Genotype–phenotype relations for episodic ataxia genes: MDSGene systematic review

Most episodic ataxias (EA) are autosomal dominantly inherited and characterized by recurrent attacks of ataxia and other paroxysmal and non‐paroxysmal features. EA is often caused by pathogenic variants in the CACNA1A, KCNA1, PDHA1, and SLC1A3 genes, listed as paroxysmal movement disorders (PxMD) by the MDS Task Force on the Nomenclature of Genetic Movement Disorders. Little is known about the genotype–phenotype correlation of the different genetic EA forms.

[1]  F. Gao,et al.  Case Report: A Novel CACNA1A Mutation Caused Flunarizine-Responsive Type 2 Episodic Ataxia and Hemiplegic Migraine With Abnormal MRI of Cerebral White Matter , 2022, Frontiers in Neurology.

[2]  C. González-Mingot,et al.  The efficacy of combining topiramate and 4-aminopyridine to reduce relapses and interictal progression in two cases of episodic ataxia type 2 , 2022, Neurological Sciences.

[3]  A. Lang,et al.  Nomenclature of Genetic Movement Disorders: Recommendations of the International Parkinson and Movement Disorder Society Task Force – An Update , 2022, Movement disorders : official journal of the Movement Disorder Society.

[4]  Ryan L. Collins,et al.  A genome-wide mutational constraint map quantified from variation in 76,156 human genomes , 2022, bioRxiv.

[5]  R. Guerreiro,et al.  Molecular Characterization of Portuguese Patients with Hereditary Cerebellar Ataxia , 2022, Cells.

[6]  Sruthi S. Nair,et al.  Pyruvate Dehydrogenase Complex Deficiency Due to PDHA1 Mutation—A Rare Treatable Cause for Episodic Ataxia in Children , 2022, Indian Journal of Pediatrics.

[7]  P. Striano,et al.  Genetic paroxysmal neurological disorders featuring episodic ataxia and epilepsy. , 2022, European journal of medical genetics.

[8]  S. Bhattacharjee,et al.  Interictal Headache, Pseudodystonia, and Persistent Ataxia in Episodic Ataxia Type 1 Due to a Novel KCNA1 Gene Mutation , 2021, Movement disorders clinical practice.

[9]  J. Lemos,et al.  Downbeat Nystagmus in Episodic Ataxia Type 1 Associated with a Novel KCNA1 Mutation , 2021, Movement disorders : official journal of the Movement Disorder Society.

[10]  A. Klimkowicz-Mrowiec,et al.  Application of a custom NGS gene panel revealed a high diagnostic utility for molecular testing of hereditary ataxias , 2021, Journal of Applied Genetics.

[11]  M. Dafotakis,et al.  Novel CACNA1A Variant p.Cys256Phe Disrupts Disulfide Bonds and Causes Spinocerebellar Ataxia , 2021, Movement disorders : official journal of the Movement Disorder Society.

[12]  H. Lerche,et al.  Genetics of Paroxysmal Dyskinesia: Novel Variants Corroborate the Role of KCNA1 in Paroxysmal Dyskinesia and Highlight the Diverse Phenotypic Spectrum of KCNA1- and SLC2A1-Related Disorders , 2021, Frontiers in Neurology.

[13]  D. Pal,et al.  Response to pyridoxine in CACNA1A epilepsy-ataxia does not imply a causal effect , 2021, Seizure.

[14]  Xiaoming Su,et al.  Pyruvate dehydrogenase deficiency disease detected by the enzyme activity of peripheral leukocytes , 2021, Molecular genetics & genomic medicine.

[15]  N. Nardocci,et al.  Pediatric Paroxysmal Exercise-Induced Neurological Symptoms: Clinical Spectrum and Diagnostic Algorithm , 2021, Frontiers in Neurology.

[16]  G. Gigli,et al.  Epilepsy and episodic ataxia type 2: family study and review of the literature , 2021, Journal of Neurology.

[17]  B. Oliva,et al.  CACNA1A Mutations Causing Early Onset Ataxia: Profiling Clinical, Dysmorphic and Structural-Functional Findings , 2021, International journal of molecular sciences.

[18]  M. Mikati,et al.  Paroxysmal Genetic Movement Disorders and Epilepsy , 2021, Frontiers in Neurology.

[19]  A. Weiss,et al.  Two Missense CACNA1A Variants in a Single Family with Variable Neurobehavioral, Cerebellar, Epileptic, and Oculomotor Features , 2021, Neuropediatrics.

[20]  J. Pera,et al.  Involvement of the Peripheral Nervous System in Episodic Ataxias , 2020, Biomedicines.

[21]  P. Giunti,et al.  Episodic Ataxias: Faux or Real? , 2020, International journal of molecular sciences.

[22]  I. Rivera,et al.  Pyruvate dehydrogenase complex deficiency: updating the clinical, metabolic and mutational landscapes in a cohort of Portuguese patients , 2020, Orphanet Journal of Rare Diseases.

[23]  Robert A. Smith,et al.  Comprehensive Exonic Sequencing of Known Ataxia Genes in Episodic Ataxia , 2020, Biomedicines.

[24]  E. Bertini,et al.  Clinical and Genetic Overview of Paroxysmal Movement Disorders and Episodic Ataxias , 2020, International journal of molecular sciences.

