Trisomy 18 in a second 20‐year‐old woman

Abstract

In a recent issue of the journal, Kelly et al. [2002] reported a case of a 20-year-old woman with trisomy 18. She presented to the cardiology service after two decades without cardiac care and presented with many physical stigmata of trisomy 18 and echocardiographic evaluation was consistent with tetralogy of Fallot. A total of 13 cells were analyzed from peripheral blood and she never had a skin biopsy. Years ago we had a very similar experience. Although not cited by these authors, we reported a patientwith a very similar history in 1981 and again in 1985 [Karayalcin et al., 1981; Davidoff et al., 1985]. Our patient was the 2,530 gm product of 38-week gestation delivered to a 37-year-old mother. She had multiple anomalies including a congenital heart defect demonstrated by cardiac catheterization at age 3 years to be tetralogy of Fallot. She was admitted to our hospital at age 11 years for evaluation of an abdominal mass. Her parents were told at birth that she had down syndrome. Our physical assessment was consistent with trisomy 18. Her karyotype was 47,XXþ 18 in 50 mitoses counted and was subsequently repeated with the same result. A skin biopsy revealed the same abnormality in 200 cells. An exploratory laparotomy uncovered a large inoperable tumor encasing and obliterating the retroperitoneal structures. The biopsy specimen was diagnostic of Wilms tumor. The patient received radiotherapy in a dose of 2,000 rad to the peritoneal cavity together with chemotherapy. Four months later, the abdomen was re-explored and the left kidney and isthmus were removed from what was observed to be a horseshoe kidney. She received chemotherapy and an additional course of radiation therapy to the abdomen following surgery. Twenty months after diagnosis, multiple bilateral pulmonary metastases developed which were treated by 1,800 rad of radiation to both lung fields. The lung metastases resolved and never recurred. This was the second reported case of trisomy 18 and Wilms’ tumor. She died at home after a cardiopulmonary arrest 7 months short of her twenty-first birthday. It is interesting that among the rare patients with trisomy 18 surviving infancy, two, ours and the oneyear-old boy reported by Geiser and Schindler [1969] should also have had aWilms tumor. Since then there have been a few more reports of Wilms’ tumor in patients with trisomy 18. We speculated then and continue to feel that there may be a causal relationship between the two. A unique condition of abnormal proliferation of cells thought to be derived from the metanephric blastema is seen in trisomy 18. The lesion known as nephroblastoma in situ is thought to be intermediate between malformation and neoplasia [Shanklin and Sotelo-Avila, 1969]. The relationship of Wilms tumor to trisomy 18 may resemble that of retinoblastoma to 13q deletion syndromes elaborated by Knudson and Strong [1972] in their two-step mutation model for cancer. The occurrence of nephroblastoma in situ in trisomy 18 may result from a prezygotic mutation. According to Kelly et al. [2002] our case represents the eleventh case of survival past age 10 years. Like their patient, our patient never underwent repair of her tetralogy of Fallot. We agree with the authors that reports of long-term survival are important for appropriate guidance and management 18.