- Email: [email protected]
Second trimester prenatal diagnosis of epignathus teratoma in ring X chromosome mosaicism with inactive ring X chromosome
Annales de Génétique 44 (2001) 179–182 © 2001 Éditions scientifiques et médicales Elsevier SAS. All rights reserved S0003399501010905/FLA
Case report
Second trimester prenatal diagnosis of epignathus teratoma in ring X chromosome mosaicism with inactive ring X chromosome Ingrid Wittersa*, Philippe Moermanb, Dirk Louwagiec, Frans-André Van Asschea, Barbara R. Migeond, Jean-Pierre Frynse a
Department of Obstetrics and Gynaecology, University Hospital Gasthuisberg of Leuven, Leuven, Belgium b Department of Pathology, University of Leuven, Herestraat 49, B-3000 Leuven, Belgium c Department of Obstetrics and Gynaecology, Bree, Belgium d McKusick-Nathans Institute of Genetic Medicine, John Hopkins University, Baltimore, Maryland, USA e Center for Human Genetics, University of Leuven, Leuven, Belgium
Received 3 August 2001; accepted 24 October 2001
Abstract – We report the second trimester prenatal echographic diagnosis of an epignathus teratoma in a female fetus with ring X chromosome mosaicism. The ring X chromosome mosaicism was present in the amniotic cell culture and in the teratoma and the ring X was inactive (X-inactive specific transcript (XIST) locus expressed). Hypoplastic left heart with valvular aortic stenosis and non-immune hydrops were additional findings, and are well-documented in Turner syndrome. The occurrence of epignathus teratoma in Turner syndrome has not been documented sofar. © 2001 Éditions scientifiques et médicales Elsevier SAS
epignathus / teratoma / Turner syndrome / ring X chromosome mosaicism / X-inactivation
1. Introduction
Epignathus teratomas are rare congenital malformations and present oropharyngeal tumours that can result in neonatal asphyxia [28]. Prenatal sonographic diagnosis has been well documented in the past [1, 3, 5, 8–10, 15, 16, 20, 22–27, 30]. Associated malformations may be present and commonly include cleft palate and bifid tongue or nose [28]. Autosomal chromosomal anomalies have been described in the presence of an epignathus in at least three cases [1, 24, 30]. We report on an epignathus teratoma in a 20 weeks old fetus with Turner syndrome and ring X chromosome mosaicism. 2. Clinical Report
A 31-year-old woman was referred in her fourth pregnancy at 20 weeks gestation for a fetal tumour * Correspondence and reprints. E-mail address: [email protected] (I. Witters).
detected by ultrasound. She had two previous uneventful pregnancies and one spontaneous miscarriage at 7 weeks. Echographic examination revealed a large solid mass with calcifications (5 x 4 x 5 cm) originating from the nasopharynx and protruding out of the mouth (figure 1). A cardiac anomaly, univentricular heart ( extreme left heart hypoplasia) , a single umbilical artery and non-immune hydrops presenting with ascites, increased amount of amniotic fluid and a thick placenta were additional findings. Amniocentesis for chromosomal analysis revealed a ring X chromosome in mosaic with a 45,X cell line. The ring X chromosome was present in 30 % of cells. The alpha-foetoprotein level on amniotic fluid was increased: 246 µg/mL (mean 18 µg/mL at 20 weeks gestation). Chromosomal analysis in both parents was normal. Pregnancy was terminated at 20 weeks gestation and a female fetus was born (weight: 275 g; head circum
180
I. Witters et al. / Ann. Génét. 44 (2001) 179–182
Figure 1. Echographic sagittal view on the fetus showing the teratoma protruding out of the mouth (white arrows).
