American Journal of Medical Genetics 39:76-77 (1991)
Brief Clinical Report
Prenatal Diagnosis of 48,XYY, + 21 Ascertained Through Ultrasound Anomalies Thomaz Rafael Gollop, Nadyr F. Naccache, Eloisa Auler-Bittencourt, Decio Hauschild, Albert0 Eigier, and Deborah K. Zveibil Seruico de Gene‘ticaHumana da Associa@o Maternidade de Scio Paul0 (T.R.G., N.F.N., E.A.-B., D.H., A.E.) and Laboratorio de Anatomia Patologica do Hospital Israelita Albert Einstein (D.K.Z.), Sao Paulo, Brazil
During a routine ultrasound study on a fetus at 21 weeks, nuchal edema was noted. At 21 weeks, repeat ultrasound study at our unit showed scalp and neck edema and a femur length/biparietal diameter ratio below the mean. Transabdominal chorionic villus sampling identified a 48.XYY,+ 21 chromosome constitution. The fetus had normal internal/ external genitalia and signs of Down Vndrome. KEY WORDS: chorionic villus sampling, Down syndrome, nuchal edema INTRODUCTION Advanced maternal age has been the main indication for fetal chromosome analysis. However, the frequencies of chromosome abnormalities observed in these cases are much lower than those associated with single or multiple malformations detected by ultrasound study, that gives frequencies of 13-33% [Nicolaides and Campbell, 1986; Palmer et al., 1987; Holzgreve et al., 1987; Basaran et al., 1988; Eydoux et al., 19891. Fetal nuchal edema and biparietal diametedfemur length ratio (BPD/FL) >1.5 SD above the mean identified 50-70% of the Down syndrome cases in the population studied by Benacerraf et al. [1987]. We report on the first second trimester diagnosis of a 48,XYY, + 21 fetus ascertained by ultrasound detection of fetal scalp and neck edema and decreased femur length.
weeks; the fetus was thought to have “hydrocephaly” and nuchal edema. In our unit, ultrasonography a t 21 weeks showed: biparietal diameter (BPD) of 52 mm, femur length (FL) of 34 mm (mean 3 9 i 4 ) , abdominal circumference of 18.1cm, cephalic circumference of 19.7 cm, FLiBDP x 100 = 65.4 (mean 75.5, SD 9.8), scalp and neck edema, and permanently open mouth (Fig. 1). With local anesthesia, ultrasound-guided placental biopsy was performed with a BD 18-gauge needle. Fetal karyotype was 48,XYY, + 21 in 50 G-banded cells. After interruption of pregnancy, the male fetus had normal external genitalia, scalp and neck edema, folded skin a t the nuchal region (Fig. 21, depressed nasal bridge, epicanthal folds, discrete retrognathia, apparently low-set ears, bilateral fifth finger clinodactyly, and simian creases. Weight was 690 g, crown-rump length 15 cm. Autopsy showed apparently normal microscopic testicular tissue and normal internal organs, including the heart. Karyotype in 50 cells obtained from fetal lung and skin was 46,XYY, +21. Parents refused chromosome analysis.
CLINICAL REPORT A 29-year-old gravida 3, para 1, abortus 1 white woman married to a nonconsanguineous 30-year-old man underwent ultrasound examination elsewhere a t 21 Received for publication February 28, 1990; revision received July 11, 1990. Address reprint request to Thomaz Rafael Gollop, MD, PhD, Serviso de Genetica Humana da Associasao Maternidade de Sao Paulo, Rua Ofelia, 248, Jd. Paulistano, CEP 05423, SBo Paulo SP, Brazil.
0 1991 Wiley-Liss, Inc.
Fig. 1. Sonographic aspects of the 48,XYY,+21 fetus. Open mouth and scalp and neck edema (arrow) can be seen.
Prenatal Diagnosis of 48,XYY, +21
77
The efficacy and applicability of fetal biometry in routine sonographic screening, especially when based on short femur length is questioned by Lockwood and Hobbins [19891. They recommended multicentered prospective studies before sonographic information such a s scalp and neck edema or short femur length is applied clinically. It is important to note that we decided not to make the final diagnosis based solely on sonographic data but rather used this information only as a n indication for fetal chromosome study. The evidence of permanently open mouth observed during our sonographic examination may represent indirect evidence of fetal hypotonia. Fig. 2. Fetus showing folded edematous neck skin, retrognathia, apparently low-set ears, and depressed nasal bridge.
