Prevalence, clinical spectrum and predictors of cancer predisposition syndromes in childhood cancer

Constitutional cancer predisposition, multiple syndromes (neurofibromatosis type 1, primary immunodeficiency, hereditary retinoblastoma)

This single-centre retrospective cohort included 888 patients aged 0 to 18 years followed between January 2002 and December 2024 for a childhood malignancy or a neoplastic manifestation arising in an established cancer predisposition syndrome. A cancer predisposition syndrome was identified and documented in 61 patients (6.9%), 72.1% of whom were diagnosed after the primary malignancy; the most frequent were neurofibromatosis type 1, primary immunodeficiency and hereditary retinoblastoma. The highest proportions were observed in other epithelial tumours and malignant melanoma (22.5%), central nervous system tumours (13.1%) and lymphomas and reticuloendothelial neoplasms (11.1%). The Jongmans criteria, re-evaluated in all patients, showed a sensitivity of 98.4% and a specificity of 57.3% at the one-criterion threshold, versus 67.2% and 93.3% at the two-criterion threshold. Congenital anomalies or clinical findings suggestive of a syndrome were most strongly associated with the diagnosis, followed by skin lesions, family history, parental consanguinity, rare tumours and multiple primary malignancies.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Syndrome diagnosis relies on available clinical and genetic records rather than systematic germline sequencing: the 6.9% prevalence is therefore probably underestimated, and the sensitivity of the criteria potentially overestimated. That 72.1% of syndromes were recognised only after the cancer argues for earlier detection. The one-criterion Jongmans threshold remains a useful referral filter where systematic germline sequencing of children is not available.

Analysis by Dr Thibaut Benquey