ference: 176 mm; foot length: 31 mm). She had discrete nuchal edema and normal external female genitalia. Foetopathological examination showed a 5 cm large tumour (weight 35 g) protruding out of the mouth. The tumour had a single implantation base in the posterior region of the nasopharynx. There was no cleft palate. The mass also protruded through the left cavum nasi with deviation of the septum nasi to the right and obliteration of the right cavum nasi. There was no intracranial expansion of the tumour. Microscopic examination of the tumour showed the presence of ecto-, endo- and mesodermal tissue. Immature components of neural tissue were predominantly present next to mature cartilage and cysts delineated with respiratory, intestinal and multiple layer squameus cell epithelium. The cardiac anomaly was an incomplete persistent AV canal with hypoplastic left ventricle and valvular aortic stenosis due to a
unicuspid unicommissural aortic valve. The left kidney showed multi cystic dysplasia. There were normal female internal genitalia. Fluorescence in situ hybridization analysis using CEP (chromosome enumeration probe) on paraffin embedded sections of the teratoma revealed the same X-chromosomal mosaicism with the same 70 %/30 % distribution of the two cell lines. Fluorescence in situ hybridization analysis using the cosmid XIST probe [17] was carried out on the amniocytes to evaluate the presence of the XIST locus on the ring X chromosome. Of the ten ring chromosomes studied, 4 of them had no signal, most likely because of not efficient hybridization. The remaining 6 were well labeled, and had at least one copy on the XIST locus. RT-PCR analysis of RNA from the amniocytes [17] showed that the XIST was transcribed. The rings varied in size, some of them being double rings.
I. Witters et al. / Ann. Génét. 44 (2001) 179–182
3. Discussion
In this report we present a 20-weeks-old female fetus with an epignathus teratoma, a hypoplastic left heart with aortic valve stenosis, non immune hydrops and Turner syndrome with 45,X/46,X,r(X) mosaicism. An epignathus tumour is a rare teratoma of the oropharynx with an incidence between 1/35 000 and 1/200 000 life births [28]. The majority of epignathus tumours are attached at the base of the skull in the posterior region of the nasopharynx and they usually involve the hard palate or sphenoid bone [9]. As noted in the present observation, they often develop into the oral cavity, obstructing the upper airways resulting in neonatal asphyxia [28]. Few cases have an intracranial extension along the craniopharyngeal canal and these are generally lethal [2, 27]. The majority of these teratomas are mature [28]. In 6 % of cases associated malformations, mainly PierreRobin sequence (cleft palate, microretrognathia, glossoptosis) [28] and bifid tongue or nose [9] are present. Antenatal diagnosis of epignathi is well documented [1, 3, 5, 8–10, 15, 16, 20, 22–27, 30] and is mainly based on the visualisation of a mass projecting from the oral cavity. Hydrops due to cardiac decompensation secondary to the increased circulation in the vascular tumour mass [13] but also polyhydramnios due to oral cavity obstruction have been reported [8]. The present fetus also presented with non-immune hydrops secondary to the large teratoma and the cardiac malformation with left heart hypoplasia, a typical finding in Turner syndrome [7]. Only a few observations of epignathus teratoma associated with autosomal chromosomal anomalies have been reported: a fetus with trisomy 13 and associated holoprosencephaly ([30] and a fetus with a balanced 1q/19p translocation of maternal origin with a trisomic cell line in the teratoma [24]. In one fetus with normal constitutional karyotype an inverted proximal 1q duplication was diagnosed in the teratoma [1]. In the present fetus the 45,X/46,X,r(X) mosaicism was also found in the teratoma, with the same distribution of both cell lines as seen in the amniotic cell culture. The phenotype of 45,X/46,X,r(X) has been described as more severely abnormal in cases where the ring X chromosome is not inactivated due to deletion
181
of the X-inactive specific transcript (XIST) gene [11, 18, 19, 29]. In the present fetus, however, the ring chromosome included the XIST locus and the locus was transcribed. The present observation demonstrates that a severe phenotype of Turner syndrome can also be present when the ring X chromosome is inactivated (XIST expressed). Although extragonadal germ cell tumors, including teratomas, occur more often in patients with sex chromosome aneuploidies an epignathus teratoma has not been previously reported in patients with Turner syndrome [4, 6, 12, 14, 21, 31].
