- Email: [email protected]
Are all cases of low-grade mosaic trisomy 13 in amniotic fluid with no fetal malformation in fact confined placental mosaicism? A case report
Morphologie (2011) 95, 142—145
CLINICAL CASE
Are all cases of low-grade mosaic trisomy 13 in amniotic fluid with no fetal malformation in fact confined placental mosaicism? A case report Les cas de faible mosaïque de trisomie 13 dans le liquide amniotique sans malformation fœtale sont-ils tous des mosaïques confinées au placenta ? À propos d’un cas C. Etoubleau a, S. Bourthoumieu a, M. Fiorenza b, V. Aubard b, C. Yardin a,∗ a
Service d’histologie et cytogénétique, comité de recherche clinique du HME (CHREC), hôpital de la mère et de l’enfant (HME), hôpital universitaire de Limoges, 8, avenue Dominique-Larrey, 87042 Limoges cedex, France b Service de gynécologie, centre pluridisciplinaire de diagnostic prénatal (CPDPN), hôpital de la mère et de l’enfant (HME), hôpital universitaire de Limoges, 8, avenue Dominique-Larrey, 87042 Limoges cedex, France Available online 10 November 2011
KEYWORDS Mosaic trisomy 13; Placental mosaicism; Prenatal diagnosis; Genetic counseling
∗
Summary We report on a case of true prenatal mosaic trisomy 13 on amniotic fluid associated with a normal phenotype at the age of 6 years. The amniocentesis was performed because of advanced maternal age and was controlled by a second sample. Morphological and cardiac ultrasonography did not reveal any fetal malformations. No trisomic cells were found in the fetal blood and a nuclear magnetic resonance imaging (IRM) of the brain was performed during the third trimester found no abnormality of the brain. Finally, at birth cytogenetic analysis was performed on two placental samples for chromosomal analysis: one in an area where the placenta seemed normal, and the other one in an area with infarcted and hemorrhagic aspect. We found a high rate of trisomic cells in the sample with abnormal aspect. Furthermore, no trisomic cell was observed by fluorescent in situ hybridation (FISH) on the buccal smears of the baby. We concluded to a confined placental mosaicism. The good outcome of the child aged 6 years confirms this diagnosis. So in the aim to predict a good development for the child in case of low rate mosaic trisomy 13 in amniotic fluid, we propose at birth: i) to take several samples from the placenta to confirm placental mosaicism; ii) to label by FISH buccal smears with a LSI 13 probe to prove that the baby is not a carrier of the trisomy. © 2011 Elsevier Masson SAS. All rights reserved.
Corresponding author. E-mail address: [email protected] (C. Yardin).
1286-0115/$ – see front matter © 2011 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.morpho.2011.07.117
Prenatal low grade trisomy 13 and placental mosaicism
MOTS CLÉS Trisomie 13 en mosaïque ; Mosaïques confinées au placenta ; Diagnostic prénatal ; Conseil génétique
143
Résumé Nous rapportons un cas de trisomie 13 en mosaïque sur liquide amniotique associé à un phénotype normal à l’âge de six ans. L’amniocentèse a été réalisée pour âge maternel supérieur à 38 ans et a été contrôlée par un second prélèvement. Aucune malformation n’a été mise en évidence à l’échographie morphologique et cardiaque. Aucune cellule trisomique 13 n’a été retrouvée sur sang fœtal et l’IRM cérébrale fœtale n’a révélé aucune anomalie. À la naissance, une analyse cytogénétique a été effectuée sur deux prélèvements placentaires : sur un fragment d’aspect normal et sur un fragment d’aspect infarci et hémorragique. Un taux important de cellules trisomiques a été retrouvé sur le fragment anormal. De plus, aucune cellule trisomique n’a été mise en évidence par hybridation fluorescente in situ (FISH) sur le frottis jugal du nouveau-né. Nous avons conclu à une mosaïque confinée au placenta. L’évolution tout à fait normale de l’enfant à six ans confirme ce diagnostic. En conclusion nous proposons en cas de faible mosaïque de trisomie 13 sur liquide amniotique de pratiquer à la naissance : i) un prélèvement de plusieurs fragments placentaires afin d’authentifier la mosaïque, ii) un frottis jugal avec FISH afin de vérifier l’absence de cellules trisomiques sur l’enfant. © 2011 Elsevier Masson SAS. Tous droits réservés.
