title: Prevalence and patterns of morphological abnormalities in patients with childhood cancer.
abstract: BACKGROUND
  Constitutional gene defects predispose to cancer in children. Such tumor predisposition syndromes can be recognized by specific patterns of morphological abnormalities.
  
  
  OBJECTIVE
  To assess the prevalence of morphological abnormalities in a large cohort of patients with childhood cancer and to identify new tumor predisposition syndromes.
  
  
  METHODS
  Patients were recruited from Emma Children's Hospital, Academic Medical Center, Amsterdam, the Netherlands, between January 2000 and March 2003. A total of 1073 patients underwent a physical examination directed at 683 morphological abnormalities. The patient cohort consisted of 898 long-term survivors of childhood cancer and 175 newly diagnosed pediatric patients with cancer. The control group consisted of 1007 schoolchildren examined in an identical way. Mean ages of patients and controls were 21.2 and 10.4 years, respectively.
  
  
  METHODS
  Prevalence and patterns of morphological abnormalities in patients compared with controls. To prevent age bias, only age-independent abnormalities were used for overall prevalence analysis. Patients younger than 9 years were excluded from the pattern analysis. The sample was restricted to white patients to prevent ethnicity bias.
  
  
  RESULTS
  Morphological abnormalities were significantly more prevalent in pediatric patients with cancer. Major abnormalities were present in 26.8% of patients vs 15.5% of controls (P < .001) and minor anomalies in 65.1% of patients vs 56.2% of controls (P < .001). Three or more minor anomalies were detected in 15.2% of patients vs 8.3% in controls (P < .001). Forty-two patients were diagnosed with an established tumor predisposition syndrome. Multivariate analyses showed 14 morphological abnormalities to occur significantly more often in the patient group. For 2 of these (blepharophimosis and asymmetric lower limbs), we identified statistically significant patterns of co-occurring morphological abnormalities suggestive of new tumor predisposition syndromes. Thirty-four patients fit 1 of the 2 novel tumor predisposition patterns.
  
  
  CONCLUSIONS
  Pediatric patients with cancer show a significantly higher prevalence of morphological abnormalities compared with controls. Specific patterns of morphological abnormalities indicate possible unrecognized tumor predisposition syndromes, but validation in an independent sample is needed.
authors.affiliation: Department of Pediatric Oncology, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands. j.h.merks@amc.uva.nl
authors.forename: Johannes H M
authors.initials: JH
authors.lastname: Merks
authors.forename: Heval M
authors.initials: HM
authors.lastname: Ozgen
authors.forename: Jan
authors.initials: J
authors.lastname: Koster
authors.forename: Aeilko H
authors.initials: AH
authors.lastname: Zwinderman
authors.forename: Huib N
authors.initials: HN
authors.lastname: Caron
authors.forename: Raoul C M
authors.initials: RC
authors.lastname: Hennekam
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D000013:Congenital Abnormalities / Q000453:epidemiology* / Q000235:genetics; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009369:Neoplasms / Q000453:epidemiology* / Q000235:genetics; D010641:Phenotype; D015995:Prevalence; D013577:Syndrome