Hereditary cancer comprehensive panel

Tumour predisposition syndromes show exceptionally heterogeneous clinical presentations rather than a unifying phenotype. Age of onset and tumour spectrum vary widely, with paediatric-onset entities most enriched in infancy and others manifesting predominantly in adulthood. Some syndromes are confined to specific organ systems or tumour types (for example breast-ovarian, colorectal, or endometrial cancers), whereas others involve a broad multi-organ tumour spectrum. The clinical pattern of any individual syndrome reflects the convergence of the germline defect with tissue-specific epigenetic architecture, regulatory networks, and environmental exposures, which explains why even pleiotropic syndromes produce a characteristic tumour distribution rather than uniform pan-cancer risk. Clinical recognition typically follows unusually young age at diagnosis, multiple primary tumours, rare or syndromic tumour types, or a striking family history of related malignancies, and triggers referral for molecular genetic evaluation.

The estimated prevalence is 5-10%.

A large number of genes have been associated with tumour predisposition syndromes. The genetic forms span DNA-repair defects, broad-spectrum tumour-suppressor disorders, and proto-oncogenes.

The genetic conditions associated with tumour predisposition syndromes follow heterogeneous inheritance patterns. Most are inherited in an autosomal dominant manner, with a 50% transmission risk to offspring; this risk may be reduced in mosaic forms. Autosomal recessive, X-linked, mosaic, also occur, and de novo variants account for a substantial subset of cases without a positive family history.

• Where a tumour predisposition syndrome is suspected to have a genetic cause, molecular genetic testing can identify the underlying condition and confirm a clinical suspicion.
• The identified entity guides further clinical management and is a prerequisite for targeted medical care; therapeutic options are evaluated individually by the treating physicians.
• Identification of the underlying pathogenic germline variant enables predictive testing of at-risk family members and provides information relevant to family planning. It is important to note that predispositions that manifest predominantly in adulthood are usually not tested until adulthood.

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