A sleep modulated Channelopathy: a novel CACNA1A pathogenic variant identified in episodic Ataxia type 2 and a potential link to sleep alleviated migraine

Abhimanyu S. Ahuja, Todd D. Rozen, Paldeep S. Atwal

Research output: Contribution to journalArticle

Abstract

BACKGROUND: To describe a patient with sleep alleviated episodic ataxia type 2 with a novel CACNA1A pathogenic variant and provide a possible link to sleep responsive migraine. CASE PRESENTATION: A 26-year-old woman with recurrent attacks of dizziness, nausea, vomiting, ataxia and dysarthria presented for a possible diagnosis of vestibular migraine. Unique to her attacks was if she could fall asleep for as little as 15 min the spells would subside. If however she remained awake the attacks would continue unabated. A presumed diagnosis of episodic ataxia type 2 was made and she became attack free on acetazolamide without recurrence. Genetic testing demonstrated a novel pathogenic variant in CACNA1A on chromosome 19. This pathogenic variant has not been previously reported in the literature and is suggested to truncate the CACNA1A polypeptide by introducing a premature stop codon. CONCLUSION: A case of episodic ataxia type 2 with a novel pathogenic variant in CACNA1A is described. Interestingly, the patient's symptoms would completely alleviate with sleep which suggests a sleep modulated channelopathy. The mechanisms by which sleep could potentially alter this pathogenic variant are hypothesized. A potential link to sleep alleviated migraine is suggested. Further study of this novel pathogenic variant may help us understand not only how sleep can modulate episodic ataxia type 2, but also migraine.

Original languageEnglish (US)
Number of pages1
JournalBMC neurology
Volume19
Issue number1
DOIs
StatePublished - Oct 22 2019

Fingerprint

Channelopathies
Migraine Disorders
Sleep
Chromosomes, Human, Pair 19
faropenem medoxomil
Dysarthria
Acetazolamide
Nonsense Codon
Genetic Testing
Dizziness
Ataxia
Type 2 Episodic Ataxia
Nausea
Vomiting
Recurrence
Peptides

Keywords

  • Acetazolamide
  • Channelopathy
  • Episodic ataxia type 2
  • Hemiplegic migraine
  • P/Q calcium channel
  • Sleep

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

A sleep modulated Channelopathy : a novel CACNA1A pathogenic variant identified in episodic Ataxia type 2 and a potential link to sleep alleviated migraine. / Ahuja, Abhimanyu S.; Rozen, Todd D.; Atwal, Paldeep S.

In: BMC neurology, Vol. 19, No. 1, 22.10.2019.

Research output: Contribution to journalArticle

@article{484d6de726334b57894c8e71c709f44d,
title = "A sleep modulated Channelopathy: a novel CACNA1A pathogenic variant identified in episodic Ataxia type 2 and a potential link to sleep alleviated migraine",
abstract = "BACKGROUND: To describe a patient with sleep alleviated episodic ataxia type 2 with a novel CACNA1A pathogenic variant and provide a possible link to sleep responsive migraine. CASE PRESENTATION: A 26-year-old woman with recurrent attacks of dizziness, nausea, vomiting, ataxia and dysarthria presented for a possible diagnosis of vestibular migraine. Unique to her attacks was if she could fall asleep for as little as 15 min the spells would subside. If however she remained awake the attacks would continue unabated. A presumed diagnosis of episodic ataxia type 2 was made and she became attack free on acetazolamide without recurrence. Genetic testing demonstrated a novel pathogenic variant in CACNA1A on chromosome 19. This pathogenic variant has not been previously reported in the literature and is suggested to truncate the CACNA1A polypeptide by introducing a premature stop codon. CONCLUSION: A case of episodic ataxia type 2 with a novel pathogenic variant in CACNA1A is described. Interestingly, the patient's symptoms would completely alleviate with sleep which suggests a sleep modulated channelopathy. The mechanisms by which sleep could potentially alter this pathogenic variant are hypothesized. A potential link to sleep alleviated migraine is suggested. Further study of this novel pathogenic variant may help us understand not only how sleep can modulate episodic ataxia type 2, but also migraine.",
keywords = "Acetazolamide, Channelopathy, Episodic ataxia type 2, Hemiplegic migraine, P/Q calcium channel, Sleep",
author = "Ahuja, {Abhimanyu S.} and Rozen, {Todd D.} and Atwal, {Paldeep S.}",
year = "2019",
month = "10",
day = "22",
doi = "10.1186/s12883-019-1491-3",
language = "English (US)",
volume = "19",
journal = "BMC Neurology",
issn = "1471-2377",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - A sleep modulated Channelopathy

