Narayanan Dhanya Lakshmi, Kutsche Kerstin, Girisha Katta M
Department of Medical Genetics Kasturba Medical College Manipal, India
Institute of Human Genetics University Medical Center Hamburg-Eppendorf Hamburg, Germany
neurodevelopmental disorder (-NDD) is associated with developmental delay (DD) / intellectual disability (ID), speech delay, gait or truncal ataxia, hypotonia, behavioral problems, and facial dysmorphism. Variability between individuals with -NDD is significant. Although all affected children have DD noted in early infancy, intellect generally ranges from mild to severe ID, with two individuals functioning in the low normal range. Less common issues can include genitourinary abnormalities and gastrointestinal and/or musculoskeletal involvement. To date, 42 symptomatic individuals from 39 families have been reported.
DIAGNOSIS/TESTING: The diagnosis of -NDD is established in a proband with suggestive findings and a heterozygous pathogenic variant in identified by molecular genetic testing.
Developmental delay / intellectual disability, speech delay, hypotonia and ataxia, behavioral issues, genitourinary abnormalities, gastrointestinal involvement, and musculoskeletal involvement are managed as per standard care. Follow up of manifestations at each clinic visit.
-NDD is an autosomal dominant disorder typically caused by a pathogenic variant. If a parent is known to have the pathogenic variant identified in the proband, the risk to the sibs of inheriting the pathogenic variant is 50%. If the pathogenic variant identified in the proband cannot be detected in the leukocyte DNA of either parent, the recurrence risk to sibs is slightly greater than that of the general population 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.
神经发育障碍（-NDD）与发育迟缓（DD）/智力残疾（ID）、语言发育迟缓、步态或躯干共济失调、肌张力减退、行为问题以及面部畸形有关。患有-NDD的个体之间差异很大。虽然所有受影响的儿童在婴儿早期都有发育迟缓的情况，但智力一般从轻度到重度智力残疾不等，有两人功能处于低正常范围。较不常见的问题可能包括泌尿生殖系统异常以及胃肠道和/或肌肉骨骼系统受累。迄今为止，已报道了来自39个家庭的42名有症状个体。
诊断/检测：通过分子遗传学检测在有提示性发现且鉴定出杂合致病变异的先证者中确立-NDD的诊断。
按照标准护理对发育迟缓/智力残疾、语言发育迟缓、肌张力减退和共济失调、行为问题、泌尿生殖系统异常、胃肠道受累以及肌肉骨骼系统受累进行管理。每次门诊就诊时对表现进行随访。
-NDD是一种常染色体显性疾病，通常由致病变异引起。如果已知父母一方具有在先证者中鉴定出的致病变异，其同胞继承该致病变异的风险为50%。如果在先证者中鉴定出的致病变异在父母任何一方的白细胞DNA中均未检测到，由于父母生殖腺嵌合的可能性，其同胞的复发风险略高于一般人群。一旦在受影响的家庭成员中鉴定出致病变异，产前和植入前基因检测是可行的。
