prenatal diagnosis of mosaic trisomy 9

4
PRENATAL DIAGNOSIS, VOL. 7,67-70 (1987) SHORT COMMUNICATION PRENATAL DIAGNOSIS OF MOSAIC TRISOMY 9 TOURAN M. ZADEH M.D., JUNE PETERS AND CONSTANCE SANDLIN M.D. Division of Genetics. Department of Pediatrics, Lorna Linda University Medical Center. Loma Linda, California 92354, U.S.A. SUMMARY Mosaic trisomy 9 was detected in an amniotic fluid cell culture from a 40-year-old woman evaluated because of advanced maternal age. After counselling, parents elected to terminate the pregnancy. On autopsy the fetus was found to have hydrocephalus and a single kidney. The diagnosis of trisomy 9 mosaicism was confirmed in cultured skin fibroblasts. This is the third reported case of trisomy 9 mosaicism diagnosed prenatally. KEY WORDS Prenatal diagnosis Trisomy 9 mosaicism INTRODUCTION Trisomy 9 was first described by Feingold and Atkins (1973) and was further delineated into a well-defined syndrome by Sutherland et al. (1976). The prenatal diagnosis of trisomy 9 has been previously reported (Francke and Benrirschke, 1975; Greenberg et al., 1982., Pfeiffer et al., 1984; Hsu and Perlis, 1984). We report a prenatal diagnosis of mosaicism for trisomy 9 and compare our findings with the previously reported cases. CASE REPORT A 4O-year-old, gravida 3, para 2 woman was referred for prenatal diagnosis because of advanced maternal age. The family history obtained at the time of preamniocen- tesis counselling was negative for any children with birth defects. This was the first child of this union. The mother had two children from a previous marriage. The father did not have any other children. Ultrasound indicated a uterine pregnancy of 15-16 weeks gestation. Biparietal diameter at that time was 3-4 cm, consistent with gestational age. The lateral ventricles appeared normal. Amniotic fluid was grossly clear, and the amniotic fluid alpha-fetoprotein concentration was 0.89 mg per cent. Four amniotic fluid cell cultures were established and harvested. Three cultures contained only one cell line, 47,XX, + 9, and the fourth culture contained two cell lines, 46,XX (four of ten cells) and 47,XX, + 9 (six of ten cells). Of 25 cells examined from the four culture flasks, 21 cells or 85 per cent were trisomic for chromosome 9 (Figure 1). The parents were informed of the chromosome results, and they elected to have the pregnancy terminated by prostaglandin induction. Gross external examination of the fetus (Figure 2) revealed a weight of 236 g and crown-heel length of 24 cm. Except for micrognathia and apparently low-set ears, no external abnormalities were noted.

Upload: touran-m-zadeh

Post on 06-Jul-2016

214 views

Category:

Documents


0 download

TRANSCRIPT

Page 1: Prenatal diagnosis of mosaic trisomy 9

PRENATAL DIAGNOSIS, VOL. 7,67-70 (1 987)

SHORT COMMUNICATION

PRENATAL DIAGNOSIS OF MOSAIC TRISOMY 9

TOURAN M. ZADEH M.D., JUNE PETERS AND CONSTANCE SANDLIN M.D. Division of Genetics. Department of Pediatrics, Lorna Linda University Medical Center. Loma Linda,

California 92354, U.S.A.

SUMMARY Mosaic trisomy 9 was detected in an amniotic fluid cell culture from a 40-year-old woman evaluated because of advanced maternal age. After counselling, parents elected to terminate the pregnancy. On autopsy the fetus was found to have hydrocephalus and a single kidney. The diagnosis of trisomy 9 mosaicism was confirmed in cultured skin fibroblasts. This is the third reported case of trisomy 9 mosaicism diagnosed prenatally.

KEY WORDS Prenatal diagnosis Trisomy 9 mosaicism

INTRODUCTION

Trisomy 9 was first described by Feingold and Atkins (1973) and was further delineated into a well-defined syndrome by Sutherland et al. (1976). The prenatal diagnosis of trisomy 9 has been previously reported (Francke and Benrirschke, 1975; Greenberg et al., 1982., Pfeiffer et al., 1984; Hsu and Perlis, 1984).

We report a prenatal diagnosis of mosaicism for trisomy 9 and compare our findings with the previously reported cases.

CASE REPORT

A 4O-year-old, gravida 3, para 2 woman was referred for prenatal diagnosis because of advanced maternal age. The family history obtained at the time of preamniocen- tesis counselling was negative for any children with birth defects. This was the first child of this union. The mother had two children from a previous marriage. The father did not have any other children. Ultrasound indicated a uterine pregnancy of 15-16 weeks gestation. Biparietal diameter at that time was 3-4 cm, consistent with gestational age. The lateral ventricles appeared normal. Amniotic fluid was grossly clear, and the amniotic fluid alpha-fetoprotein concentration was 0.89 mg per cent.

Four amniotic fluid cell cultures were established and harvested. Three cultures contained only one cell line, 47,XX, + 9, and the fourth culture contained two cell lines, 46,XX (four of ten cells) and 47,XX, + 9 (six of ten cells). Of 25 cells examined from the four culture flasks, 21 cells or 85 per cent were trisomic for chromosome 9 (Figure 1).

The parents were informed of the chromosome results, and they elected to have the pregnancy terminated by prostaglandin induction.

Gross external examination of the fetus (Figure 2) revealed a weight of 236 g and crown-heel length of 24 cm. Except for micrognathia and apparently low-set ears, no external abnormalities were noted.

