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Am J Med Genet A. 2018 Jan;176(1):235-240. doi: 10.1002/ajmg.a.38502. Epub 2017 Nov 1.

Novel pregnancy-triggered episodes of CAPOS syndrome.

Author information

1
Division of Medical Genetics, Department of Medicine, University of Washington Medical Center, Seattle, Washington.
2
Division of Genetic Medicine, Department of Pediatrics, Seattle Children's Hospital and University of Washington, Seattle, Washington.
3
Department of Neurology, University of Washington Medical Center, Seattle, Washington.
4
Geriatric Research, Education and Clinical Center (GRECC), VA Puget Sound Health Care System, Seattle, Washington.
5
Department of Neurology, Seattle Children's Hospital and University of Washington, Seattle, Washington.

Abstract

Cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS) syndrome (OMIM# 601338) is a rare autosomal dominant disorder characterized by episodic, fever-induced ataxic encephalopathy in childhood with residual symptoms. All identified patients have the same heterozygous missense variant c.2452G>A (p.Glu818Lys) in the ATP1A3 gene, encoding Na+ /K+ ATPase α3. We describe a large CAPOS pedigree with three generations of affected members, the first ascertained in the United States. Deafness, optic atrophy, and pes cavus were present in all three members of the family evaluated. In addition, one of the affected individuals experienced markedly worsening features during her three pregnancies and in the immediate postpartum period, a potential element of the natural history of CAPOS previously unreported. We conclude that the triggering factors and clinical spectrum of pathogenic ATP1A3 variants may be broader than previously described. Targeted sequencing of ATP1A3 should be considered in any patient presenting with cerebellar ataxia triggered by febrile illness, or pregnancy and delivery, especially in the presence of sensorineural hearing loss, optic atrophy, pes cavus, or early childhood history of acute encephalopathic ataxia. Prophylactic administration of acetazolamide or flunarizine may prevent acute episodes of ataxia or mitigate neurologic symptoms, although their efficacies have not been well studied.

KEYWORDS:

ATP1A3; CAPOS syndrome; cerebellar ataxia; optic atrophy; pregnancy; sensorineural hearing loss

PMID:
29090527
PMCID:
PMC5726903
DOI:
10.1002/ajmg.a.38502
[Indexed for MEDLINE]
Free PMC Article

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