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Journal of Pediatric Neurology 2024; 22(06): 478-482
DOI: 10.1055/s-0044-1787061
Case Report

CAPOS Syndrome with Fluctuating Symptoms

Paul Wang
1   Department of Neurology, Case Western Reserve University, Cleveland, Ohio, United States
,
Yoon-Hee Cha 
2   Department of Neurology, University of Minnesota, Minneapolis, Minnesota, United States
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Abstract

We report a patient with CAPOS syndrome (Cerebellar ataxia, Areflexia, Pes cavus, Optic atrophy, and Sensorineural hearing loss) with classic features who also exhibited fluctuating vestibulocochlear symptoms that met the criteria for Meniere's disease. A male patient was initially symptomatic at 13 months of age with ataxia and loss of deep tendon reflexes in the setting of fever. This was followed by the development of baseline ataxia with superimposed spells of vertigo and ataxia, progressive hearing loss with episodic fluctuations, optic atrophy, pes cavus, and areflexia. Spells lasted minutes to hours and were frequently triggered by ambient heat and fever. He was diagnosed with a de novo pathogenic variant p.Glu818Lys mutation in ATP1A3. We provide detailed clinical features of this case, a summary of CAPOS cases reported to date, and an overview of allelically related syndromes.

Keywords

CAPOS - episodic ataxia - ATP1A3

Human/Animal Rights

All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards including the Helsinki Declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines.


Authors' Contributions

All authors were involved in the analysis, preparation, and review of the manuscript.