Introduction It is not so rare to diagnose a prenatal trisomy mosaicism in amniotic fluid. Two situations are clearly very different in genetic counseling: • when fetal malformations are present, it is relatively easy to explain to the parents the correlation between the karyotyping and the ultrasound (US) findings. In that case, the parents are somewhat aware of the possibility of chromosomal aberration and may be relieved to receive an explanation for the reason of fetal malformations; • the genetic counseling is much more difficult when a prenatal ‘‘unexpected’’ trisomy is found after chromosomal analysis performed for example because of advanced maternal age or maternal anxiety, and when US examination is normal. In this situation, it is difficult to predict the fetal outcome, since even if the morphology and the structures are completely normal, functional abnormalities such as mental and development delay may occur. All of this leads to most of the time an enhanced parental anxiety. Furthermore, the parents might have asked questions to the mother’s gynecologist or to their general physician and these responses may have enhanced their worries.
Clinical report We describe a case where trisomy 13 mosaicism was detected prenatally by amniocentesis because of advanced maternal age (39 years) in 2005. Three out of 21 clones scored (14%) showed trisomy 13 in a female fetus. The three trisomic clones provided from two different cultures and a trisomy resulting from an abnormality occurring during the culture was then excluded. The couple was referred to the hospital by their gynecologist for a request of termination of pregnancy. Morphological and cardiac ultrasonography was performed and did not reveal any fetal malformation. A second amniocentesis was recommended with interphasic fluorescent in situ hybridization (FISH) analysis (LSI 13 probe, Vysis Inc, Abbott® Diagnostic, Rungis, France). A total of 235 nuclei were observed: 213 (90.6%) showed two signals for
chromosome 13, 14 (6%) revealed three signals and eight (3.4%) were considered as aberrant signals (> 3 or < 2). The in situ cultured clones (total of 14) displayed normal karyotyping (46, XX), whereas on a total of 61 mitoses from the trypsinized culture, seven (11.5%) were trisomic for the chromosome 13. So the mosaicism was considered as low, around 10%. Even so the parents remained quite worried and we proposed further investigations. Cord blood sample was analyzed: 40 metaphases (100%) showed normal karyotyping and two signals for chromosome 13 were observed on 80 additional mitosis using FISH. None of the fetal lymphocytes were found to be trisomic. The parents, along with the pluridisciplinary center of prenatal diagnosis, decided to continue the pregnancy with a monthly ultrasonography and a nuclear magnetic resonance imaging (IRM) of the brain during the third trimester. The later was normal and pregnancy went to full term. Finally, a female baby named Chloé was born at 38 weeks of gestation with a birth weight of 3180 g and a birth length of 50 cm. The physical examination of the baby was normal. The parents agreed for a placental chromosomal analysis and two samples were taken: one in an area where the placenta seemed normal, and the other one in an area with infarcted and hemorrhagic aspect. All the 11 examined cells providing from the normal area were 46, XX, whereas 12 out of 16 mitoses from the abnormal area showed a trisomy 13 (47, XX, + 13). Cells from the buccal smear were analyzed by FISH with 13 and 21 labelling (LSI 13 and LSI 21 probes, Vysis Inc, Abbott® Diagnostic, Rungis, France). Only two cells out of 203 were found to have three 13 signals, that is less than 1%, and FISH was then interpreted as normal. Table 1 summarizes all the cytogenetic studies performed prenatally and postnatally on the different tissues. Chloé is now six years old and presents nor developmental problem (see Fig. 1 displaying photographs of Chloé given by her parents), neither pigmentary disturbance such as phylloid hypomelanosis known to be associated with mosaic trisomy 13 [1,2].
