[S3-1C-1] Genotype–Phenotype Correlations in Japanese Patients with Alternating Hemiplegia of Childhood
Objective: The clinical severity of alternating hemiplegia of childhood (AHC) is variable among patients. To investigate genotype–phenotype correlations in Japanese patients with AHC, we analyzed the clinical information and ATP1A3 mutations in patients with AHC. Methods: Forty seven 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 the family members of AHC patients and clinicians responsible for their care. Results: Gene analysis revealed 43 patients with de novo heterozygous missense mutations in ATP1A3: Glu815Lys mutation in 13 cases (30%), Asp801Asn mutation in 14 cases (33%), and other missense mutations in 16 cases (37%). Clinical information was compared among the Glu815Lys, Asp801Asn, and other mutation groups. Patients with Glu815Lys showed neonatal onset and severely delayed motor development; they did not specifically develop walking ability, except for one case. 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 those in the other groups. In addition, nine 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 considered as a progressive disorder, it should be considered as a disorder that deteriorates abruptly or in a stepwise manner, particularly in patients with the Glu815Lys mutation.