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  • CN375955 has been replaced by C5882738, showing C5882738

Spastic ataxia 10, autosomal recessive(SPAX10)

MedGen UID:
1851662
Concept ID:
C5882738
Disease or Syndrome
Synonym: SPAX10
 
Gene (location): COQ4 (9q34.11)
 
Monarch Initiative: MONDO:0958009
OMIM®: 620666

Definition

Autosomal recessive spastic ataxia-10 (SPAX10) is a slowly progressive movement disorder with a variable age at onset (range infancy to adulthood). Affected individuals present with gait abnormalities due to spasticity and hyperreflexia of the lower limbs and/or cerebellar gait and limb ataxia. More variable features may include dysarthria, saccadic eye movements, and mild cognitive impairment. Some patients show cerebellar atrophy on brain imaging. The disorder can be classified as a movement disorder on the ataxia-spasticity spectrum (ASS) (Cordts et al., 2022). For a discussion of genetic heterogeneity of spastic ataxia, see SPAX1 (108600). [from OMIM]

Clinical features

From HPO
Ankle clonus
MedGen UID:
68672
Concept ID:
C0238651
Finding
Clonus is an involuntary tendon reflex that causes repeated flexion and extension of the foot. Ankle clonus is tested by rapidly flexing the foot upward.
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.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Postural tremor
MedGen UID:
66696
Concept ID:
C0234378
Sign or Symptom
A type of tremors that is triggered by holding a limb in a fixed position.
Hoffmann sign
MedGen UID:
78828
Concept ID:
C0277839
Sign or Symptom
A Hoffmann test is performed by flicking the fingernail of the long finger, from dorsal to volar, on each hand while the hand was supported by the examiner's hand. The test was done with the neck in the neutral position and then with the neck maximally forward flexed. Any flexion of the ipsilateral thumb and/or index finger was interpreted as a positive test.
Cognitive impairment
MedGen UID:
90932
Concept ID:
C0338656
Mental or Behavioral Dysfunction
Abnormal cognition is characterized by deficits in thinking, reasoning, or remembering.
Knee clonus
MedGen UID:
488908
Concept ID:
C0520823
Finding
Clonus is an involuntary tendon reflex that causes repeated flexion and extension of the foot. Knee clonus can be tested by rapidly pushing the patella towards the toes.
Cerebellar atrophy
MedGen UID:
196624
Concept ID:
C0740279
Disease or Syndrome
Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event.
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.
Lower limb spasticity
MedGen UID:
220865
Concept ID:
C1271100
Finding
Spasticity (velocity-dependent increase in tonic stretch reflexes with increased muscle tone and hyperexcitable tendon reflexes) in the muscles of the lower limbs, hips, and pelvis.
Upper limb spasticity
MedGen UID:
220882
Concept ID:
C1273957
Finding
Hippocampal sclerosis
MedGen UID:
1778719
Concept ID:
C1504404
Disease or Syndrome
Hippocampal sclerosis is a neuropathologic finding characterized by neuronal loss and gliosis in the CA-1 and subiculum of the hippocampus.
Lower limb hyperreflexia
MedGen UID:
322973
Concept ID:
C1836696
Finding
Loss of ambulation
MedGen UID:
332305
Concept ID:
C1836843
Finding
Inability to walk in a person who previous had the ability to walk.
Cerebellar vermis hypoplasia
MedGen UID:
333548
Concept ID:
C1840379
Finding
Underdevelopment of the vermis of cerebellum.
Hyperreflexia in upper limbs
MedGen UID:
375112
Concept ID:
C1843175
Finding
Postural instability
MedGen UID:
334529
Concept ID:
C1843921
Finding
A tendency to fall or the inability to keep oneself from falling; imbalance. The retropulsion test is widely regarded as the gold standard to evaluate postural instability, Use of the retropulsion test includes a rapid balance perturbation in the backward direction, and the number of balance correcting steps (or total absence thereof) is used to rate the degree of postural instability. Healthy subjects correct such perturbations with either one or two large steps, or without taking any steps, hinging rapidly at the hips while swinging the arms forward as a counterweight. In patients with balance impairment, balance correcting steps are often too small, forcing patients to take more than two steps. Taking three or more steps is generally considered to be abnormal, and taking more than five steps is regarded as being clearly abnormal. Markedly affected patients continue to step backward without ever regaining their balance and must be caught by the examiner (this would be called true retropulsion). Even more severely affected patients fail to correct entirely, and fall backward like a pushed toy soldier, without taking any corrective steps.
Hypertonia
MedGen UID:
10132
Concept ID:
C0026826
Finding
A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move.
Visual impairment
MedGen UID:
777085
Concept ID:
C3665347
Finding
Visual impairment (or vision impairment) is vision loss (of a person) to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive correction, medication, or surgery.