References [1] Abendstein B., Auer A., Pumpel R., Mark E., Desch B., Tscharf J., [Epignathus: prenatal diagnosis by sonography and magnetic resonance imaging], Ultraschall Med. 20 (1999) 207–211. [2] Ang A.T., Ho N.K., Ong C.L., Giant epignathus with intracranial teratoma in a newborn infant, Australas. Radiol. 34 (1990) 358–360. [3] Bruhwiler H., Mueller M.D., Rabner M., [Ultrasound diagnosis of epignathus in the 17th week of pregnancy. Case report and review of the literature], Ultraschall Med. 16 (1995) 238–240. [4] Casalone R., Righi R., Granata P., Portentoso P., Minelli E., Meroni, Solero C.L., Allegranza A, Cerebral germ cell tumor and XXY karyotype, Cancer Genet. Cytogenet. 74 (1994) 25–29. [5] Crimail P., Hainaut F., Legris M., [Pharyngeal epignathus teratoma. Echographic and prognostic study], J. Gynecol. Obstet. Biol. Reprod. (Paris) 17 (1988) 1069–1074. [6] Czauderna P., Stoba C., Wysocka B., Iliszko M., Association of Klinefelter syndrome and abdominal teratoma: a case report, J. Pediatr. Surg. 33 (1998) 774–775. [7] Douchin S., Rossignol A.M., Klein S.K., Siche J.P., Baguet J.P., Bost M., [Heart malformations and vascular complications associated with Turner’s syndrome. Prospective study of 26 patients], Arch. Mal Coeur Vaiss. 93 (2000) 565–570. [8] Ekici E., Soysal M., Kara S., Dogan M., Gokmen O., Prenatal diagnosis of epignathus causing acute polyhydramnios, Acta Obstet. Gynecol. Scand. 75 (1996) 498–501. [9] Gull I., Wolman I., Har-Toov J., Amster R., Schreiber L., Lessing J.B., Jaffa A., Antenatal sonographic diagnosis of epignathus at 15 weeks of pregnancy, Ultrasound Obstet. Gynecol. 13 (1999) 271–273. [10] Holmgren G., Rydnert J., Male fetus with epignathus originating from the ethmoidal sinus, Eur J. Obstet. Gynecol. Reprod. Biol. 24 (1987) 69–72. [11] Jani M.M., Torchia B.S., Pai G.S., Migeon B.R., Molecular characterization of tiny ring X chromosomes from females with functional X chromosome disomy and lack of cis X inactivation, Genomics 27 (1995) 182–188. [12] Joos H., Frick J., Wessely K., Rittinger O., Moritz E., Dietze O., Galvan G., Mediastinal tumor and Klinefelter’s syndrome, Eur Urol. 26 (1994) 344–346. [13] Kaplan C., Perlmutter S., Molinoff S., Epignathus with placental hydrops, Arch. Pathol. Lab Med. 104 (1980) 374–375.
182
I. Witters et al. / Ann. Génét. 44 (2001) 179–182
[14] Konig R., Schonberger W., Grimm W., [Mediastinal teratocarcinoma and hypophyseal stalk germinoma in a patient with Klinefelter syndrome], Klin. Padiatr. 202 (1990) 53–56. [15] Levine A.B., Alvarez M., Wedgwood J., Berkowitz R.L., Holzman I., Contemporary anagement of a potentially lethal fetal anomaly: a successful perinatal approach to epignathus, Obstet. Gynecol. 76 (1990) 962–966. [16] Lodeiro J.G., Feinstein S.J., McLaren R.A., Shapiro S.L., Antenatal diagnosis of epignathus with neonatal survival. A case report, J. Reprod. Med. 34 (1989) 997–999. [17] Migeon B.R., Ausems M., Giltay J., Hasley-Royster C., Kazi E., Lydon T.J., Engelen J.J., Raymond G.V., Severe phenotypes associated with inactive ring X chromosomes, Am. J. Med. Genet. 93 (2000) 52–57. [18] Migeon B.R., Luo S., Jani M., Jeppesen P., The severe phenotype of females with tiny ring X chromosomes is associated with inability of these chromosomes to undergo X inactivation, Am. J. Hum. Genet. 55 (1994) 497–504. [19] Migeon B.R., Luo S., Stasiowski B.A., Jani M., Axelman J., Van Dyke D.L., Weiss L., Jacobs P.A., Yang-Feng T.L., Wiley J.E., Deficient transcription of XIST from tiny ring X chromosomes in females with severe phenotypes, Proc. Natl. Acad. Sci. U. S. A 90 (1993) 12025–12029. [20] Ng H.N., Ong C.L., Two case reports of intracranial teratoma diagnosed antenatally, Ann. Acad. Med. Singapore 22 (1993) 823–825. [21] Okada H., Fujioka H., Tatsumi N., Kanzaki M., Okuda Y., Fujisawa M., Hazama M., Matsumoto O., Gohji K., Arakawa S., Kamidono S., Klinefelter’s syndrome in the male infertility clinic, Hum. Reprod. 14 (1999) 946–952. [22] Papageorgiou C., Papathanasiou K., Panidis D., Vlassis G., Prenatal diagnosis of epignathus in the first half of pregnancy: a case report and review of the literature, Clin. Exp. Obstet. Gynecol. 27 (2000) 67–68.