Discussion In our case, the normal outcome was expected since:
144
C. Etoubleau et al.
Table 1 Cytogenetic results in the patient before and after birth. Résultats cytogénétiques du patient avant et après la naissance. Amniocytes (1st sample)
Amniocytes (2nd sample)
Fetal blood
Placenta
Buccal smear
mos 47,XX, + 13 [3] / 46,XX [18] (IS) /
46,XX [14] (IS)
40
(no 1) 46, XX [11]
/
14.3
≈ 10
0
(no 2) mos 47,XX, + 13 [12] / 46,XX [4] 44.5
/
/ /
/ 235 213 14 8
80 / 80 / / 0
Karyotype
% trisomic cells FISH Examinated metaphases Examinated nuclei 2 signals 3 signals aberrant signals % trisomic cells
/
mos 47,XX, + 13 [7] / 46,XX [54] (T)
/ /
/
/ 203 180 2 21 <1
IS: in situ culture; T: trypsinized culture.
Figure 1 Chloé at 9 months (A), 3 years (B) and 6 years (C) of age. The legal representatives of the child appearing on pictures have given the authorization of publication. Chloé à l’âge de neuf mois (A), trois ans (B) et six ans (C). Les représentants légaux de l’enfant ont donné l’autorisation de publication.
Prenatal low grade trisomy 13 and placental mosaicism • a mosaic trisomy 13 was found on the chromosomal investigations of the placenta; • the fetal blood displayed no trisomic lymphocytes and; • the FISH analysis on buccal smear cells was considered as normal, leading to the diagnosis of confined placental mosaicism. Some other cases with low grade of mosaic trisomy 13 in amniotic fluid and normal outcome after birth have been published, but with no proven placental mosaicism [3,4]. Furthermore, many anatomic examination after medical terminations of pregnancy for trisomy 13 mosaicism concluded to be normal abortus ([5], for review see [6]). The confined placental mosaicism is most of the time evoked when the cytogenetic analysis is performed on chorionic villus sampling and not on amniotic cells. However, placental cells may be present in amniotic fluid at a low level and may reflect the placental abnormality leading to a mosaicism, even if one of the main sources of the cells in amniotic fluid is the desquamation of the fetal skin. There is unfortunately no way to determine the origin of the cytogenetically examined cells. In our case, we hypothesized during pregnancy that the trisomic 13 cells originated from the placenta and this was confirmed after birth with the chromosomal analysis of two parts of the placenta. It is important to take at least two samples from the placenta, since no trisomic cells were found in one of the samples. Furthermore, buccal mucosa cells did not show significant trisomy 13, leading to the conclusion (along with fetal blood) that the baby girl was not a carrier of any mosaic trisomy 13. It is noteworthy that Di Giacomo et al. (2007) reported on a case of a phenotypically normal child with a proved trisomy 13 mosaicism [7]. Interestingly all the buccal mucosa cells were normal, whereas 16% of peripheral blood lymphocytes, 5% of skin fibroblasts and 23% of urinary cells were trisomic. The buccal cells could then be the cells that reflect most of the future phenotype. Griffith et al. (2010) suggest not to be ‘‘overly optimistic’’ during genetic counselling in the case of a child with trisomy 13 mosaicism [8]. This situation in prenatal diagnosis is much more difficult, since the parents may ask for a termination of pregnancy. Some findings predicting a good outcome are then useful, for example the low rate of trisomic cells in amniotic fluid or the absence of trisomic cells in fetal blood [4]. But even the percentage of trisomic cells is not a good predictor of the clinical outcome, since Chen et al. (2004) described a case of true trisomy 13 mosaicism with 77% of abnormal cells in the amniotic fluid and a normal outcome after birth (until eight months age) with a decrease
145 in percentage of abnormal cells probably due to a natural selection against them [9]. Nevertheless in case of continuation of the pregnancy, it is important to know whether the baby is a carrier or not of a mosaic trisomy by performing non-invasive examinations. So in our opinion, it could be useful at birth in the aim to predict a good future development for the child: • to take several samples from the placenta that may lead to the diagnosis of (confined) placental mosaicism; • to label by FISH buccal smears with a LSI 13 probe to prove that no (or very few) trisomic cells are present in an ectoblastic-derived tissue.
