Prader-Willi综合征Ⅰ型和Ⅱ型缺失新生儿表型分析

The genotype-phenotype analysis in 13 neonates with Prader-Willi syndrome caused by type Ⅰ or type Ⅱ deletion

目的分析Prader-Willi综合征(PWS)父源性Ⅰ型、Ⅱ型缺失新生儿的表型差异。方法纳入在复旦大学附属儿科医院临床诊断为PWS的新生儿,应用甲基化特异性多重连接探针扩增技术(MS-MLPA)和SNP芯片检测方法行PWS基因型分类,收集父源性Ⅰ型、Ⅱ型缺失患儿的临床表型资料,分析表型的差异。结果 13例PWS父源性缺失新生儿进入分析,其中MS-MLPA诊断10例,3例采用AffymetrixSNP芯片筛查诊断。Ⅰ型缺失5例,平均胎龄为36.2周,3例早产;Ⅱ型缺失8例,平均胎龄为38.9周,均为足月儿。Ⅰ型和Ⅱ型缺失各表型的发生率:肌张力低下和吸吮力差均为100%,特殊面容分别为80%和50%,色素减退分别为40%和37.5%,生殖系统异常分别为40%和87.5%。结论肌张力低下和吸吮力差是PWS新生儿共同的临床特征,Ⅰ型缺失可能更易发生早产,特殊面容;Ⅱ型缺失生殖系统异常发生率较高,Ⅰ型缺失可能存在临床表型多样性。

Objective To discriminate the genotype of neonates with Prader-Willi syndrome （PWS） by using methylation specificity muhiple connected probe amplification technology （MS - MLPA ） and Affymetrix SNP chip, identify the correlation between genotype and phenotype in deletion subtypes. Methods 13 Prader-Willi syndrome neonates with confirmed diagnosis by molecular biological methods were included in the study. Among them 3 cases were tested by cytogenetic SNP chip for detection of pathogenic copy number variations（CNVs） and the rest were tested by multiplex ligation-dependent probe amplification （MLPA）. Clinical features according to the diagnostic criteria were recorded. Results 5 individuals with type I deletion（ del I ）, 8 with type 11 deletion（ del 1] ） were analyzed. Central hypotonia and poor suck were observed in all the patients. Characteristic, facial feature was found in 4 neonates with del I （80%） ,and in 4 neonates with del II （50%）. Hypopigmentation was found in 2 with del I （40%） and in 3 with del I] （37.5%）. Hypogonadism was found in 2 with del I （40%） and in 7 with del lI （87.5%）. Conclusion Central hypotonia and poor suck were common in PWS neonates. Characteristic facial feature and premature birth may be more likely found in neonates with deletion I , whereas high incidence of hypogonadism was found in deletion Ⅱ noenates. Type Ⅰ deletion may have various phenotypes.