T2 - a novel CACNA1A pathogenic variant identified in episodic Ataxia type 2 and a potential link to sleep alleviated migraine

AU - Ahuja, Abhimanyu S.

AU - Rozen, Todd D.

AU - Atwal, Paldeep S.

PY - 2019/10/22

Y1 - 2019/10/22

N2 - BACKGROUND: To describe a patient with sleep alleviated episodic ataxia type 2 with a novel CACNA1A pathogenic variant and provide a possible link to sleep responsive migraine. CASE PRESENTATION: A 26-year-old woman with recurrent attacks of dizziness, nausea, vomiting, ataxia and dysarthria presented for a possible diagnosis of vestibular migraine. Unique to her attacks was if she could fall asleep for as little as 15 min the spells would subside. If however she remained awake the attacks would continue unabated. A presumed diagnosis of episodic ataxia type 2 was made and she became attack free on acetazolamide without recurrence. Genetic testing demonstrated a novel pathogenic variant in CACNA1A on chromosome 19. This pathogenic variant has not been previously reported in the literature and is suggested to truncate the CACNA1A polypeptide by introducing a premature stop codon. CONCLUSION: A case of episodic ataxia type 2 with a novel pathogenic variant in CACNA1A is described. Interestingly, the patient's symptoms would completely alleviate with sleep which suggests a sleep modulated channelopathy. The mechanisms by which sleep could potentially alter this pathogenic variant are hypothesized. A potential link to sleep alleviated migraine is suggested. Further study of this novel pathogenic variant may help us understand not only how sleep can modulate episodic ataxia type 2, but also migraine.

AB - BACKGROUND: To describe a patient with sleep alleviated episodic ataxia type 2 with a novel CACNA1A pathogenic variant and provide a possible link to sleep responsive migraine. CASE PRESENTATION: A 26-year-old woman with recurrent attacks of dizziness, nausea, vomiting, ataxia and dysarthria presented for a possible diagnosis of vestibular migraine. Unique to her attacks was if she could fall asleep for as little as 15 min the spells would subside. If however she remained awake the attacks would continue unabated. A presumed diagnosis of episodic ataxia type 2 was made and she became attack free on acetazolamide without recurrence. Genetic testing demonstrated a novel pathogenic variant in CACNA1A on chromosome 19. This pathogenic variant has not been previously reported in the literature and is suggested to truncate the CACNA1A polypeptide by introducing a premature stop codon. CONCLUSION: A case of episodic ataxia type 2 with a novel pathogenic variant in CACNA1A is described. Interestingly, the patient's symptoms would completely alleviate with sleep which suggests a sleep modulated channelopathy. The mechanisms by which sleep could potentially alter this pathogenic variant are hypothesized. A potential link to sleep alleviated migraine is suggested. Further study of this novel pathogenic variant may help us understand not only how sleep can modulate episodic ataxia type 2, but also migraine.

KW - Acetazolamide

KW - Channelopathy

KW - Episodic ataxia type 2

KW - Hemiplegic migraine

KW - P/Q calcium channel

KW - Sleep

UR - http://www.scopus.com/inward/record.url?scp=85073753870&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85073753870&partnerID=8YFLogxK

U2 - 10.1186/s12883-019-1491-3

DO - 10.1186/s12883-019-1491-3

M3 - Article

C2 - 31640633

AN - SCOPUS:85073753870

VL - 19

JO - BMC Neurology

JF - BMC Neurology

SN - 1471-2377

IS - 1

ER -