Developmental defects and childhood cancer.
OBJECTIVE
Childhood cancer syndromes are rare but easily recognizable in the clinical setting. Early detection of a potential underlying genetic defect by the general practitioner can be lifesaving. Additionally, important clinical clues that can aid in recognition, or lead to diagnostic referral, for a possible cancer-predisposing syndrome in the individual patient or family are discussed.


RESULTS
Recent advancements in genetics have increased our understanding of many genetic developmental pathways involved in cancer predisposition syndromes. Importantly, some of the defects in these pathways can explain the wide phenotypic variability in overall growth, physical dysmorphisms, and cancer risk in children. Genetic testing is now available for many disorders and important guidelines for screening are quickly evolving. The current diagnostic criteria, genetics, and cancer screening guidelines for neurofibromatosis type 1, Beckwith-Wiedemann syndrome/ hemihypertrophy, and PTEN hamartoma tumor syndrome, among others, are reviewed.


CONCLUSIONS
Early recognition of a possible underlying genetic defect with a resultant diagnostic work-up can lessen or prevent tumor burden, improve screening for possible cancer recurrence, and optimize care for children and their family members. Important clues from the history and physical include a family history of cancer, a specific cancer type frequently associated with a genetic defect, synchronous or metachronous cancers in the same individual, growth abnormalities, abnormal skin pigmentation, and/or thumb/radius malformations. Many cases can be recognized by the general practitioner and referred to the appropriate specialists for completion of the diagnostic work-up and recommendations for appropriate management.
Slavin
Thomas P
TP
Center for Human Genetics, University Hospitals Case Medical Center and Case Western Reserve University, Cleveland, Ohio 44116, USA.
Wiesner
Georgia L
GL
D000293:Adolescent; D001506:Beckwith-Wiedemann Syndrome / Q000175:diagnosis / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006223:Hamartoma Syndrome, Multiple / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics*; D009456:Neurofibromatosis 1 / Q000175:diagnosis / Q000235:genetics