Beckwith-Wiedemann综合征(BWS)是一种罕见的遗传性疾病,以巨大儿为特征,先天性畸形和肿瘤倾向,与11p15区域的遗传和表观遗传改变有关。大多数病例是在出生后诊断的,产前诊断很困难,并且取决于特定超声异常的识别,也就是巨大儿,巨舌,脐膨出和肾发育不良。病例1:正常阵列的孤立性脐膨出13周时的超声诊断。在20周,有缩短的胎儿长骨,足部畸形,巨舌,call体发育不全和双侧肾肿大。由于多畸形综合征,终止妊娠(TOP).胎盘的解剖病理学研究确定了间充质发育不良。通过MS-MLPA搜索11p15区域的甲基化模式是正常的,并且CDKN1C基因的分子研究鉴定出可能的致病变异体,继承自母亲。病例2:21周时的形态超声显示巨大儿,巨舌,脐膨出,双侧肾发育不良,和羊水过多。细胞遗传学研究,羊膜穿刺术后,正常(46,XX核型)。进行TOP。胎儿的解剖病理学研究证实了所描述的畸形,而有关胎盘的畸形则确定了胎盘肿大。通过MS-MLPA搜索11p15区域的甲基化模式显示异常甲基化。这些结果证实了两种情况下BWS的诊断。产前超声怀疑这种病理对于指导怀孕和/或预防围产期并发症非常重要。缩短的胎儿长骨和足畸形补充了这种综合征的广谱。阳性分子检测可以确认诊断,评估复发风险并指导未来妊娠的监测。
Beckwith-Wiedemann syndrome (BWS) is a rare genetic disease, characterized by macrosomia, congenital malformations and tumor predisposition, associated with genetic and epigenetic alterations in the 11p15 region. Most cases are diagnosed after birth, with prenatal diagnosis being difficult and depending on the identification of specific ultrasound anomalies, namely macrosomia, macroglossia, omphalocele and renal dysplasia.
Case 1: Ultrasound diagnosis at 13 weeks of isolated omphalocele with normal array. At 20 weeks, there were shortened fetal long bones, foot deformity, macroglossia, corpus callosum hypoplasia and bilateral nephromegaly. Due to the polymalformative syndrome, a termination of pregnancy (TOP) was performed. The anatomopathological study of the placenta identified mesenchymal dysplasia. The search for the methylation pattern of the 11p15 region by MS-MLPA was normal and the molecular study of the CDKN1C gene identified a likely pathogenic variant, inherited from the mother.
Case 2: Morphological ultrasound at 21 weeks revealed macrosomia, macroglossia, omphalocele, bilateral renal dysplasia, and hydramnios. The cytogenetic study, after amniocentesis, was normal (46,XX karyotype). TOP was performed. The anatomopathological study of the fetus confirmed the described malformations and the one concerning the placenta identified placentomegaly. The search for the methylation pattern of the 11p15 region by MS-MLPA revealed abnormal methylation. These results confirmed the diagnosis of BWS in both cases. Prenatal ultrasound suspicion of this pathology is extremely important to guide the conduct in pregnancy and/or the prevention of perinatal complications. Shortened fetal long bones and foot deformity complement the broad spectrum of this syndrome. Positive molecular tests allow confirming the diagnosis, assessing the risk of recurrence and guiding the surveillance of future pregnancy.