A Rare Case of Coexisting 22q11.2 Deletion Syndrome and Cornelia De Lange Syndrome: A Case Report and Review of the Literature

The coexistence of multiple genetic syndromes in a single individual is rare but clinically significant, as it can lead to delays in diagnosis and management. To ensure high-quality, patient-centred care, clinicians must remain alert to the possibility of dual diagnoses. This case report describes a rare presentation encountered in a clinical genetics setting and highlights its key learning points, complemented by a review of the relevant literature. We report the case of a 15-year-old girl born prematurely with a complex medical history including developmental delay, feeding difficulties, joint hypermobility, vacant episodes, and endocrine disturbances. At age three, she received a diagnosis of 22q11.2 deletion syndrome. However, there remained concerns that this diagnosis did not fully account for her severe neurodevelopmental and feeding difficulties. As such, at age 14, a decade later, she was enrolled in the Deciphering Developmental Disorders (DDD) study, which identified a pathogenic variant in SMC3, confirming an additional diagnosis of Cornelia de Lange syndrome. This case highlights the challenges associated with coexisting diagnoses, illustrated by the 10-year interval between this patient's first and second diagnoses. Confirmation of the second additional genetic diagnosis clarified previously unexplained features. This clarification enabled targeted multidisciplinary care and informed discussions with the patient and family regarding prognosis and management. With advances in genomic knowledge and improved access to genetic testing, cases of coexisting genetic syndromes are likely to become increasingly common. Recognising when a patient's presentation is not fully explained by a single syndrome is critical. Identifying coexisting genetic conditions enables a comprehensive approach to surveillance, follow-up, and genetic counselling for the patient and wider family.