Recognition and management of childhood cancer syndromes: A systems approach

Abstract

Recognition of congenital anomalies that predispose to childhood cancer allows for the institution of a cancer surveillance program, identification of relatives with increased cancer risk, and recurrence risk counseling. In this article, a systems approach to the diagnosis of 21 childhood cancer syndromes is set forth in the format of the pediatric physical examination. In the second part of this article, guidelines are presented for genetic testing, cancer screening, and genetic counseling for the 21 cancer syndromes.

Impact of genotype-first diagnosis: the detection of microdeletion and microduplication syndromes with cancer predisposition by aCGH

“…Many cancer syndromes have associated congenital anomalies that bring the child to clinical attention before the onset or suspicion of neoplasia. 10,11 Although most mutations that cause cancer predisposition are sequence mutations within critical genes that would not be detectable by aCGH, many deletions have been reported of various cancer predisposition genes, such as PTEN, WT1, RB1, and APC. 12,13 In addition, patients with deletions often have larger regions deleted than just the immediate gene, which can cause features more typical of chromosomal abnormalities, such as mental retardation, birth defects, and behavioral anomalies.…”

Timely identification of children with cancer

“…Knowledge of the age-and sex Gpt/l, Plt < 150-250 Gpt/l and nocturnal bone pain are present. Coincidence of those three parameters is predictive of childhood ALL with a sensitivity of 100% and a specificity of 84% [7].…”

“…In case of known mutations close meshed preventive examinations should be scheduled, aiming to diagnose the disease as early as possible and to improve the prognosis. In some cases, known mutations allow for performing preemptive therapeutic interventions [7,34].…”

Hemihypertrophy Spectrum

“…The asymmetry can be due to differences in the growth of soft tissue, bone, or both [2] Hemihyperplasia may be an isolated finding, or it may be part of multiple malformation syndromes, such as Russell-Silver syndrome, Proteus syndrome, Beckwith-Wiedemann Syndrome (BWS), and Sotos syndrome [3,4]. Isolated hemihyperplasia (IH, OMIM 235000) is defined as asymmetric regional body overgrowth due to an underlying abnormality of cell proliferation without any other underlying diagnosis [5].…”