[23] Ramirez Robles L.J., Gomez P.G., Trujillo Gomez J.J., [Epignatus: ultrasonic diagnosis. Report of a case and review of the literature], Ginecol. Obstet. Mex. 67 (1999) 512–515. [24] Schwartz S., Raffel L.J., Sun C.C., Waters E., An unusual mosaic karyotype detected through prenatal diagnosis with duplication of 1q and 19p and associated teratoma development, Teratology 46 (1992) 399–404. [25] Shouno H., Matsuo N., Miyabara S., Yamasaki M., Kuriyama K., Sugimori H., Intrauterine diagnosis of epignathus using ultrasonic tomography, Asia Oceania J. Obstet. Gynaecol. 14 (1988) 199–205. [26] Smart P.J., Schwarz C., Kelsey A., Ultrasonographic and biochemical abnormalities associated with the prenatal diagnosis of epignathus, Prenat. Diagn. 10 (1990) 327–332. [27] Smith N.M., Chambers S.E., Billson V.R., Laing I., West C.P., Bell J.E., Oral teratoma (epignathus) with intracranial extension: a report of two cases, Prenat. Diagn. 13 (1993) 945–952. [28] Vandenhaute B., Leteurtre E., Lecomte-Houcke M., Pellerin P., Nuyts J.P., Cuisset J.M., Soto-Ares G., Epignathus teratoma: report of three cases with a review of the literature, Cleft Palate Craniofac. J. 37 (2000) 83–91. [29] Wolff D.J., Brown C.J., Schwartz S., Duncan A.M., Surti U., Willard H.F., Small marker X chromosomes lack the X inactivation center: implications for karyotype/phenotype correlations, Am. J. Hum. Genet. 55 (1994) 87–95. [30] Yapar E.G., Ekici E., Gokmen O., Sonographic diagnosis of epignathus (oral teratoma), prosencephaly, meromelia and oligohydramnios in a fetus with trisomy 13, Clin. Dysmorphol. 4 (1995) 266–271. [31] Yu I.T., Griffin C.A., Phillips P.C., Strauss L.C., Perlman E.J., Numerical sex chromosomal abnormalities in pineal teratomas by cytogenetic analysis and fluorescence in situ hybridization, Lab Invest 72 (1995) 419–423.
Case report
Second trimester prenatal diagnosis of epignathus teratoma in ring X chromosome mosaicism with inactive ring X chromosome Ingrid Wittersa*, Philippe Moermanb, Dirk Louwagiec, Frans-André Van Asschea, Barbara R. Migeond, Jean-Pierre Frynse a
Department of Obstetrics and Gynaecology, University Hospital Gasthuisberg of Leuven, Leuven, Belgium b Department of Pathology, University of Leuven, Herestraat 49, B-3000 Leuven, Belgium c Department of Obstetrics and Gynaecology, Bree, Belgium d McKusick-Nathans Institute of Genetic Medicine, John Hopkins University, Baltimore, Maryland, USA e Center for Human Genetics, University of Leuven, Leuven, Belgium
Received 3 August 2001; accepted 24 October 2001
Abstract – We report the second trimester prenatal echographic diagnosis of an epignathus teratoma in a female fetus with ring X chromosome mosaicism. The ring X chromosome mosaicism was present in the amniotic cell culture and in the teratoma and the ring X was inactive (X-inactive specific transcript (XIST) locus expressed). Hypoplastic left heart with valvular aortic stenosis and non-immune hydrops were additional findings, and are well-documented in Turner syndrome. The occurrence of epignathus teratoma in Turner syndrome has not been documented sofar. © 2001 Éditions scientifiques et médicales Elsevier SAS
epignathus / teratoma / Turner syndrome / ring X chromosome mosaicism / X-inactivation
1. Introduction
Epignathus teratomas are rare congenital malformations and present oropharyngeal tumours that can result in neonatal asphyxia [28]. Prenatal sonographic diagnosis has been well documented in the past [1, 3, 5, 8–10, 15, 16, 20, 22–27, 30]. Associated malformations may be present and commonly include cleft palate and bifid tongue or nose [28]. Autosomal chromosomal anomalies have been described in the presence of an epignathus in at least three cases [1, 24, 30]. We report on an epignathus teratoma in a 20 weeks old fetus with Turner syndrome and ring X chromosome mosaicism. 2. Clinical Report
A 31-year-old woman was referred in her fourth pregnancy at 20 weeks gestation for a fetal tumour * Correspondence and reprints. E-mail address: [email protected] (I. Witters).
