Chung Wendy, Okur Volkan
Departments of Pediatrics and Medicine, Columbia University, New York, New York
New York Genome Center, New York, New York
Individuals with Okur-Chung neurodevelopmental syndrome (OCNDS) frequently have nonspecific clinical features, delayed language development, motor delay, intellectual disability (typically in the mild-to-moderate range), generalized hypotonia starting in infancy, difficulty feeding, and nonspecific dysmorphic facial features. Developmental delay affects all areas of development, but language is more impaired than gross motor skills in most individuals. Intellectual disability has been reported in about three quarters of individuals. Less common findings may include kyphoscoliosis, postnatal short stature, disrupted circadian rhythm leading to sleep disturbance, seizures, and poor coordination.
DIAGNOSIS/TESTING: The diagnosis of OCNDS is established in a proband with suggestive findings and a heterozygous pathogenic variant in identified by molecular genetic testing.
Feeding therapy and consideration of gastrostomy tube placement in those with persistent feeding issues; consideration of growth hormone therapy (as directed by an endocrinologist) in those with short stature and evidence of partial growth hormone deficiency; standard treatment of epilepsy (as directed by a neurologist) with anti-seizure medication; consideration of intravenous immune globulin treatment (as directed by an immunologist) for demonstrated hypogammaglobulinemia; physical therapy / occupational therapy / rehabilitation medicine for those with hypotonia and/or motor coordination issues; standard supportive developmental therapies; standard treatment of scoliosis, constipation, congenital heart defects, renal anomalies / pelviectasis, and sleep disorders. : At each visit: measure growth parameters, growth velocity, and nutritional status; monitor for signs of ongoing feeding issues / safety of oral intake and constipation; assess new neurologic manifestations (seizures, changes in tone, movement disorders, poor coordination); monitor developmental progress, behavior, and educational needs; monitor for evidence of frequent or unusual infections and for signs and symptoms of sleep disturbance. Every one to three years: ophthalmology evaluation.
OCNDS disorder is expressed in an autosomal dominant manner and typically caused by a pathogenic variant. Therefore, the risk to other family members is presumed to be low. Rarely, individuals diagnosed with OCNDS have the disorder as the result of a pathogenic variant inherited from an affected parent or an unaffected parent with low-level mosaicism in the blood. Once a pathogenic variant has been identified in an affected family member, prenatal testing and preimplantation genetic testing are possible.
奥库尔-钟神经发育综合征（OCNDS）患者通常具有非特异性临床特征、语言发育迟缓、运动发育迟缓、智力残疾（通常为轻度至中度）、婴儿期开始出现的全身性肌张力减退、喂养困难以及非特异性面部畸形特征。发育迟缓影响发育的各个方面，但在大多数个体中，语言功能比粗大运动技能受损更严重。约四分之三的患者有智力残疾报告。较少见的表现可能包括脊柱侧凸、出生后身材矮小、昼夜节律紊乱导致睡眠障碍、癫痫发作以及协调性差。
诊断/检测：OCNDS的诊断基于先证者具有提示性表现且通过分子遗传学检测鉴定出杂合致病性变异。
对于持续存在喂养问题的患者进行喂养治疗并考虑放置胃造瘘管；对于身材矮小且有部分生长激素缺乏证据的患者（在内分泌科医生指导下）考虑生长激素治疗；使用抗癫痫药物对癫痫进行标准治疗（在神经科医生指导下）；对于已证实的低丙种球蛋白血症患者（在免疫科医生指导下）考虑静脉注射免疫球蛋白治疗；对于有肌张力减退和/或运动协调问题的患者进行物理治疗/职业治疗/康复医学治疗；进行标准的支持性发育治疗；对脊柱侧凸、便秘、先天性心脏病、肾脏异常/肾盂扩张以及睡眠障碍进行标准治疗。每次就诊时：测量生长参数、生长速度和营养状况；监测持续存在的喂养问题迹象/经口摄入安全性和便秘情况；评估新出现的神经学表现（癫痫发作、肌张力变化、运动障碍、协调性差）；监测发育进展、行为和教育需求；监测频繁或不寻常感染的证据以及睡眠障碍的体征和症状。每1至3年：进行眼科评估。
OCNDS以常染色体显性方式表达，通常由致病性变异引起。因此，其他家庭成员的患病风险被认为较低。很少有被诊断为OCNDS的患者是由于从患病父母或血液中存在低水平嵌合体的未患病父母遗传的致病性变异而患病。一旦在受影响的家庭成员中鉴定出致病性变异，产前检测和植入前基因检测是可行的。
