CHU Bordeaux, Service de Génétique Médicale, Bordeaux, France.
Service d'Histologie, Embryologie, Cytogénétique, GH Necker-Enfants Malades, APHP, Paris, France.
Clin Genet. 2019 Mar;95(3):420-426. doi: 10.1111/cge.13493. Epub 2019 Jan 11.
Rubinstein-Taybi syndrome (RSTS; OMIM 180849) is an autosomal dominant developmental disorder characterized by facial dysmorphism, broad thumbs and halluces associated with intellectual disability. RSTS is caused by alterations in CREBBP (about 60%) and EP300 genes (8%). RSTS is often diagnosed at birth or during early childhood but generally not suspected during antenatal period. We report nine cases of well-documented fetal RSTS. Two cases were examined after death in utero at 18 and 35 weeks of gestation and seven cases after identification of ultrasound abnormalities and termination of pregnancy. On prenatal sonography, a large gallbladder was detected in two cases, and brain malformations were noted in four cases, especially cerebellar hypoplasia. However, the diagnosis of RSTS has not been suggested during pregnancy. Fetal autopsy showed that all fetuses had large thumbs and/or suggestive facial dysmorphism. A CREBBP gene anomaly was identified in all cases. Alterations were similar to those found in typical RSTS children. This report will contribute to a better knowledge of the fetal phenotype to consider the hypothesis of RSTS during pregnancy. Genotyping allows reassuring genetic counseling.
鲁宾斯坦-泰比综合征（RSTS；OMIM 180849）是一种常染色体显性发育障碍，其特征为面部畸形、宽拇指和宽足趾，伴有智力障碍。RSTS 是由 CREBBP（约 60%）和 EP300 基因（8%）改变引起的。RSTS 通常在出生时或幼儿期诊断，但在产前期间通常不会怀疑。我们报告了 9 例有明确记录的胎儿 RSTS。2 例在宫内妊娠 18 周和 35 周时死亡后进行了检查，7 例在超声异常发现并终止妊娠后进行了检查。产前超声检查显示，2 例胎儿胆囊增大，4 例胎儿脑畸形，特别是小脑发育不全。然而，在怀孕期间并未提示 RSTS 的诊断。胎儿尸检显示，所有胎儿均有宽大的拇指和/或提示面部畸形。所有病例均发现 CREBBP 基因异常。改变与典型 RSTS 儿童中发现的异常相似。本报告将有助于更好地了解胎儿表型，以便在怀孕期间考虑 RSTS 的假说。基因分型可提供令人放心的遗传咨询。
