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Spinocerebellar ataxia, autosomal recessive 22(SCAR22)

MedGen UID:
934748
Concept ID:
C4310781
Disease or Syndrome
Synonym: SCAR22
 
Gene (location): VWA3B (2q11.2)
 
Monarch Initiative: MONDO:0014845
OMIM®: 616948

Definition

Any autosomal recessive cerebellar ataxia in which the cause of the disease is a mutation in the VWA3B gene. [from MONDO]

Clinical features

From HPO
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
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.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Unsteady gait
MedGen UID:
68544
Concept ID:
C0231686
Finding
A shaky or wobbly manner of walking.
Abnormal pyramidal sign
MedGen UID:
68582
Concept ID:
C0234132
Sign or Symptom
Functional neurological abnormalities related to dysfunction of the pyramidal tract.
Dysmetria
MedGen UID:
68583
Concept ID:
C0234162
Finding
A type of ataxia characterized by the inability to carry out movements with the correct range and motion across the plane of more than one joint related to incorrect estimation of the distances required for targeted movements.
Hypoplasia of the corpus callosum
MedGen UID:
138005
Concept ID:
C0344482
Congenital Abnormality
Underdevelopment of the corpus callosum.
Truncal ataxia
MedGen UID:
96535
Concept ID:
C0427190
Sign or Symptom
Truncal ataxia is a sign of ataxia characterized by instability of the trunk. It usually occurs during sitting.
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.
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.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Intention tremor
MedGen UID:
1642960
Concept ID:
C4551520
Sign or Symptom
A type of kinetic tremor that occurs during target directed movement is called intention tremor. That is, an oscillatory cerebellar ataxia that tends to be absent when the limbs are inactive and during the first part of voluntary movement but worsening as the movement continues and greater precision is required (e.g., in touching a target such as the patient's nose or a physician's finger).
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.

Professional guidelines

PubMed

van Os NJ, Roeleveld N, Weemaes CM, Jongmans MC, Janssens GO, Taylor AM, Hoogerbrugge N, Willemsen MA
Clin Genet 2016 Aug;90(2):105-17. Epub 2016 Jan 20 doi: 10.1111/cge.12710. PMID: 26662178

Recent clinical studies

Etiology

Colucci F, Neri M, Fortunato F, Ferlini A, Carrozzo R, Torraco A, Lamantea E, Legati A, Tecilla G, Pugliatti M, Sensi M
Cerebellum 2023 Dec;22(6):1313-1319. Epub 2022 Nov 30 doi: 10.1007/s12311-022-01497-y. PMID: 36447112
Rezende Filho FM, Bremner F, Pedroso JL, de Andrade JBC, Marianelli BF, Lourenço CM, Marques-Júnior W, França MC Jr, Kok F, Sallum JMF, Parkinson MH, Barsottini OG, Giunti P
Mov Disord 2021 Sep;36(9):2027-2035. Epub 2021 Apr 23 doi: 10.1002/mds.28612. PMID: 33893680
Perkins E, Suminaite D, Jackson M
J Physiol 2016 Aug 15;594(16):4661-76. Epub 2016 Apr 24 doi: 10.1113/JP271195. PMID: 26821241Free PMC Article
Ruano L, Melo C, Silva MC, Coutinho P
Neuroepidemiology 2014;42(3):174-83. Epub 2014 Mar 5 doi: 10.1159/000358801. PMID: 24603320
Mariotti C, Di Donato S
Neurol Sci 2001 Nov;22 Suppl 2:S88-92. doi: 10.1007/s100720100042. PMID: 11794486

Diagnosis

Alvarez C, Grimmel M, Ebrahimi-Fakhari D, Paul VG, Deininger N, Riess A, Haack T, Gardella E, Møller RS, Bayat A
Clin Genet 2023 May;103(5):566-573. Epub 2023 Jan 11 doi: 10.1111/cge.14275. PMID: 36453471
Colucci F, Neri M, Fortunato F, Ferlini A, Carrozzo R, Torraco A, Lamantea E, Legati A, Tecilla G, Pugliatti M, Sensi M
Cerebellum 2023 Dec;22(6):1313-1319. Epub 2022 Nov 30 doi: 10.1007/s12311-022-01497-y. PMID: 36447112
Ruano L, Melo C, Silva MC, Coutinho P
Neuroepidemiology 2014;42(3):174-83. Epub 2014 Mar 5 doi: 10.1159/000358801. PMID: 24603320
Manto M, Marmolino D
Curr Opin Neurol 2009 Aug;22(4):419-29. doi: 10.1097/WCO.0b013e32832b9897. PMID: 19421057
Mariotti C, Di Donato S
Neurol Sci 2001 Nov;22 Suppl 2:S88-92. doi: 10.1007/s100720100042. PMID: 11794486