Acknowledgements The authors are grateful to the parents who gave photographs and accepted to collaborate to the manuscript. We would also like to thank Mrs Cornelia Wilson for checking through our manuscript.
References [1] Horn D, Rommeck M, Sommer D, Körner H. Phylloid pigmentary pattern with mosaic trisomy 13. Pediatr Dermatol 1997;14:278—80. [2] Happle R. Phylloid hypomelanosis is closely related to mosaic trisomy 13. Eur J Dermatol 2000;10:511—2. [3] Delatycki MB, Pertile MD, Gardner RJ. Trisomy 13 mosaicism at prenatal diagnosis: dilemnas in interpretation. Prenat Diagn 1998;18:45—9. [4] Wallerstein R, Yu MT, Neu RL, Benn P, Lee Bowen C, Crandall B, et al. Common trisomy mosaicism diagnosed in amniocytes involving chromosomes 13, 18, 20 and 21: karyotype-phenotype correlations. Prenat Diagn 2000;20:103—22. [5] Eubanks SR, Kuller JA, Amjadi D, Powell M. Prenatal diagnosis of mosaic trisomy 13: a case report. Prenat Diagn 1998;18:971—4. [6] Chen CP. Prenatal diagnosis and genetic counseling for mosaic trisomy 13. Taiwan J Obstet Gynecol 2010;49:13—22. [7] Di Giacomo MC, Susca FC, Resta N, Bukvic N, Vimercati A, Guanti G. Trisomy 13 mosaicism in a phenotypically normal child: description of cytogenetic and clinical findings from early pregnancy beyond 2 years of age. Am J Med Genet (Part A) 2007;143A:518—20. [8] Griffith CB, Vance GH, Weaver DD. Phenotypic variability in trisomy 13 mosaicism: two new patients and literature review. Am J Med Genet (Part A) 2009;149A:1346—58. [9] Chen M, Yeh GP, Shih JC, Wang BT. Trisomy 13 mosaicism: study of serial cytogenetic changes in a case from early pregnancy to infancy. Prenat Diagn 2004;24:137—43.
CLINICAL CASE
Are all cases of low-grade mosaic trisomy 13 in amniotic fluid with no fetal malformation in fact confined placental mosaicism? A case report Les cas de faible mosaïque de trisomie 13 dans le liquide amniotique sans malformation fœtale sont-ils tous des mosaïques confinées au placenta ? À propos d’un cas C. Etoubleau a, S. Bourthoumieu a, M. Fiorenza b, V. Aubard b, C. Yardin a,∗ a
Service d’histologie et cytogénétique, comité de recherche clinique du HME (CHREC), hôpital de la mère et de l’enfant (HME), hôpital universitaire de Limoges, 8, avenue Dominique-Larrey, 87042 Limoges cedex, France b Service de gynécologie, centre pluridisciplinaire de diagnostic prénatal (CPDPN), hôpital de la mère et de l’enfant (HME), hôpital universitaire de Limoges, 8, avenue Dominique-Larrey, 87042 Limoges cedex, France Available online 10 November 2011
KEYWORDS Mosaic trisomy 13; Placental mosaicism; Prenatal diagnosis; Genetic counseling
∗
Summary We report on a case of true prenatal mosaic trisomy 13 on amniotic fluid associated with a normal phenotype at the age of 6 years. The amniocentesis was performed because of advanced maternal age and was controlled by a second sample. Morphological and cardiac ultrasonography did not reveal any fetal malformations. No trisomic cells were found in the fetal blood and a nuclear magnetic resonance imaging (IRM) of the brain was performed during the third trimester found no abnormality of the brain. Finally, at birth cytogenetic analysis was performed on two placental samples for chromosomal analysis: one in an area where the placenta seemed normal, and the other one in an area with infarcted and hemorrhagic aspect. We found a high rate of trisomic cells in the sample with abnormal aspect. Furthermore, no trisomic cell was observed by fluorescent in situ hybridation (FISH) on the buccal smears of the baby. We concluded to a confined placental mosaicism. The good outcome of the child aged 6 years confirms this diagnosis. So in the aim to predict a good development for the child in case of low rate mosaic trisomy 13 in amniotic fluid, we propose at birth: i) to take several samples from the placenta to confirm placental mosaicism; ii) to label by FISH buccal smears with a LSI 13 probe to prove that the baby is not a carrier of the trisomy. © 2011 Elsevier Masson SAS. All rights reserved.
