RESUMEN
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.
Asunto(s)
Hemiplejía/genética , Trastornos de la Destreza Motora/genética , Parálisis Respiratoria/genética , ATPasa Intercambiadora de Sodio-Potasio/genética , Estado Epiléptico/genética , Adolescente , Adulto , Niño , Preescolar , Femenino , Estudios de Asociación Genética , Hemiplejía/complicaciones , Hemiplejía/fisiopatología , Heterocigoto , Humanos , Lactante , Masculino , Trastornos de la Destreza Motora/etiología , Trastornos de la Destreza Motora/fisiopatología , Mutación Missense/genética , Parálisis Respiratoria/etiología , Parálisis Respiratoria/fisiopatología , Índice de Severidad de la Enfermedad , Estado Epiléptico/etiología , Estado Epiléptico/fisiopatología , Adulto JovenRESUMEN
OBJECTIVE: There is little systematic data on early neurodevelopmental functioning of infants with Smith-Magenis syndrome, since early diagnosis is rare. METHODS: A boy with cytogenetically confirmed Smith-Magenis syndrome was videotaped at 4 months and 1 week of age. His posture and spontaneous movements were analysed without knowing the diagnosis. RESULTS: The motor repertoire appeared significantly reduced; fidgety general movements, which are typical of that age, were missing. Posture was abnormal and overall movements were jerky and monotonous. The findings indicate a severe motor impairment by no more than 4 months of age. CONCLUSION: It was concluded that an absence of fidgety movements that goes along with subtle dysmorphic features indicates an increased risk of maldevelopment and justifies the need to refer for genetic evaluation with the potential of facilitating earlier diagnosis.