PDF(Pubmed)
Abstract：
Beckwith-Wiedemann syndrome (BWS) is a common genetic congenital disease characterized by somatic overgrowth and its broad clinical spectrum includes pre- and post-natal macrosomia, macroglossia, visceromegaly, increased risk of neonatal hypoglycemia, and development of embryonic tumors. BWS occurs due to genetic/epigenetic changes involving growth-regulating genes, located on region 11p15, with an important genotype-phenotype correlation. Congenital adrenal hyperplasia (CAH) comprises a spectrum of autosomal recessive diseases presenting a variety of clinical manifestations due to a deficiency in one of the enzymes involved in cortisol secretion. Early diagnosis based on newborn screening prevents the adrenal crisis and early infant death. However, high 17-hydroxyprogesterone (17-OHP) levels can occur in newborns or premature infants without CAH, in situations of stress due to maternal or neonatal factors. Here, we report new cases of false-positive diagnosis of 21-hydroxylase deficiency during newborn screening - two girls and one boy with BWS. Methylation-specific multiplex ligation-dependent probe amplification revealed a gain of methylation in the H19 differentially methylated region. Notably, all three cases showed a complete normalization of biochemical changes, highlighting the transient nature of these hormonal findings that imitate the classical form of CAH. This report sheds light on a new cause of false-positive 21-hydroxylase deficiency diagnosis during newborn screening: Beckwith-Wiedemann syndrome.
摘要：
Beckwith-Wiedemann综合征（BWS）是一种常见的遗传性先天性疾病，其特征是躯体过度生长，其广泛的临床范围包括产前和产后巨大儿，巨舌,内脏肿大,新生儿低血糖的风险增加，和胚胎肿瘤的发展。BWS的发生是由于涉及生长调节基因的遗传/表观遗传变化，位于11p15区域，具有重要的基因型-表型相关性。先天性肾上腺增生（CAH）包括一系列常染色体隐性遗传疾病，由于缺乏涉及皮质醇分泌的一种酶而表现出多种临床表现。基于新生儿筛查的早期诊断可预防肾上腺危象和婴儿早期死亡。然而,高17-羟孕酮（17-OHP）水平可发生在新生儿或早产儿无CAH，在由于母亲或新生儿因素造成的压力的情况下。这里,我们报告了新生儿筛查期间21-羟化酶缺乏症假阳性诊断的新病例-两名女孩和一名男孩患有BWS。甲基化特异性多重连接依赖性探针扩增显示H19差异甲基化区域的甲基化增加。值得注意的是,所有三例都显示生化变化完全正常化，突出了这些模仿CAH经典形式的激素发现的短暂性。该报告揭示了新生儿筛查期间假阳性21-羟化酶缺乏症诊断的新原因：Beckwith-Wiedemann综合征。
