5 50
LETTERS TO THE EDITOR
sex determination ofintact cells, J . Clin. Puthoi., 38,1085-1092. Cremer, T., Landegent, J., Brucknec, A,, ef ul. ( I 986). Detection of chromosome aberrations in the human interphase nucleus by visualization of specific target DNA's with radioactive and non-radioactive in sifu hybridization techniques: diagnosis of trisomy 18 with probe L1-84, Hum. Genet., 74,346-352. Marcais, B., Bellis, M., Gerard, A. ef al. (1991). Structural organization and polymorphism of the alpha satellite DNA sequences of chromosomes 13 and 21 as revealed by pulse field gel electrophoresis, Hum. Gene/.,86, 311-316.
Peculiar haematological features of fetuses with triploidy
Four women were referred for fetal investigation because of the discovery of an abnormal sonogram suggesting the possibility of chromosomal abnormalities. All fetuses were small for age (below the third centile); the first fetus also had club-feet; the second had a ventricular septa1defect; the third case had an omphalocele; and the fourth case had a hypoplastic left ventricle. At the time of referral, the gestational age was 22-29 weeks of gestation. Cordocentesis for obtaining a rapid fetal karyotype was performed in all cases without problems, as previously reported (Boulot et al., 1990), and cytogenetic results that each fetus had triploidy. During the same procedure, fetal blood was removed for haematological investigation; the results are reported in Table 1. No haematological anomaly was found on the mother's blood simultaneously sampled and analysed with the same techniques. The results reported suggest that fetal triploidy is associated with severe haematopoietic anomalies. The increase in the mean red cell volume has previously been reported as a feature of chromosomally abnormal
fetuses, and triploid fetuses appear to have very marked macrocytotic red cells (Nicolaides et al., 1989). This is the first report of thrombocytopenia associated with anaemia in three cases of triploidic fetuses. We suggest that the association of IUGR, thrombocytopenia, anaemia, and rnacrocytosis may represent a biological feature of triploidy. Explaining this abnormal platelet count remains difficult. Indeed, thrombocytopenia has been found in fetuses with severe and acidotic growth retardation as part of an intravascular disseminated coagulation (Weiner and Williamson, 1989). In other respects, the thrombocytopenia, as well as macrocytosis, may bedue to a delay in the maturation of medullary haematopoeisis (Nicolaides et al., 1989). From a practical point of view, these biological aspects strongly suggest triploidy when waiting for the results of karyotypes after cordocentesis. These findings have to be confirmed on a larger series. P. BOULOT*,B. BACHELARD*, G. LEFORTt, B. HEDON*AND C . H U M E A U ~ *Fetal Medicine Unit, Department of Obstetrics and Gynaecology, 13 Avenue du Pr Grasset. 34 000, Montpellier. France; TCy togenetic Unit, Hopital St Charles. 34 000,Mon tpellier, France REFERENCES Boulot, P., Deschdmps, F., Lefort, G., Sarda, P., Mares, P., Hedon, B., Laffargue, F., Viala, J.L. (1990). Pure fetal blood samples obtained by cordocentesis: technical aspects of 322 consecutive cases, Prenar. Diugn., 10,93-100. Nicolaides, K.H., Snidjers, R.J., Thorpe-Beeston, J.G., Van den Hof, M.C., Gosden, C.M., Bellingham, A.J. (1989). Mean red cell volume in normal, anemic, small, trisomic and triploid fetuses, Feral Ther.,4, 1-13.