[25]  L. Silveira-Moriyama,et al.  Paroxysmal movement disorders – practical update on diagnosis and management , 2019, Expert review of neurotherapeutics.

[26]  Zheyu Xu,et al.  Paroxysmal Movement Disorders: Recent Advances , 2019, Current Neurology and Neuroscience Reports.

[27]  P. Jouk,et al.  Major intra-familial phenotypic heterogeneity and incomplete penetrance due to a CACNA1A pathogenic variant. , 2019, European journal of medical genetics.

[28]  Zheyu Xu,et al.  Paroxysmal movement disorders: Recent advances and proposal of a classification system. , 2019, Parkinsonism & related disorders.

[29]  W. Poewe,et al.  The neuropsychiatric phenotype in CACNA1A mutations: a retrospective single center study and review of the literature , 2018, European journal of neurology.

[30]  E. Roze,et al.  The expanding spectrum of paroxysmal movement disorders: update from clinical features to therapeutics , 2018, Current opinion in neurology.

[31]  J. Mink,et al.  Phenotypes, genotypes, and the management of paroxysmal movement disorders , 2018, Developmental medicine and child neurology.

[32]  I. König,et al.  Genotype‐Phenotype Relations for the Parkinson's Disease Genes Parkin, PINK1, DJ1: MDSGene Systematic Review , 2018, Movement disorders : official journal of the Movement Disorder Society.

[33]  Ludger Schöls,et al.  Comprehensive systematic review summary: Treatment of cerebellar motor dysfunction and ataxia , 2018, Neurology.

[34]  A. Lang,et al.  Nomenclature of genetic movement disorders: Recommendations of the International Parkinson and Movement Disorder Society task force , 2017, Movement disorders : official journal of the Movement Disorder Society.

[35]  M. King,et al.  SCN2A p.Ala263Val Variant a Phenotype of Neonatal Seizures Followed by Paroxysmal Ataxia in Toddlers. , 2017, Pediatric neurology.

[36]  H. Lerche,et al.  Letter to the editor: confirming neonatal seizure and late onset ataxia in SCN2A Ala263Val , 2016, Journal of Neurology.

[37]  A. Lang,et al.  Nomenclature of genetic movement disorders: Recommendations of the international Parkinson and movement disorder society task force , 2016, Movement disorders : official journal of the Movement Disorder Society.

[38]  L. Gagnon,et al.  CACNA1A haploinsufficiency causes cognitive impairment, autism and epileptic encephalopathy with mild cerebellar symptoms , 2015, European Journal of Human Genetics.

[39]  François Schiettecatte,et al.  OMIM.org: Online Mendelian Inheritance in Man (OMIM®), an online catalog of human genes and genetic disorders , 2014, Nucleic Acids Res..

[40]  D. Burke,et al.  Clinical, genetic, neurophysiological and functional study of new mutations in episodic ataxia type 1 , 2013, Journal of Neurology, Neurosurgery & Psychiatry.

[41]  P. Kovermann,et al.  A point mutation associated with episodic ataxia 6 increases glutamate transporter anion currents. , 2012, Brain : a journal of neurology.

[42]  J. Jen.  Hereditary Episodic Ataxias , 2008, Annals of the New York Academy of Sciences.

[43]  R. Baloh,et al.  Mutation in the glutamate transporter EAAT1 causes episodic ataxia, hemiplegia, and seizures , 2005, Neurology.

[44]  R. Baloh,et al.  Clinical spectrum of episodic ataxia type 2 , 2004, Neurology.

[45]  P. Maddison.  Neuromyotonia , 2002, Clinical Neurophysiology.

[46]  T. Mayer,et al.  Coding and noncoding variation of the human calcium-channel beta4-subunit gene CACNB4 in patients with idiopathic generalized epilepsy and episodic ataxia. , 2000, American journal of human genetics.

[47]  O. Suchowersky,et al.  A review of the inherited ataxias: recent advances in genetic, clinical and neuropathologic aspects. , 1998, Parkinsonism & related disorders.

[48]  R. Ophoff,et al.  Episodic ataxia type 2 (EA2) and spinocerebellar ataxia type 6 (SCA6) due to CAG repeat expansion in the CACNA1A gene on chromosome 19p. , 1997, Human molecular genetics.

[49]  M. Strupp,et al.  Episodic ataxia type 1 and 2 (familial periodic ataxia/vertigo). , 1997, Audiology & neuro-otology.

[50]  V. Vedanarayanan.  Paroxysmal movement disorders. , 1997, Pediatric annals.

[51]  Dennis E Bulman,et al.  Familial Hemiplegic Migraine and Episodic Ataxia Type-2 Are Caused by Mutations in the Ca2+ Channel Gene CACNL1A4 , 1996, Cell.

[52]  Michael Litt,et al.  Episodic ataxia/myokymia syndrome is associated with point mutations in the human potassium channel gene, KCNA1 , 1994, Nature Genetics.

[53]  S. Amara,et al.  The mouse and human excitatory amino acid transporter gene (EAAT1) maps to mouse chromosome 15 and a region of syntenic homology on human chromosome 5. , 1994, Genomics.

[54]  R. Wadia,et al.  The hereditary ataxias. , 1976, Neurology India.