Professional guidelines

PubMed

Perry SE, Troche M, Huber JE, Curtis J, Kiefer B, Sevitz J, Dennard Q, Borders J, Browy JR, Dakin A, Gonzalez V, Chapman J, Wu T, Katz L, Britton D
Am J Speech Lang Pathol 2024 Mar 7;33(2):1069-1097. Epub 2024 Jan 17 doi: 10.1044/2023_AJSLP-23-00274. PMID: 38232176

Recent clinical studies

Etiology

Perry SE, Troche M, Huber JE, Curtis J, Kiefer B, Sevitz J, Dennard Q, Borders J, Browy JR, Dakin A, Gonzalez V, Chapman J, Wu T, Katz L, Britton D
Am J Speech Lang Pathol 2024 Mar 7;33(2):1069-1097. Epub 2024 Jan 17 doi: 10.1044/2023_AJSLP-23-00274. PMID: 38232176
Lessard I, Masterman V, Côté I, Gagnon C, Duchesne E
PLoS One 2022;17(12):e0279406. Epub 2022 Dec 28 doi: 10.1371/journal.pone.0279406. PMID: 36576926Free PMC Article
Santos M, Damásio J, Carmona S, Neto JL, Dehghani N, Guedes LC, Barbot C, Barros J, Brás J, Sequeiros J, Guerreiro R
Cells 2022 Mar 12;11(6) doi: 10.3390/cells11060981. PMID: 35326432Free PMC Article
Pilliod J, Moutton S, Lavie J, Maurat E, Hubert C, Bellance N, Anheim M, Forlani S, Mochel F, N'Guyen K, Thauvin-Robinet C, Verny C, Milea D, Lesca G, Koenig M, Rodriguez D, Houcinat N, Van-Gils J, Durand CM, Guichet A, Barth M, Bonneau D, Convers P, Maillart E, Guyant-Marechal L, Hannequin D, Fromager G, Afenjar A, Chantot-Bastaraud S, Valence S, Charles P, Berquin P, Rooryck C, Bouron J, Brice A, Lacombe D, Rossignol R, Stevanin G, Benard G, Burglen L, Durr A, Goizet C, Coupry I
Ann Neurol 2015 Dec;78(6):871-86. Epub 2015 Nov 14 doi: 10.1002/ana.24509. PMID: 26288984
Finsterer J
Can J Neurol Sci 2009 Jul;36(4):409-28. doi: 10.1017/s0317167100007733. PMID: 19650351

Diagnosis

Perry SE, Troche M, Huber JE, Curtis J, Kiefer B, Sevitz J, Dennard Q, Borders J, Browy JR, Dakin A, Gonzalez V, Chapman J, Wu T, Katz L, Britton D
Am J Speech Lang Pathol 2024 Mar 7;33(2):1069-1097. Epub 2024 Jan 17 doi: 10.1044/2023_AJSLP-23-00274. PMID: 38232176
Ashrafi MR, Mohammadi P, Tavasoli AR, Heidari M, Hosseinpour S, Rasulinejad M, Rohani M, Akbari MG, Malamiri RA, Badv RS, Fathi D, Dehnavi AZ, Savad S, Rabbani A, Synofzik M, Mahdieh N, Rezaei Z
Cerebellum 2023 Aug;22(4):640-650. Epub 2022 Jun 22 doi: 10.1007/s12311-022-01430-3. PMID: 35731353
Sharma R, Aravindhan A, Puente C, Veerapandiyan A
J Investig Med High Impact Case Rep 2022 Jan-Dec;10:23247096221139670. doi: 10.1177/23247096221139670. PMID: 36458808Free PMC Article
Santos M, Damásio J, Carmona S, Neto JL, Dehghani N, Guedes LC, Barbot C, Barros J, Brás J, Sequeiros J, Guerreiro R
Cells 2022 Mar 12;11(6) doi: 10.3390/cells11060981. PMID: 35326432Free PMC Article
Pilliod J, Moutton S, Lavie J, Maurat E, Hubert C, Bellance N, Anheim M, Forlani S, Mochel F, N'Guyen K, Thauvin-Robinet C, Verny C, Milea D, Lesca G, Koenig M, Rodriguez D, Houcinat N, Van-Gils J, Durand CM, Guichet A, Barth M, Bonneau D, Convers P, Maillart E, Guyant-Marechal L, Hannequin D, Fromager G, Afenjar A, Chantot-Bastaraud S, Valence S, Charles P, Berquin P, Rooryck C, Bouron J, Brice A, Lacombe D, Rossignol R, Stevanin G, Benard G, Burglen L, Durr A, Goizet C, Coupry I
Ann Neurol 2015 Dec;78(6):871-86. Epub 2015 Nov 14 doi: 10.1002/ana.24509. PMID: 26288984