Page 2: Prenatal diagnosis of mosaic trisomy 9

68 T. M. ZADEH, J. PETERS AND C. SANDLIN

Figure 1. G-banded karyotype of fetus with trisomy 9 mosaicism

Autopsy revealed a massively dilated intracranial ventricular system with marked cortical thinning. No abnormalities of heart or great vessels were found. A single transverse kidney with two ureters and two arteries was found. Skin for fibroblast culture was established. From 19 cells analysed, five cells had an extra chromosome 9, the rest had a normal 46,XX chromosome complement.

DISCUSSION

The features commonly associated with trisomy 9 include microcephaly, prominent occiput, hypertelorism, enophthalmos, small and upward slanting palpebral fis- sures, large bulbous nose, micrognathia, low-set and malformed ears with excess- ively folded helix and prominent antihelix, congenital heart disease, abnormalities of the central nervous system (Sutherland et al., 1976) and skeletal system (Akat- suka et al., 1979). The present case revealed major malformations of the central nervous and genitourinary systems.

Feingold and Atkins (1 973) reported a case with Dandy-Walker malformation. The cases of Mace et al. (1978) and of Sutherland et al. (1976) both revealed increased size of the fourth ventricle. Akatsuka et al. (1979) found dilatation of the lateral ventricles on CT scan of the head. Tropp and Currie (1977) found a

Page 3: Prenatal diagnosis of mosaic trisomy 9

PRENATAL DIAGNOSIS OF TRISOMY 9 69

Figure 2. Profile of fetus with trisomy 9 mosaicism

subependymal cyst of the left lateral ventricle. In our case, the ventricles did not appear to be enlarged when examined by ultrasound at 16 weeks gestation; how- ever, they were dilated with a thin cortical mantle on autopsy at 20 weeks.

Renal abnormalities have also commonly been reported in patients with trisomy 9 syndrome : cystic changes of the glomeruli and tubules (Mace et al., 1978 ; Tropp and Currie, 1977), small kidneys (Sutherland et al., 1976), hydronephrosis and hydroureters in addition to renal cyst (Katayama et al., 1980) and a right pelvic kidney (Qazi et al., 1977). In our case, a single transverse kidney with two ureters and two arteries was found.

The skeletal malformations reported in some cases of trisomy 9 (Akatsuka et al., 1979) were not seen on X-ray of the fetus.

Although prenatal diagnosis of trisomy 9 mosaicism has been reported the majority of cases have not been confirmed by the fetal studies. In the case reported by Greenberg et al. (1982), the mosaicism for trisomy 9 was not confirmed post-

Page 4: Prenatal diagnosis of mosaic trisomy 9

70 T. M. ZADEH, J. PETERS A N D C. SANDLIN

natally and may have been pseudomosaicism. The report of prenatal diagnosis of trisomy 9 mosaicism by Pfeiffer et al. (1984) was not confirmed from fetal tissue but rather, limited to fetal membranes only. Hsu and Perlis (1984) reported six additional cases of trisomy 9 mosaicism by prenatal diagnosis. Of the five success- fully studied cases, the mosaicism for trisomy 9 was confirmed in only two. Our case is the third reported case of true mosaicism for trisomy 9. Every effort should be made to confirm the prenatal diagnosis of trisomy 9 mosaicism for the sake of accurate genetic counselling.

REFERENCES Akatsuka, A., Nishiya, O., Kitagawa, T., Kogeyama, A., Inana, I., Nakahome, Y. (1979).

Trisomy 9 mosaicism with punctate mineralization in developing cartilages, Eur. J. Pediatr., 131,271-275.

Bowen, P., Ying, K.L., Chung, G.S.H. (1974). Trisomy 9 mosaicism in a newborn infant with multiple malformations, J. Pediatr., 85,95-97.

Feingold, J., Atkins, L. (1973). A case of trisomy 9. J. Med. Genet., 10,181-187. Francke, U., Benrirschke, K. (1975). Prenatal diagnosis of trisomy 9. Hum. Genet., 29,

243-250. Greenberg, F., Elsas, N.T., Reidy, J.A., Chen, A.T.L., Stone, L.B. (1982). Autosomal mosai-

cism inamniotic fluid cells from a twin pregnancy. Am. J. Med. Genet., 11,109-1 12. Hsu, L.Y.F., Perlis, T.E. (1984). United states survey on chromosome mosaicism and

pseudomosaicism in prenatal diagnosis. Prenat. diag., 4,97-130. Katayama, K.P., Wilkinson, E.J., Herrmann, J., Glaspey, J.C., Agarival, A.B., Roesler,

M.R., Mattingly, R.F. (1980). Clinical delineation of trisomy 9 syndrome, Obstet. Gyne- col., 56,665-668.

Mace, S.E., Macintyre, M.N., Turk, K.B., Johnson, W.E. (1978). The trisomy 9 syndrome: Multiple congenital anomalies, unusual pathological findings, J. Pediatr., 92,446-448.

Pfeiffer, R.A., Ulmer, R., Kniewald, A., Wagner-Theissen, E. (1984). Prenatal diagnosis of trisomy 9 mosaicism possibly limited to fetal membranes. Prenat. diug. 4,387-389.

Qazi, Q.H., Masakawa, A., Madabar, C., Ehrlich, R. (1977). Trisomy 9 syndrome, Clin. Genet., 12,221-226.

Sutherland, G.R., Carter, R.F., Morris, L.L. (1976). Partial and complete trisomy 9 : Delineation of a trisomy 9 syndrome, Hum. Genef., 32, 133-140.

Tropp, M.R., Currie, M. (1977). Mosaic trisomy 9: Two additional cases, Hum. Genet., 38,131-135.