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Alternating hemiplegia of childhood 1(AHC1)

MedGen UID:
762361
Concept ID:
C3549447
Disease or Syndrome
Synonym: AHC1
 
Gene (location): ATP1A2 (1q23.2)
 
Monarch Initiative: MONDO:0007087
OMIM®: 104290

Definition

Alternating hemiplegia of childhood is a rare syndrome of episodic hemi- or quadriplegia lasting minutes to days. Most cases are accompanied by dystonic posturing, choreoathetoid movements, nystagmus, other ocular motor abnormalities, autonomic disturbances, and progressive cognitive impairment (Mikati et al., 1992). The disorder may mimic or overlap with other disorders, including familial hemiplegic migraine (FHM1; 141500) and GLUT1 deficiency syndrome (606777) (Rotstein et al., 2009). Genetic Heterogeneity of Alternating Hemiplegia of Childhood See also AHC2 (614820), caused by mutation in the ATP1A3 gene (182350). [from OMIM]

Additional description

From MedlinePlus Genetics
Alternating hemiplegia of childhood is a neurological condition characterized by recurrent episodes of temporary paralysis, often affecting one side of the body (hemiplegia). During some episodes, the paralysis alternates from one side of the body to the other or affects both sides at the same time. These episodes begin in infancy or early childhood, usually before 18 months of age, and the paralysis lasts from minutes to days.

In addition to paralysis, affected individuals can have sudden attacks of uncontrollable muscle activity; these can cause involuntary limb movements (choreoathetosis), muscle tensing (dystonia), movement of the eyes (nystagmus), or shortness of breath (dyspnea). People with alternating hemiplegia of childhood may also experience sudden redness and warmth (flushing) or unusual paleness (pallor) of the skin. These attacks can occur during or separately from episodes of hemiplegia.

The episodes of hemiplegia or uncontrolled movements can be triggered by certain factors, such as stress, extreme tiredness, cold temperatures, or bathing, although the trigger is not always known. A characteristic feature of alternating hemiplegia of childhood is that all symptoms disappear while the affected person is sleeping but can reappear shortly after awakening. The number and length of the episodes initially worsen throughout childhood but then begin to decrease over time. The uncontrollable muscle movements may disappear entirely, but the episodes of hemiplegia occur throughout life.

Alternating hemiplegia of childhood also causes mild to severe cognitive problems. Almost all affected individuals have some level of developmental delay and intellectual disability. Their cognitive functioning typically declines over time.  https://medlineplus.gov/genetics/condition/alternating-hemiplegia-of-childhood

Clinical features

From HPO
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.
Headache
MedGen UID:
9149
Concept ID:
C0018681
Sign or Symptom
Cephalgia, or pain sensed in various parts of the head, not confined to the area of distribution of any nerve.
Choreoathetosis
MedGen UID:
39313
Concept ID:
C0085583
Disease or Syndrome
Involuntary movements characterized by both athetosis (inability to sustain muscles in a fixed position) and chorea (widespread jerky arrhythmic movements).
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.
Developmental regression
MedGen UID:
324613
Concept ID:
C1836830
Disease or Syndrome
Loss of developmental skills, as manifested by loss of developmental milestones.
Episodic hemiplegia
MedGen UID:
350828
Concept ID:
C1863061
Finding
Transient episodes of weakness of the arm, leg, and in some cases the face on one side of the body.
Episodic quadriplegia
MedGen UID:
350829
Concept ID:
C1863062
Disease or Syndrome
Intermittent episodes of paralysis of all four limbs.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
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

Muthaffar OY, Alqarni A, Shafei JA, Bahowarth SY, Alyazidi AS, Naseer MI
Genes Genomics 2024 Apr;46(4):475-487. Epub 2024 Jan 19 doi: 10.1007/s13258-023-01481-8. PMID: 38243045
Pisciotta L, Gherzi M, Stagnaro M, Calevo MG, Giannotta M, Vavassori MR, Veneselli E; I.B.AHC Consortium, De Grandis E
Brain Dev 2017 Jun;39(6):521-528. Epub 2017 Feb 27 doi: 10.1016/j.braindev.2017.02.001. PMID: 28249736
Silver K, Andermann F
Neurology 1993 Jan;43(1):36-41. doi: 10.1212/wnl.43.1_part_1.36. PMID: 8423908

