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Episodic ataxia, type 9(EA9)

MedGen UID:
1714171
Concept ID:
C5394520
Disease or Syndrome
Synonyms: EA9; EPISODIC ATAXIA, TYPE 9
 
Gene (location): SCN2A (2q24.3)
 
Monarch Initiative: MONDO:0030064
OMIM®: 618924

Definition

Episodic ataxia type 9 (EA9) is a neurologic disorder characterized by onset of ataxic episodes in the first years of life. Features may include difficulty walking, dizziness, slurred speech, headache, vomiting, and pain. The ataxic episodes vary in frequency and duration; most tend to occur every few weeks or months and last minutes to hours. Prior to the EA, most patients have neonatal- or infantile-onset tonic or generalized tonic-clonic (GTC) seizures that may be severe and refractory to medication, but remit later in infancy or early childhood, either spontaneously or concurrently with medication. Some patients have mildly delayed development with speech delay and/or autistic features or mildly impaired intellectual development. However, others show normal psychomotor development. Treatment of the ataxic episodes with acetazolamide is effective in about 50% of patients (summary by Schwarz et al., 2019). For a phenotypic description and discussion of genetic heterogeneity of episodic ataxia, see EA1 (160120). [from OMIM]

Clinical features

From HPO
Vomiting
MedGen UID:
12124
Concept ID:
C0042963
Sign or Symptom
Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions.
Vertigo
MedGen UID:
53006
Concept ID:
C0042571
Sign or Symptom
An abnormal sensation of spinning while the body is actually stationary.
Paroxysmal vertigo
MedGen UID:
99296
Concept ID:
C0522357
Finding
Paroxysmal episodes of vertigo.
Dystonic disorder
MedGen UID:
3940
Concept ID:
C0013421
Sign or Symptom
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Status epilepticus
MedGen UID:
11586
Concept ID:
C0038220
Disease or Syndrome
Status epilepticus is a type of prolonged seizure resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms which lead to abnormally prolonged seizures (after time point t1). It is a condition that can have long-term consequences (after time point t2), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures.
Arachnoid cyst
MedGen UID:
86860
Concept ID:
C0078981
Disease or Syndrome
An extra-parenchymal and intra-arachnoidal collection of fluid with a composition similar to that of cerebrospinal fluid.
Encephalopathy
MedGen UID:
39314
Concept ID:
C0085584
Disease or Syndrome
Encephalopathy is a term that means brain disease, damage, or malfunction. In general, encephalopathy is manifested by an altered mental state.
Clonic seizure
MedGen UID:
66708
Concept ID:
C0234535
Disease or Syndrome
A clonic seizure is a type of motor seizure characterized by sustained rhythmic jerking, that is regularly repetitive.
Tonic seizure
MedGen UID:
82855
Concept ID:
C0270844
Disease or Syndrome
A tonic seizure is a type of motor seizure characterized by unilateral or bilateral limb stiffening or elevation, often with neck stiffening.
Bilateral tonic-clonic seizure
MedGen UID:
141670
Concept ID:
C0494475
Sign or Symptom
A bilateral tonic-clonic seizure is a seizure defined by a tonic (bilateral increased tone, lasting seconds to minutes) and then a clonic (bilateral sustained rhythmic jerking) phase.
Hereditary episodic ataxia
MedGen UID:
314033
Concept ID:
C1720189
Disease or Syndrome
Periodic spells of incoordination and imbalance, that is, episodes of ataxia typically lasting from 10 minutes to several hours or days.
Cerebellar edema
MedGen UID:
1375706
Concept ID:
C4316985
Pathologic Function
Swelling from fluid accumulation (serous fluid infiltration into the interstitial space) in the cerebellum.
Delayed ability to stand
MedGen UID:
1370611
Concept ID:
C4476709
Finding
A failure to achieve the ability to stand up at an appropriate developmental stage. Most children begin to walk alone at 11 to 15 months of age. On average, children can stand while holding on at the age of 9 to 10 months, can pull up to stand and walk with one hand being held at 12 months, and can stand alone and walk well at 18 months.
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.

Professional guidelines

PubMed

Garces P, Antoniades CA, Sobanska A, Kovacs N, Ying SH, Gupta AS, Perlman S, Szmulewicz DJ, Pane C, Németh AH, Jardim LB, Coarelli G, Dankova M, Traschütz A, Tarnutzer AA
Cerebellum 2024 Feb;23(1):121-135. Epub 2023 Jan 14 doi: 10.1007/s12311-023-01514-8. PMID: 36640220Free PMC Article
De Gusmao CM, Silveira-Moriyama L
Expert Rev Neurother 2019 Sep;19(9):807-822. Epub 2019 Aug 8 doi: 10.1080/14737175.2019.1648211. PMID: 31353980

