Vergano Samantha A, van der Sluijs Pleuntje J, Santen Gijs
Division of Medical Genetics and Metabolism, Children's Hospital of the King's Daughters, Norfolk, Virginia
Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
-related disorder (-RD) constitutes a clinical continuum, from classic Coffin-Siris syndrome to intellectual disability with or without nonspecific dysmorphic features. Coffin-Siris syndrome is classically characterized by aplasia or hypoplasia of the distal phalanx or nail of the fifth and additional digits, developmental or cognitive delay of varying degree, distinctive facial features, hypotonia, hypertrichosis, and sparse scalp hair. Frequencies of other features, such as developmental delay (with speech often more affected than motor development), is consistent across the clinical spectrum, and may include malformations of the cardiac, gastrointestinal, genitourinary, and/or central nervous systems. Other findings seen in individuals with -RD include feeding difficulties, slow growth, ophthalmologic abnormalities, hearing impairment, seizures, attention-deficit/hyperactivity disorder, and autistic features.
DIAGNOSIS/TESTING: The diagnosis of RD is established by identification of a heterozygous pathogenic variant in by molecular genetic testing.
Standard treatment for strabismus, refractive error, hearing loss, congenital heart defects, obstructive sleep apnea, constipation, gastroesophageal reflux, cryptorchidism, scoliosis, and seizure disorders. For significant feeding issues, a nasogastric and/or gastrostomy tube may be required. Developmental therapies, including speech/language and feeding therapy, is recommended for those with developmental delay. At least annual assessment of developmental progress and educational needs; annual ophthalmology evaluation and assessment for scoliosis (until growth is complete). Audiology evaluation, behavior assessment, and hormonal evaluation/bone age as needed based on symptoms. Those with seizures should be monitored as clinically indicated.
-related disorder is inherited in an autosomal dominant fashion. With the exception of two families in which a parent and child had features consistent with -related disorder, all individuals diagnosed to date have the disorder as the result of a pathogenic variant. Once the pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.
相关疾病（-RD）构成了一个临床连续谱，从典型的科芬-西里斯综合征到伴有或不伴有非特异性畸形特征的智力残疾。科芬-西里斯综合征的典型特征是第五指及其他手指的远端指骨或指甲发育不全或发育不良、不同程度的发育或认知延迟、独特的面部特征、肌张力减退、多毛症和头皮毛发稀疏。其他特征的发生率，如发育延迟（言语通常比运动发育受影响更严重），在整个临床谱中是一致的，并且可能包括心脏、胃肠道、泌尿生殖系统和/或中枢神经系统的畸形。患有-RD的个体中还可见到其他表现，包括喂养困难、生长缓慢、眼科异常、听力障碍、癫痫发作、注意力缺陷多动障碍和自闭症特征。
诊断/检测：通过分子基因检测在中鉴定出杂合致病性变异来确立RD的诊断。
斜视、屈光不正、听力损失、先天性心脏缺陷、阻塞性睡眠呼吸暂停、便秘、胃食管反流、隐睾症、脊柱侧弯和癫痫疾病的标准治疗。对于严重的喂养问题，可能需要鼻胃管和/或胃造口管。对于发育延迟的患者，建议进行包括言语/语言和喂养治疗在内的发育治疗。至少每年评估发育进展和教育需求；每年进行眼科评估和脊柱侧弯评估（直至生长完成）。根据症状按需进行听力评估、行为评估和激素评估/骨龄评估。癫痫患者应根据临床指征进行监测。
相关疾病以常染色体显性方式遗传。除了两个家庭中父母和孩子具有与相关疾病一致特征外，迄今为止所有被诊断的个体患有该疾病均是由于致病性变异所致。一旦在受影响的家庭成员中鉴定出致病性变异，产前和植入前基因检测都是可行的。