Corresponding author. E-mail address: [email protected] (C. Yardin).
1286-0115/$ – see front matter © 2011 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.morpho.2011.07.117
Prenatal low grade trisomy 13 and placental mosaicism
MOTS CLÉS Trisomie 13 en mosaïque ; Mosaïques confinées au placenta ; Diagnostic prénatal ; Conseil génétique
143
Résumé Nous rapportons un cas de trisomie 13 en mosaïque sur liquide amniotique associé à un phénotype normal à l’âge de six ans. L’amniocentèse a été réalisée pour âge maternel supérieur à 38 ans et a été contrôlée par un second prélèvement. Aucune malformation n’a été mise en évidence à l’échographie morphologique et cardiaque. Aucune cellule trisomique 13 n’a été retrouvée sur sang fœtal et l’IRM cérébrale fœtale n’a révélé aucune anomalie. À la naissance, une analyse cytogénétique a été effectuée sur deux prélèvements placentaires : sur un fragment d’aspect normal et sur un fragment d’aspect infarci et hémorragique. Un taux important de cellules trisomiques a été retrouvé sur le fragment anormal. De plus, aucune cellule trisomique n’a été mise en évidence par hybridation fluorescente in situ (FISH) sur le frottis jugal du nouveau-né. Nous avons conclu à une mosaïque confinée au placenta. L’évolution tout à fait normale de l’enfant à six ans confirme ce diagnostic. En conclusion nous proposons en cas de faible mosaïque de trisomie 13 sur liquide amniotique de pratiquer à la naissance : i) un prélèvement de plusieurs fragments placentaires afin d’authentifier la mosaïque, ii) un frottis jugal avec FISH afin de vérifier l’absence de cellules trisomiques sur l’enfant. © 2011 Elsevier Masson SAS. Tous droits réservés.
Introduction It is not so rare to diagnose a prenatal trisomy mosaicism in amniotic fluid. Two situations are clearly very different in genetic counseling: • when fetal malformations are present, it is relatively easy to explain to the parents the correlation between the karyotyping and the ultrasound (US) findings. In that case, the parents are somewhat aware of the possibility of chromosomal aberration and may be relieved to receive an explanation for the reason of fetal malformations; • the genetic counseling is much more difficult when a prenatal ‘‘unexpected’’ trisomy is found after chromosomal analysis performed for example because of advanced maternal age or maternal anxiety, and when US examination is normal. In this situation, it is difficult to predict the fetal outcome, since even if the morphology and the structures are completely normal, functional abnormalities such as mental and development delay may occur. All of this leads to most of the time an enhanced parental anxiety. Furthermore, the parents might have asked questions to the mother’s gynecologist or to their general physician and these responses may have enhanced their worries.