detected by ultrasound. She had two previous uneventful pregnancies and one spontaneous miscarriage at 7 weeks. Echographic examination revealed a large solid mass with calcifications (5 x 4 x 5 cm) originating from the nasopharynx and protruding out of the mouth (figure 1). A cardiac anomaly, univentricular heart ( extreme left heart hypoplasia) , a single umbilical artery and non-immune hydrops presenting with ascites, increased amount of amniotic fluid and a thick placenta were additional findings. Amniocentesis for chromosomal analysis revealed a ring X chromosome in mosaic with a 45,X cell line. The ring X chromosome was present in 30 % of cells. The alpha-foetoprotein level on amniotic fluid was increased: 246 µg/mL (mean 18 µg/mL at 20 weeks gestation). Chromosomal analysis in both parents was normal. Pregnancy was terminated at 20 weeks gestation and a female fetus was born (weight: 275 g; head circum
180
I. Witters et al. / Ann. Génét. 44 (2001) 179–182
Figure 1. Echographic sagittal view on the fetus showing the teratoma protruding out of the mouth (white arrows).
ference: 176 mm; foot length: 31 mm). She had discrete nuchal edema and normal external female genitalia. Foetopathological examination showed a 5 cm large tumour (weight 35 g) protruding out of the mouth. The tumour had a single implantation base in the posterior region of the nasopharynx. There was no cleft palate. The mass also protruded through the left cavum nasi with deviation of the septum nasi to the right and obliteration of the right cavum nasi. There was no intracranial expansion of the tumour. Microscopic examination of the tumour showed the presence of ecto-, endo- and mesodermal tissue. Immature components of neural tissue were predominantly present next to mature cartilage and cysts delineated with respiratory, intestinal and multiple layer squameus cell epithelium. The cardiac anomaly was an incomplete persistent AV canal with hypoplastic left ventricle and valvular aortic stenosis due to a
unicuspid unicommissural aortic valve. The left kidney showed multi cystic dysplasia. There were normal female internal genitalia. Fluorescence in situ hybridization analysis using CEP (chromosome enumeration probe) on paraffin embedded sections of the teratoma revealed the same X-chromosomal mosaicism with the same 70 %/30 % distribution of the two cell lines. Fluorescence in situ hybridization analysis using the cosmid XIST probe [17] was carried out on the amniocytes to evaluate the presence of the XIST locus on the ring X chromosome. Of the ten ring chromosomes studied, 4 of them had no signal, most likely because of not efficient hybridization. The remaining 6 were well labeled, and had at least one copy on the XIST locus. RT-PCR analysis of RNA from the amniocytes [17] showed that the XIST was transcribed. The rings varied in size, some of them being double rings.
I. Witters et al. / Ann. Génét. 44 (2001) 179–182
3. Discussion
In this report we present a 20-weeks-old female fetus with an epignathus teratoma, a hypoplastic left heart with aortic valve stenosis, non immune hydrops and Turner syndrome with 45,X/46,X,r(X) mosaicism. An epignathus tumour is a rare teratoma of the oropharynx with an incidence between 1/35 000 and 1/200 000 life births [28]. The majority of epignathus tumours are attached at the base of the skull in the posterior region of the nasopharynx and they usually involve the hard palate or sphenoid bone [9]. As noted in the present observation, they often develop into the oral cavity, obstructing the upper airways resulting in neonatal asphyxia [28]. Few cases have an intracranial extension along the craniopharyngeal canal and these are generally lethal [2, 27]. The majority of these teratomas are mature [28]. In 6 % of cases associated malformations, mainly PierreRobin sequence (cleft palate, microretrognathia, glossoptosis) [28] and bifid tongue or nose [9] are present. Antenatal diagnosis of epignathi is well documented [1, 3, 5, 8–10, 15, 16, 20, 22–27, 30] and is mainly based on the visualisation of a mass projecting from the oral cavity. Hydrops due to cardiac decompensation secondary to the increased circulation in the vascular tumour mass [13] but also polyhydramnios due to oral cavity obstruction have been reported [8]. The present fetus also presented with non-immune hydrops secondary to the large teratoma and the cardiac malformation with left heart hypoplasia, a typical finding in Turner syndrome [7]. Only a few observations of epignathus teratoma associated with autosomal chromosomal anomalies have been reported: a fetus with trisomy 13 and associated holoprosencephaly ([30] and a fetus with a balanced 1q/19p translocation of maternal origin with a trisomic cell line in the teratoma [24]. In one fetus with normal constitutional karyotype an inverted proximal 1q duplication was diagnosed in the teratoma [1]. In the present fetus the 45,X/46,X,r(X) mosaicism was also found in the teratoma, with the same distribution of both cell lines as seen in the amniotic cell culture. The phenotype of 45,X/46,X,r(X) has been described as more severely abnormal in cases where the ring X chromosome is not inactivated due to deletion
181
of the X-inactive specific transcript (XIST) gene [11, 18, 19, 29]. In the present fetus, however, the ring chromosome included the XIST locus and the locus was transcribed. The present observation demonstrates that a severe phenotype of Turner syndrome can also be present when the ring X chromosome is inactivated (XIST expressed). Although extragonadal germ cell tumors, including teratomas, occur more often in patients with sex chromosome aneuploidies an epignathus teratoma has not been previously reported in patients with Turner syndrome [4, 6, 12, 14, 21, 31].
