Prenatal Diagnosis of Rubinstein‐Taybi Syndrome—Reporting Twelve Cases of a Rare Disease

ABSTRACT Objective To present the prenatal sonographic features and genomic spectrum of pregnancies with fetal Rubinstein‐Taybi syndrome (RSTS). Methods This was a retrospective study of 12 cases with RSTS with fetal features identified by prenatal ultrasound and confirmed by genetic testing. Chromosomal microarray analysis utilizing an Affymetrix CytoScan 750k SNP array was employed to detect pathogenic copy number variations (CNVs). Trio exome sequencing was used to detect monogenic conditions. Clinical and laboratory data were collected and reviewed for these cases, including maternal demographics, prenatal sonographic findings, molecular testing sequencing results, and pregnancy outcomes. Results All cases had unremarkable first‐trimester ultrasound scans without reporting limb malformations. Seven cases presented with abnormal second‐trimester ultrasounds: three instances of cardiac defects, two instances of limb abnormalities (one with short long bones and one with duplication of big toes), one case of intracranial malformation (dysgenesis of the corpus callosum), and one instance of restricted fetal growth. Five pregnancies exhibited abnormal sonographic signs in the third trimester: two cases of restricted fetal growth, one with clubfeet and polyhydramnios, one with hypospadias, and one with isolated polyhydramnios. CNVs involving CREBBP deletions were detected in two cases. Variants were identified in two genes: CREBBP in six instances and EP300 in four instances; all CNVs or variants were de novo. Conclusion Our results underscore the challenges faced in the prenatal detection of RSTS due to the lack of specific clinical presentations. Our study highlights that even nonspecific findings on prenatal ultrasound may justify exome sequencing, enabling timely potential genetic diagnoses and improving clinical management.