Clinical report We describe a case where trisomy 13 mosaicism was detected prenatally by amniocentesis because of advanced maternal age (39 years) in 2005. Three out of 21 clones scored (14%) showed trisomy 13 in a female fetus. The three trisomic clones provided from two different cultures and a trisomy resulting from an abnormality occurring during the culture was then excluded. The couple was referred to the hospital by their gynecologist for a request of termination of pregnancy. Morphological and cardiac ultrasonography was performed and did not reveal any fetal malformation. A second amniocentesis was recommended with interphasic fluorescent in situ hybridization (FISH) analysis (LSI 13 probe, Vysis Inc, Abbott® Diagnostic, Rungis, France). A total of 235 nuclei were observed: 213 (90.6%) showed two signals for
chromosome 13, 14 (6%) revealed three signals and eight (3.4%) were considered as aberrant signals (> 3 or < 2). The in situ cultured clones (total of 14) displayed normal karyotyping (46, XX), whereas on a total of 61 mitoses from the trypsinized culture, seven (11.5%) were trisomic for the chromosome 13. So the mosaicism was considered as low, around 10%. Even so the parents remained quite worried and we proposed further investigations. Cord blood sample was analyzed: 40 metaphases (100%) showed normal karyotyping and two signals for chromosome 13 were observed on 80 additional mitosis using FISH. None of the fetal lymphocytes were found to be trisomic. The parents, along with the pluridisciplinary center of prenatal diagnosis, decided to continue the pregnancy with a monthly ultrasonography and a nuclear magnetic resonance imaging (IRM) of the brain during the third trimester. The later was normal and pregnancy went to full term. Finally, a female baby named Chloé was born at 38 weeks of gestation with a birth weight of 3180 g and a birth length of 50 cm. The physical examination of the baby was normal. The parents agreed for a placental chromosomal analysis and two samples were taken: one in an area where the placenta seemed normal, and the other one in an area with infarcted and hemorrhagic aspect. All the 11 examined cells providing from the normal area were 46, XX, whereas 12 out of 16 mitoses from the abnormal area showed a trisomy 13 (47, XX, + 13). Cells from the buccal smear were analyzed by FISH with 13 and 21 labelling (LSI 13 and LSI 21 probes, Vysis Inc, Abbott® Diagnostic, Rungis, France). Only two cells out of 203 were found to have three 13 signals, that is less than 1%, and FISH was then interpreted as normal. Table 1 summarizes all the cytogenetic studies performed prenatally and postnatally on the different tissues. Chloé is now six years old and presents nor developmental problem (see Fig. 1 displaying photographs of Chloé given by her parents), neither pigmentary disturbance such as phylloid hypomelanosis known to be associated with mosaic trisomy 13 [1,2].
Discussion In our case, the normal outcome was expected since:
144
C. Etoubleau et al.
Table 1 Cytogenetic results in the patient before and after birth. Résultats cytogénétiques du patient avant et après la naissance. Amniocytes (1st sample)
Amniocytes (2nd sample)
Fetal blood
Placenta
Buccal smear
mos 47,XX, + 13 [3] / 46,XX [18] (IS) /
46,XX [14] (IS)
40
(no 1) 46, XX [11]
/
14.3
≈ 10
0
(no 2) mos 47,XX, + 13 [12] / 46,XX [4] 44.5
/
/ /
/ 235 213 14 8
80 / 80 / / 0
Karyotype
% trisomic cells FISH Examinated metaphases Examinated nuclei 2 signals 3 signals aberrant signals % trisomic cells
/
mos 47,XX, + 13 [7] / 46,XX [54] (T)
/ /
/
/ 203 180 2 21 <1
IS: in situ culture; T: trypsinized culture.
Figure 1 Chloé at 9 months (A), 3 years (B) and 6 years (C) of age. The legal representatives of the child appearing on pictures have given the authorization of publication. Chloé à l’âge de neuf mois (A), trois ans (B) et six ans (C). Les représentants légaux de l’enfant ont donné l’autorisation de publication.
