Spinocerebellar ataxia type 11
General Information (adopted from Orphanet):
Synonyms, Signs: |
SCA11 |
Number of Symptoms | 7 |
OrphanetNr: | 98767 |
OMIM Id: |
604432
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ICD-10: |
G11 |
UMLs: |
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MeSH: |
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MedDRA: |
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Snomed: |
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Prevalence, inheritance and age of onset:
Prevalence: | No data available. |
Inheritance: |
Autosomal dominant [Orphanet] |
Age of onset: |
Childhood Adolescent Adult Elderly [Orphanet] |
Disease classification (adopted from Orphanet):
Parent Diseases: |
Autosomal dominant cerebellar ataxia type 3
-Rare eye disease -Rare genetic disease -Rare neurologic disease |
Symptom Information:
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(HPO:0000639) | Nystagmus | 555 / 7739 | ||||
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(HPO:0002073) | Progressive cerebellar ataxia | 27 / 7739 | ||||
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(HPO:0001260) | Dysarthria | 329 / 7739 | ||||
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(HPO:0001347) | Hyperreflexia | 363 / 7739 | ||||
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(HPO:0001272) | Cerebellar atrophy | 197 / 7739 | ||||
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(HPO:0003581) | Adult onset | 117 / 7739 | ||||
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(HPO:0000006) | Autosomal dominant inheritance | 2518 / 7739 |
Associated genes:
ClinVar (via SNiPA)
Gene symbol | Variation | Clinical significance | Reference |
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Additional Information:
Clinical Description OMIM |
Worth et al. (1999) identified 2 British families with a relatively pure form of autosomal dominant cerebellar ataxia in which affected individuals did not have the CAG expansion in the CACNA1A gene (601011), excluding a diagnosis of SCA6 ... |
Molecular genetics OMIM |
After screening 54 genes in the linked region identified on chromosome 15q15-q21, none of which had a pathogenic mutation, Houlden et al. (2007) analyzed the gene encoding tau tubulin kinase-2 (TTBK2; 611695) and found a 1-base insertion of ... |
Diagnosis GeneReviews | Spinocerebellar ataxia type 11 (SCA11) is characterized by the following:... Gene SymbolTest MethodMutations DetectedMutation Detection Frequency by Test Method 1Test AvailabilityTTBK2Sequence analysis | Sequence variantsSequence variants, including c.1329dupA, c.1284_1285delAG 2 ClinicalTargeted mutation analysisc.1329dupA, c.1284_1285delAG 2Unknown 3 1. The ability of the test method used to detect a mutation that is present in the indicated gene2. Houlden et al [2007]; see Molecular Genetics.3. TTBK2 mutations have been identified in four families to date [Houlden et al 2007, Bauer et al 2010].Interpretation of test results. For issues to consider in interpretation of sequence analysis results, click here.Information on specific allelic variants may be available in Molecular Genetics (see Table A. Genes and Databases and/or Pathologic allelic variants).Testing Strategy The diagnosis of a pure SCA is based on the clinical assessment; the molecular diagnosis of SCA11 is based on molecular genetic test results identifying a TTBK2 disease-causing mutation.Because SCA11 is rare, it is recommended that individuals with autosomal dominant pure SCA be tested first for mutations associated with more common types of autosomal dominant SCA (e.g., SCA1, 2, 3, 6, 7, 12, and 17).To confirm/establish the diagnosis in a proband requires identification of a TTBK2 mutation on molecular genetic testing.Targeted mutation or sequence analysis can be used to detect mutations in TTBK2. Prenatal diagnosis and preimplantation genetic diagnosis (PGD) for at-risk pregnancies require prior identification of the disease-causing mutation in the family.Genetically Related (Allelic) DisordersNo other phenotypes are known to be associated with mutations in TTBK2.
Clinical Description GeneReviews | In the four families described with spinocerebellar ataxia type 11 (SCA11) the mean age of onset ranged from the early teens in the family of Pakistani origin to between 40 and 50 years of age in the families from France and Germany. The ataxia was clinically similar in all four families, presenting with difficulty walking and balance, is slowly progressive with abnormal eye signs (jerky pursuit and horizontal and vertical nystagmus) and pyramidal features. Dysarthria and swallowing difficulties are common in SCA11. The severity ranged from very mild balance problems, usually at disease onset, to severe speech and swallowing problems and ataxia requiring the use of a wheelchair.... |
Genotype-Phenotype Correlations GeneReviews | All four families had frameshift mutations and remarkably similar phenotypes. The same mutation was found in two unrelated families from France and Germany, suggesting that they could be related; this, however, is unlikely as they live more than 600 km apart [Bauer et al 2010].... |
Differential Diagnosis GeneReviews | According to Harding’s classification, spinocerebellar ataxia type 11 (SCA11) is included in the pure autosomal dominant cerebellar ataxias (ADCA III) [Worth et al 1999], the most common group of inherited ataxias. SCA11 accounts for approximately 2% of ADCA III.... |
Management GeneReviews | To establish the extent of disease and needs in an individual diagnosed with spinocerebellar ataxia type 11 (SCA11), the following evaluations are recommended:... |
Molecular genetics GeneReviews |
Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.... Gene SymbolChromosomal LocusProtein NameLocus SpecificHGMDTTBK215q15 | Tau-tubulin kinase 2TTBK2 homepage - Mendelian genesTTBK2Data are compiled from the following standard references: gene symbol from HGNC; chromosomal locus, locus name, critical region, complementation group from OMIM; protein name from UniProt. For a description of databases (Locus Specific, HGMD) to which links are provided, click here.Table B. OMIM Entries for Spinocerebellar Ataxia Type 11 (View All in OMIM) View in own window 604432SPINOCEREBELLAR ATAXIA 11; SCA11 611695TAU TUBULIN KINASE 2; TTBK2Normal allelic variants. No normal variants or polymorphisms have been detected in the coding exons.Pathologic allelic variants. All mutations to date have been frameshift mutations that predict loss of function. The mutation in the original family from Devon, England with 36 affected members from eight generations was c.1329dupA. Onset of ataxia was in the mid-20s.The mutation in the family from Pakistan with four affected individuals from three generations was c.1287_1288delAG. Onset of ataxia was in the early teen years.The mutation identified in two unrelated families from France and Germany was c.1306_1307delGA.Table 2. Selected TTBK2 Pathologic Allelic VariantsView in own windowDNA Nucleotide Change