Publication History

Received: 27 November 2023

Accepted: 18 April 2024

Article published online:
26 June 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Nicolaides P, Appleton RE, Fryer A. Cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS): a new syndrome. J Med Genet 1996; 33 (05) 419-421
    CrossrefPubMedSearch in Google Scholar
  • 2 Demos MK, van Karnebeek CDM, Ross CJD. et al; FORGE Canada Consortium. A novel recurrent mutation in ATP1A3 causes CAPOS syndrome. Orphanet J Rare Dis 2014; 9: 15-15
    CrossrefPubMedSearch in Google Scholar
  • 3 Roenn CP, Li M, Schack VR. et al. Functional consequences of the CAPOS mutation E818K of Na+,K+-ATPase. J Biol Chem 2019; 294 (01) 269-280
    CrossrefPubMedSearch in Google Scholar
  • 4 Brashear A, Sweadner KJ, Cook JF. et al. ATP1A3-Related Neurologic Disorders. Seattle: University of Washington; 2018
    Search in Google Scholar
  • 5 Paciorkowski AR, McDaniel SS, Jansen LA. et al. Novel mutations in ATP1A3 associated with catastrophic early life epilepsy, episodic prolonged apnea, and postnatal microcephaly. Epilepsia 2015; 56 (03) 422-430
    CrossrefPubMedSearch in Google Scholar
  • 6 Yano ST, Silver K, Young R. et al. Fever-induced paroxysmal weakness and encephalopathy, a new phenotype of ATP1A3 mutation. Pediatr Neurol 2017; 73: 101-105
    CrossrefPubMedSearch in Google Scholar
  • 7 Dard R, Mignot C, Durr A. et al. Relapsing encephalopathy with cerebellar ataxia related to an ATP1A3 mutation. Dev Med Child Neurol 2015; 57 (12) 1183-1186
    CrossrefPubMedSearch in Google Scholar
  • 8 Smedemark-Margulies N, Brownstein CA, Vargas S. et al. A novel de novo mutation in ATP1A3 and childhood-onset schizophrenia. Cold Spring Harb Mol Case Stud 2016; 2 (05) a001008
    CrossrefPubMedSearch in Google Scholar
  • 9 Sweadner KJ, Toro C, Whitlow CT. et al. ATP1A3 mutation in adult rapid-onset ataxia. PLoS One 2016; 11 (03) e0151429
    CrossrefPubMedSearch in Google Scholar
  • 10 Miyatake S, Kato M, Kumamoto T. et al. De novo ATP1A3 variants cause polymicrogyria. Sci Adv 2021; 7 (13) eabd2368
    CrossrefPubMedSearch in Google Scholar
  • 11 Prange L, Pratt M, Herman K. et al. D-DEMØ, a distinct phenotype caused by ATP1A3 mutations. Neurol Genet 2020; 6 (05) e466
    CrossrefPubMedSearch in Google Scholar
  • 12 Sasaki M, Sumitomo N, Shimizu-Motohashi Y. et al. ATP1A3 variants and slowly progressive cerebellar ataxia without paroxysmal or episodic symptoms in children. Dev Med Child Neurol 2021; 63 (01) 111-115
    CrossrefPubMedSearch in Google Scholar
  • 13 Lopez-Escamez JA, Carey J, Chung WH. et al. [Diagnostic criteria for Menière's disease. Consensus document of the Bárány Society, the Japan Society for Equilibrium Research, the European Academy of Otology and Neurotology (EAONO), the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) and the Korean Balance Society]. Acta Otorrinolaringol Esp 2016; 67 (01) 1-7
    CrossrefPubMedSearch in Google Scholar
  • 14 Jen J, Kim GW, Baloh RW. Clinical spectrum of episodic ataxia type 2. Neurology 2004; 62 (01) 17-22
    CrossrefPubMedSearch in Google Scholar
  • 15 Cader MZ, Steckley JL, Dyment DA, McLachlan RS, Ebers GC. A genome-wide screen and linkage mapping for a large pedigree with episodic ataxia. Neurology 2005; 65 (01) 156-158
    CrossrefPubMedSearch in Google Scholar
  • 16 Steckley JL, Ebers GC, Cader MZ, McLachlan RS. An autosomal dominant disorder with episodic ataxia, vertigo, and tinnitus. Neurology 2001; 57 (08) 1499-1502
    CrossrefPubMedSearch in Google Scholar
  • 17 Sweney MT, Newcomb TM, Swoboda KJ. The expanding spectrum of neurological phenotypes in children with ATP1A3 mutations, Alternating Hemiplegia of Childhood, Rapid-onset Dystonia-Parkinsonism, CAPOS and beyond. Pediatr Neurol 2015; 52 (01) 56-64
    CrossrefPubMedSearch in Google Scholar
  • 18 Salles PA, Mata IF, Brünger T, Lal D, Fernandez HH. ATP1A3-Related Disorders: An Ever-Expanding Clinical Spectrum. Front Neurol 2021; 12: 637890
    CrossrefPubMedSearch in Google Scholar
  • 19 Stenshorne I, Rasmussen M, Salvanos P, Tallaksen CME, Bindoff LA, Koht J. Fever-related ataxia: a case report of CAPOS syndrome. Cerebellum Ataxias 2019; 6: 2-2
    CrossrefPubMedSearch in Google Scholar
  • 20 Li Y, Liu X, Wang C. et al. Molecular and clinical characteristics of ATP1A3-related diseases. Front Neurol 2022; 13: 924788
    CrossrefPubMedSearch in Google Scholar
  • 21 Rosewich H, Weise D, Ohlenbusch A, Gärtner J, Brockmann K. Phenotypic overlap of alternating hemiplegia of childhood and CAPOS syndrome. Neurology 2014; 83 (09) 861-863
    CrossrefPubMedSearch in Google Scholar
  • 22 Heimer G, Sadaka Y, Israelian L. et al. CAOS-Episodic Cerebellar Ataxia, Areflexia, Optic Atrophy, and Sensorineural Hearing Loss: A Third Allelic Disorder of the ATP1A3 Gene. J Child Neurol 2015; 30 (13) 1749-1756
    CrossrefPubMedSearch in Google Scholar