Prenatal low grade trisomy 13 and placental mosaicism • a mosaic trisomy 13 was found on the chromosomal investigations of the placenta; • the fetal blood displayed no trisomic lymphocytes and; • the FISH analysis on buccal smear cells was considered as normal, leading to the diagnosis of confined placental mosaicism. Some other cases with low grade of mosaic trisomy 13 in amniotic fluid and normal outcome after birth have been published, but with no proven placental mosaicism [3,4]. Furthermore, many anatomic examination after medical terminations of pregnancy for trisomy 13 mosaicism concluded to be normal abortus ([5], for review see [6]). The confined placental mosaicism is most of the time evoked when the cytogenetic analysis is performed on chorionic villus sampling and not on amniotic cells. However, placental cells may be present in amniotic fluid at a low level and may reflect the placental abnormality leading to a mosaicism, even if one of the main sources of the cells in amniotic fluid is the desquamation of the fetal skin. There is unfortunately no way to determine the origin of the cytogenetically examined cells. In our case, we hypothesized during pregnancy that the trisomic 13 cells originated from the placenta and this was confirmed after birth with the chromosomal analysis of two parts of the placenta. It is important to take at least two samples from the placenta, since no trisomic cells were found in one of the samples. Furthermore, buccal mucosa cells did not show significant trisomy 13, leading to the conclusion (along with fetal blood) that the baby girl was not a carrier of any mosaic trisomy 13. It is noteworthy that Di Giacomo et al. (2007) reported on a case of a phenotypically normal child with a proved trisomy 13 mosaicism [7]. Interestingly all the buccal mucosa cells were normal, whereas 16% of peripheral blood lymphocytes, 5% of skin fibroblasts and 23% of urinary cells were trisomic. The buccal cells could then be the cells that reflect most of the future phenotype. Griffith et al. (2010) suggest not to be ‘‘overly optimistic’’ during genetic counselling in the case of a child with trisomy 13 mosaicism [8]. This situation in prenatal diagnosis is much more difficult, since the parents may ask for a termination of pregnancy. Some findings predicting a good outcome are then useful, for example the low rate of trisomic cells in amniotic fluid or the absence of trisomic cells in fetal blood [4]. But even the percentage of trisomic cells is not a good predictor of the clinical outcome, since Chen et al. (2004) described a case of true trisomy 13 mosaicism with 77% of abnormal cells in the amniotic fluid and a normal outcome after birth (until eight months age) with a decrease
145 in percentage of abnormal cells probably due to a natural selection against them [9]. Nevertheless in case of continuation of the pregnancy, it is important to know whether the baby is a carrier or not of a mosaic trisomy by performing non-invasive examinations. So in our opinion, it could be useful at birth in the aim to predict a good future development for the child: • to take several samples from the placenta that may lead to the diagnosis of (confined) placental mosaicism; • to label by FISH buccal smears with a LSI 13 probe to prove that no (or very few) trisomic cells are present in an ectoblastic-derived tissue.
Acknowledgements The authors are grateful to the parents who gave photographs and accepted to collaborate to the manuscript. We would also like to thank Mrs Cornelia Wilson for checking through our manuscript.
References [1] Horn D, Rommeck M, Sommer D, Körner H. Phylloid pigmentary pattern with mosaic trisomy 13. Pediatr Dermatol 1997;14:278—80. [2] Happle R. Phylloid hypomelanosis is closely related to mosaic trisomy 13. Eur J Dermatol 2000;10:511—2. [3] Delatycki MB, Pertile MD, Gardner RJ. Trisomy 13 mosaicism at prenatal diagnosis: dilemnas in interpretation. Prenat Diagn 1998;18:45—9. [4] Wallerstein R, Yu MT, Neu RL, Benn P, Lee Bowen C, Crandall B, et al. Common trisomy mosaicism diagnosed in amniocytes involving chromosomes 13, 18, 20 and 21: karyotype-phenotype correlations. Prenat Diagn 2000;20:103—22. [5] Eubanks SR, Kuller JA, Amjadi D, Powell M. Prenatal diagnosis of mosaic trisomy 13: a case report. Prenat Diagn 1998;18:971—4. [6] Chen CP. Prenatal diagnosis and genetic counseling for mosaic trisomy 13. Taiwan J Obstet Gynecol 2010;49:13—22. [7] Di Giacomo MC, Susca FC, Resta N, Bukvic N, Vimercati A, Guanti G. Trisomy 13 mosaicism in a phenotypically normal child: description of cytogenetic and clinical findings from early pregnancy beyond 2 years of age. Am J Med Genet (Part A) 2007;143A:518—20. [8] Griffith CB, Vance GH, Weaver DD. Phenotypic variability in trisomy 13 mosaicism: two new patients and literature review. Am J Med Genet (Part A) 2009;149A:1346—58. [9] Chen M, Yeh GP, Shih JC, Wang BT. Trisomy 13 mosaicism: study of serial cytogenetic changes in a case from early pregnancy to infancy. Prenat Diagn 2004;24:137—43.