References [1] Abendstein B., Auer A., Pumpel R., Mark E., Desch B., Tscharf J., [Epignathus: prenatal diagnosis by sonography and magnetic resonance imaging], Ultraschall Med. 20 (1999) 207–211. [2] Ang A.T., Ho N.K., Ong C.L., Giant epignathus with intracranial teratoma in a newborn infant, Australas. Radiol. 34 (1990) 358–360. [3] Bruhwiler H., Mueller M.D., Rabner M., [Ultrasound diagnosis of epignathus in the 17th week of pregnancy. Case report and review of the literature], Ultraschall Med. 16 (1995) 238–240. [4] Casalone R., Righi R., Granata P., Portentoso P., Minelli E., Meroni, Solero C.L., Allegranza A, Cerebral germ cell tumor and XXY karyotype, Cancer Genet. Cytogenet. 74 (1994) 25–29. [5] Crimail P., Hainaut F., Legris M., [Pharyngeal epignathus teratoma. Echographic and prognostic study], J. Gynecol. Obstet. Biol. Reprod. (Paris) 17 (1988) 1069–1074. [6] Czauderna P., Stoba C., Wysocka B., Iliszko M., Association of Klinefelter syndrome and abdominal teratoma: a case report, J. Pediatr. Surg. 33 (1998) 774–775. [7] Douchin S., Rossignol A.M., Klein S.K., Siche J.P., Baguet J.P., Bost M., [Heart malformations and vascular complications associated with Turner’s syndrome. Prospective study of 26 patients], Arch. Mal Coeur Vaiss. 93 (2000) 565–570. [8] Ekici E., Soysal M., Kara S., Dogan M., Gokmen O., Prenatal diagnosis of epignathus causing acute polyhydramnios, Acta Obstet. Gynecol. Scand. 75 (1996) 498–501. [9] Gull I., Wolman I., Har-Toov J., Amster R., Schreiber L., Lessing J.B., Jaffa A., Antenatal sonographic diagnosis of epignathus at 15 weeks of pregnancy, Ultrasound Obstet. Gynecol. 13 (1999) 271–273. [10] Holmgren G., Rydnert J., Male fetus with epignathus originating from the ethmoidal sinus, Eur J. Obstet. Gynecol. Reprod. Biol. 24 (1987) 69–72. [11] Jani M.M., Torchia B.S., Pai G.S., Migeon B.R., Molecular characterization of tiny ring X chromosomes from females with functional X chromosome disomy and lack of cis X inactivation, Genomics 27 (1995) 182–188. [12] Joos H., Frick J., Wessely K., Rittinger O., Moritz E., Dietze O., Galvan G., Mediastinal tumor and Klinefelter’s syndrome, Eur Urol. 26 (1994) 344–346. [13] Kaplan C., Perlmutter S., Molinoff S., Epignathus with placental hydrops, Arch. Pathol. Lab Med. 104 (1980) 374–375.
