A rare coexistence of 47,XXX and Silver–Russell syndrome: a case report

The concurrent diagnosis of 47,XXX (Triple X syndrome) and Silver–Russell syndrome (SRS) is exceptionally uncommon. The coexistence of a sex chromosome aneuploidy and an imprinting disorder poses diagnostic challenges and may complicate clinical evaluation and management. A 15-month-old Chinese girl was prenatally identified with intrauterine growth restriction (IUGR) and a 47,XXX karyotype by amniocentesis. She was born by spontaneous vaginal delivery at 39 + 6 weeks of gestation with a birth weight of 2.05 kg (− 3.0 SD for gestational age). Postnatal evaluation revealed severe growth failure, frontal bossing, downturned oral commissures, micrognathia, and skeletal anomalies including clinodactyly of the right fifth finger and limb asymmetry. The patient fulfilled five criteria of the Netchine–Harbison Clinical Scoring System (NH-CSS) for SRS. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) analysis revealed hypomethylation at the H19/IGF2 imprinting control region (IC1) on chromosome 11p15.5, establishing the molecular diagnosis of SRS. Peripheral blood karyotyping validated the 47,XXX chromosomal complement. This case presents the first detailed case of a female infant with cytogenetically confirmed 47,XXX and molecularly confirmed SRS, highlighting the diagnostic workflow, phenotypic correlations, and implications for multidisciplinary care. This report expands the understanding of rare co-occurrence of chromosomal aneuploidy and imprinting disorders and emphasizes the need for comprehensive diagnostic evaluation guided by clinical features.