Recent clinical studies

Etiology

Hassan A
Tremor Other Hyperkinet Mov (N Y) 2023;13:9. Epub 2023 Mar 28 doi: 10.5334/tohm.747. PMID: 37008993Free PMC Article
Silvetti MS, Favoccia C, Saputo FA, Tamburri I, Mizzon C, Campisi M, Gimigliano F, Rinelli G, Rava L, Drago F
Europace 2023 Apr 15;25(4):1482-1490. doi: 10.1093/europace/euad026. PMID: 36794445Free PMC Article
Feil K, Strobl R, Schindler A, Krafczyk S, Goldschagg N, Frenzel C, Glaser M, Schöberl F, Zwergal A, Strupp M
Cerebellum 2019 Jun;18(3):320-332. doi: 10.1007/s12311-018-0992-8. PMID: 30552638
Laasonen M, Kauppinen J, Leppämäki S, Tani P, Harno H, Hokkanen L, Wikgren J
Exp Brain Res 2012 Nov;223(1):19-32. Epub 2012 Sep 5 doi: 10.1007/s00221-012-3237-y. PMID: 22948736
Klockgether T, Evert B
Trends Neurosci 1998 Sep;21(9):413-8. doi: 10.1016/s0166-2236(98)01315-0. PMID: 9735950

Diagnosis

Hassan A
Tremor Other Hyperkinet Mov (N Y) 2023;13:9. Epub 2023 Mar 28 doi: 10.5334/tohm.747. PMID: 37008993Free PMC Article
De Gusmao CM, Silveira-Moriyama L
Expert Rev Neurother 2019 Sep;19(9):807-822. Epub 2019 Aug 8 doi: 10.1080/14737175.2019.1648211. PMID: 31353980
Yu-Wai-Man P, Gorman G, Bateman DE, Leigh RJ, Chinnery PF
J Neurol 2009 Jan;256(1):78-82. Epub 2009 Feb 9 doi: 10.1007/s00415-009-0068-2. PMID: 19224313
Jen J, Kim GW, Baloh RW
Neurology 2004 Jan 13;62(1):17-22. doi: 10.1212/01.wnl.0000101675.61074.50. PMID: 14718690
Gordon N
Brain Dev 1998 Jan;20(1):9-13. doi: 10.1016/s0387-7604(97)00086-7. PMID: 9533553

Therapy

Hassan A
Tremor Other Hyperkinet Mov (N Y) 2023;13:9. Epub 2023 Mar 28 doi: 10.5334/tohm.747. PMID: 37008993Free PMC Article
De Gusmao CM, Silveira-Moriyama L
Expert Rev Neurother 2019 Sep;19(9):807-822. Epub 2019 Aug 8 doi: 10.1080/14737175.2019.1648211. PMID: 31353980
Löhle M, Schrempf W, Wolz M, Reichmann H, Storch A
Mov Disord 2008 Jul 15;23(9):1314-6. doi: 10.1002/mds.22071. PMID: 18442126
Jen J, Kim GW, Baloh RW
Neurology 2004 Jan 13;62(1):17-22. doi: 10.1212/01.wnl.0000101675.61074.50. PMID: 14718690
Gordon N
Brain Dev 1998 Jan;20(1):9-13. doi: 10.1016/s0387-7604(97)00086-7. PMID: 9533553

Prognosis

Yu-Wai-Man P, Gorman G, Bateman DE, Leigh RJ, Chinnery PF
J Neurol 2009 Jan;256(1):78-82. Epub 2009 Feb 9 doi: 10.1007/s00415-009-0068-2. PMID: 19224313
Jen J, Kim GW, Baloh RW
Neurology 2004 Jan 13;62(1):17-22. doi: 10.1212/01.wnl.0000101675.61074.50. PMID: 14718690

Clinical prediction guides

Rinaldi D, Tangari MM, Ledda C, Dematteis F, Rizzone MG, Lopiano L, Artusi CA
Neurol Sci 2024 Sep;45(9):4589-4592. Epub 2024 May 14 doi: 10.1007/s10072-024-07592-8. PMID: 38743163
Graves TD, Cha YH, Hahn AF, Barohn R, Salajegheh MK, Griggs RC, Bundy BN, Jen JC, Baloh RW, Hanna MG; CINCH Investigators
Brain 2014 Apr;137(Pt 4):1009-18. Epub 2014 Feb 26 doi: 10.1093/brain/awu012. PMID: 24578548Free PMC Article
Yu-Wai-Man P, Gorman G, Bateman DE, Leigh RJ, Chinnery PF
J Neurol 2009 Jan;256(1):78-82. Epub 2009 Feb 9 doi: 10.1007/s00415-009-0068-2. PMID: 19224313
Jen J, Kim GW, Baloh RW
Neurology 2004 Jan 13;62(1):17-22. doi: 10.1212/01.wnl.0000101675.61074.50. PMID: 14718690
Klockgether T, Evert B
Trends Neurosci 1998 Sep;21(9):413-8. doi: 10.1016/s0166-2236(98)01315-0. PMID: 9735950

Recent systematic reviews

Hassan A
Tremor Other Hyperkinet Mov (N Y) 2023;13:9. Epub 2023 Mar 28 doi: 10.5334/tohm.747. PMID: 37008993Free PMC Article

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