Table 1. Haematological features obtained on fetuses affected by triploidy Mean Red blood corpuscular Platelets Haemoglobin Haematocrit cells Fetal Case No. volume (fl) ( 103/pl) (g/100 ml) (ml/100) (millions/mrn3) karyotype 1 2 3 4
178 157 152 180
88 000 84 000 11 800 11 700
10.8 8 13.6 10.9
33 25 40
29
1.85 1.59 2.52 1.61
69,XXX 69,XXY 69,XXY 69,XXX
55 1
LETTERS TO THE EDITOR
Weiner, C.P., Williamson, R.A. (1989). Evaluation of severe growth retardation using cordocentesis-hematologic and metabolic alterations by etiology, Obslet. Gynecol., 73,
1420 g, length 40 cm, and Apgar scores of 7 and 8 was born. A cord blood sample revealed a normal karyotype. Samples from the placenta, fetal 225-229. membranes, and umbilical cord showed various degrees of mosaicism (Table I), suggesting that the trisomic cell line was confined Addressee for correspondence: Dr P. Boulot, Fetal Medicine Unit, Department of Obstetrics to extraembryonic tissues only, which is in and Gynaecology, 13 Avenue du Pr Grasset, accordance with the embryogenic model (Crane and Cheung, 1988). 34 000, Montpellier, France. A heart murmur was observed after birth and echocardiography revealed a hypoplastic left ventricle, mitral atresia, subvalvular Mosaic trisomy 15 found at amniocentesis aortic stenosis, an atrial septal defect with We report a case with trisomy 15 mosaicism left-to-right shunt and a ventricular septal observed at amniocentesis. A 40-year-old defect with right-to-left flow, and persistent mother, gravida 5, para 1, was referred for ductus, with flow from the pulmonary artery prenatal diagnosis because of advanced to the aorta. The heart defect was considered maternal age. Amniocentesis and ultrasound inoperable and the girl died at 13 days of age. examination were performed at 16 weeks’ A fibroblast culture made from a skin biopsy gestation, with no fetal abnormalities taken immediately post-mortem failed to observed. Amniotic fluid alpha-fetoprotein grow. Autopsy confirmed the left heart concentration was in the normal range. hypoplasia; no other abnormalities were Chromosome analysis with the G-banding observed. Trisomy 15 is observed in 1.68 per cent of technique of two independent cultures revealed the presence of trisomy 15 mosaic- first-trimester abortions (Simpson, 1990). It ism (Table I). A repeat amniocentesis at 19 has been observed once in a dysmorphic weeks’ gestation confirmed the presence of female baby who had severe congenital malmosaicism (Table 1). Intrauterine growth formations including a heart defect (venretardation (1UGR)ofthe fetuswasobserved tricular septal defect and coarctation of the by ultrasound from 19 weeks onwards. The aorta) and died at 4 days of age from intractable heart failure (Coldwell et al., 1981). parents opted to continue the pregnancy. IUGR was present at 35 weeks’ gestation Mosaicism of trisomy 15 observed at amnioand ultrasonography revealed oligohydram- centesis and fetal pathology has been nios and breech presentation. A Caesarean reported by Gimelli e t a [ . (1983). The cardiac section was performed at 37 2 weeks and a malformation of the female fetus was a persmall-for-dates girl with a birth weight of sistent common atrio-ventricular canal. In
+
Table 1. Cytogenetic findings of the reported case
Source of tissue Amniocentesis I (multiple flasks) Amniocentesis I1 (multiple flasks) Placenta (at term) Culture I Culture I1 Culture 111 Fetal membranes Umbilical cord Cord blood
No. of cells analysed
47,XX,
+ 15
46,XX
% abnormal
81
8
73
9.9
34
2
32
5.8
31 42 125 17 121
26 41 116 8 10 0
5 1 9 9 111
83.9 97.6 92.8 47.1 8.3 0.0
100
100
LETTERS TO THE EDITOR
sex determination ofintact cells, J . Clin. Puthoi., 38,1085-1092. Cremer, T., Landegent, J., Brucknec, A,, ef ul. ( I 986). Detection of chromosome aberrations in the human interphase nucleus by visualization of specific target DNA's with radioactive and non-radioactive in sifu hybridization techniques: diagnosis of trisomy 18 with probe L1-84, Hum. Genet., 74,346-352. Marcais, B., Bellis, M., Gerard, A. ef al. (1991). Structural organization and polymorphism of the alpha satellite DNA sequences of chromosomes 13 and 21 as revealed by pulse field gel electrophoresis, Hum. Gene/.,86, 311-316.
Peculiar haematological features of fetuses with triploidy
Four women were referred for fetal investigation because of the discovery of an abnormal sonogram suggesting the possibility of chromosomal abnormalities. All fetuses were small for age (below the third centile); the first fetus also had club-feet; the second had a ventricular septa1defect; the third case had an omphalocele; and the fourth case had a hypoplastic left ventricle. At the time of referral, the gestational age was 22-29 weeks of gestation. Cordocentesis for obtaining a rapid fetal karyotype was performed in all cases without problems, as previously reported (Boulot et al., 1990), and cytogenetic results that each fetus had triploidy. During the same procedure, fetal blood was removed for haematological investigation; the results are reported in Table 1. No haematological anomaly was found on the mother's blood simultaneously sampled and analysed with the same techniques. The results reported suggest that fetal triploidy is associated with severe haematopoietic anomalies. The increase in the mean red cell volume has previously been reported as a feature of chromosomally abnormal
fetuses, and triploid fetuses appear to have very marked macrocytotic red cells (Nicolaides et al., 1989). This is the first report of thrombocytopenia associated with anaemia in three cases of triploidic fetuses. We suggest that the association of IUGR, thrombocytopenia, anaemia, and rnacrocytosis may represent a biological feature of triploidy. Explaining this abnormal platelet count remains difficult. Indeed, thrombocytopenia has been found in fetuses with severe and acidotic growth retardation as part of an intravascular disseminated coagulation (Weiner and Williamson, 1989). In other respects, the thrombocytopenia, as well as macrocytosis, may bedue to a delay in the maturation of medullary haematopoeisis (Nicolaides et al., 1989). From a practical point of view, these biological aspects strongly suggest triploidy when waiting for the results of karyotypes after cordocentesis. These findings have to be confirmed on a larger series. P. BOULOT*,B. BACHELARD*, G. LEFORTt, B. HEDON*AND C . H U M E A U ~ *Fetal Medicine Unit, Department of Obstetrics and Gynaecology, 13 Avenue du Pr Grasset. 34 000, Montpellier. France; TCy togenetic Unit, Hopital St Charles. 34 000,Mon tpellier, France REFERENCES Boulot, P., Deschdmps, F., Lefort, G., Sarda, P., Mares, P., Hedon, B., Laffargue, F., Viala, J.L. (1990). Pure fetal blood samples obtained by cordocentesis: technical aspects of 322 consecutive cases, Prenar. Diugn., 10,93-100. Nicolaides, K.H., Snidjers, R.J., Thorpe-Beeston, J.G., Van den Hof, M.C., Gosden, C.M., Bellingham, A.J. (1989). Mean red cell volume in normal, anemic, small, trisomic and triploid fetuses, Feral Ther.,4, 1-13.
