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    Topic review

    Alternating Hemiplegia of Childhood

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    Submitted by: Catherine Yang
    (This entry belongs to Entry Collection "MedlinePlus ")

    Definition

    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.

    1. Introduction

    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.

    2. Frequency

    Alternating hemiplegia of childhood is a rare condition that affects approximately 1 in 1 million people.

    3. Causes

    Alternating hemiplegia of childhood is primarily caused by mutations in the ATP1A3 gene. Very rarely, a mutation in the ATP1A2 gene is involved in the condition. These genes provide instructions for making very similar proteins. They function as different forms of one piece, the alpha subunit, of a larger protein complex called Na+/K+ ATPase; the two versions of the complex are found in different parts of the brain. Both versions play a critical role in the normal function of nerve cells (neurons). Na+/K+ ATPase transports charged atoms (ions) into and out of neurons, which is an essential part of the signaling process that controls muscle movement.

    Mutations in the ATP1A3 or ATP1A2 gene reduce the activity of the Na+/K+ ATPase, impairing its ability to transport ions normally. It is unclear how a malfunctioning Na+/K+ ATPase causes the episodes of paralysis or uncontrollable movements characteristic of alternating hemiplegia of childhood.

    4. Inheritance

    Alternating hemiplegia of childhood is considered an autosomal dominant condition, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases of alternating hemiplegia of childhood result from new mutations in the gene and occur in people with no history of the disorder in their family. However, the condition can also run in families. For unknown reasons, the signs and symptoms are typically milder when the condition is found in multiple family members than when a single individual is affected.

    5. Other Names for This Condition

    • alternating hemiplegia syndrome

    This entry is adapted from https://medlineplus.gov/genetics/condition/alternating-hemiplegia-of-childhood

    References

    1. Bassi MT, Bresolin N, Tonelli A, Nazos K, Crippa F, Baschirotto C, Zucca C,Bersano A, Dolcetta D, Boneschi FM, Barone V, Casari G. A novel mutation in theATP1A2 gene causes alternating hemiplegia of childhood. J Med Genet. 2004Aug;41(8):621-8.
    2. Heinzen EL, Swoboda KJ, Hitomi Y, Gurrieri F, Nicole S, de Vries B, TizianoFD, Fontaine B, Walley NM, Heavin S, Panagiotakaki E; European AlternatingHemiplegia of Childhood (AHC) Genetics Consortium; Biobanca e Registro Clinicoper l'Emiplegia Alternante (I.B.AHC) Consortium; European Network for Research onAlternating Hemiplegia (ENRAH) for Small and Medium-sized Enterpriese (SMEs)Consortium, Fiori S, Abiusi E, Di Pietro L, Sweney MT, Newcomb TM, Viollet L,Huff C, Jorde LB, Reyna SP, Murphy KJ, Shianna KV, Gumbs CE, Little L, Silver K, Ptáček LJ, Haan J, Ferrari MD, Bye AM, Herkes GK, Whitelaw CM, Webb D, Lynch BJ, Uldall P, King MD, Scheffer IE, Neri G, Arzimanoglou A, van den Maagdenberg AM,Sisodiya SM, Mikati MA, Goldstein DB. De novo mutations in ATP1A3 causealternating hemiplegia of childhood. Nat Genet. 2012 Sep;44(9):1030-4. doi:10.1038/ng.2358.
    3. Panagiotakaki E, De Grandis E, Stagnaro M, Heinzen EL, Fons C, Sisodiya S, de Vries B, Goubau C, Weckhuysen S, Kemlink D, Scheffer I, Lesca G, Rabilloud M,Klich A, Ramirez-Camacho A, Ulate-Campos A, Campistol J, Giannotta M, Moutard ML,Doummar D, Hubsch-Bonneaud C, Jaffer F, Cross H, Gurrieri F, Tiziano D,Nevsimalova S, Nicole S, Neville B, van den Maagdenberg AM, Mikati M, GoldsteinDB, Vavassori R, Arzimanoglou A; Italian IBAHC Consortium; French AHC Consortium;International AHC Consortium. Clinical profile of patients with ATP1A3 mutations in Alternating Hemiplegia of Childhood-a study of 155 patients. Orphanet J RareDis. 2015 Sep 26;10:123. doi: 10.1186/s13023-015-0335-5.
    4. Rosewich H, Thiele H, Ohlenbusch A, Maschke U, Altmüller J, Frommolt P, ZirnB, Ebinger F, Siemes H, Nürnberg P, Brockmann K, Gärtner J. Heterozygous de-novo mutations in ATP1A3 in patients with alternating hemiplegia of childhood: awhole-exome sequencing gene-identification study. Lancet Neurol. 2012Sep;11(9):764-73. doi: 10.1016/S1474-4422(12)70182-5.
    5. Sweney MT, Silver K, Gerard-Blanluet M, Pedespan JM, Renault F, ArzimanoglouA, Schlesinger-Massart M, Lewelt AJ, Reyna SP, Swoboda KJ. Alternating hemiplegiaof childhood: early characteristics and evolution of a neurodevelopmentalsyndrome. Pediatrics. 2009 Mar;123(3):e534-41. doi: 10.1542/peds.2008-2027.
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