Entry - %606552 - EPISODIC ATAXIA, TYPE 4; EA4 - OMIM
% 606552

EPISODIC ATAXIA, TYPE 4; EA4


Alternative titles; symbols

PERIODIC VESTIBULOCEREBELLAR ATAXIA; PATX
ATAXIA, PERIODIC VESTIBULOCEREBELLAR


Clinical Synopsis
 
Phenotypic Series
 

INHERITANCE
- Autosomal dominant
HEAD & NECK
Ears
- Tinnitus
Eyes
- Diplopia
- Oscillopsia
- Abnormal smooth pursuits
- Inability to suppress vestibuloocular reflex (VOR)
- Gaze-evoked nystagmus
- Esophoria
ABDOMEN
Gastrointestinal
- Nausea
NEUROLOGIC
Central Nervous System
- Ataxia, episodic
- Vertigo
- Spasticity
MISCELLANEOUS
- Age of onset 30 to 60 years
- Symptoms precipitated by sudden movement, stress, exertion, fatigue' Attacks typically last for hours
- Attacks are not responsive to acetazolamide

TEXT

For a phenotypic description and a discussion of genetic heterogeneity of episodic ataxia, see EA1 (160120).


Clinical Features

In 16 members of a white, rural North Carolina family, Farmer and Mustian (1963) described recurrent attacks of vertigo, diplopia, and ataxia beginning in early adulthood. Slowly progressive cerebellar ataxia occurred in some. Vance et al. (1984) identified a second extensively affected kindred which, like the family of Farmer and Mustian (1963), lived in North Carolina. Although no relationship between the 2 kindreds could be established, such was suspected. Small et al. (1996) examined ocular motility in these families.

Damji et al. (1996) isolated DNA from 19 affected individuals from the 2 multigenerational North Carolina families originally described by Farmer and Mustian (1963) and Vance et al. (1984) who had periodic vestibulocerebellar ataxia in an autosomal dominant pedigree pattern. The disorder was characterized by defective smooth pursuit, gaze-evoked nystagmus, ataxia, and vertigo. The age of onset ranged from the third to the sixth decade.


Mapping

In the families originally described by Farmer and Mustian (1963) and Vance et al. (1984), Damji et al. (1996) excluded linkage to loci linked to EA1 and EA2 (108500), as well as to spinocerebellar ataxia types 1 (164400), 2 (183090), 3 (109150), 4 (600223), and 5 (600224).


Nomenclature

Damji et al. (1996) symbolized the disorder PATX for periodic ataxia.

Although Steckley et al. (2001) referred to PATX as episodic ataxia-3 (EA3) and the disorder in 606554 as EA4, the same group (Cader et al., 2005) later referred to the disorder described by Steckley et al. (2001) in 606554 as EA3. We have thus chosen to designate PATX as episodic ataxia-4 (EA4).


REFERENCES

  1. 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, related citations] [Full Text]

  2. Damji, K. F., Allingham, R. R., Pollock, S. C., Small, K., Lewis, K. E., Stajich, J. M., Yamaoka, L. H., Vance, J. M., Pericak-Vance, M. A. Periodic vestibulocerebellar ataxia, an autosomal dominant ataxia with defective smooth pursuit, is genetically distinct from other autosomal dominant ataxias. Arch. Neurol. 53: 338-344, 1996. [PubMed: 8929156, related citations] [Full Text]

  3. Farmer, T. W., Mustian, V. M. Vestibulo-cerebellar ataxia: a newly defined hereditary syndrome with periodic manifestations. Arch. Neurol. 8: 471-480, 1963. [PubMed: 13944410, related citations] [Full Text]

  4. Small, K. W., Pollock, S. C., Vance, J. M., Stajich, J. M., Pericak-Vance, M. Ocular motility in North Carolina autosomal dominant ataxia. J. Neuroophthalmol. 16: 91-95, 1996. [PubMed: 8797163, related citations] [Full Text]

  5. 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, related citations] [Full Text]

  6. Vance, J. M., Pericak-Vance, M. A., Payne, C. S., Coin, J. T., Olanow, C. W. Linkage and genetic analysis in adult onset periodic vestibulo-cerebellar ataxia: report of a new family. (Abstract) Am. J. Hum. Genet. 36: 78S, 1984.


