A Case of a Fetus With SETD5 Mutation: Prenatal Phenotype and Literature Review

BACKGROUND: Pathogenic variants in the SETD5 gene cause autosomal dominant intellectual developmental disorder 23. The limited number of published clinical case reports has hindered a comprehensive understanding of the associated phenotypic spectrum and mutational landscape. METHODS: We report a fetal case identified by cardiac ultrasound with an ostium primum atrial septal defect and a suspected high ventricular septal defect. RESULTS: Whole-exome sequencing revealed a novel, previously unreported frameshift variant in SETD5 (NM_001080517.3; exon21: c.3601_3605del, p. Trp1201GlufsTer2). Segregation analysis confirmed it to be a de novo variant. CONCLUSION: This case expands the known mutational spectrum of SETD5. A review of the literature allows for a synthesis of the characteristic clinical features of this rare disorder. Congenital heart defects, including atrial and ventricular septal defects, can serve as early diagnostic indicators. Fetal cardiac ultrasound represents a valuable tool for early screening, underscoring the critical importance of prenatal whole-exome sequencing in such cases.