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

Williams syndrome (WS) is a multisystem disorder caused by a 1.5–1.8 Mb heterozygous microdeletion at chromosome 7q11.23. Lynch syndrome (LS) is a cancer predisposition syndrome resulting from germline mutations in DNA mismatch repair genes. Co-occurrence of both conditions in a single pediatric patient has not been reported to date. A 20-month-old male presented with an 8-month history of motor developmental delay. Clinical examination revealed global developmental delay, characteristic facial dysmorphisms, knee hyperextension on assisted standing, generalized hypotonia, and asymmetric dermatoglyphs of the lower extremities. Diagnostic workup identified left hip dysplasia, visual and auditory abnormalities, and proteinuria. Whole-exome sequencing revealed a heterozygous 1.48 Mb de novo deletion at 7q11.23, classified as pathogenic, alongside a heterozygous frameshift variant in MSH2 (c.1457_1460del, p.Asn486Thrfs*10), also designated as pathogenic and identified as an American College of Medical Genetics and Genomics (ACMG) secondary finding. To our knowledge, this represents the first pediatric case of coexisting WS and LS, providing critical insights into the individualized clinical management and genetic counseling of patients with dual Mendelian disorder diagnoses.