Pinchefsky Elana, Laneuville Laurence, Srour Myriam
Division of Pediatric Neurology, Department of Pediatrics, Montreal Children's Hospital, McGill University Health Centre (MUHC), Montreal, Québec, Canada.
Department of Medicine, McGill University, Montreal, Québec, Canada.
Child Neurol Open. 2017 Nov 1;4:2329048X17737651. doi: 10.1177/2329048X17737651. eCollection 2017 Jan-Dec.
Distal chromosome 22q11.2 microduplications are associated with a wide range of phenotypes and unclear pathogenicity. The authors report on a 3-year-old girl with global developmental delay harboring a de novo 1.24 Mb distal chromosome 22q11.2 microduplication and a paternally inherited 0.25 Mb chromosome 4p14 microduplication. The authors review clinical features of 30 reported cases of distal 22q11.2 duplications. Common features include developmental delay (93%), neuropsychiatric features (26%), and nonspecific facial dysmorphisms (74%). In 70% of cases, the distal 22q11.2 duplications were inherited, and the majority of the carrier parents were phenotypically normal. Furthermore, 30% of probands carried an additional copy number variant. Review of the phenotype in individuals carrying microduplications involving similar low copy repeats (LCR) failed to establish any clear genotype-phenotype correlations. Distal 22q11.2 duplications represent a major challenge for genetic counseling and prediction of clinical consequences. Our report suggests a pathogenic role of distal 22q11.2 duplications and supports a "multiple hit" hypothesis underlying its variable expressivity and phenotypic severity.
22号染色体长臂末端11.2微重复与多种表型及不明致病机制相关。作者报告了一名3岁女童，存在1.24 Mb的22号染色体长臂末端11.2新生微重复及父源性遗传的0.25 Mb 4号染色体短臂14微重复，伴有全面发育迟缓。作者回顾了30例已报道的22号染色体长臂末端11.2微重复病例的临床特征。常见特征包括发育迟缓（93%）、神经精神特征（26%）及非特异性面部畸形（74%）。70%的病例中，22号染色体长臂末端11.2微重复为遗传性，大多数携带者父母表型正常。此外，30%的先证者携带额外的拷贝数变异。对携带涉及相似低拷贝重复序列（LCR）微重复个体的表型回顾未能确立任何明确的基因型-表型相关性。22号染色体长臂末端11.2微重复对遗传咨询及临床后果预测构成重大挑战。我们的报告提示22号染色体长臂末端11.2微重复具有致病作用，并支持其可变表达及表型严重程度的“多重打击”假说。
