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Review
. 2025 Feb;21(2):131-148.
doi: 10.1007/s12519-024-00853-8. Epub 2024 Dec 6.

Non-malignant features of cancer predisposition syndromes manifesting in childhood and adolescence: a guide for the general pediatrician

Michaela Kuhlen  1 , Andreas B Weins  2   3 , Nicole Stadler  2 , Daniela Angelova-Toshkina  2 , Michael C Frühwald  2
Affiliations
Review

Non-malignant features of cancer predisposition syndromes manifesting in childhood and adolescence: a guide for the general pediatrician

Michaela Kuhlen et al. World J Pediatr. 2025 Feb.

Abstract

Purpose: Cancer predisposition syndromes are genetic disorders that significantly raise the risk of developing malignancies. Although the malignant manifestations of cancer predisposition syndromes are well-studied, recognizing their non-malignant features is crucial for early diagnosis, especially in children and adolescents.

Methods: A comprehensive literature search was conducted using the PubMed database, focusing on non-malignant manifestations of cancer predisposition syndromes in children and adolescents. Key sources included the Clinical Cancer Research pediatric oncology series and ORPHANET. Studies that described clinical signs and symptoms affecting specific organ systems were included.

Results: Non-malignant dermatological features often serve as early indicators of cancer predisposition syndromes, including café-au-lait spots in Neurofibromatosis Type 1 and facial angiofibromas in Tuberous Sclerosis Complex. Neurological and developmental anomalies such as cerebellar ataxia in ataxia-telangiectasia and intellectual disabilities in neurofibromatosis type 1 and tuberous sclerosis complex are significant indicators. Growth and metabolic anomalies are also notable, including overgrowth in Beckwith-Wiedemann syndrome and growth hormone deficiency in neurofibromatosis Type 1. In addition, facial anomalies, ocular manifestations, hearing issues, and thyroid anomalies are prevalent across various cancer predisposition syndromes. For instance, hearing loss may be significant in neurofibromatosis Type 2, while thyroid nodules are common in PTEN hamartoma tumor syndrome and DICER1 syndrome. Cardiovascular, abdominal, musculoskeletal, pulmonary, genitourinary manifestations, and prenatal deviations further complicate the clinical picture.

Conclusions: Recognizing non-malignant features of cancer predisposition syndromes is essential for early diagnosis and management. This organ-specific overview furthers awareness among healthcare providers, facilitating timely genetic counseling, surveillance programs, and preventive measures, ultimately improving patient outcomes.

Keywords: Cancer predisposition; Children; Non-malignant manifestations; Psychosocial needs; Surveillance.

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Conflict of interest statement

Declaration. Conflict of interest: No financial or non-financial benefits have been received or will be received from any party related directly or indirectly to the subject of this article. Ethical approval: Informed consent was obtained from the patients for scientific usage of the material.

Figures

Fig. 1
Fig. 1
Flowchart of cancer predisposition syndrome (CPS) diagnosis process based on non-malignant features.This flowchart illustrates the step-by-step process for diagnosing CPS in pediatric patients, highlighting the role of recognizing non-malignant features, conducting genetic testing, and reaching a final diagnosis
Fig. 2
Fig. 2
Organ-specific manifestations. Infographic showing which organ systems are affected by different cancer predisposition syndromes
Fig. 3
Fig. 3
Illustrative photos of key dermatological signs: a typical café-au-lait spots; b atypical café-au-lait spots; c hypomelanotic macule; d mucosal neuromas; e Shagreen patches; f white spots; g facial angiofibromas; h (mucocutaneous) perioral pigmentation
See this image and copyright information in PMC

References

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