Contributors:
Cassandra L. Kniffin - updated : 11/10/2005
Creation Date:
Victor A. McKusick : 12/11/2001
carol : 06/11/2019
carol : 10/18/2016
carol : 11/29/2005
ckniffin : 11/10/2005
ckniffin : 11/10/2005
mgross : 3/18/2004
alopez : 12/12/2001
alopez : 12/12/2001
alopez : 12/11/2001

% 606552

EPISODIC ATAXIA, TYPE 4; EA4


Alternative titles; symbols

PERIODIC VESTIBULOCEREBELLAR ATAXIA; PATX
ATAXIA, PERIODIC VESTIBULOCEREBELLAR


SNOMEDCT: 718754008;   ORPHA: 79136;   DO: 0050992;  



TEXT

For a phenotypic description and a discussion of genetic heterogeneity of episodic ataxia, see EA1 (160120).


Clinical Features

In 16 members of a white, rural North Carolina family, Farmer and Mustian (1963) described recurrent attacks of vertigo, diplopia, and ataxia beginning in early adulthood. Slowly progressive cerebellar ataxia occurred in some. Vance et al. (1984) identified a second extensively affected kindred which, like the family of Farmer and Mustian (1963), lived in North Carolina. Although no relationship between the 2 kindreds could be established, such was suspected. Small et al. (1996) examined ocular motility in these families.

Damji et al. (1996) isolated DNA from 19 affected individuals from the 2 multigenerational North Carolina families originally described by Farmer and Mustian (1963) and Vance et al. (1984) who had periodic vestibulocerebellar ataxia in an autosomal dominant pedigree pattern. The disorder was characterized by defective smooth pursuit, gaze-evoked nystagmus, ataxia, and vertigo. The age of onset ranged from the third to the sixth decade.


Mapping

In the families originally described by Farmer and Mustian (1963) and Vance et al. (1984), Damji et al. (1996) excluded linkage to loci linked to EA1 and EA2 (108500), as well as to spinocerebellar ataxia types 1 (164400), 2 (183090), 3 (109150), 4 (600223), and 5 (600224).


Nomenclature

Damji et al. (1996) symbolized the disorder PATX for periodic ataxia.

Although Steckley et al. (2001) referred to PATX as episodic ataxia-3 (EA3) and the disorder in 606554 as EA4, the same group (Cader et al., 2005) later referred to the disorder described by Steckley et al. (2001) in 606554 as EA3. We have thus chosen to designate PATX as episodic ataxia-4 (EA4).


REFERENCES

  1. 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]

  2. Damji, K. F., Allingham, R. R., Pollock, S. C., Small, K., Lewis, K. E., Stajich, J. M., Yamaoka, L. H., Vance, J. M., Pericak-Vance, M. A. Periodic vestibulocerebellar ataxia, an autosomal dominant ataxia with defective smooth pursuit, is genetically distinct from other autosomal dominant ataxias. Arch. Neurol. 53: 338-344, 1996. [PubMed: 8929156] [Full Text: https://doi.org/10.1001/archneur.1996.00550040074016]

  3. Farmer, T. W., Mustian, V. M. Vestibulo-cerebellar ataxia: a newly defined hereditary syndrome with periodic manifestations. Arch. Neurol. 8: 471-480, 1963. [PubMed: 13944410] [Full Text: https://doi.org/10.1001/archneur.1963.00460050021002]

  4. Small, K. W., Pollock, S. C., Vance, J. M., Stajich, J. M., Pericak-Vance, M. Ocular motility in North Carolina autosomal dominant ataxia. J. Neuroophthalmol. 16: 91-95, 1996. [PubMed: 8797163] [Full Text: https://doi.org/10.3109/01658109609009667]

  5. 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]

  6. Vance, J. M., Pericak-Vance, M. A., Payne, C. S., Coin, J. T., Olanow, C. W. Linkage and genetic analysis in adult onset periodic vestibulo-cerebellar ataxia: report of a new family. (Abstract) Am. J. Hum. Genet. 36: 78S, 1984.


Contributors:
Cassandra L. Kniffin - updated : 11/10/2005

Creation Date:
Victor A. McKusick : 12/11/2001

Edit History:
carol : 06/11/2019
carol : 10/18/2016
carol : 11/29/2005
ckniffin : 11/10/2005
ckniffin : 11/10/2005
mgross : 3/18/2004
alopez : 12/12/2001
alopez : 12/12/2001
alopez : 12/11/2001