Douzgou Sofia, Janssens Veerle, Houge Gunnar
Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway
Laboratory of Protein Phosphorylation & Proteomics, Department of Cellular & Molecular Medicine, KU Leuven, Leuven, Belgium
-related neurodevelopmental disorder (NDD) is characterized by: severe, persistent hypotonia; developmental delay with variable intellectual outcomes, typically in the moderate-to-severe intellectual disability range; seizures (more commonly seen in individuals with microcephaly and/or severe intellectual disability); attention-deficit/hyperactivity disorder and other behavioral problems (anxiousness, repetitive movements, self-injurious or destructive behavior, and autism spectrum disorder); feeding and swallowing issues; and dysmorphic features of the head and face. A minority of affected individuals have ear anomalies, hearing loss, ptosis, generalized joint hypermobility, and patent ductus arteriosus. Brain MRI findings are nonspecific but typically include complete or partial agenesis of the corpus callosum. Nonprogressive ventriculomegaly may be seen in a subset of affected individuals and is often associated with specific pathogenic variants in : c.544C>T (p.Arg182Trp) and c.547C>T (p.Arg183Trp).
DIAGNOSIS/TESTING: The diagnosis of -NDD is established in a proband with suggestive clinical findings and a heterozygous pathogenic variant in identified by molecular genetic testing.
Feeding therapy with consideration of gastrostomy tube placement for persistent feeding issues; standard treatment for epilepsy, developmental delay / intellectual disability, scoliosis, ear anomalies, hearing loss, dental crowding, congenital heart defects, and ptosis. : At each visit: measure growth parameters; evaluate nutritional status and oral intake; assess for new neurologic manifestations such as seizures and changes in muscle tone; monitor developmental progress and educational needs; assess mobility, self-help skills, and need for developmental therapies. At each visit until skeletal maturity: physical exam to assess for scoliosis. Annually or as clinically indicated: dental evaluation, audiology evaluation (through childhood), and behavioral assessment for anxiety, attention, and aggressive or self-injurious behavior.
-related NDD 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 testing and preimplantation genetic testing are possible.
[疾病名称]相关神经发育障碍（NDD）的特征包括：严重、持续性肌张力减退；发育迟缓，智力结果各异，通常在中度至重度智力残疾范围内；癫痫发作（在小头畸形和/或严重智力残疾个体中更常见）；注意力缺陷多动障碍和其他行为问题（焦虑、重复性动作、自我伤害或破坏性行为以及自闭症谱系障碍）；喂养和吞咽问题；以及头面部畸形特征。少数受影响个体有耳部异常、听力丧失、上睑下垂、全身关节活动过度和动脉导管未闭。脑部磁共振成像（MRI）结果无特异性，但通常包括胼胝体完全或部分发育不全。在一部分受影响个体中可见非进行性脑室扩大，且常与[基因名称]中的特定致病变异相关：c.544C>T（p.Arg182Trp）和c.547C>T（p.Arg183Trp）。
诊断/检测：[疾病名称] - NDD的诊断是在具有提示性临床发现且通过分子基因检测在[基因名称]中鉴定出杂合致病变异的先证者中确立的。
对于持续性喂养问题，考虑进行胃造口管置入的喂养治疗；对癫痫、发育迟缓/智力残疾、脊柱侧弯、耳部异常、听力丧失、牙齿拥挤、先天性心脏缺陷和上睑下垂进行标准治疗。每次就诊时：测量生长参数；评估营养状况和口服摄入量；评估是否有新的神经学表现，如癫痫发作和肌张力变化；监测发育进展和教育需求；评估活动能力、自理技能以及对发育治疗的需求。在骨骼成熟前的每次就诊时：进行体格检查以评估脊柱侧弯。每年或根据临床指征：进行牙科评估、听力评估（贯穿儿童期）以及针对焦虑、注意力和攻击或自我伤害行为的行为评估。
[疾病名称]相关NDD以常染色体显性方式表达，通常由[基因名称]的致病变异引起。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[基因名称]的致病变异，产前检测和植入前基因检测是可行的。
