A tumor profile in Edwards syndrome (trisomy 18)

Abstract

Constitutional trisomy 18 causes Edwards syndrome, which is characterized by intellectual disability and a particular set of malformations. Although this condition carries high mortality during prenatal and early postnatal life, some of the rare infants who survive the first months develop benign and malignant tumors. To determine the tumor profile associated with Edwards syndrome, we performed a systematic review of the literature. This review reveals a tumor profile differing from those of Down (trisomy 21) and Patau (trisomy 13) syndromes. The literature covers 45 malignancies: 29 were liver cancers, mainly hepatoblastomas found in Japanese females; 13 were kidney tumors, predominantly nephroblastomas; 1 was neuroblastoma; 1 was a Hodgkin disease; and 1 was acute myeloid leukemia in an infant with both trisomy 18 and type 1 neurofibromatosis. No instances of the most frequent malignancies of early life-cerebral tumors, germ cell tumors, or leukemia--are reported in children with pure trisomy 18. Tumor occurrence does not appear to correlate with body weight, tissue growth, or cancer genes mapping to chromosome 18. Importantly, the most recent clinical histories report successful treatment; this raises ethical concerns about cancer treatment in infants with Edwards syndrome. In conclusion, knowledge of the Edwards' syndrome tumor profile will enable better clinical surveillance in at-risk organs (i.e., liver, kidney). This knowledge also provides clues to understanding oncogenesis, including the probably reduced frequency of some neoplasms in infants and children with this genetic condition. © 2016 Wiley Periodicals, Inc.

Surveillance Recommendations for Children with Overgrowth Syndromes and Predisposition to Wilms Tumors and Hepatoblastoma

“…Trisomy 18 is characterized by a variety of major and minor malformations, growth retardation, psychomotor delays, and intellectual disability (41,42). Only 5–10% of affected infants live past the first year, and the infants who survive this period are at increased risk to develop benign and malignant tumors (43). The high mortality rate is a result of many factors including cardiac and renal malformations, feeding difficulties, sepsis, and central apnea (44).…”

“…A systematic review found 45 malignancies in 56 patients, mostly HB and WT (43). Nephroblastomatosis was also reported in autopsies of infants with trisomy 18 who did not die from a WT (45,46).…”

Possible Japanese Racial Predisposition for Particular Tumors in Edwards Syndrome

“…In this article, the same references employed in our previous article [1] are used. Using the key words "trisomy 18", "malignancy", "hepatoblastoma", "Wilms tumor", "leukemia", "neuroblastoma", and so on, articles and abstracts reporting patients with trisomy 18 and malignant neoplasms were gathered from "Pubmed" and …”

“…Among them, there are 2 mosaic cases. In congress abstracts a total of 14 cases were reported [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] (Table 1; these 14 cases are arranged according to our previous report [1] ). Among them there are no mosaic cases, and many females.…”

“…For example, it is well known that persons with Down syndrome have an increased risk of leukemia. Employing articles and abstracts, we reported a tumor profile in those with Edwards syndrome, or trisomy 18 (T18), and they are at high risk for several malignant tumors such as hepatoblastoma (HB) or Wilms tumor (WT), etc [1] . At the same time, however, it was noted that there were regional differences (Japan vs the USA) in the frequency of developing them.…”