Abdul-Rahman Omar, May Francis
Department of Pediatrics, Weill Cornell Medicine, New York, NY
Memorial Sloan Kettering Cancer Center;, NewYork-Presbyterian/Weill Cornell Medical Center, New York, NY
-related Nicolaides-Baraitser syndrome (-NCBRS) is characterized by commonly shared dysmorphic features including sparse scalp hair, prominence of the interphalangeal joints and distal phalanges due to decreased subcutaneous fat, characteristic coarse facial features, microcephaly (typically acquired), seizures, and developmental delay / intellectual disability. Developmental delay / intellectual disability is severe in nearly half of affected individuals, moderate in one third, and mild in the remainder. Nearly one third never develop speech or language skills. Seizures are of various types and can be difficult to manage, requiring multiple anti-seizure medications to achieve reasonable control. Regression or lack of developmental progress has been noted with the onset of seizures in some affected individuals. Behavioral issues can include autistic-like features (perseveration, hyperacusis), with a minority of affected individuals being diagnosed clinically with an autism spectrum disorder. Cryptorchidism is common in males. About half of affected individuals have growth deficiency and short stature. Delayed tooth eruption with hypo- or oligodontia has also been reported. Radiographic findings may include cone-shaped epiphyses, metaphyseal flaring of the phalanges, and shortening of the phalanges, metacarpals, and/or metatarsals (especially of the 4th and 5th rays) of the hands; platyspondyly; flat intervertebral disc space; and pelvic/femoral anomalies. Rare findings include conductive hearing loss, refractive error / astigmatism, and congenital heart defects.
DIAGNOSIS/TESTING: The diagnosis of -NCBRS is established in a proband with suggestive findings and a heterozygous pathogenic variant identified by molecular genetic testing.
Standard therapy for developmental delay / intellectual disability, behavioral issues, epilepsy, poor growth, myopia, astigmatism, hearing loss, dental issues, cryptorchidism, and congenital heart defects. At each visit, measure growth parameters; evaluate nutritional status and safety of oral intake; monitor those with seizures; assess for new manifestations; monitor developmental progress and educational needs; assess for behavioral issues such as short attention span, sensitivity to loud noises, and oral sensitivity; and evaluate mobility and self-help skills. Dental evaluation at least every six months after the eruption of first dentition. Annual audiology evaluation in childhood. Ophthalmology evaluation per treating ophthalmologist.
-NCBRS is expressed in an autosomal dominant manner and typically caused by a pathogenic variant; the risk to other family members is presumed to be low. Once a pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.
与尼古拉德斯 - 巴拉伊泽综合征（-NCBRS）相关的特征通常包括共同的畸形特征，如头皮毛发稀疏、由于皮下脂肪减少导致的指间关节和远端指骨突出、典型的粗糙面部特征、小头畸形（通常为后天性）、癫痫发作以及发育迟缓/智力残疾。近一半的受影响个体发育迟缓/智力残疾严重，三分之一为中度，其余为轻度。近三分之一的个体从未发展出言语或语言技能。癫痫发作类型多样且难以控制，需要多种抗癫痫药物才能实现合理控制。在一些受影响个体中，癫痫发作开始后出现了发育倒退或发育停滞。行为问题可能包括自闭症样特征（重复行为、听觉过敏），少数受影响个体临床上被诊断为自闭症谱系障碍。男性隐睾症常见。约一半的受影响个体有生长发育不足和身材矮小。也有乳牙萌出延迟伴牙发育不全或牙列稀疏的报道。影像学检查结果可能包括椎体骨骺呈锥形、指骨干骺端增宽以及手部的指骨、掌骨和/或跖骨（尤其是第4和第5射线）缩短；椎体扁平；椎间盘间隙变窄；以及骨盆/股骨异常。罕见的发现包括传导性听力损失、屈光不正/散光和先天性心脏缺陷。
诊断/检测：在具有提示性发现且通过分子遗传学检测鉴定出杂合致病变异的先证者中确立-NCBRS的诊断。
针对发育迟缓/智力残疾、行为问题、癫痫、生长发育不良、近视、散光、听力损失、牙齿问题、隐睾症和先天性心脏缺陷的标准治疗。每次就诊时，测量生长参数；评估营养状况和口服摄入的安全性；监测癫痫患者；评估新出现的症状；监测发育进展和教育需求；评估行为问题，如注意力持续时间短、对噪音敏感和口腔敏感；评估运动能力和自理技能。首次出牙后至少每六个月进行一次牙科评估。儿童期每年进行听力评估。由主治眼科医生进行眼科评估。
-NCBRS以常染色体显性方式表达，通常由致病变异引起；其他家庭成员的风险被认为较低。一旦在受影响的家庭成员中鉴定出致病变异，产前和植入前基因检测是可行的。