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
Traschütz A, Adarmes-Gómez AD, Anheim M, Baets J, Brais B, Gagnon C, Gburek-Augustat J, Doss S, Hanağası HA, Kamm C, Klivenyi P, Klockgether T, Klopstock T, Minnerop M, Münchau A, Renaud M, Santorelli FM, Schöls L, Thieme A, Vielhaber S, van de Warrenburg BP, Zanni G, Hilgers RD; PREPARE Consortium, Synofzik M
Ann Neurol 2023 Sep;94(3):470-485. Epub 2023 Jun 12 doi: 10.1002/ana.26712. PMID: 37243847
Gagnon C, Brais B, Lessard I, Lavoie C, Côté I, Mathieu J
Orphanet J Rare Dis 2018 Sep 19;13(1):165. doi: 10.1186/s13023-018-0898-z. PMID: 30231904Free PMC Article

Prognosis

Sharma R, Aravindhan A, Puente C, Veerapandiyan A
J Investig Med High Impact Case Rep 2022 Jan-Dec;10:23247096221139670. doi: 10.1177/23247096221139670. PMID: 36458808Free 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
Gagnon C, Brais B, Lessard I, Lavoie C, Côté I, Mathieu J
Neurology 2019 Oct 15;93(16):e1543-e1549. Epub 2019 Sep 18 doi: 10.1212/WNL.0000000000008313. PMID: 31534027Free PMC Article
Gagnon C, Lessard I, Lavoie C, Côté I, St-Gelais R, Mathieu J, Brais B
Neurology 2018 Oct 2;91(14):e1307-e1311. Epub 2018 Aug 29 doi: 10.1212/WNL.0000000000006290. PMID: 30158165Free PMC Article
De Braekeleer M, Giasson F, Mathieu J, Roy M, Bouchard JP, Morgan K
Genet Epidemiol 1993;10(1):17-25. doi: 10.1002/gepi.1370100103. PMID: 8472930

Clinical prediction guides

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
Gagnon C, Brais B, Lessard I, Lavoie C, Côté I, Mathieu J
Neurology 2019 Oct 15;93(16):e1543-e1549. Epub 2019 Sep 18 doi: 10.1212/WNL.0000000000008313. PMID: 31534027Free 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
Minnerop M, Kurzwelly D, Wagner H, Soehn AS, Reichbauer J, Tao F, Rattay TW, Peitz M, Rehbach K, Giorgetti A, Pyle A, Thiele H, Altmüller J, Timmann D, Karaca I, Lennarz M, Baets J, Hengel H, Synofzik M, Atasu B, Feely S, Kennerson M, Stendel C, Lindig T, Gonzalez MA, Stirnberg R, Sturm M, Roeske S, Jung J, Bauer P, Lohmann E, Herms S, Heilmann-Heimbach S, Nicholson G, Mahanjah M, Sharkia R, Carloni P, Brüstle O, Klopstock T, Mathews KD, Shy ME, de Jonghe P, Chinnery PF, Horvath R, Kohlhase J, Schmitt I, Wolf M, Greschus S, Amunts K, Maier W, Schöls L, Nürnberg P, Zuchner S, Klockgether T, Ramirez A, Schüle R
Brain 2017 Jun 1;140(6):1561-1578. doi: 10.1093/brain/awx095. PMID: 28459997Free PMC Article
Pilliod J, Moutton S, Lavie J, Maurat E, Hubert C, Bellance N, Anheim M, Forlani S, Mochel F, N'Guyen K, Thauvin-Robinet C, Verny C, Milea D, Lesca G, Koenig M, Rodriguez D, Houcinat N, Van-Gils J, Durand CM, Guichet A, Barth M, Bonneau D, Convers P, Maillart E, Guyant-Marechal L, Hannequin D, Fromager G, Afenjar A, Chantot-Bastaraud S, Valence S, Charles P, Berquin P, Rooryck C, Bouron J, Brice A, Lacombe D, Rossignol R, Stevanin G, Benard G, Burglen L, Durr A, Goizet C, Coupry I
Ann Neurol 2015 Dec;78(6):871-86. Epub 2015 Nov 14 doi: 10.1002/ana.24509. PMID: 26288984

Recent systematic reviews

Perry SE, Troche M, Huber JE, Curtis J, Kiefer B, Sevitz J, Dennard Q, Borders J, Browy JR, Dakin A, Gonzalez V, Chapman J, Wu T, Katz L, Britton D
Am J Speech Lang Pathol 2024 Mar 7;33(2):1069-1097. Epub 2024 Jan 17 doi: 10.1044/2023_AJSLP-23-00274. PMID: 38232176

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