Jiao Xianru, Gong Pan, Wu Ye, Zhang Yuehua, Yang Zhixian
Department of Pediatrics, Peking University First Hospital, Beijing, China.
Front Genet. 2021 Apr 1;12:644447. doi: 10.3389/fgene.2021.644447. eCollection 2021.
To describe the clinical characteristics of 12 patients from six families with pyridoxine-dependent epilepsy (PDE) carrying mutations, and analyze the impact of early diagnosis and treatment, as well as possible genotype-phenotype relationship.
Clinical and genetics data of 12 patients were collected.
Family 1-3 presented with symptoms in the neonatal period, while family 4-6 presented during early infancy. In the same family, the age of onset was similar. The focal motor seizure appeared in all patients. The affected identical twins from family 4 were diagnosed with infantile spasms. Mutation analysis identified nine different mutations among six families. The neurodevelopment of siblings in family 1 was mild delay and normal separately due to the minor difference of delayed diagnosis time. Siblings in family 2 showed severely delayed and normal development respectively due to the significant difference of a delayed diagnosis for 4 years. In family 5, although the difference of the delayed diagnosis time is up to 7 years, the nearly normal psychomotor development in both patients might be due to infrequent seizures before the delayed diagnosis. A severe phenotype exhibited in family 3, 4, and 6. The survived affected patients presented with severe developmental delay or refractory seizures and their twins or older sisters presented a similar clinical history and died in the early days of life. Mutation analysis showed D511N and IVS11 + 1G > A in family 3, V188A and exon1 deletion in family 4, and Y354C and exon 8-13 deletion in family 6.
Patients from the same family often have the same phenotype, including onset age and seizure type. Early treatment with pyridoxine and infrequent seizures showed positive relationship with prognosis. The deletion of exon 1 and exon 8-13 might be associated with the severe phenotype.
描述6个家族中12例携带突变的吡哆醇依赖性癫痫（PDE）患者的临床特征，分析早期诊断和治疗的影响以及可能的基因型-表型关系。
收集12例患者的临床和遗传学数据。
1-3家族在新生儿期出现症状，而4-6家族在婴儿早期出现症状。在同一家族中，发病年龄相似。所有患者均出现局灶性运动性发作。4家族中受影响的同卵双胞胎被诊断为婴儿痉挛症。突变分析在6个家族中鉴定出9种不同的突变。1家族中兄弟姐妹的神经发育因诊断延迟时间的微小差异分别为轻度延迟和正常。2家族中的兄弟姐妹由于延迟诊断4年的显著差异分别表现为严重延迟和正常发育。在5家族中，尽管延迟诊断时间相差达7年，但两名患者几乎正常的精神运动发育可能是由于延迟诊断前发作不频繁。3、4和6家族表现出严重的表型。存活的受影响患者出现严重发育迟缓或难治性癫痫发作，他们的双胞胎或姐姐有类似的临床病史并在生命早期死亡。突变分析显示3家族中有D511N和IVS11+1G>A，4家族中有V188A和外显子1缺失，6家族中有Y354C和外显子8-13缺失。
同一家族的患者通常具有相同的表型，包括发病年龄和癫痫发作类型。吡哆醇早期治疗和发作不频繁与预后呈正相关。外显子1和外显子8-13的缺失可能与严重表型有关。