Table 1. Haematological features obtained on fetuses affected by triploidy Mean Red blood corpuscular Platelets Haemoglobin Haematocrit cells Fetal Case No. volume (fl) ( 103/pl) (g/100 ml) (ml/100) (millions/mrn3) karyotype 1 2 3 4
178 157 152 180
88 000 84 000 11 800 11 700
10.8 8 13.6 10.9
33 25 40
29
1.85 1.59 2.52 1.61
69,XXX 69,XXY 69,XXY 69,XXX
55 1
LETTERS TO THE EDITOR
Weiner, C.P., Williamson, R.A. (1989). Evaluation of severe growth retardation using cordocentesis-hematologic and metabolic alterations by etiology, Obslet. Gynecol., 73,
1420 g, length 40 cm, and Apgar scores of 7 and 8 was born. A cord blood sample revealed a normal karyotype. Samples from the placenta, fetal 225-229. membranes, and umbilical cord showed various degrees of mosaicism (Table I), suggesting that the trisomic cell line was confined Addressee for correspondence: Dr P. Boulot, Fetal Medicine Unit, Department of Obstetrics to extraembryonic tissues only, which is in and Gynaecology, 13 Avenue du Pr Grasset, accordance with the embryogenic model (Crane and Cheung, 1988). 34 000, Montpellier, France. A heart murmur was observed after birth and echocardiography revealed a hypoplastic left ventricle, mitral atresia, subvalvular Mosaic trisomy 15 found at amniocentesis aortic stenosis, an atrial septal defect with We report a case with trisomy 15 mosaicism left-to-right shunt and a ventricular septal observed at amniocentesis. A 40-year-old defect with right-to-left flow, and persistent mother, gravida 5, para 1, was referred for ductus, with flow from the pulmonary artery prenatal diagnosis because of advanced to the aorta. The heart defect was considered maternal age. Amniocentesis and ultrasound inoperable and the girl died at 13 days of age. examination were performed at 16 weeks’ A fibroblast culture made from a skin biopsy gestation, with no fetal abnormalities taken immediately post-mortem failed to observed. Amniotic fluid alpha-fetoprotein grow. Autopsy confirmed the left heart concentration was in the normal range. hypoplasia; no other abnormalities were Chromosome analysis with the G-banding observed. Trisomy 15 is observed in 1.68 per cent of technique of two independent cultures revealed the presence of trisomy 15 mosaic- first-trimester abortions (Simpson, 1990). It ism (Table I). A repeat amniocentesis at 19 has been observed once in a dysmorphic weeks’ gestation confirmed the presence of female baby who had severe congenital malmosaicism (Table 1). Intrauterine growth formations including a heart defect (venretardation (1UGR)ofthe fetuswasobserved tricular septal defect and coarctation of the by ultrasound from 19 weeks onwards. The aorta) and died at 4 days of age from intractable heart failure (Coldwell et al., 1981). parents opted to continue the pregnancy. IUGR was present at 35 weeks’ gestation Mosaicism of trisomy 15 observed at amnioand ultrasonography revealed oligohydram- centesis and fetal pathology has been nios and breech presentation. A Caesarean reported by Gimelli e t a [ . (1983). The cardiac section was performed at 37 2 weeks and a malformation of the female fetus was a persmall-for-dates girl with a birth weight of sistent common atrio-ventricular canal. In
+
Table 1. Cytogenetic findings of the reported case
Source of tissue Amniocentesis I (multiple flasks) Amniocentesis I1 (multiple flasks) Placenta (at term) Culture I Culture I1 Culture 111 Fetal membranes Umbilical cord Cord blood
No. of cells analysed
47,XX,
+ 15
46,XX
% abnormal
81
8
73
9.9
34
2
32
5.8
31 42 125 17 121
26 41 116 8 10 0
5 1 9 9 111
83.9 97.6 92.8 47.1 8.3 0.0
100
100
