Alternative titles; symbols
SNOMEDCT: 718755009; ORPHA: 79135; DO: 0050991;
Cytogenetic location: 1q42 Genomic coordinates (GRCh38): 1:223,900,001-236,400,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 1q42 | Episodic ataxia, type 3 | 606554 | Autosomal dominant | 2 |
For a phenotypic description and a discussion of genetic heterogeneity of episodic ataxia, see EA1 (160120).
Steckley et al. (2001) presented a large Canadian kindred of Mennonite heritage with an autosomal dominant episodic ataxia clinically distinct from other reported episodic ataxias. Vestibular ataxia, vertigo, tinnitus, and interictal myokymia were prominent. Attacks were diminished by acetazolamide. At least 26 members of the family were affected; 12 described frequent bouts of interictal myokymia. Myokymia was visible in 1 patient upon examination. Steckley et al. (2001) distinguished the disorder in their family from the features of EA1 by noting the presence, in their family, of vertigo and tinnitus, neither of which is typical of EA1. Similarly, the absence of interictal nystagmus and shorter episodes distinguished this disorder from EA2 (108500). The variable age of onset contrasted with the typical EA1 onset of late childhood or early adolescence, and the typical childhood onset of EA2. Although vertigo and tinnitus were also prominent in periodic vestibulocerebellar ataxia (PATX; 606552), Steckley et al. (2001) noted that PATX differs in having abnormal eye movements, including abnormal smooth pursuit, nystagmus, and abnormal vestibuloocular reflex; no response to acetazolamide; and absence of interictal myokymia.
By linkage analysis of markers flanking the EA1 (160120) and EA2 (108500) loci (12p13 and 19p13, respectively), Steckley et al. (2001) excluded their family from those 2 forms of autosomal dominant episodic ataxia.
By a genomewide screen of the family reported by Steckley et al. (2001), Cader et al. (2005) found linkage to a 4-cM region on chromosome 1q42 between markers D1S2712 and D1S2678, which the authors termed EA3 (maximum 2-point lod score of 4.12 at marker D1S235). Although a common haplotype between D1S251 and D1S2678 was present in 22 of 25 affected family members, 3 affected individuals did not have the putative disease haplotype, and 4 unaffected individuals carried the disease haplotype. Cader et al. (2005) suggested that phenocopies and reduced penetrance may explain the family members whose disease status did not match the linkage data. Mutation analysis excluded the KCNK1 gene (601745).
Although Steckley et al. (2001) referred to this disorder as episodic ataxia-4 (EA4) and to periodic vestibulocerebellar ataxia (PATX; 606552) as EA3, the same group (Cader et al., 2005) later referred to the disorder reported by Steckley et al. (2001) as EA3. We have thus chosen to designate the disorder originally reported by Steckley et al. (2001) as EA3.
Cader, M. Z., Steckley, J. L., Dyment, D. A., McLachlan, R. S., Ebers, G. C. A genome-wide screen and linkage mapping for a large pedigree with episodic ataxia. Neurology 65: 156-158, 2005. [PubMed: 16009908] [Full Text: https://doi.org/10.1212/01.wnl.0000167186.05465.7c]
Steckley, J. L., Ebers, G. C., Cader, M. Z., McLachlan, R. S. An autosomal dominant disorder with episodic ataxia, vertigo, and tinnitus. Neurology 57: 1499-1502, 2001. [PubMed: 11673600] [Full Text: https://doi.org/10.1212/wnl.57.8.1499]