染色体1p36缺失综合征(1p36DS)是最常见的终末缺失综合征之一(在美国人口中,发病率介于1/5000至1/10,000活产之间)。由于1号染色体短臂部分的杂合缺失。1p36DS的特点是典型的颅面特征,发育迟缓/智力残疾,低张力,癫痫,心肌病/先天性心脏病,大脑异常,听力损失,眼睛/视力问题,身材矮小。我们研究的目的是(1)与22q11.2缺失综合征和21三体相比,评估法国人群中1p36DS的发生率;(2)回顾与微阵列数据相关的出生后表型,与以前发布的产前数据相比。多亏了与ACLF(法国自行车协会)的合作,我们收集了86名患者的数据,据我们所知,文献中第二大的1p36DS患者队列。我们估计法国每年平均至少有10例。1p36DS似乎比22q11.2缺失综合征和21三体综合征少得多。患者主要表现为畸形,小头畸形,发育迟缓/智力残疾,低张力,癫痫,大脑畸形,行为障碍,心肌病,或心血管畸形,出生前和/或出生后生长迟缓。心脏异常,大脑畸形,癫痫在远端缺失中更常见,而小头畸形在近端缺失中更为常见。定位和基因型-表型相关性使我们能够确定四个导致智力障碍的关键区域。这项研究强调了一些表型变异,根据删除位置,并有助于细化1p36DS的表型,改善患者的管理和随访。
Chromosome 1p36 deletion syndrome (1p36DS) is one of the most common terminal deletion syndromes (incidence between 1/5000 and 1/10,000 live births in the American population), due to a heterozygous deletion of part of the short arm of chromosome 1. The 1p36DS is characterized by typical craniofacial features, developmental delay/intellectual disability, hypotonia, epilepsy, cardiomyopathy/congenital heart defect, brain abnormalities, hearing loss, eyes/vision problem, and short stature. The aim of our study was to (1) evaluate the incidence of the 1p36DS in the French population compared to 22q11.2 deletion syndrome and trisomy 21; (2) review the postnatal phenotype related to microarray data, compared to previously publish prenatal data. Thanks to a collaboration with the ACLF (Association des Cytogénéticiens de Langue Française), we have collected data of 86 patients constituting, to the best of our knowledge, the second-largest cohort of 1p36DS patients in the literature. We estimated an average of at least 10 cases per year in France. 1p36DS seems to be much less frequent than 22q11.2 deletion syndrome and trisomy 21. Patients presented mainly dysmorphism, microcephaly, developmental delay/intellectual disability, hypotonia, epilepsy, brain malformations, behavioral disorders, cardiomyopathy, or cardiovascular malformations and, pre and/or postnatal growth retardation. Cardiac abnormalities, brain malformations, and epilepsy were more frequent in distal deletions, whereas microcephaly was more common in proximal deletions. Mapping and genotype-phenotype correlation allowed us to identify four critical regions responsible for intellectual disability. This study highlights some phenotypic variability, according to the deletion position, and helps to refine the phenotype of 1p36DS, allowing improved management and follow-up of patients.