The clinical spectrum associated with ATP1A2 variants in Chinese pediatric patients |
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| Affiliation: | 1. Department of Neurology, Beijing Children''s Hospital, Capital Medical University, National Center for Children''s Health, 100045, China;2. Department of Neurology, Baoding Children’s Hospital, Baoding, Hebei 071000, China;1. Department of Paediatric Neurology, Oxford Children''s Hospital, Oxford, UK;2. Royal Berkshire Hospital, Reading, UK;3. North East Thames Regional Genetics Service, Great Ormond Street Hospital, London, UK;1. Department of Pediatrics, Kobe University Graduate School of Medicine, Hyogo, Japan;2. Department of Pediatrics, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan;3. Department of Clinical and Molecular Genetics, Takatsuki General Hospital, Takatsuki, Japan;4. Department of Neurology, Hyogo Prefectural Kobe Children’s Hospital, Hyogo, Japan;5. Department of Genetics, Hyogo Prefectural Kobe Children’s Hospital, Hyogo, Japan;6. Department of Physical Rehabilitation and Research Center for Locomotion Biology, Kobe Gakuin University, Hyogo, Japan;1. Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Japan;2. Department of Human Genetics, Yokohama City University Graduate School of Medicine, Japan;3. Division of Glycopathology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, Japan;4. Center for Medical Education, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Japan;5. Division of Neurology, Department of Internal Medicine, St. Marianna University School of Medicine, Japan;6. Department of Neurosurgery, National Center Hospital, National Center of Neurology and Psychiatry, Japan;7. Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Japan;8. Department of Laboratory Medicine, St. Marianna University, School of Medicine, Japan;9. Forefront Research Center, Graduate School of Science, Osaka University, Japan;1. Department of Pediatrics and Adolescent Medicine, Tokyo Medical University, 6-7-1 Nishi-Shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan;2. Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan;1. Department of Neurology, Sydney Children’s Hospital, Randwick, Australia;2. Rehab2Kids, Sydney Children’s Hospital, Randwick, Australia;3. Discipline of Pediatrics and Child Health, School of Clinical Medicine, UNSW Medicine and Health, UNSW Sydney, Australia;4. Department of Immunology and Infectious Diseases, Sydney Children’s Hospital, Randwick, Australia;5. Centre for Clinical Genetics, Sydney Children’s Hospital, Randwick, Australia;6. Graduate School of Biomedical Engineering, UNSW Sydney, Australia |
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| Abstract: | PurposeTo evaluate the clinical spectrum associated with ATP1A2 variants in Chinese children with hemiplegia, migraines, encephalopathy or seizures.MethodsSixteen children (12 males and 4 females), including ten patients with ATP1A2 variants whose cases had been published previously, were identified using next-generation sequencing.ResultsFifteen patients had FHM2 (familial hemiplegic migraine type 2), including three who had AHC (alternating hemiplegia of childhood) and one who had drug-resistant focal epilepsy. Thirteen patients had DD (developmental delay). The onset of febrile seizures, which occurred between 5 months and 2 years 5 months (median 1 year 3 months) was earlier than the onset of HM (hemiplegic migraine), which occurred between 1 year 5 months and 13 years (median 3 years 11 months). Disturbance of consciousness subsided first, at 40 h to 9 days (median 4.5 days); hemiplegia and aphasia were resolved slowly, taking 30 min to 6 months (median 17.5 days) for the former and 24 h to over 1 year (median 14.5 days) for the latter. Cranial MRI showed edema in the cerebral hemispheres, mainly the left hemisphereacute attacks. All thirteen FHM2 patients recovered to baseline in 30 min to 6 months. Fifteen patients had between 1 and 7 (median 2) total attacks between the baseline and follow-up timepoints. We report twelve missense variants, including a novel variant ATP1A2 variant, p.G855E.ConclusionsThe known genotypic and phenotypic spectra of Chinese patients with ATP1A2-related disorders were further expanded. Recurrent febrile seizures and DD combined with paroxysmal hemiplegia and encephalopathy should raise the clinical suspicion of FHM2. The avoidance of triggers and thus the prevention of attacks may be the most effective therapy for FHM2. |
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| Keywords: | Familial hemiplegic migraine type 2 Alternating hemiplegia of childhood Epilepsy Encephalopathy |
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