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World journal of pediatrics : WJP
Feb, 2025;21 (2): 131-148.

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

Michaela Kuhlen, Andreas B Weins, Nicole Stadler, Daniela Angelova-Toshkina, Michael C Fr��hwald
Author Information
  1. Michaela Kuhlen: Pediatrics and Adolescent Medicine, Faculty of Medicine, University of Augsburg, 86156, Augsburg, Germany. Michaela.Kuhlen@uk-augsburg.de. ORCID
  2. Andreas B Weins: Pediatrics and Adolescent Medicine, Faculty of Medicine, University of Augsburg, 86156, Augsburg, Germany.
  3. Nicole Stadler: Pediatrics and Adolescent Medicine, Faculty of Medicine, University of Augsburg, 86156, Augsburg, Germany.
  4. Daniela Angelova-Toshkina: Pediatrics and Adolescent Medicine, Faculty of Medicine, University of Augsburg, 86156, Augsburg, Germany.
  5. Michael C Fr��hwald: Pediatrics and Adolescent Medicine, Faculty of Medicine, University of Augsburg, 86156, Augsburg, Germany. ORCID
PMID: 39641826 DOI: 10.1007/s12519-024-00853-8

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 caf��-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

References

  1. J Med Genet. 2014 Jun;51(6):355-65 [PMID: 24737826]
  2. Lancet. 2009 Jun 6;373(9679):1974-86 [PMID: 19476995]
  3. Lancet Neurol. 2014 Aug;13(8):834-43 [PMID: 25030515]
  4. Genet Med. 2004 Nov-Dec;6(6):530-9 [PMID: 15545751]
  5. Pediatr Blood Cancer. 2021 Aug;68(8):e29021 [PMID: 33788392]
  6. Genet Med. 2021 Aug;23(8):1506-1513 [PMID: 34012067]
  7. Clin Cancer Res. 2017 Jun 15;23(12):e62-e67 [PMID: 28620006]
  8. J Med Genet. 1994 Jun;31(6):471-7 [PMID: 8071974]
  9. Am J Med Genet A. 2019 Sep;179(9):1725-1744 [PMID: 31222966]
  10. Cancer Med. 2024 May;13(10):e7234 [PMID: 38752459]
  11. Clin Cancer Res. 2018 Apr 1;24(7):1594-1603 [PMID: 29351919]
  12. Eur J Hum Genet. 2011 Jun;19(6):617-23 [PMID: 21386872]
  13. Semin Pediatr Neurol. 2021 Apr;37:100875 [PMID: 33892851]
  14. Orphanet J Rare Dis. 2007 Jan 14;2:4 [PMID: 17222357]
  15. Eur J Pediatr. 2022 Apr;181(4):1585-1596 [PMID: 34950979]
  16. Mol Cell Pediatr. 2022 Feb 21;9(1):3 [PMID: 35187600]
  17. Glob Med Genet. 2022 Sep 05;9(3):237-241 [PMID: 36071913]
  18. Lancet. 2008 Aug 23;372(9639):657-68 [PMID: 18722871]
  19. Int J Nurs Stud. 2013 Jun;50(6):870-80 [PMID: 23026156]
  20. Front Pediatr. 2021 Dec 14;9:733018 [PMID: 34970513]
  21. Clin Cancer Res. 2024 Aug 15;30(16):3378-3387 [PMID: 38860976]
  22. Clin Cancer Res. 2017 Jun 15;23(12):e54-e61 [PMID: 28620005]
  23. Fam Cancer. 2021 Oct;20(4):337-348 [PMID: 34170462]
  24. Clin Cancer Res. 2017 Jun 15;23(12):e76-e82 [PMID: 28620008]
  25. Lancet Child Adolesc Health. 2021 Feb;5(2):142-154 [PMID: 33484663]
  26. Orphanet J Rare Dis. 2010 Jan 29;5:2 [PMID: 20113479]
  27. AMA J Ethics. 2022 Jul 1;24(7):E685-693 [PMID: 35838399]
  28. Orphanet J Rare Dis. 2008 Nov 25;3:32 [PMID: 19032739]
  29. Clin Cancer Res. 2017 Jun 1;23(11):e6-e13 [PMID: 28572262]
  30. J Multidiscip Healthc. 2024 Apr 23;17:1803-1817 [PMID: 38680880]
  31. Orphanet J Rare Dis. 2016 Nov 25;11(1):159 [PMID: 27884168]
  32. Eur J Hum Genet. 2006 Nov;14(11):1151-7 [PMID: 16883308]
  33. Am J Med Genet A. 2011 Sep;155A(9):2091-7 [PMID: 21834049]
  34. Clin Cancer Res. 2017 Jul 1;23(13):e107-e114 [PMID: 28674119]
