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Autosomal recessive spinocerebellar ataxia 7(SCAR7)

MedGen UID:
324520
Concept ID:
C1836474
Disease or Syndrome
Synonym: Childhood-onset autosomal recessive slowly progressive spinocerebellar ataxia
SNOMED CT: Autosomal recessive spinocerebellar ataxia type 7 (785301002); Childhood-onset autosomal recessive slowly progressive spinocerebellar ataxia (785301002); SCAR7 - autosomal recessive spinocerebellar ataxia type 7 (785301002)
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): TPP1 (11p15.4)
 
Monarch Initiative: MONDO:0012235
OMIM®: 609270
Orphanet: ORPHA284324

Definition

Autosomal recessive spinocerebellar ataxia is a neurologic disorder characterized by onset of progressive gait difficulties, eye movement abnormalities, and dysarthria in the first or second decade of life (summary by Dy et al., 2015). [from OMIM]

Clinical features

From HPO
Urinary urgency
MedGen UID:
39315
Concept ID:
C0085606
Finding
Urge incontinence is the strong, sudden need to urinate.
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
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.
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.
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.
Clumsiness
MedGen UID:
66690
Concept ID:
C0233844
Sign or Symptom
Lack of physical coordination resulting in an abnormal tendency to drop items or bump into objects.
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.
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.
Scanning speech
MedGen UID:
116113
Concept ID:
C0240952
Mental or Behavioral Dysfunction
An abnormal pattern of speech in which the words are as if measured or scanned; there is a pause after every syllable, and the syllables themselves are pronounced slowly.
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.
Impaired vibratory sensation
MedGen UID:
220959
Concept ID:
C1295585
Finding
A decrease in the ability to perceive vibration. Clinically, this is usually tested with a tuning fork which vibrates at 128 Hz and is applied to bony prominences such as the malleoli at the ankles or the metacarpal-phalangeal joints. There is a slow decay of vibration from the tuning fork. The degree of vibratory sense loss can be crudely estimated by counting the number of seconds that the examiner can perceive the vibration longer than the patient.
Truncal titubation
MedGen UID:
382380
Concept ID:
C2674512
Finding
Tremor of the trunk in an anterior-posterior plane at 3-4 Hz.
Oculomotor apraxia
MedGen UID:
483686
Concept ID:
C3489733
Disease or Syndrome
Ocular motor apraxia is a deficiency in voluntary, horizontal, lateral, fast eye movements (saccades) with retention of slow pursuit movements. The inability to follow objects visually is often compensated by head movements. There may be decreased smooth pursuit, and cancelation of the vestibulo-ocular reflex.
Diplopia
MedGen UID:
41600
Concept ID:
C0012569
Disease or Syndrome
Diplopia is a condition in which a single object is perceived as two images, it is also known as double vision.
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.
Hypermetric saccades
MedGen UID:
140835
Concept ID:
C0423083
Finding
A saccade that overshoots the target with the dynamic saccade.
Saccadic smooth pursuit
MedGen UID:
373096
Concept ID:
C1836479
Finding
An abnormality of tracking eye movements in which smooth pursuit is interrupted by an abnormally high number of saccadic movements.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVAutosomal recessive spinocerebellar ataxia 7
Follow this link to review classifications for Autosomal recessive spinocerebellar ataxia 7 in Orphanet.

Professional guidelines

PubMed

Amirifar P, Ranjouri MR, Lavin M, Abolhassani H, Yazdani R, Aghamohammadi A
Expert Rev Clin Immunol 2020 Sep;16(9):859-871. Epub 2020 Oct 15 doi: 10.1080/1744666X.2020.1810570. PMID: 32791865
Levy A, Lang AE
Mov Disord 2018 Aug;33(8):1238-1247. Epub 2018 Feb 13 doi: 10.1002/mds.27319. PMID: 29436738
Braga Neto P, Pedroso JL, Kuo SH, Marcondes Junior CF, Teive HA, Barsottini OG
Arq Neuropsiquiatr 2016 Mar;74(3):244-52. doi: 10.1590/0004-282X20160038. PMID: 27050855Free PMC Article

Recent clinical studies

Etiology

Amirifar P, Ranjouri MR, Lavin M, Abolhassani H, Yazdani R, Aghamohammadi A
Expert Rev Clin Immunol 2020 Sep;16(9):859-871. Epub 2020 Oct 15 doi: 10.1080/1744666X.2020.1810570. PMID: 32791865
Synofzik M, Németh AH
Handb Clin Neurol 2018;155:73-89. doi: 10.1016/B978-0-444-64189-2.00005-6. PMID: 29891078
Ruano L, Melo C, Silva MC, Coutinho P
Neuroepidemiology 2014;42(3):174-83. Epub 2014 Mar 5 doi: 10.1159/000358801. PMID: 24603320
Jayadev S, Bird TD
Genet Med 2013 Sep;15(9):673-83. Epub 2013 Mar 28 doi: 10.1038/gim.2013.28. PMID: 23538602
Evidente VG, Gwinn-Hardy KA, Caviness JN, Gilman S
Mayo Clin Proc 2000 May;75(5):475-90. doi: 10.4065/75.5.475. PMID: 10807077

