Bonkowski Emily, Fathi Esmat, Mefford Heather C
Center for Pediatric Neurological Disease Research, St Jude Children's Research Hospital, Memphis, Tennessee
-related neurodevelopmental disorder (-NDD) is characterized by mild-to-profound developmental delay and intellectual disability, hypotonia, neurobehavioral and/or psychiatric manifestations, and epilepsy. The neurobehavioral and/or psychiatric manifestations include features of autism spectrum disorder such as stereotypic behaviors (hand flapping, head banging, hand wringing, repetitive noises, teeth grinding, mouthing behaviors), sensory sensitivities, and poor eye contact. Temper tantrums, anxiety, agitation, aggression, and attention-deficit/hyperactivity disorder are also reported. Seizure onset typically occurs within the first six months of life; seizure types include absence, generalized tonic-clonic, and focal-onset impaired awareness. Additional common features include scoliosis, hip dysplasia, feeding difficulties or obesity with insatiable appetite, constipation, and strabismus.
DIAGNOSIS/TESTING: The diagnosis of -NDD is established in a proband with characteristic clinical features and a heterozygous pathogenic variant in identified by molecular genetic testing.
Developmental and educational services; standard epilepsy treatment with anti-seizure medications by an experienced neurologist; physical medicine and rehabilitation, physical therapy, and occupational therapy to include stretching to help avoid contractures and falls; feeding therapy with gastrostomy tube placement as needed; standard treatments for constipation and strabismus; social work support and care coordination as needed. At each visit, assess developmental progress, educational needs, mobility and self-help skills, growth, nutrition, and family needs, as well as for new seizures or changes in seizures, scoliosis, and constipation; behavioral assessment for autistic features, anxiety, attention-deficit/hyperactivity disorder, and aggressive or self-injurious behaviors as needed.
-NDD is an autosomal dominant disorder typically caused by a pathogenic variant. If the pathogenic variant identified in the proband is not identified in either parent, the recurrence risk to sibs is estimated to be 1%-8% because of the possibility of parental germline mosaicism. Once the pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.
-相关神经发育障碍（-NDD）的特点是存在轻度至重度发育迟缓、智力残疾、肌张力减退、神经行为和/或精神症状以及癫痫。神经行为和/或精神症状包括自闭症谱系障碍的特征，如刻板行为（拍手、撞头、扭手、重复发声、磨牙、口部动作）、感觉敏感和眼神接触不良。还报告有发脾气、焦虑、激动、攻击行为以及注意力缺陷多动障碍。癫痫发作通常在出生后的头六个月内出现；发作类型包括失神发作、全身强直阵挛发作和局灶性发作伴意识障碍。其他常见特征包括脊柱侧弯、髋关节发育不良、喂养困难或食欲旺盛导致的肥胖、便秘和斜视。
诊断/检测：-NDD的诊断是在具有特征性临床特征且通过分子基因检测在 中鉴定出杂合致病变异的先证者中确立的。
发育和教育服务；由经验丰富的神经科医生使用抗癫痫药物进行标准的癫痫治疗；物理医学与康复、物理治疗和职业治疗，包括伸展运动以帮助避免挛缩和跌倒；根据需要进行喂养治疗并放置胃造瘘管；便秘和斜视的标准治疗；根据需要提供社会工作支持和护理协调。每次就诊时，评估发育进展、教育需求、活动能力和自助技能、生长发育、营养状况和家庭需求，以及新的癫痫发作或癫痫发作的变化、脊柱侧弯和便秘情况；根据需要对自闭症特征、焦虑、注意力缺陷多动障碍以及攻击或自伤行为进行行为评估。
-NDD是一种常染色体显性疾病，通常由 致病变异引起。如果在先证者中鉴定出的 致病变异在父母双方中均未被鉴定出，由于父母生殖系嵌合体的可能性，同胞的复发风险估计为1%-8%。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。
