Two Siblings with Cerebellar Ataxia, Mental Retardation, and Disequilibrium Syndrome 4 and a Novel Variant of ATP8A2

Yuta Narishige, Hisao Yaoita, Moriei Shibuya, Miki Ikeda, Kaori Kodama, Aritomo Kawashima, Yukimune Okubo, Wakaba Endo, Takehiko Inui, Noriko Togashi, Soichiro Tanaka, Yasuko Kobayashi, Akira Onuma, Jun Takayama, Gen Tamiya, Atsuo Kikuchi, Shigeo Kure, Kazuhiro Haginoya

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


Cerebellar ataxia, mental retardation, and disequilibrium syndrome 4 (CAMRQ4) is early onset neuromotor disorder and intellectual disabilities caused by variants of ATP8A2. We report sibling cases and systematically analyze previous literature to increase our understanding of CAMRQ4. Japanese siblings presented with athetotic movements at 1 and 2 months of age. They also had ptosis, ophthalmoplegia, feeding difficulty, hypotonia, and severely delayed development. One patient had retinal degeneration and optic atrophy. Flattening of the auditory brainstem responses and areflexia developed. At the last follow-up, neither patient could sit or achieve head control, although some nonverbal communication was preserved. Whol e exome sequenci ng reveal ed compound het erozygous vari ant s of ATP8A2: NM_016529.6:c.[1741C>T];[2158C>T] p.[(Arg581*)];[(Arg720*)]. The p.(Arg581*) variant has been reported, while the variant p.(Arg720*) was novel. The symptoms did not progress in the early period of development, which makes it difficult to distinguish from dyskinetic cerebral palsy, particularly in solitary cases. However, visual and hearing impairments associated with involuntary movements and severe developmental delay may be a clue to suspect CAMRQ4.

Original languageEnglish
Pages (from-to)321-326
Number of pages6
JournalTohoku Journal of Experimental Medicine
Issue number4
Publication statusPublished - 2022 Apr


  • ATP8A2
  • CAMRQ4
  • auditory brainstem responses
  • dyskinetic cerebral palsy
  • ophthalmoplegia

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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