Diagnosis

Amirifar P, Ranjouri MR, Lavin M, Abolhassani H, Yazdani R, Aghamohammadi A
Expert Rev Clin Immunol 2020 Sep;16(9):859-871. Epub 2020 Oct 15 doi: 10.1080/1744666X.2020.1810570. PMID: 32791865
Amirifar P, Ranjouri MR, Yazdani R, Abolhassani H, Aghamohammadi A
Pediatr Allergy Immunol 2019 May;30(3):277-288. Epub 2019 Mar 20 doi: 10.1111/pai.13020. PMID: 30685876
Synofzik M, Németh AH
Handb Clin Neurol 2018;155:73-89. doi: 10.1016/B978-0-444-64189-2.00005-6. PMID: 29891078
Bereznyakova O, Dupré N
Handb Clin Neurol 2018;155:191-203. doi: 10.1016/B978-0-444-64189-2.00012-3. PMID: 29891058
Rothblum-Oviatt C, Wright J, Lefton-Greif MA, McGrath-Morrow SA, Crawford TO, Lederman HM
Orphanet J Rare Dis 2016 Nov 25;11(1):159. doi: 10.1186/s13023-016-0543-7. PMID: 27884168Free PMC Article

Therapy

Kuhn K, Lederman HM, McGrath-Morrow SA
Expert Opin Investig Drugs 2023 Jul-Dec;32(8):693-704. Epub 2023 Aug 28 doi: 10.1080/13543784.2023.2249399. PMID: 37622329Free PMC Article
Kanack AJ, Newsom OJ, Scaglione KM
J Biol Chem 2018 Feb 23;293(8):2735-2743. Epub 2018 Jan 9 doi: 10.1074/jbc.RA117.000477. PMID: 29317501Free PMC Article
Woelke S, Pommerening H, Kieslich M, Schubert R, Zielen S
Growth Factors 2017 Jun;35(2-3):125-130. doi: 10.1080/08977194.2017.1367681. PMID: 28948852
Bouhlal Y, Amouri R, El Euch-Fayeche G, Hentati F
Parkinsonism Relat Disord 2011 Jul;17(6):418-22. Epub 2011 Mar 30 doi: 10.1016/j.parkreldis.2011.03.005. PMID: 21450511
Zlotogora J
Hum Genet 2010 Nov;128(5):473-9. Epub 2010 Sep 18 doi: 10.1007/s00439-010-0890-8. PMID: 20852892

Prognosis

Amirifar P, Ranjouri MR, Lavin M, Abolhassani H, Yazdani R, Aghamohammadi A
Expert Rev Clin Immunol 2020 Sep;16(9):859-871. Epub 2020 Oct 15 doi: 10.1080/1744666X.2020.1810570. PMID: 32791865
Arias M
Neurologia (Engl Ed) 2019 May;34(4):248-258. Epub 2016 Jul 25 doi: 10.1016/j.nrl.2016.06.006. PMID: 27460185
Levy A, Lang AE
Mov Disord 2018 Aug;33(8):1238-1247. Epub 2018 Feb 13 doi: 10.1002/mds.27319. PMID: 29436738
Rothblum-Oviatt C, Wright J, Lefton-Greif MA, McGrath-Morrow SA, Crawford TO, Lederman HM
Orphanet J Rare Dis 2016 Nov 25;11(1):159. doi: 10.1186/s13023-016-0543-7. PMID: 27884168Free PMC Article
Nissenkorn A, Ben-Zeev B
Handb Clin Neurol 2015;132:199-214. doi: 10.1016/B978-0-444-62702-5.00014-7. PMID: 26564081

Clinical prediction guides

Phulpagar P, Holla VV, Tomar D, Kamble N, Yadav R, Pal PK, Muthusamy B
J Hum Genet 2023 Dec;68(12):859-866. Epub 2023 Sep 26 doi: 10.1038/s10038-023-01195-5. PMID: 37752213
Bagaria J, Bagyinszky E, An SSA
Int J Mol Sci 2022 Jan 4;23(1) doi: 10.3390/ijms23010552. PMID: 35008978Free PMC Article
Teive HAG, Camargo CHF, Munhoz RP
Parkinsonism Relat Disord 2018 Jan;46:3-8. Epub 2017 Dec 12 doi: 10.1016/j.parkreldis.2017.12.009. PMID: 29249681
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
Sandoval N, Platzer M, Rosenthal A, Dörk T, Bendix R, Skawran B, Stuhrmann M, Wegner RD, Sperling K, Banin S, Shiloh Y, Baumer A, Bernthaler U, Sennefelder H, Brohm M, Weber BH, Schindler D
Hum Mol Genet 1999 Jan;8(1):69-79. doi: 10.1093/hmg/8.1.69. PMID: 9887333

Recent systematic reviews

Milovanović A, Westenberger A, Stanković I, Tamaš O, Branković M, Marjanović A, Laabs BH, Brand M, Rajalingam R, Marras C, Lohmann K, Branković V, Novaković I, Petrović I, Svetel M, Klein C, Kostić VS, Dragašević-Mišković N
Mov Disord 2024 May;39(5):887-892. Epub 2024 Mar 12 doi: 10.1002/mds.29729. PMID: 38469933
Petley E, Yule A, Alexander S, Ojha S, Whitehouse WP
PLoS One 2022;17(3):e0264177. Epub 2022 Mar 15 doi: 10.1371/journal.pone.0264177. PMID: 35290391Free PMC Article
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
Corben LA, Georgiou-Karistianis N, Bradshaw JL, Evans-Galea MV, Churchyard AJ, Delatycki MB
Adv Exp Med Biol 2012;769:169-84. doi: 10.1007/978-1-4614-5434-2_11. PMID: 23560311

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