Recent clinical studies

Etiology

Hashimoto Y, Greene C, Munnich A, Campbell M
Fluids Barriers CNS 2023 Mar 28;20(1):22. doi: 10.1186/s12987-023-00424-5. PMID: 36978081Free PMC Article
Poole J, Zagaglia S, Demurtas R, Farrell F, Walker MC, Sisodiya SM, Balestrini S, Vivekananda U
PLoS One 2022;17(9):e0268720. Epub 2022 Sep 30 doi: 10.1371/journal.pone.0268720. PMID: 36178910Free PMC Article
Parker LE, Wallace K, Thevathasan A, Funk E, Pratt M, Thamby J, Tran L, Prange L, Uchitel J, Boggs A, Minton M, Jasien J, Nagao KJ, Richards A, Cruse B, De-Lisle Dear G, Landstrom AP, Mikati MA
Eur J Paediatr Neurol 2022 May;38:47-52. Epub 2022 Mar 29 doi: 10.1016/j.ejpn.2022.03.007. PMID: 35390560
Yang X, Yang X, Chen J, Li S, Zeng Q, Huang AY, Ye AY, Yu Z, Wang S, Jiang Y, Wu X, Wu Q, Wei L, Zhang Y
Clin Genet 2019 Jul;96(1):43-52. Epub 2019 Apr 3 doi: 10.1111/cge.13539. PMID: 30891744Free PMC Article
Pisciotta L, Gherzi M, Stagnaro M, Calevo MG, Giannotta M, Vavassori MR, Veneselli E; I.B.AHC Consortium, De Grandis E
Brain Dev 2017 Jun;39(6):521-528. Epub 2017 Feb 27 doi: 10.1016/j.braindev.2017.02.001. PMID: 28249736

Diagnosis

Vezyroglou A, Akilapa R, Barwick K, Koene S, Brownstein CA, Holder-Espinasse M, Fry AE, Németh AH, Tofaris GK, Hay E, Hughes I, Mansour S, Mordekar SR, Splitt M, Turnpenny PD, Demetriou D, Koopmann TT, Ruivenkamp CAL, Agrawal PB, Carr L, Clowes V, Ghali N, Holder SE, Radley J, Male A, Sisodiya SM, Kurian MA, Cross JH, Balasubramanian M
Neurology 2022 Oct 4;99(14):e1511-e1526. Epub 2022 Jul 18 doi: 10.1212/WNL.0000000000200927. PMID: 36192182Free PMC Article
Poole J, Zagaglia S, Demurtas R, Farrell F, Walker MC, Sisodiya SM, Balestrini S, Vivekananda U
PLoS One 2022;17(9):e0268720. Epub 2022 Sep 30 doi: 10.1371/journal.pone.0268720. PMID: 36178910Free PMC Article
Pratt M, Uchitel J, McGreal N, Gordon K, Prange L, McLean M, Noel RJ, Rikard B, Rogers Boruta MK, Mikati MA
Orphanet J Rare Dis 2020 Sep 3;15(1):231. doi: 10.1186/s13023-020-01474-w. PMID: 32883312Free PMC Article
Uchitel J, Helseth A, Prange L, McLean M, Ghusayni R, Sachdev M, Hunanyan A, Mikati MA
Neurology 2019 Sep 24;93(13):e1248-e1259. Epub 2019 Sep 4 doi: 10.1212/WNL.0000000000008159. PMID: 31484714
Blumenfeld AE, Victorio MC, Berenson FR
Semin Pediatr Neurol 2016 Feb;23(1):18-22. Epub 2016 Jan 22 doi: 10.1016/j.spen.2016.01.007. PMID: 27017017

Therapy

Parker LE, Wallace K, Thevathasan A, Funk E, Pratt M, Thamby J, Tran L, Prange L, Uchitel J, Boggs A, Minton M, Jasien J, Nagao KJ, Richards A, Cruse B, De-Lisle Dear G, Landstrom AP, Mikati MA
Eur J Paediatr Neurol 2022 May;38:47-52. Epub 2022 Mar 29 doi: 10.1016/j.ejpn.2022.03.007. PMID: 35390560
Samanta D, Ramakrishnaiah R
Clin Neuropharmacol 2021 Jan-Feb 01;44(1):23-26. doi: 10.1097/WNF.0000000000000420. PMID: 33177352
Uchitel J, Helseth A, Prange L, McLean M, Ghusayni R, Sachdev M, Hunanyan A, Mikati MA
Neurology 2019 Sep 24;93(13):e1248-e1259. Epub 2019 Sep 4 doi: 10.1212/WNL.0000000000008159. PMID: 31484714
Pisciotta L, Gherzi M, Stagnaro M, Calevo MG, Giannotta M, Vavassori MR, Veneselli E; I.B.AHC Consortium, De Grandis E
Brain Dev 2017 Jun;39(6):521-528. Epub 2017 Feb 27 doi: 10.1016/j.braindev.2017.02.001. PMID: 28249736
Kanavakis E, Xaidara A, Papathanasiou-Klontza D, Papadimitriou A, Velentza S, Youroukos S
Dev Med Child Neurol 2003 Dec;45(12):833-6. doi: 10.1017/s0012162203001543. PMID: 14667076