Therapy

Beyraghi-Tousi M, Sahebkar A, Houra M, Sarvghadi P, Jamialahmadi T, Bagheri R, Tavallaie S, Gumpricht E, Saberi-Karimian M
Eur J Paediatr Neurol 2024 May;50:57-63. Epub 2024 Apr 22 doi: 10.1016/j.ejpn.2024.04.009. PMID: 38669738
Saberi-Karimian M, Beyraghi-Tousi M, Mirzadeh M, Gumpricht E, Sahebkar A
Cerebellum 2023 Feb;22(1):96-101. Epub 2022 Feb 7 doi: 10.1007/s12311-022-01371-x. PMID: 35128617
Fields T, Patterson M, Bremova-Ertl T, Belcher G, Billington I, Churchill GC, Davis W, Evans W, Flint S, Galione A, Granzer U, Greenfield J, Karl R, Kay R, Lewi D, Mathieson T, Meyer T, Pangonis D, Platt FM, Tsang L, Verburg C, Factor M, Strupp M
Trials 2021 Jan 22;22(1):84. doi: 10.1186/s13063-020-05009-3. PMID: 33482890Free PMC Article
Reetz K, Dogan I, Costa AS, Dafotakis M, Fedosov K, Giunti P, Parkinson MH, Sweeney MG, Mariotti C, Panzeri M, Nanetti L, Arpa J, Sanz-Gallego I, Durr A, Charles P, Boesch S, Nachbauer W, Klopstock T, Karin I, Depondt C, vom Hagen JM, Schöls L, Giordano IA, Klockgether T, Bürk K, Pandolfo M, Schulz JB
Lancet Neurol 2015 Feb;14(2):174-82. Epub 2015 Jan 5 doi: 10.1016/S1474-4422(14)70321-7. PMID: 25566998
Lockman JL, Iskander AJ, Bembea M, Crawford TO, Lederman HM, McGrath-Morrow S, Easley RB
Paediatr Anaesth 2012 Mar;22(3):256-62. Epub 2011 Nov 21 doi: 10.1111/j.1460-9592.2011.03739.x. PMID: 22098343

Prognosis

Chen J, Zhao Z, Shen H, Bing Q, Li N, Guo X, Hu J
BMC Neurol 2022 May 16;22(1):180. doi: 10.1186/s12883-022-02708-z. PMID: 35578252Free PMC Article
Naruse H, Ishiura H, Mitsui J, Takahashi Y, Matsukawa T, Toda T, Tsuji S
Amyotroph Lateral Scler Frontotemporal Degener 2021 Nov;22(7-8):576-578. Epub 2020 Sep 1 doi: 10.1080/21678421.2020.1813312. PMID: 32870032
Reetz K, Dogan I, Costa AS, Dafotakis M, Fedosov K, Giunti P, Parkinson MH, Sweeney MG, Mariotti C, Panzeri M, Nanetti L, Arpa J, Sanz-Gallego I, Durr A, Charles P, Boesch S, Nachbauer W, Klopstock T, Karin I, Depondt C, vom Hagen JM, Schöls L, Giordano IA, Klockgether T, Bürk K, Pandolfo M, Schulz JB
Lancet Neurol 2015 Feb;14(2):174-82. Epub 2015 Jan 5 doi: 10.1016/S1474-4422(14)70321-7. PMID: 25566998
Di Donato S, Gellera C, Mariotti C
Neurol Sci 2001 Jun;22(3):219-28. doi: 10.1007/s100720100017. PMID: 11731874
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

Beyraghi-Tousi M, Sahebkar A, Houra M, Sarvghadi P, Jamialahmadi T, Bagheri R, Tavallaie S, Gumpricht E, Saberi-Karimian M
Eur J Paediatr Neurol 2024 May;50:57-63. Epub 2024 Apr 22 doi: 10.1016/j.ejpn.2024.04.009. PMID: 38669738
Divya KP, Cherian A, Dhing HK, Kumar S, Thomas B, Faruq M
Acta Neurol Belg 2024 Apr;124(2):475-484. Epub 2023 Oct 29 doi: 10.1007/s13760-023-02400-0. PMID: 37898963
Rezende Filho FM, Bremner F, Pedroso JL, de Andrade JBC, Marianelli BF, Lourenço CM, Marques-Júnior W, França MC Jr, Kok F, Sallum JMF, Parkinson MH, Barsottini OG, Giunti P
Mov Disord 2021 Sep;36(9):2027-2035. Epub 2021 Apr 23 doi: 10.1002/mds.28612. PMID: 33893680
Reetz K, Dogan I, Costa AS, Dafotakis M, Fedosov K, Giunti P, Parkinson MH, Sweeney MG, Mariotti C, Panzeri M, Nanetti L, Arpa J, Sanz-Gallego I, Durr A, Charles P, Boesch S, Nachbauer W, Klopstock T, Karin I, Depondt C, vom Hagen JM, Schöls L, Giordano IA, Klockgether T, Bürk K, Pandolfo M, Schulz JB
Lancet Neurol 2015 Feb;14(2):174-82. Epub 2015 Jan 5 doi: 10.1016/S1474-4422(14)70321-7. PMID: 25566998
Synofzik M, Soehn AS, Gburek-Augustat J, Schicks J, Karle KN, Schüle R, Haack TB, Schöning M, Biskup S, Rudnik-Schöneborn S, Senderek J, Hoffmann KT, MacLeod P, Schwarz J, Bender B, Krüger S, Kreuz F, Bauer P, Schöls L
Orphanet J Rare Dis 2013 Mar 15;8:41. doi: 10.1186/1750-1172-8-41. PMID: 23497566Free PMC Article

Recent systematic reviews

van Os NJ, Roeleveld N, Weemaes CM, Jongmans MC, Janssens GO, Taylor AM, Hoogerbrugge N, Willemsen MA
Clin Genet 2016 Aug;90(2):105-17. Epub 2016 Jan 20 doi: 10.1111/cge.12710. PMID: 26662178
Ruano L, Melo C, Silva MC, Coutinho P
Neuroepidemiology 2014;42(3):174-83. Epub 2014 Mar 5 doi: 10.1159/000358801. PMID: 24603320

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