia L, Grisoli M, Malaguti C, Rivieri F, D'Amico MC, Di Bella D, Franceschetti S, Mariotti C, Taroni F
J Neurol 2019 Feb;266(2):378-385. Epub 2018 Dec 4 doi: 10.1007/s00415-018-9141-z. PMID: 30515630
Parkinson MH, Bartmann AP, Clayton LMS, Nethisinghe S, Pfundt R, Chapple JP, Reilly MM, Manji H, Wood NJ, Bremner F, Giunti P
Brain 2018 Apr 1;141(4):989-999. doi: 10.1093/brain/awy028. PMID: 29538656
Lotti M, Moretto A
Toxicol Rev 2005;24(1):37-49. doi: 10.2165/00139709-200524010-00003. PMID: 16042503

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