  35. Clin Cancer Res. 2017 Nov 1;23(21):e133-e137 [PMID: 29093018]
  36. J Med Genet. 2023 Jul;60(7):679-684 [PMID: 36411031]
  37. Clin Chem Lab Med. 2020 Oct 01;59(2):353-363 [PMID: 33001846]
  38. Clin Cancer Res. 2024 Aug 1;30(15):3137-3143 [PMID: 38860978]
  39. Nat Rev Endocrinol. 2018 Apr;14(4):229-249 [PMID: 29377879]
  40. N Engl J Med. 2015 Dec 10;373(24):2336-2346 [PMID: 26580448]
  41. Clin Cancer Res. 2017 Jul 1;23(13):e123-e132 [PMID: 28674121]
  42. J Cancer Surviv. 2021 Feb;15(1):151-162 [PMID: 32676793]
  43. Am J Med Genet C Semin Med Genet. 2018 Sep;178(3):274-277 [PMID: 30325570]
  44. Clin Cancer Res. 2017 Jun 1;23(11):e1-e5 [PMID: 28572261]
  45. Pediatr Blood Cancer. 2020 Feb;67(2):e28056 [PMID: 31724322]
  46. Clin Cancer Res. 2017 Jul 1;23(13):e98-e106 [PMID: 28674118]
  47. Orphanet J Rare Dis. 2011 Nov 01;6:70 [PMID: 22044607]
  48. Lancet Oncol. 2005 Dec;6(12):980-7 [PMID: 16321766]
  49. Lancet Oncol. 2016 Sep;17(9):1295-305 [PMID: 27501770]
  50. Lancet Oncol. 2008 May;9(5):462-72 [PMID: 18452857]
  51. Lancet Oncol. 2024 May;25(5):668-682 [PMID: 38552658]
  52. Eur J Hum Genet. 2021 Aug;29(8):1301-1311 [PMID: 33840814]
  53. Pediatr Blood Cancer. 2017 Aug;64(8): [PMID: 28097779]
  54. Pediatr Blood Cancer. 2020 Apr;67(4):e28171 [PMID: 31925938]
  55. Sci Rep. 2023 Feb 20;13(1):2959 [PMID: 36805510]
  56. Nat Rev Endocrinol. 2019 May;15(5):299-311 [PMID: 30842651]
  57. Clin Cancer Res. 2017 Jun 15;23(12):e68-e75 [PMID: 28620007]
  58. Orphanet J Rare Dis. 2014 Jul 15;9:101 [PMID: 25022750]
  59. Clin Cancer Res. 2017 Jun 1;23(11):e32-e37 [PMID: 28572265]
  60. Clin Cancer Res. 2017 Jun 1;23(11):e38-e45 [PMID: 28572266]
  61. Front Pediatr. 2024 Jun 03;12:1410061 [PMID: 38887560]
  62. Curr Opin Pediatr. 2023 Feb 1;35(1):55-62 [PMID: 36354292]
  63. Clin Cancer Res. 2024 Jun 3;30(11):2342-2350 [PMID: 38573059]
  64. PLoS Genet. 2020 Dec 17;16(12):e1009231 [PMID: 33332384]
  65. JAMA Netw Open. 2023 Feb 1;6(2):e2254157 [PMID: 36735256]
  66. Clin Cancer Res. 2017 Jun 1;23(11):e14-e22 [PMID: 28572263]
  67. Oncol Res Treat. 2014;37(12):761-71 [PMID: 25531723]
  68. Trends Cancer. 2024 Jun;10(6):481-485 [PMID: 38503638]
  69. Orphanet J Rare Dis. 2009 Jun 19;4:16 [PMID: 19545378]
  70. Support Care Cancer. 2024 Feb 22;32(3):179 [PMID: 38383874]
  71. Orphanet J Rare Dis. 2006 Nov 14;1:45 [PMID: 17105651]
  72. Am J Med Genet A. 2017 Apr;173(4):1017-1037 [PMID: 28168833]
  73. Pediatr Blood Cancer. 2013 Aug;60(8):1247-52 [PMID: 23625733]
  74. Clin Cancer Res. 2017 Jul 1;23(13):e91-e97 [PMID: 28674117]
  75. Clin Cancer Res. 2017 Jul 1;23(13):e115-e122 [PMID: 28674120]
  76. J Med Genet. 2015 Nov;52(11):770-8 [PMID: 26318770]
  77. Orphanet J Rare Dis. 2014 Sep 20;9:138 [PMID: 25238977]
  78. Digestion. 2023;104(5):335-347 [PMID: 37054692]
  79. Eur J Paediatr Neurol. 2023 Mar;43:52-61 [PMID: 36905830]
  80. Am J Med Genet C Semin Med Genet. 2024 Dec;196(4):e32088 [PMID: 38766979]
  81. EClinicalMedicine. 2023 Jan 13;56:101818 [PMID: 36684394]
  82. Genet Med. 2022 Sep;24(9):1978-1985 [PMID: 35713653]
  83. Clin Cancer Res. 2017 Jun 15;23(12):e83-e90 [PMID: 28620009]
  84. Clin Cancer Res. 2017 Jun 1;23(11):e23-e31 [PMID: 28572264]
  85. J Natl Cancer Inst. 2013 Nov 6;105(21):1607-16 [PMID: 24136893]

