Novel compound heterozygous ATP1A2 variants in a patient with fetal akinesia/hypokinesia sequence

Am J Med Genet A. 2024 Mar;194(3):e63453. doi: 10.1002/ajmg.a.63453. Epub 2023 Oct 23.

Abstract

ATP1A2 encodes a subunit of sodium/potassium-transporting adenosine triphosphatase (Na+ /K+ -ATPase). Heterozygous pathogenic variants of ATP1A2 cause familial hemiplegic migraine, alternating hemiplegia of childhood, and developmental and epileptic encephalopathy. Biallelic loss-of-function variants in ATP1A2 lead to fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, and dysmorphic facies, resulting in fetal death. Here, we describe a patient with compound heterozygous ATP1A2 variants consisting of missense and nonsense variants. He survived after birth with brain malformations and the fetal akinesia/hypokinesia sequence. We report a novel type of compound heterozygous variant that might extend the disease spectrum of ATP1A2.

Keywords: ATP1A2; fetal akinesia/hypokinesia sequence.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Hemiplegia
  • Humans
  • Hypokinesia
  • Male
  • Microcephaly* / diagnosis
  • Microcephaly* / genetics
  • Migraine with Aura*
  • Sodium-Potassium-Exchanging ATPase / genetics
  • Syndrome

Substances

  • Sodium-Potassium-Exchanging ATPase
  • ATP1A2 protein, human