Genotype-phenotype correlations in alternating hemiplegia of childhood

Masayuki Sasaki, Atsushi Ishii, Yoshiaki Saito, Naoya Morisada, Kazumoto Iijima, Satoshi Takada, Atsushi Araki, Yuko Tanabe, Hidee Arai, Sumimasa Yamashita, Tsukasa Ohashi, Yoichiro Oda, Hiroshi Ichiseki, Shininchi Hirabayashi, Akihiro Yasuhara, Hisashi Kawawaki, Sadami Kimura, Masayuki Shimono, Seiro Narumiya, Motomasa SuzukiTakeshi Yoshida, Yoshinobu Oyazato, Shuichi Tsuneishi, Shiro Ozasa, Kenji Yokochi, Sunao Dejima, Tomoyuki Akiyama, Nobuyuki Kishi, Ryutaro Kira, Toshio Ikeda, Hirokazu Oguni, Bo Zhang, Shoji Tsuji, Shinichi Hirose

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Abstract

Objective: Clinical severity of alternating hemiplegia of childhood (AHC) is extremely variable. To investigate genotype-phenotype correlations in AHC, we analyzed the clinical information and ATP1A3 mutations in patients with AHC. Methods: Thirty-five Japanese patients who were clinically diagnosed with AHC participated in this study. ATP1A3 mutations were analyzed using Sanger sequencing. Detailed clinical information was collected from family members of patients with AHC and clinicians responsible for their care. Results: Gene analysis revealed 33 patients with de novo heterozygous missense mutations of ATP1A3: Glu815Lys in 12 cases (36%), Asp801Asn in 10 cases (30%), and other missense mutations in 11 cases. Clinical information was compared among the Glu815Lys, Asp801Asn, and other mutation groups. Statistical analysis revealed significant differences in the history of neonatal onset, gross motor level, status epilepticus, and respiratory paralysis in the Glu815Lys group compared with the other groups. In addition, 8 patients who did not receive flunarizine had severe motor deteriorations. Conclusions: The Glu815Lys genotype appears to be associated with the most severe AHC phenotype. Although AHC is not generally seen as a progressive disorder, it should be considered a disorder that deteriorates abruptly or in a stepwise fashion, particularly in patients with the Glu815Lys mutation.

Original languageEnglish
Pages (from-to)482-490
Number of pages9
JournalNeurology
Volume82
Issue number6
DOIs
Publication statusPublished - Feb 11 2014

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ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

Cite this

Sasaki, M., Ishii, A., Saito, Y., Morisada, N., Iijima, K., Takada, S., Araki, A., Tanabe, Y., Arai, H., Yamashita, S., Ohashi, T., Oda, Y., Ichiseki, H., Hirabayashi, S., Yasuhara, A., Kawawaki, H., Kimura, S., Shimono, M., Narumiya, S., ... Hirose, S. (2014). Genotype-phenotype correlations in alternating hemiplegia of childhood. Neurology, 82(6), 482-490. https://doi.org/10.1212/WNL.0000000000000102