182
I. Witters et al. / Ann. Génét. 44 (2001) 179–182
[14] Konig R., Schonberger W., Grimm W., [Mediastinal teratocarcinoma and hypophyseal stalk germinoma in a patient with Klinefelter syndrome], Klin. Padiatr. 202 (1990) 53–56. [15] Levine A.B., Alvarez M., Wedgwood J., Berkowitz R.L., Holzman I., Contemporary anagement of a potentially lethal fetal anomaly: a successful perinatal approach to epignathus, Obstet. Gynecol. 76 (1990) 962–966. [16] Lodeiro J.G., Feinstein S.J., McLaren R.A., Shapiro S.L., Antenatal diagnosis of epignathus with neonatal survival. A case report, J. Reprod. Med. 34 (1989) 997–999. [17] Migeon B.R., Ausems M., Giltay J., Hasley-Royster C., Kazi E., Lydon T.J., Engelen J.J., Raymond G.V., Severe phenotypes associated with inactive ring X chromosomes, Am. J. Med. Genet. 93 (2000) 52–57. [18] Migeon B.R., Luo S., Jani M., Jeppesen P., The severe phenotype of females with tiny ring X chromosomes is associated with inability of these chromosomes to undergo X inactivation, Am. J. Hum. Genet. 55 (1994) 497–504. [19] Migeon B.R., Luo S., Stasiowski B.A., Jani M., Axelman J., Van Dyke D.L., Weiss L., Jacobs P.A., Yang-Feng T.L., Wiley J.E., Deficient transcription of XIST from tiny ring X chromosomes in females with severe phenotypes, Proc. Natl. Acad. Sci. U. S. A 90 (1993) 12025–12029. [20] Ng H.N., Ong C.L., Two case reports of intracranial teratoma diagnosed antenatally, Ann. Acad. Med. Singapore 22 (1993) 823–825. [21] Okada H., Fujioka H., Tatsumi N., Kanzaki M., Okuda Y., Fujisawa M., Hazama M., Matsumoto O., Gohji K., Arakawa S., Kamidono S., Klinefelter’s syndrome in the male infertility clinic, Hum. Reprod. 14 (1999) 946–952. [22] Papageorgiou C., Papathanasiou K., Panidis D., Vlassis G., Prenatal diagnosis of epignathus in the first half of pregnancy: a case report and review of the literature, Clin. Exp. Obstet. Gynecol. 27 (2000) 67–68.
[23] Ramirez Robles L.J., Gomez P.G., Trujillo Gomez J.J., [Epignatus: ultrasonic diagnosis. Report of a case and review of the literature], Ginecol. Obstet. Mex. 67 (1999) 512–515. [24] Schwartz S., Raffel L.J., Sun C.C., Waters E., An unusual mosaic karyotype detected through prenatal diagnosis with duplication of 1q and 19p and associated teratoma development, Teratology 46 (1992) 399–404. [25] Shouno H., Matsuo N., Miyabara S., Yamasaki M., Kuriyama K., Sugimori H., Intrauterine diagnosis of epignathus using ultrasonic tomography, Asia Oceania J. Obstet. Gynaecol. 14 (1988) 199–205. [26] Smart P.J., Schwarz C., Kelsey A., Ultrasonographic and biochemical abnormalities associated with the prenatal diagnosis of epignathus, Prenat. Diagn. 10 (1990) 327–332. [27] Smith N.M., Chambers S.E., Billson V.R., Laing I., West C.P., Bell J.E., Oral teratoma (epignathus) with intracranial extension: a report of two cases, Prenat. Diagn. 13 (1993) 945–952. [28] Vandenhaute B., Leteurtre E., Lecomte-Houcke M., Pellerin P., Nuyts J.P., Cuisset J.M., Soto-Ares G., Epignathus teratoma: report of three cases with a review of the literature, Cleft Palate Craniofac. J. 37 (2000) 83–91. [29] Wolff D.J., Brown C.J., Schwartz S., Duncan A.M., Surti U., Willard H.F., Small marker X chromosomes lack the X inactivation center: implications for karyotype/phenotype correlations, Am. J. Hum. Genet. 55 (1994) 87–95. [30] Yapar E.G., Ekici E., Gokmen O., Sonographic diagnosis of epignathus (oral teratoma), prosencephaly, meromelia and oligohydramnios in a fetus with trisomy 13, Clin. Dysmorphol. 4 (1995) 266–271. [31] Yu I.T., Griffin C.A., Phillips P.C., Strauss L.C., Perlman E.J., Numerical sex chromosomal abnormalities in pineal teratomas by cytogenetic analysis and fluorescence in situ hybridization, Lab Invest 72 (1995) 419–423.