Cooley Coleman Jessica, Skinner Steven A
Greenwood Genetic Center, Greenwood, South Carolina
-related disorder is characterized by moderate-to-profound developmental delay with subsequent intellectual disability, hypotonia, dysmorphic features, seizures, neurobehavioral manifestations (autistic features, sleep issues, stereotypic movements particularly of the hands), vision issues, and cardiac manifestations. Individuals who are able to speak typically only use a few words and are not able to communicate in sentences. Approximately half of individuals are unable to walk independently; however, many are able to walk with some assistance.
DIAGNOSIS/TESTING: The diagnosis of -related disorder is established in a proband by identification of a heterozygous pathogenic variant in by molecular genetic testing.
Developmental and educational services; treatment of gait abnormalities per orthopedist, physical medicine and rehabilitation specialist, and/or physical or occupational therapist; feeding support as needed; standard treatment for gastroesophageal reflux disease, constipation, and seizures; treatment of cardiac manifestations per cardiologist; treatment of refractive errors and strabismus per ophthalmologist; more complex findings or treatment per ophthalmic subspecialist; antibiotics as needed for recurrent respiratory infections and recurrent otitis media; referral to otolaryngologist for tympanostomy tubes as needed for recurrent otitis; family and social work support. At each visit, assess developmental progress, educational needs, gait issues, motor abnormalities, growth parameters, nutritional status, safety of oral intake, gastroesophageal reflux disease, and constipation; assess new or changing seizures, tone, and movement disorders at each visit or per neurologist; annual behavioral assessment; cardiology assessment per cardiologist; ophthalmology evaluation for strabismus and refractive errors per ophthalmologist; assessment for recurrent respiratory infections and/or recurrent otitis media annually or as needed; hearing evaluation in those with recurrent otitis annually or as needed; assess family needs at each visit.
-related disorder is an autosomal dominant disorder. Most probands reported to date with -related disorder whose parents have undergone molecular genetic testing have the disorder as the result of a pathogenic variant. Rarely, a proband diagnosed with -related disorder has the disorder as the result of a pathogenic variant inherited from an affected heterozygous parent or an unaffected mosaic parent. Each child of an individual with -related disorder has a 50% chance of inheriting the pathogenic variant. Once the pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.
-相关疾病的特征为中度至重度发育迟缓，随后出现智力残疾、肌张力减退、畸形特征、癫痫发作、神经行为表现（自闭症特征、睡眠问题、特别是手部的刻板动作）、视力问题和心脏表现。能够说话的个体通常只会说几个单词，无法用句子进行交流。大约一半的个体无法独立行走；然而，许多人在一些帮助下能够行走。
诊断/检测：通过分子基因检测在先证者中鉴定出-中的杂合致病变异，从而确立-相关疾病的诊断。
发育和教育服务；由骨科医生、物理医学与康复专家和/或物理治疗师或职业治疗师治疗步态异常；根据需要提供喂养支持；胃食管反流病、便秘和癫痫发作的标准治疗；由心脏病专家治疗心脏表现；由眼科医生治疗屈光不正和斜视；由眼科亚专科医生处理更复杂的检查结果或进行治疗；根据需要为反复呼吸道感染和反复中耳炎使用抗生素；根据需要将反复中耳炎患者转诊至耳鼻喉科医生进行鼓膜置管；提供家庭和社会工作支持。每次就诊时，评估发育进展、教育需求、步态问题、运动异常、生长参数、营养状况、经口摄入安全性、胃食管反流病和便秘；每次就诊或根据神经科医生的建议评估新出现或变化的癫痫发作、肌张力和运动障碍；每年进行行为评估；由心脏病专家进行心脏评估；由眼科医生评估斜视和屈光不正；每年或根据需要评估反复呼吸道感染和/或反复中耳炎；每年或根据需要对反复中耳炎患者进行听力评估；每次就诊时评估家庭需求。
-相关疾病是一种常染色体显性疾病。迄今为止报告的大多数患有-相关疾病且其父母已接受分子基因检测的先证者，该疾病是由-致病变异引起的。很少有被诊断为-相关疾病的先证者是由于从受影响的杂合父母或未受影响的嵌合父母遗传而来致病变异。患有-相关疾病的个体的每个孩子都有50%的机会继承致病变异。一旦在受影响的家庭成员中鉴定出-致病变异，就可以进行产前和植入前基因检测。
