PRENATAL DIAGNOSIS, VOL. 9,601-602 (1989)

LETTER TO THE EDITOR

Trisomy 20 mosaicism identified prenatally and confirmed in foreskin fibroblasts

Lillian Y. F. Hsu and her colleagues (1987) recently called for continued data collection on trisomy 20 cases that are identified prenatally. The risks associated with this karyotype are still poorly understood. For continued pregnancies, the majority of newborns have an apparently normal pheno- type, but only a few have been followed for developmental assessment.

Since 1981 we have identified trisomy 20 mosaicism in 4 of about 9500 amniotic fluid cell chromosome studies. All four families decided to continue the pregnancy, after a discussion about the current state of knowl- edge regarding trisomy 20 mosaicism ident- ified prenatally. One case is of interest because a large proportion of the amniotic fluid cells had trisomy 20, the mosaicism was confirmed in fibroblasts cultured from the circumcision foreskin, and the phenotypi- cally normal child has been followed for 4 years.

Case A84-507. In July, 1984 we obtained an amniotic fluid specimen for karyotyping because of maternal age 35. All four tissue culture vessels had a mixture of normal male and trisomy 20 cells, with a total of 1 1 normal and 19 trisomy 20 cells. The parents decided to continue the pregnancy, and a normal appearing male was born at term. A mild hydrocele resolved without therapy. Fore- skin fibroblast cultures had a karyotype of 46,XY in 12 cells and 47,XY, + 20 in 18 cells. No other tissues were obtained for karyo- typing. We have had two contacts with the parents to follow the progress of the child. He walked at age 9 months, and at age 28 months weighed 34 pounds and was 37in tall. His mother reported that he was talking in sentences and that his receptive language was good. At age 4 years his height is 42 in, weight 50 pounds. His mother reported that he is a normal, active, child with good gross and fine motor coordination. He dresses and buttons-up with little supervision, draws a 3-part person, has good expressive language and comprehension. In short, at age 4 he appears normal.

0 1989 by John Wiley & Sons, Ltd.

Case A86-236. In March, 1986 we obtained an amniotic fluid specimen for karyotyping because of maternal age 36. From five coverslip cultures, 4 colonies were 47,XX,+20 and 19 colonies were 46,XX. The parents elected to continue the pregnancy, and although the newborn girl had severe jaundice, she appeared normal otherwise, and at age 8mo was sitting up and pulling herself to a standing position. A peripheral blood karyotype was normal.

Case A88-388. This amniotic fluid speci- men was obtained in March, 1988 because of maternal age 34. From six coverslip cultures, 23 colonies were 46,XX, three colonies were 47,XX, + 20, and one colony had two 46,XX cells and one 47,XX,+20 cell. From a newborn cord blood specimen, none of 50 metaphase cells had trisomy 20. From an amnion cell culture, none of 50 metaphase cells has trisomy 20. The infant appeared phenotypically normal.

Case A88-1316. This amniotic fluid speci- men was obtained in September, 1988 because of maternal age 35. From four coverslip cultures, 30 colonies were 46,XX and one colony was 47,XX + 20. The parents were counselled about trisomy 20 mosaicism as well as the possibility that a single trisomy 20 colony may reflect an artifact of tissue cul- ture, and they have continued the pregnancy. The infant appeared phenotypically normal. Chromosomes were normal in 25 metaphase cells and 41 metaphase cells from fibroblast cultures established from umbilical cord and placental villi, respectively.

Some of the prenatally identified trisomy 20 mosaicism reflects true tissue-limited fetal mosaicism, even though the pro- portion of cases with true fetal mosaicism is not known yet. Trisomy 20 has not been found in peripheral blood cultures, but has been identified in cultures from several other tissues (Hsu et al., 1987). It appears to represent yet another example of tissue tolerance (Hall, 1988) or tissue-limited mosaicism, along with trisomy 8, second- ary trisomies 9p, and 12p, and possibly secondary trisomy 8p and diploid/polyp- loid mosaicism (Donnai el al., 1986; Van Dyke, 1988; Robinow et al., 1988).

602 LETTER TO THE EDITOR

The four cases described here are consis- tent with Dr Hsu’s observations of a normal phenotype in most cases, although many uncertainties remain, including the range of intellectual development in these children. These uncertainties do little to relieve anxiety in the expectant parents, in our opinion. We join Dr Hsu in calling for continued obser- vation of these children and the addition of newly identified cases to her survey or to the literature.

DANIEL L. VAN DYKE, JACQUELYN R. ROBERSON,

V. RAMFSH BABU, and LESTER WEISS Medical Genetics and Birth Defects Center,

Henry Ford Hospital, Detroit, MI48202, U .S .A .

MICHAEL TYRKUS Damon Clinical Laboratories- D M C , Wayne State University,

Detroit, MI , U.S.A.

REFERENCES Donnai, D., McKeown, C., Andrews, T., Read,

A.P. (1986). Diploid/triploid mixoploidy and hypomelanosis of Ito, Lancet, 2,1443-1444.

Hall, J.G. (1988). Somatic mosaicism: obser- vations related to clinical genetics, Am. J. Hum. Genet.. 43,355-363.

Hsu, L.Y.F., Kafk, S., Perlis, T.E. (1987). Tri- somy 20 mosaicism in prenatal diagnosis-A review and update, Prenat. Diagn., 7,581-596.

Robinow, M., Haney, N., Chen, H., Sorauf, T., Van Dyke, D.L., Babu, V.R., Powell, S., Maliszewski, W., Guerin, S., Landers, T.W. (1989). Secondary trisomy or mosaic ‘tetra- somy’ 8p, Am. J. Med. Genet.. 32,330-324.

Van Dyke, D.L. (1988). Isochromosornes and interstitial tandem direct and inverted dupli- cations. In Daniel A. (ed.), The Cytogenetics of Mammalian Aurosomal Rearrangements, New York: A. R. Liss, 635-665.