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Constitutional Cancer Predisposition Syndromes

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This guideline lists genetic cancer predisposition syndromes that may be elicited by history and/or examination at the time of diagnosis.

Many of these conditions exhibit variable penetrance - therefore patients may have few or no examination findings but still have the condition.This list has only a brief comment on each syndrome. If history or examination finding suggest one of the syndromes listed below then seek further information from the more detailed texts listed below and discuss with the treating oncologist before discussing the findings with the patient or family

Constitutional chromosomal abnormalities

Down syndrome - Trisomy 21

  • Short stature
  • variably low IQ
  • classic facial features
  • single palmar crease
  • numerous congenital abnormalities.

Associated with a group of myeloid proliferations including "transient abnormal myelopoesis", "Myelodysplasia related to Down Syndrome" and "Acute Myeloid Leukaemia related to Down Syndrome" (often M7 - acute megakaryoblastic leukaemia). These have been classified together by the World Health Organisation under "Myeloid proliferations related to Down syndrome". Also have higher lifetime risk of Acute Lymphoblastic Leukaemia.

Wilms' tumour predisposition

Disruptions of WT1 gene at 11p13.

  • WAGR: Wilms' tumour, Aniridia, Genitourinary abnormalities and Mental Retardation.
  • Beckwith-Weidemann: Macroglossia, straight ear crease, somatic gigantism, neonatal hypoglycaemia and abdominal wall defects.
  • Isolated hemi hypertrophy
  • Denys-Drash syndrome (DDS): Intersex disorder, nephropathy and Wilms' tumour. Hot spot mutation R394W/Q/L
  • Frasier Syndrome and WT1 (?clinical overlap with DDS)
  • Recommendation: test patients for WT1 mutations if:
    • disease onset early (12-24 months)
    • bilateral Wilms
    • stromal-predominant/FRN (fetal rhabdomyomatous nephroblastoma) histology
    • males with GU anomalies

Other cancer predisposition syndromes

May have findings on examination:

Isolated hemi hypertrophy

  • predisposition (reported as 5.9%) to cancer: Wilms' Tumour, Hepatoblastoma and Adrenal cell carcinoma

Neurofibromatosis 1 (17q11)

  • may have multiple neurofibroma, café au lait spots, lisch nodules, axillary or inguinal freckling and associated with multiple cancers especially optic gliomas <6yrs and malignant peripheral nerve sheath tumours.

Tuberous sclerosis (more than 1 gene involved - 9q34 and 16p13)

  • seizures
  • developmental delay
  • adenoma sebaceum
  • ash leaf patch associated with in-utero cardiac RMS that often remits spontaneously
  • retinal hamartomas
  • giant cell astrocytomas
  • renal angiomyolipomas tumours.

Gorlin syndrome (basal cell naevus syndrome) (9q22)

  • jaw cysts
  • bifid ribs
  • palmar and plantar pits
  • facial dysmorphism
  • short 4th metacarpal
  • multiple basal cell naevus with BCCs
  • medulloblastoma

May have a family history:

Pleuropulmonary blastoma

  • alteration of DICER1 function leading to multiple childhood cancers.

Retinoblastoma (13q14)

  • increased risk of other cancers especially sarcomas.

Turcot syndrome (5q)

  • CNS tumours in teenagers followed by bowel cancers that are often fatal before 20 years.

Von Hippel Lindau (3p25)

  • autosomal dominant associated with the development of multiple benign and malignant lesions. Mostly familial but 20% cases are sporadic and caused by a new mutation:
  • Retinal hamartomas and haemangioblastomas
  • Cerebellar haemangioblastomas
  • Renal cell carcinomas 
  • Phaeochromocytomas
  • Pancreatic tumours

Li-Fraumeni syndrome

DNA repair defects

Xeroderma pigmentosum

  • several types with different genes involved. Skin cancers in sun exposed areas.

Fanconi anaemia

  • several types with different genes involved
  • short stature
  • triphalengeal thumbs
  • radius and ulna defects
  • facial dysmorphism
  • café au lait spots
  • aplastic anaemia with high risk of childhood leukaemia and a later risk of solid tumours.

Dyskeratosis congenita

  • short telomeres due to a defect in telomerase enzyme
  • short stature
  • pitted nails
  • abnormal reticular skin hyperpigmentation
  • oral leukoplakia
  • aplastic anaemia with risk of leukaemia
  • pulmonary hypertension and hepatic fibrosis

Ataxia telangiectasia

  • ataxia
  • chorioathetosis and telangiectasia by 3 - 5 years
  • immunodeficiency and leukaemia/lymphoma common.


Severe Combined Immunodeficiency Disease

Wiskott Aldrich syndrome

  • thrombocytopenia
  • eczema
  • immunodeficiency

X linked Lymphoproliferative disorder

Selective IgA deficiency

Screening in cancer predisposition syndromes

See the guidelines below:





  1. Teplick A, Kowalski M, Biegel JA, Nichols KE. Screening in cancer predisposition syndromes: guidelines for the general paediatrician. Eur J Pediatr 2011 170:285-294
  2. Zhang J, Walsh M et al Germline mutations in predisposition genes in Pediatric Cancer: NEJM 2015 373; 24: 2336-2345

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Document Control

  • Date last published: 06 July 2016
  • Document type: Clinical Guideline
  • Services responsible: National Child Cancer Network
  • Owner: Jane Skeen
  • Review frequency: 2 years