Prognosis

Poole J, Zagaglia S, Demurtas R, Farrell F, Walker MC, Sisodiya SM, Balestrini S, Vivekananda U
PLoS One 2022;17(9):e0268720. Epub 2022 Sep 30 doi: 10.1371/journal.pone.0268720. PMID: 36178910Free PMC Article
Vetro A, Nielsen HN, Holm R, Hevner RF, Parrini E, Powis Z, Møller RS, Bellan C, Simonati A, Lesca G, Helbig KL, Palmer EE, Mei D, Ballardini E, Van Haeringen A, Syrbe S, Leuzzi V, Cioni G, Curry CJ, Costain G, Santucci M, Chong K, Mancini GMS, Clayton-Smith J, Bigoni S, Scheffer IE, Dobyns WB, Vilsen B, Guerrini R; ATP1A2/A3-collaborators
Brain 2021 Jun 22;144(5):1435-1450. doi: 10.1093/brain/awab052. PMID: 33880529
Wallace K, Greene E, Moya-Mendez M, Freemark M, Prange L, Mikati MA
Eur J Paediatr Neurol 2021 May;32:1-7. Epub 2021 Mar 11 doi: 10.1016/j.ejpn.2021.03.007. PMID: 33756210
Maas RPPWM, Kamsteeg EJ, Mangano S, Vázquez López ME, Nicolai J, Silver K, Fernández-Alvarez E, Willemsen MAAP
Eur J Paediatr Neurol 2018 Nov;22(6):1110-1117. Epub 2018 Aug 15 doi: 10.1016/j.ejpn.2018.07.012. PMID: 30194039
Villéga F, Picard F, Espil-Taris C, Husson M, Michel V, Pedespan JM
Brain Dev 2011 Jun;33(6):525-9. Epub 2010 Sep 2 doi: 10.1016/j.braindev.2010.08.008. PMID: 20817433

Clinical prediction guides

Vezyroglou A, Akilapa R, Barwick K, Koene S, Brownstein CA, Holder-Espinasse M, Fry AE, Németh AH, Tofaris GK, Hay E, Hughes I, Mansour S, Mordekar SR, Splitt M, Turnpenny PD, Demetriou D, Koopmann TT, Ruivenkamp CAL, Agrawal PB, Carr L, Clowes V, Ghali N, Holder SE, Radley J, Male A, Sisodiya SM, Kurian MA, Cross JH, Balasubramanian M
Neurology 2022 Oct 4;99(14):e1511-e1526. Epub 2022 Jul 18 doi: 10.1212/WNL.0000000000200927. PMID: 36192182Free PMC Article
Poole J, Zagaglia S, Demurtas R, Farrell F, Walker MC, Sisodiya SM, Balestrini S, Vivekananda U
PLoS One 2022;17(9):e0268720. Epub 2022 Sep 30 doi: 10.1371/journal.pone.0268720. PMID: 36178910Free PMC Article
Vetro A, Nielsen HN, Holm R, Hevner RF, Parrini E, Powis Z, Møller RS, Bellan C, Simonati A, Lesca G, Helbig KL, Palmer EE, Mei D, Ballardini E, Van Haeringen A, Syrbe S, Leuzzi V, Cioni G, Curry CJ, Costain G, Santucci M, Chong K, Mancini GMS, Clayton-Smith J, Bigoni S, Scheffer IE, Dobyns WB, Vilsen B, Guerrini R; ATP1A2/A3-collaborators
Brain 2021 Jun 22;144(5):1435-1450. doi: 10.1093/brain/awab052. PMID: 33880529
Pratt M, Uchitel J, McGreal N, Gordon K, Prange L, McLean M, Noel RJ, Rikard B, Rogers Boruta MK, Mikati MA
Orphanet J Rare Dis 2020 Sep 3;15(1):231. doi: 10.1186/s13023-020-01474-w. PMID: 32883312Free PMC Article
Uchitel J, Helseth A, Prange L, McLean M, Ghusayni R, Sachdev M, Hunanyan A, Mikati MA
Neurology 2019 Sep 24;93(13):e1248-e1259. Epub 2019 Sep 4 doi: 10.1212/WNL.0000000000008159. PMID: 31484714

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