Medico-Salsench Eva, Kaya Namik, Barakat Tahsin Stefan
Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, the Netherlands
Department of Translational Genomics, King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia
-related neurodevelopmental disorder (-NDD) is characterized by severe-to-profound developmental delay / intellectual disability with variable motor abnormalities including axial hypotonia, peripheral hypertonia, dystonia, and dyskinesia; absence of speech in most individuals or very limited speech subject to regression; feeding difficulties; seizures; postnatal microcephaly with nonspecific brain MRI abnormalities; and ophthalmologic involvement (strabismus, nystagmus, optic atrophy, and cortical blindness). Some individuals have hypoventilation.
DIAGNOSIS/TESTING: The diagnosis of -NDD is established in a proband with suggestive findings and biallelic pathogenic variants in identified by molecular genetic testing.
Developmental and educational support; feeding therapy; gastrostomy tube placement if required for persistent feeding issues; standardized treatments for movement disorder and seizures by an experienced neurologist; treatment per ophthalmologist for refractive errors and strabismus; low vision services as needed; consider ventilation therapy when hypoventilation becomes evident; social work and family support. Monitor developmental progress, educational needs, growth, nutritional status, safety of oral intake, and changes in seizures at each visit; assess for any new manifestations including seizures, changes in tone, movement disorders, or manifestations of central hypoventilation at each visit; ophthalmology evaluation per treating ophthalmologist; behavioral assessment annually.
-NDD is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for a pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives and prenatal/preimplantation genetic testing are possible.
-相关神经发育障碍（-NDD）的特征为严重至极重度发育迟缓/智力残疾，伴有多种运动异常，包括轴性肌张力减退、外周肌张力亢进、肌张力障碍和运动障碍；大多数患者无言语能力或言语能力非常有限且会出现倒退；喂养困难；癫痫发作；出生后小头畸形伴非特异性脑磁共振成像异常；以及眼科受累（斜视、眼球震颤、视神经萎缩和皮质盲）。部分患者有通气不足。
诊断/检测：-NDD的诊断基于先证者具有提示性发现且经分子遗传学检测鉴定出双等位基因致病变异。
发育和教育支持；喂养治疗；若持续存在喂养问题则进行胃造口管置入；由经验丰富的神经科医生对运动障碍和癫痫发作进行标准化治疗；眼科医生针对屈光不正和斜视进行治疗；根据需要提供低视力服务；当通气不足明显时考虑通气治疗；社会工作和家庭支持。每次就诊时监测发育进展、教育需求、生长、营养状况、经口摄入安全性以及癫痫发作变化；每次就诊时评估是否有任何新的表现，包括癫痫发作、肌张力变化、运动障碍或中枢性通气不足的表现；由主治眼科医生进行眼科评估；每年进行行为评估。
-NDD以常染色体隐性方式遗传。如果已知父母双方均为某一致病变异的杂合子，受影响个体的每个同胞在受孕时有25%的几率受影响，50%的几率为无症状携带者，25%的几率不受影响且不是携带者。一旦在受影响的家庭成员中鉴定出致病变异，就可以对有风险的亲属进行携带者检测以及进行产前/植入前基因检测。
