Genetic predisposition to childhood cancer

Table 1 Recognition of genetic predisposition in pediatric cancer patients[6-9]

Characteristics	Conditions
Family history	≥ 2 malignancies occurred in family members before the age of 18 years, including the affected child
	First-degree relative (parent or sibling) with cancer < 45 years of age
	≥ 2 first- or second-degree relatives with cancer in the same parental lineage < 45 years
	Cancer in consanguineous family
Tumor type and/or cancer features known to be strongly associated with cancer predisposition syndrome
	Adrenocortical carcinoma/adenoma
	ALL (low hypodiploid)
	ALL (ring chromosome 21)
	ALL (Robertsonian translocation 15;21)
	ALL relapse (TP53 mutated)
	AML (Monosomy 7)
	Basal cell carcinoma
	Botryoid rhabdomyosarcoma of the urogenital tract (fusion-negative)
	Chondromesenchymal hamartoma
	Choroid plexus carcinoma/tumor
	Colorectal carcinoma
	Cystic nephroma
	Endolymphatic sack tumor
	Fetal rhabdomyoma
	Gastrointestinal stromal tumor
	Glioma of the optic pathway (with signs of NF1)
	Gonadoblastoma
	Hemangioblastoma
	Hepatoblastoma (CTNNB1 wildtype)
	Hepatocellular carcinoma
	Infantile myofibromatosis
	Juvenile myelomonocytic leukemia
	Keratocystic odontogenic tumor
	Large cell calcifying Sertoli-cell-tumor
	Malignant peripheral nerve sheath tumor
	Medullary thyroid carcinoma
	Medulloblastoma (SHH activated)
	Medulloblastoma (WNT activated, CTNNB1 wildtype)
	Medullary renal cell carcinoma
	Medulloepithelioma
	Melanoma
	Meningioma
	Myelodysplastic syndrome
	Myeloproliferative neoplasms (except CML)
	Myxoma
	Neuroendocrine tumor
	Paraganglioma/pheochromocytoma
	Parathyroid carcinoma/adenoma
	Pineoblastoma
	Pituitary adenoma/tumor
	Pituitary blastoma
	Pleuropulmonary blastoma
	Renal cell carcinoma
	Retinoblastoma
	Rhabdoid tumor
	Rhabdomyosarcoma with diffuse anaplasia
	Schwannoma
	Schwannomatosis
	Sertoli-Leydig cell tumor
	Sex cord-stromal tumor with annular tubules
	Small-cell carcinoma of the ovary, hypercalcemic type
	Squamous cell carcinoma
	Subependymal giant cell astrocytoma
	Thyroid carcinoma (non-medullary)
	Transient myeloproliferative disease
Other rare cancers or cancers that typically occur in adults, unusually early manifestation age
Genetic tumor analysis reveals a defect suggesting germline cancer predisposition
A child with ≥ 2 malignancies (secondary, bilateral in paired organs, multifocal, synchronous, or metachronous)
A child with cancer and obvious nonmalignant signs suggestive of a genetic condition	Congenital anomalies
	Facial dysmorphism
	Mental impairment, developmental delay
	Abnormal growth
	Skin anomalies (abnormal pigmentation, i.e. ≥ 2 café-au-lait spots, vascular lesions, hypersensitivity to sunlight, benign tumors)
	Immune deficiency
	Endocrine anomalies
A child with excessive treatment toxicity

ALL: Acute lymphoblastic leukemia; AML: Acute myeloid leukemia; CML: Chronic myeloid leukemia; SHH: Sonic hedgehog protein; WNT: Wingless/integrated signaling pathway.