Makwana Rikhil, Christ Carolina, Marchi Elaine, Harpell Randie, Lyon Gholson J
Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, United States of America.
George A. Jervis Clinic, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, United States of America.
medRxiv. 2024 Feb 24:2024.02.23.24303144. doi: 10.1101/2024.02.23.24303144.
Ogden syndrome, also known as NAA10-related neurodevelopmental syndrome, is a rare genetic condition associated with pathogenic variants in the NAA10 N-terminal acetylation family of proteins. The condition was initially described in 2011, and is characterized by a range of neurologic symptoms, including intellectual disability and seizures, as well as developmental delays, psychiatric symptoms, congenital heart abnormalities, hypotonia and others. Previously published articles have described the etiology and phenotype of Ogden syndrome, mostly with retrospective analyses; herein, we report prospective data concerning its progress over time. Additionally, we describe the nature of seizures in this condition in greater detail, as well as investigate how already-available non-pharmaceutical therapies impact individuals with NAA10-related neurodevelopmental syndrome. Using Vineland-3 scores, we show decline in cognitive function over time in individuals with Ogden syndrome. Sub-domain analysis found the decline to be present across all modalities. Additional investigation between seizure and non-seizure groups showed no significant difference in adaptive behavior outcomes. Therapy investigation showed speech therapy to be the most commonly used therapy by individuals with NAA10-related neurodevelopmental syndrome, followed by occupational and physical therapy. with more severely affected individuals receiving more types of therapy than their less-severe counterparts. Early intervention analysis was only significantly effective for speech therapy, with analyses of all other therapies being non-significant. Our study portrays the decline in cognitive function over time of individuals within our cohort, independent of seizure status and therapies being received, and highlights the urgent need for the development of effective treatments for Ogden syndrome.
奥格登综合征，也称为与NAA10相关的神经发育综合征，是一种罕见的遗传性疾病，与NAA10 N端乙酰化蛋白家族中的致病变异有关。该病症最初于2011年被描述，其特征是一系列神经症状，包括智力残疾和癫痫发作，以及发育迟缓、精神症状、先天性心脏异常、肌张力减退等。先前发表的文章描述了奥格登综合征的病因和表型，大多采用回顾性分析；在此，我们报告有关其随时间进展的前瞻性数据。此外，我们更详细地描述了这种病症中癫痫发作的性质，并研究了现有的非药物疗法如何影响患有与NAA10相关的神经发育综合征的个体。使用文兰适应性行为量表第三版（Vineland-3）评分，我们发现奥格登综合征患者的认知功能随时间下降。子领域分析发现这种下降在所有模式中均存在。癫痫发作组和非癫痫发作组之间的进一步调查显示，适应性行为结果没有显著差异。治疗调查显示，言语治疗是患有与NAA10相关的神经发育综合征的个体最常用的治疗方法，其次是职业治疗和物理治疗。受影响更严重的个体比病情较轻的个体接受更多类型的治疗。早期干预分析仅对言语治疗有显著效果，对所有其他治疗的分析均无显著意义。我们的研究描绘了我们队列中个体的认知功能随时间下降的情况，与癫痫发作状态和所接受的治疗无关，并强调了迫切需要开发针对奥格登综合征的有效治疗方法。
