The association of childhood cancer with speciยฎc congenital malformations and chromosomal anomalies (e.g., Down syndrome, WAGR syndrome, Beckwithยฑ Wiedemann syndrome) is well established. In an increasing number of these associations underlying genetic changes have been documented, identifying new genes that are involved in both organogenesis and carcinogenesis.
Several large population-based studies have investigated the association between nonsyndromic congenital malformations and childhood cancer [1ยฑ3]. Although heterogeneous, these studies have conยฎrmed an increased overall frequency of congenital malformations in children with cancer, and pointed toward common genetic defects. However, it is necessary to emphasize that investigations of major malformations have certain limitations. Some major congenital defects are associated with high rates of infant mortality and the affected children may die before cancer can develop. On the other hand, some malformations may remain undiscovered at the onset of a rapidly lethal neoplasm, before a systemic review can be completely carried out. In rare cases premalignant dysplasia may regress in the child with a malformation [4]. Besides, most of the population-based studies use registry statistics (birth-defect registries, cancer registries, or birth certiยฎcates), telephone interviews, and postal questionnaires, each of which have important limitations.
It is worth noting that these limitations can be overcome by the investigation of minor anomalies, studied by means of meticulous physical examination, anthropometric measurements, photography, and subjective description. Developmentally and anatomically, minor anomalies are phenogenetic variants that show a continuous distribution in the normal population [5]. These easily recognizable features do not inยฏuence the normal development of the affected child. They are indicators of disturbed phenogenesis in the broadest sense, and may suggest the prenatal (fetal) origin of the associated disorder [6].
We undertook a study on the frequency and type of minor anomalies in 64 children (39 boys and 25 girls) with hematologic malignancies (HM) treated between 1983 and 1997 at the Division of Hematology, Department of Pediatrics, University of Rijeka, Croatia. Their ages ranged from 5 months to 16 years. Thirty-nine children with acute lymphocytic leukemia (ALL), 5 with acute myelocytic leukemia (AML), 13 with non-Hodgkin lymphoma, and 7 with Hodgkin disease were included in the study. The control group consisted of 64 healthy children of the same age and gender. For each subject the presence or absence of 65 minor anomalies was recorded. No distinction between unilateral and bilateral occurrence was made. w 2 test was used for statistical analysis.