Table 2.

Allelic Disorders

GeneClinical Characteristics
ATP1A2 Alternating hemiplegia of childhood (OMIM 104290), characterized by intermittent recurrent prolonged hemiplegic episodes that mimic hemiplegic migraine
Polymicrogyric syndrome 1
CACNA1A Episodic ataxia type 2 (OMIM 108500). Episodes of ataxia & sometimes migrainous headache w/interictal nystagmus. In 1 family, affected members experienced hemiplegia; 1 family member had migraine during episodes of ataxia. 2 Assoc pathogenic variants: nonsense, frameshift, & splice site variants & multiexon deletions that disrupt the open reading frame
Progressive cerebellar ataxia. Severe progressive ataxia & cerebellar atrophy. Assoc pathogenic variants: missense variants incl p.Gly293Arg in P loop of 1st domain; p.Ala454Thr in I-II loop; p.Arg1664Gln
Spinocerebellar ataxia type 6 (SCA6). Adult-onset, slowly progressive cerebellar ataxia, dysarthria, & nystagmus. Assoc w/a CAG repeat expansion; this expansion has not been observed in families w/FHM 3 but some persons w/SCA6 may have migraine.
Developmental & epileptic encephalopathy 42 (OMIM 617106). De novo pathogenic variants in CACNA1A are recognized to be an important cause of epileptic encephalopathy. 4
PRRT2 Paroxysmal kinesigenic dyskinesia (see PRRT2-Related Disorder). Paroxysmal attacks are often characterized by dystonia, followed by choreoathetosis, & rarely ballism.
Self-limited (familial) infantile epilepsy (see PRRT2-Related Disorder). Characterized by complex partial or generalized tonic-clonic seizures in clusters with onset between age three to 12 months.
Paroxysmal kinesigenic dyskinesia with infantile convulsions (see PRRT2-Related Disorder)
SCN1A The vast majority of pathogenic variants in SCN1A cause epilepsy. SCN1A seizure disorders encompass a spectrum from simple febrile seizures & generalized epilepsy w/febrile seizures plus to Dravet syndrome & intractable childhood epilepsy w/generalized tonic-clonic seizures. Phenotypes w/intractable seizures incl Dravet syndrome are usually assoc w/progressive cognitive & motor decline.
Interstitial deletions of 2q24-q3 (incl a cluster of voltage-gated sodium channel genes: SCN1A, SCN2A, SCN3A, SCN7A, SCN9A) are assoc w/tonic focal & myoclonic jerks that tend to appear in infancy & are later followed by mixed-type seizures, which persist to late childhood & are drug resistant. 5
Larger deletions of 2q24.3 are assoc w/dysmorphic features (e.g., microcephaly, ptosis, downslanting palpebral fissures, long eyelashes, micrognathia), 6 & digit anomalies in persons w/2q24-q31 deletions. 7
Reported duplications of 2q24.2-q3 involving the cluster of voltage-gated sodium channel genes SCN1A, SCN2A, SCN3A, SCN7A, & SCN9A vary in size. Reported persons presented w/focal seizures & epileptic spasms w/neonatal onset (as early as 3rd day of life). 8
Familial autism 9
Rasmussen encephalitis assoc w/pathogenic variant p.Arg1575Cys 10

From: Familial Hemiplegic Migraine

Cover of GeneReviews®
GeneReviews® [Internet].
Adam MP, Feldman J, Mirzaa GM, et al., editors.
Seattle (WA): University of Washington, Seattle; 1993-2025.
Copyright © 1993-2025, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

GeneReviews® chapters are owned by the University of Washington. Permission is hereby granted to reproduce, distribute, and translate copies of content materials for noncommercial research purposes only, provided that (i) credit for source (http://www.genereviews.org/) and copyright (© 1993-2025 University of Washington) are included with each copy; (ii) a link to the original material is provided whenever the material is published elsewhere on the Web; and (iii) reproducers, distributors, and/or translators comply with the GeneReviews® Copyright Notice and Usage Disclaimer. No further modifications are allowed. For clarity, excerpts of GeneReviews chapters for use in lab reports and clinic notes are a permitted use.

For more information, see the GeneReviews® Copyright Notice and Usage Disclaimer.

For questions regarding permissions or whether a specified use is allowed, contact: ude.wu@tssamda.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.