  • 23 Potic A, Nmezi B, Padiath QS. CAPOS syndrome and hemiplegic migraine in a novel pedigree with the specific ATP1A3 mutation. J Neurol Sci 2015; 358 (1-2): 453-456
    CrossrefPubMedSearch in Google Scholar
  • 24 Maas RPPWM, Schieving JH, Schouten M, Kamsteeg EJ, van de Warrenburg BP. The Genetic Homogeneity of CAPOS Syndrome: Four New Patients With the c.2452G>A (p.Glu818Lys) Mutation in the ATP1A3 Gene. Pediatr Neurol 2016; 59: 71-75.e1
    CrossrefPubMedSearch in Google Scholar
  • 25 Duat Rodriguez A, Prochazkova M, Santos Santos S, Rubio Cabezas O, Cantarin Extremera V, Gonzalez-Gutierrez-Solana L. Early Diagnosis of CAPOS Syndrome Before Acute-Onset Ataxia-Review of the Literature and a New Family. Pediatr Neurol 2017; 71: 60-64
    CrossrefPubMedSearch in Google Scholar
  • 26 Han K-H, Oh D-Y, Lee S. et al. ATP1A3 mutations can cause progressive auditory neuropathy: a new gene of auditory synaptopathy. Sci Rep 2017; 7 (01) 16504-16504
    CrossrefPubMedSearch in Google Scholar
  • 27 Paquay S, Wiame E, Deggouj N. et al. Childhood hearing loss is a key feature of CAPOS syndrome: A case report. Int J Pediatr Otorhinolaryngol 2018; 104: 191-194
    CrossrefPubMedSearch in Google Scholar
  • 28 Chang IJ, Adam MP, Jayadev S, Bird TD, Natarajan N, Glass IA. Novel pregnancy-triggered episodes of CAPOS syndrome. Am J Med Genet A 2018; 176 (01) 235-240
    CrossrefPubMedSearch in Google Scholar
  • 29 Tranebjærg L, Strenzke N, Lindholm S. et al. The CAPOS mutation in ATP1A3 alters Na/K-ATPase function and results in auditory neuropathy which has implications for management. Hum Genet 2018; 137 (02) 111-127
    CrossrefPubMedSearch in Google Scholar
  • 30 Hayashida T, Saito Y, Ishii A. et al. Further characterization of CAPOS/CAOS syndrome with the Glu818Lys mutation in the ATP1A3 gene: A case report. Brain Dev 2018; 40 (07) 576-581
    CrossrefPubMedSearch in Google Scholar
  • 31 Atilgan A, Yüksel M, Ciprut A. Cochlear Implantation in a Case of Auditory Neuropathy Spectrum Disorder with CAPOS Syndrome. Medeniyet Med J 2019; 34 (03) 318-323
    CrossrefPubMedSearch in Google Scholar
  • 32 Hashimoto A, Kuki I, Fukuoka M. et al. Chronological dynamic changes in cortico-subcortical imbalance of cerebral blood flow in a boy with CAPOS syndrome. Brain Dev 2019; 41 (07) 625-629
    CrossrefPubMedSearch in Google Scholar
  • 33 Balestrini S, Mikati MA, Álvarez-García-Rovés R. et al. Cardiac phenotype in ATP1A3-related syndromes: A multicenter cohort study. Neurology 2020; 95 (21) e2866-e2879
    CrossrefPubMedSearch in Google Scholar
  • 34 Chouksey A, Pandey S. ATP1A3 mutation presenting as CAPOS syndrome + dystonia phenotype. Parkinsonism Relat Disord 2020; 78: 192-194
    CrossrefPubMedSearch in Google Scholar
  • 35 Sharawat IK, Kasinathan A, Suthar R, Sankhyan N. CAPOS syndrome: A rare ATP1A3-related disorder. Ann Indian Acad Neurol 2020; 23 (03) 397-398
    CrossrefPubMedSearch in Google Scholar
  • 36 You H, Liu M, Zhao J. et al. Cerebellar ataxia, areflexia, pes cavus, optic atrophy and sensorineural hearing loss syndrome: a case report and literature review. Chin J Neurol 2020; 12: 38-45
    PubMedSearch in Google Scholar
  • 37 González Plata A, Marcos Toledano MM, Correa Martínez L, Fernández-Burriel Tercero M. A new case of CAPOS/CAOS syndrome. Neurología (Engl Ed) 2020; 35 (08) 612-614
    CrossrefPubMedSearch in Google Scholar
  • 38 Zhang F, Wang J, Zou LP, Zhang MN, Dun S, Yang G. [A novel variation in ATP1A3 gene in a child with CAPOS syndrome]. Zhonghua Er Ke Za Zhi 2020; 58 (03) 233-235
    CrossrefPubMedSearch in Google Scholar
  • 39 Lax DN, Bieri P, Patel P. The diagnostic spectrum of ATP1A3-related disorders: 3 new patients. J Neurol Sci 2021; 430: 120003-120003
    CrossrefPubMedSearch in Google Scholar
  • 40 Gao Y, Li F, Luo R. et al. [Clinical features of CAPOS syndrome caused by maternal ATP1A3 gene variation: a case report]. Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2024; 38 (01) 73-76
    CrossrefPubMedSearch in Google Scholar
  • 41 Miller MJ, Lindsey JW, Pakravan M. et al. Progressive Optic Neuropathy in Cerebellar Ataxia, Areflexia, Optic Atrophy, and Sensorineural Hearing Loss Syndrome: The Importance of Targeted Gene Testing. J Neuroophthalmol 2024; 44 (01) e23-e25
    CrossrefPubMedSearch in Google Scholar
  • 42 Schirinzi T, Graziola F, Nicita F. et al. Childhood rapid-onset ataxia: expanding the phenotypic spectrum of ATP1A3 mutations. Cerebellum 2018; 17 (04) 489-493
    CrossrefPubMedSearch in Google Scholar
  • 43 Vetro A, Nielsen HN, Holm R. et al; ATP1A2/A3-collaborators. ATP1A2- and ATP1A3-associated early profound epileptic encephalopathy and polymicrogyria. Brain 2021; 144 (05) 1435-1450
    CrossrefPubMedSearch in Google Scholar
  • 44 Smith RS, Florio M, Akula SK. et al. Early role for a Na+,K+-ATPase (ATP1A3) in brain development. Proc Natl Acad Sci U S A 2021; 118 (25) e2023333118
    CrossrefPubMedSearch in Google Scholar