Williams syndrome is a multisystem disorder caused by a heterozygous microdeletion at 7q11.23, a region typically spanning approximately 1.5–1.8 megabases. In this case, sequencing found a heterozygous 1.48 Mb deletion that was classified as pathogenic. The variant was de novo, meaning it was not inherited from either parent. Examination of the boy showed global developmental delay, characteristic facial dysmorphisms, generalized hypotonia, knee hyperextension during assisted standing, and asymmetric dermatoglyphs of the lower extremities. The diagnostic workup also identified left hip dysplasia, visual and auditory abnormalities, and proteinuria, showing that the clinical presentation involved developmental, musculoskeletal, sensory, and renal findings.

Analysis of the boy’s whole-exome sequence also revealed a heterozygous MSH2 frameshift variant designated c.1457_1460del, p.Asn486Thrfs*10. The variant was classified as pathogenic and identified as a secondary finding under American College of Medical Genetics and Genomics criteria. Lynch syndrome is a cancer-predisposition syndrome resulting from germline pathogenic variants in DNA mismatch-repair genes. The combined genetic findings therefore established a molecular diagnosis of Williams syndrome alongside Lynch syndrome in the same child.

As a case report, the study documents one patient and cannot establish the prevalence of the dual diagnosis, the clinical course of other children with the same combination, or the broader relationship between the two conditions. Its scope is limited by the single-patient design, but the findings show how whole-exome sequencing can identify both a chromosomal microdeletion and an independent pathogenic gene variant in a child with a complex phenotype. The authors said the report may provide information relevant to individualized clinical management and genetic counseling for patients who receive dual Mendelian disorder diagnoses.

Subject of Research: Co-occurrence of Williams syndrome and Lynch syndrome in a 20-month-old boy

Article Title: A case of dual diagnosis of Williams syndrome and Lynch syndrome: clinical and genetic analysis

Article References: Yang, Z., Tian, C., Yang, Y., Ma, G., Wasim, M., Huang, X., & Chen, R. (2026). A case of dual diagnosis of Williams syndrome and Lynch syndrome: clinical and genetic analysis. BMC Pediatrics. https://doi.org/10.1186/s12887-026-07626-4

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07626-4

Keywords: Williams syndrome, Lynch syndrome, dual genetic diagnosis, MSH2 variant, 7q11.23 deletion, whole-exome sequencing, pediatric genetics, rare disease, case report, case, dual, diagnosis