Grants

  1. 70115888/Deutsche Krebshilfe
  2. 70113981/Deutsche Krebshilfe
  3. KU3764/3-1/Deutsche Forschungsgemeinschaft

MeSH Term

Humans
Adolescent
Child
Genetic Predisposition to Disease
Neoplastic Syndromes, Hereditary
Neoplasms
Journal Article Review
Article has an altmetric score of 2

Word Cloud

Created with Highcharts 10.0.0predispositionsyndromescancermanifestationsfeaturesanomaliesCancernon-malignantearlyNon-malignantType1neurofibromatosissyndromegeneticdiagnosischildrenadolescentsincludedclinicalindicatorsincludingfacialsignificanthearingthyroidPURPOSE:disorderssignificantlyraiseriskdevelopingmalignanciesAlthoughmalignantwell-studiedrecognizingcrucialespeciallyMETHODS:comprehensiveliteraturesearchconductedusingPubMeddatabasefocusingKeysourcesClinicalResearchpediatriconcologyseriesORPHANETStudiesdescribedsignssymptomsaffectingspecificorgansystemsRESULTS:dermatologicaloftenservecaf��-au-laitspotsNeurofibromatosisangiofibromasTuberousSclerosisComplexNeurologicaldevelopmentalcerebellarataxiaataxia-telangiectasiaintellectualdisabilitiestypetuberoussclerosiscomplexGrowthmetabolicalsonotableovergrowthBeckwith-Wiedemanngrowthhormonedeficiencyadditionocularissuesprevalentacrossvariousinstancelossmay2nodulescommonPTENhamartomatumorDICER1CardiovascularabdominalmusculoskeletalpulmonarygenitourinaryprenataldeviationscomplicatepictureCONCLUSIONS:Recognizingessentialmanagementorgan-specificoverviewfurthersawarenessamonghealthcareprovidersfacilitatingtimelycounselingsurveillanceprogramspreventivemeasuresultimatelyimprovingpatientoutcomesmanifestingchildhoodadolescence:guidegeneralpediatricianChildrenPsychosocialneedsSurveillance

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