Agarwal Manisha, Kumar Vivek, Dwivedi Aradhana
Classified Specialist (Pathology) & Cytogeneticist, Command Hospital (Eastern Command), Kolkata, India.
Senior Adviser (Pediatrics) & Pediatric Cardiologist, Command Hospital (Air Force), Bengaluru, India.
Med J Armed Forces India. 2023 Dec;79(Suppl 1):S196-S201. doi: 10.1016/j.mjafi.2022.05.014. Epub 2022 Aug 1.
Congenital heart diseases (CHDs) are the leading cause of birth defects. Approximately, 30% of CHDs are related to genetic syndromes accompanied by extracardiac anomalies. Aneuploidies and 22q11.2 deletions account for majority of cases. 22q11.2 deletion involves deletion of 30-40 genes, and varying deletions in this region lead to different phenotypes. Fluorescent in situ hybridization probes span a narrow region on chromosome 22 as compared to other recent techniques like multiplex ligation probe amplification assay (MLPA) which may also identify any gene duplications if present.
Present study was a cross-sectional descriptive study. In total, 350 children with CHD reported to pediatric cardiology clinic during the study period. Of these, 60 children had associated facial dysmorphism. Out of these 60 children, 18 children had clinical phenotype characteristic of Down syndrome and hence these children were excluded from the study. Forty-two children with CHDs (conotruncal and other defects) and craniofacial features (subtle or obvious) suggestive of 22q11.2 deletion spectrum disorder were included in this study.
Nineteen percent of children presenting with CHDs and facial dysmorphisms had 22q11.2 deletion syndrome. All the samples were subjected to karyotyping.
Metaphase FISH has been the method of choice for microdeletions. However, apart from technical challenges and longer turnaround time, FISH probes span a very narrow region in 22q11.2 chromosome (LCR22 D) and provide information about DiGeorge syndrome (DGS) only. Take home message is that patients of CHDs with facial dysmorphism should be investigated in an approach-based manner.
先天性心脏病（CHD）是出生缺陷的主要原因。大约30%的CHD与伴有心外畸形的遗传综合征有关。非整倍体和22q11.2缺失占大多数病例。22q11.2缺失涉及30 - 40个基因的缺失，该区域不同的缺失导致不同的表型。与其他近期技术如多重连接探针扩增分析（MLPA）相比，荧光原位杂交探针覆盖22号染色体上的狭窄区域，MLPA还可识别任何基因重复（如果存在）。
本研究为横断面描述性研究。在研究期间，共有350名患有CHD的儿童到儿科心脏病诊所就诊。其中，60名儿童伴有面部畸形。在这60名儿童中，18名儿童具有唐氏综合征的临床表型特征，因此这些儿童被排除在研究之外。本研究纳入了42名患有CHD（圆锥动脉干及其他缺陷）且具有提示22q11.2缺失谱障碍的颅面特征（轻微或明显）的儿童。
患有CHD和面部畸形的儿童中，19%患有22q11.2缺失综合征。所有样本均进行了核型分析。
中期荧光原位杂交一直是微缺失的首选方法。然而，除了技术挑战和较长的周转时间外，荧光原位杂交探针覆盖22q11.2染色体上非常狭窄的区域（LCR22 D），仅提供有关迪格奥尔格综合征（DGS）的信息。重要的是，对于患有面部畸形的CHD患者，应以基于方法的方式进行调查。
