并非所有癫痫性脑病都是德拉韦综合征：早期严重的苏氨酸226甲硫氨酸表型。
Not all epileptic encephalopathies are Dravet syndrome: Early profound Thr226Met phenotype.
作者信息
Sadleir Lynette G, Mountier Emily I, Gill Deepak, Davis Suzanne, Joshi Charuta, DeVile Catherine, Kurian Manju A, Mandelstam Simone, Wirrell Elaine, Nickels Katherine C, Murali Hema R, Carvill Gemma, Myers Candace T, Mefford Heather C, Scheffer Ingrid E
机构信息
From the Department of Paediatrics and Child Health (L.G.S., E.I.M.), University of Otago, Wellington, New Zealand; Department of Neurology (D.G.), University of Sydney, Australia; Department of Neurology (S.D.), Starship Children's Health, Auckland, New Zealand; Department of Neurology (C.J.), Children's Hospital Colorado, Anschutz Medical Campus, University of Colorado, Denver; Department of Neurology (C.D.V., M.A.K.), Great Ormond Street Hospital for Children; Developmental Neurosciences (M.A.K.), UCL Great Ormond Street Institute of Child Health, London; Wellcome Trust Sanger Institute (DDD Study Group), Hinxton, Cambridge, UK; Departments of Paediatrics and Radiology (S.M.), University of Melbourne; The Florey Institute of Neuroscience and Mental Health (S.M., I.E.S.); Department of Medical Imaging (S.M.), Royal Children's Hospital, Melbourne, Australia; Department of Neurology (E.W., K.C.N.), Mayo Clinic, Rochester, MN; Department of Neurology (H.R.M.), Marshfield Clinic, WI; Division of Genetic Medicine (G.C., C.T.M., H.C.M.), Department of Pediatrics, University of Washington, Seattle; and Departments of Medicine and Paediatrics (I.E.S.), University of Melbourne, Austin Health and Royal Children's Hospital, Australia.
出版信息
Neurology. 2017 Sep 5;89(10):1035-1042. doi: 10.1212/WNL.0000000000004331. Epub 2017 Aug 9.
OBJECTIVE
To define a distinct developmental and epileptic encephalopathy with early onset, profound impairment, and movement disorder.
METHODS
A case series of 9 children were identified with a profound developmental and epileptic encephalopathy and mutation.
RESULTS
We identified 9 children 3 to 12 years of age; 7 were male. Seizure onset was at 6 to 12 weeks with hemiclonic seizures, bilateral tonic-clonic seizures, or spasms. All children had profound developmental impairment and were nonverbal and nonambulatory, and 7 of 9 required a gastrostomy. A hyperkinetic movement disorder occurred in all and was characterized by dystonia and choreoathetosis with prominent oral dyskinesia and onset from 2 to 20 months of age. Eight had a recurrent missense mutation, p.Thr226Met. The remaining child had the missense mutation p.Pro1345Ser. The mutation arose de novo in 8 of 9; for the remaining case, the mother was negative and the father was unavailable.
CONCLUSIONS
Here, we present a phenotype-genotype correlation for . We describe a distinct phenotype, early infantile encephalopathy, which is readily distinguishable from the well-recognized entities of Dravet syndrome and genetic epilepsy with febrile seizures plus. This disorder has an earlier age at onset, profound developmental impairment, and a distinctive hyperkinetic movement disorder, setting it apart from Dravet syndrome. Remarkably, 8 of 9 children had the recurrent missense mutation p.Thr226Met.
目的
定义一种具有早发性、严重损害和运动障碍的独特发育性和癫痫性脑病。
方法
确定了9例患有严重发育性和癫痫性脑病及突变的儿童病例系列。
结果
我们确定了9名年龄在3至12岁的儿童；7名男性。癫痫发作始于6至12周，表现为半侧阵挛性发作、双侧强直阵挛性发作或痉挛。所有儿童都有严重的发育障碍，不能言语且不能行走，9名中有7名需要胃造口术。所有儿童均出现运动增多性运动障碍，其特征为肌张力障碍和舞蹈手足徐动症，伴有明显的口部运动障碍，发病年龄为2至20个月。8名儿童有复发性错义突变p.Thr226Met。其余1名儿童有错义突变p.Pro1345Ser。9名中有8名的突变是新发的；对于其余病例，母亲检测为阴性，父亲无法联系到。
结论
在此，我们展示了一种[疾病名称]的表型-基因型相关性。我们描述了一种独特的表型，即早期婴儿型[疾病名称]脑病，它很容易与公认的Dravet综合征和伴有热性惊厥附加症的遗传性癫痫区分开来。这种疾病起病年龄更早，有严重的发育障碍，以及独特的运动增多性运动障碍，使其有别于Dravet综合征。值得注意的是，9名儿童中有8名有复发性错义突变p.Thr226Met。
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