REFERENCES
DISCUSSION To the best of our knowledge, this is the first report of a 48,XYY, + 21 fetus detected by sonographic anomalies including scalp and neck edema and short femora. In a survey of 107 fetuses with ultrasonically diagnosed fetal anomalies Palmer et al. [1987] documented 2 47,XX,+21 cases, one suspected a t 31 weeks due to a probable duodenal atresia and the other referred a t 19 weeks because of scalp and neck edema and cystic hygromas. Eydoux et al. [1989] in a larger series of 936 fetuses referred for cytogenetic study after observation of fetal anomalies on ultrasound found 47,XYY and trisomy 21 in one case and 26 cases, respectively, none with both chromosomal abnormalities. It is remarkable that their 47,XYY case showed hydramnios and a clubfoot, a n ultrasonographic sign in a usually phenotypically normal syndrome.
Basaran S, Miny P, Pawlowitzki IH, Horst J , Holzgreve W (1988):Rapid karyotyping for prenatal diagnosis in the second and third trimesters of pregnancy. Prenat Diagn 8:315-320. Benacerraf BR, Gelman R, Frigoletto FD (1987):Sonographic identification of second trimester fetuses with Down’s syndrome. N Engl J Med 317:1371-1376. Eydoux P, Choiset A, Le Porrier N, Thepot F, Szpiro-Tapia S, Alliet J , Ramond S, Vie1 JF, Gautier E, Morichon N, Girard-Orgeolet S 11989): Chromosomal prenatal diagnosis: Study of 936 cases of intrauterine abnormalities after ultrasound assessment. Prenat Diagn 9:255-268. Holzgreve W, Miny P, Basaran S, Fuhrmann W, Beller FK (1987): Safety ofplacental biopsy in the second and third trimesters. N Engl J Med 317:1159-1160. Lockwood C, Hobbins J C (1989):Prenatal detection of Down syndrome. Letter to the Editor. Am J Obstet Gynecol 160:1536-1537. Nicolaides KH, Campbell S (1986):Diagnosis of fetal abnormalities by ultrasound. In Milunsky A (ed):“Genetic Disorders and the F e t u s Diagnosis, Prevention, and Treatment.” New York: Plenum Press, pp 521-570. Palmer CG, Miles JH, Howard-Peebles PN, Magenis RE, Patil S, Friedman JM (1987): Fetal karyotype following ascertainment of fetal anomalies by ultrasound. Prenat Diagn 7:551-555.
Brief Clinical Report
Prenatal Diagnosis of 48,XYY, + 21 Ascertained Through Ultrasound Anomalies Thomaz Rafael Gollop, Nadyr F. Naccache, Eloisa Auler-Bittencourt, Decio Hauschild, Albert0 Eigier, and Deborah K. Zveibil Seruico de Gene‘ticaHumana da Associa@o Maternidade de Scio Paul0 (T.R.G., N.F.N., E.A.-B., D.H., A.E.) and Laboratorio de Anatomia Patologica do Hospital Israelita Albert Einstein (D.K.Z.), Sao Paulo, Brazil
During a routine ultrasound study on a fetus at 21 weeks, nuchal edema was noted. At 21 weeks, repeat ultrasound study at our unit showed scalp and neck edema and a femur length/biparietal diameter ratio below the mean. Transabdominal chorionic villus sampling identified a 48.XYY,+ 21 chromosome constitution. The fetus had normal internal/ external genitalia and signs of Down Vndrome. KEY WORDS: chorionic villus sampling, Down syndrome, nuchal edema INTRODUCTION Advanced maternal age has been the main indication for fetal chromosome analysis. However, the frequencies of chromosome abnormalities observed in these cases are much lower than those associated with single or multiple malformations detected by ultrasound study, that gives frequencies of 13-33% [Nicolaides and Campbell, 1986; Palmer et al., 1987; Holzgreve et al., 1987; Basaran et al., 1988; Eydoux et al., 19891. Fetal nuchal edema and biparietal diametedfemur length ratio (BPD/FL) >1.5 SD above the mean identified 50-70% of the Down syndrome cases in the population studied by Benacerraf et al. [1987]. We report on the first second trimester diagnosis of a 48,XYY, + 21 fetus ascertained by ultrasound detection of fetal scalp and neck edema and decreased femur length.
