Prenatally diagnosed chromosome 1p36 deletions: a retrospective case series, literature review, and genotype-phenotype correlations

Chromosome 1p36 deletion syndrome is the most common terminal autosomal deletion disorder. While postnatal features are well-defined, prenatal characterization remains less comprehensive. This study aims to delineate the prenatal sonographic and genetic spectrum of this syndrome and explore genotype-phenotype correlations. A retrospective analysis was conducted on 21 consecutive prenatally diagnosed cases of 1p36 deletion (2017–2025) from a single tertiary center. Data on maternal demographics, ultrasound findings, genetic results, inheritance patterns, and pregnancy outcomes were collected. A pooled analysis included 10 isolated cases (with complete ultrasound data) from our cohort and 33 previously reported cases. The cohort demonstrated a strong female predominance (71.4%, 15/21). Fifteen (71.4%) involved isolated 1p36 deletions, while six (28.6%) exhibited additional chromosomal aberrations. Pooled analysis of 43 prenatally diagnosed isolated cases (10 current and 33 published) revealed brain anomalies to be the most common prenatal feature (58.1%, 25/43), with ventriculomegaly (37.2%, 16/43), corpus callosum hypoplasia (9.3%, 4/43), and choroid plexus cysts (9.3%, 4/43) being the most frequent subtypes. Cardiac defects were observed in 39.5% (17/43) of cases, predominantly atrial/ventricular septal defects (ASD/VSD, 23.3%, 10/43) and Ebstein anomaly (11.6%, 5/43). Other frequently observed features included increased nuchal translucency (16.3%, 7/43) and single umbilical artery (14%, 6/43). Parental genetic analysis demonstrated de novo deletions in 80.0% (12/15) of cases, while 20.0% (3/15) were inherited from phenotypically normal parents. Congenital brain anomalies (particularly ventriculomegaly) and cardiac defects are hallmark prenatal features of isolated 1p36 deletion syndrome. Our findings underscore the role of key genes (RERE, SPEN, PRDM16, MMP23B) in shaping the phenotype and highlight the importance of parental genetic testing in counseling, given the potential for inherited variants with variable expressivity.