weeks; the fetus was thought to have “hydrocephaly” and nuchal edema. In our unit, ultrasonography a t 21 weeks showed: biparietal diameter (BPD) of 52 mm, femur length (FL) of 34 mm (mean 3 9 i 4 ) , abdominal circumference of 18.1cm, cephalic circumference of 19.7 cm, FLiBDP x 100 = 65.4 (mean 75.5, SD 9.8), scalp and neck edema, and permanently open mouth (Fig. 1). With local anesthesia, ultrasound-guided placental biopsy was performed with a BD 18-gauge needle. Fetal karyotype was 48,XYY, + 21 in 50 G-banded cells. After interruption of pregnancy, the male fetus had normal external genitalia, scalp and neck edema, folded skin a t the nuchal region (Fig. 21, depressed nasal bridge, epicanthal folds, discrete retrognathia, apparently low-set ears, bilateral fifth finger clinodactyly, and simian creases. Weight was 690 g, crown-rump length 15 cm. Autopsy showed apparently normal microscopic testicular tissue and normal internal organs, including the heart. Karyotype in 50 cells obtained from fetal lung and skin was 46,XYY, +21. Parents refused chromosome analysis.
CLINICAL REPORT A 29-year-old gravida 3, para 1, abortus 1 white woman married to a nonconsanguineous 30-year-old man underwent ultrasound examination elsewhere a t 21 Received for publication February 28, 1990; revision received July 11, 1990. Address reprint request to Thomaz Rafael Gollop, MD, PhD, Serviso de Genetica Humana da Associasao Maternidade de Sao Paulo, Rua Ofelia, 248, Jd. Paulistano, CEP 05423, SBo Paulo SP, Brazil.
0 1991 Wiley-Liss, Inc.
Fig. 1. Sonographic aspects of the 48,XYY,+21 fetus. Open mouth and scalp and neck edema (arrow) can be seen.
Prenatal Diagnosis of 48,XYY, +21
77
The efficacy and applicability of fetal biometry in routine sonographic screening, especially when based on short femur length is questioned by Lockwood and Hobbins [19891. They recommended multicentered prospective studies before sonographic information such a s scalp and neck edema or short femur length is applied clinically. It is important to note that we decided not to make the final diagnosis based solely on sonographic data but rather used this information only as a n indication for fetal chromosome study. The evidence of permanently open mouth observed during our sonographic examination may represent indirect evidence of fetal hypotonia. Fig. 2. Fetus showing folded edematous neck skin, retrognathia, apparently low-set ears, and depressed nasal bridge.
REFERENCES
DISCUSSION To the best of our knowledge, this is the first report of a 48,XYY, + 21 fetus detected by sonographic anomalies including scalp and neck edema and short femora. In a survey of 107 fetuses with ultrasonically diagnosed fetal anomalies Palmer et al. [1987] documented 2 47,XX,+21 cases, one suspected a t 31 weeks due to a probable duodenal atresia and the other referred a t 19 weeks because of scalp and neck edema and cystic hygromas. Eydoux et al. [1989] in a larger series of 936 fetuses referred for cytogenetic study after observation of fetal anomalies on ultrasound found 47,XYY and trisomy 21 in one case and 26 cases, respectively, none with both chromosomal abnormalities. It is remarkable that their 47,XYY case showed hydramnios and a clubfoot, a n ultrasonographic sign in a usually phenotypically normal syndrome.
Basaran S, Miny P, Pawlowitzki IH, Horst J , Holzgreve W (1988):Rapid karyotyping for prenatal diagnosis in the second and third trimesters of pregnancy. Prenat Diagn 8:315-320. Benacerraf BR, Gelman R, Frigoletto FD (1987):Sonographic identification of second trimester fetuses with Down’s syndrome. N Engl J Med 317:1371-1376. Eydoux P, Choiset A, Le Porrier N, Thepot F, Szpiro-Tapia S, Alliet J , Ramond S, Vie1 JF, Gautier E, Morichon N, Girard-Orgeolet S 11989): Chromosomal prenatal diagnosis: Study of 936 cases of intrauterine abnormalities after ultrasound assessment. Prenat Diagn 9:255-268. Holzgreve W, Miny P, Basaran S, Fuhrmann W, Beller FK (1987): Safety ofplacental biopsy in the second and third trimesters. N Engl J Med 317:1159-1160. Lockwood C, Hobbins J C (1989):Prenatal detection of Down syndrome. Letter to the Editor. Am J Obstet Gynecol 160:1536-1537. Nicolaides KH, Campbell S (1986):Diagnosis of fetal abnormalities by ultrasound. In Milunsky A (ed):“Genetic Disorders and the F e t u s Diagnosis, Prevention, and Treatment.” New York: Plenum Press, pp 521-570. Palmer CG, Miles JH, Howard-Peebles PN, Magenis RE, Patil S, Friedman JM (1987): Fetal karyotype following ascertainment of fetal anomalies by ultrasound. Prenat Diagn 7:551-555.
