Sacrococcygeal teratoma in a fetus with prenatally diagnosed partial trisomy 10q (10q24.3-->qter) and partial monosomy 17p (p13.3-->pter)

OBJECTIVE: Clinical features of the distal 10q trisomy syndrome consist of mental retardation, facial dysmorphism and renal and cardiac anomalies. The presence of a sacrococcygeal teratoma (SCT) in a fetus with distal 10q trisomy has not been reported yet. METHODS: A 33-year-old, G5, P2 woman with a singleton pregnancy was referred to our clinic at 24 weeks of gestation for further evaluation of a fetal sacral exophytic mass. Detailed fetal sonographic examination together with chromosomal analysis by amniocentesis was performed. RESULTS: The scan revealed a large SCT together with a persistent right umbilical vein, cardiomegaly, bilateral mild hydronephrosis and intrauterine growth retardation. The fetal karyotype showed distal 10q trisomy (10q24.3-->qter) distal monosomy 17 (p13-->pter). The fetus died after a preterm delivery at 28 weeks of gestation. Postnatal examination confirmed the prenatal findings and added the typical facial features of this syndrome, which consisted of prominent forehead, small nose with depressed nasal bridge, micrognathia and bow-shaped mouth. CONCLUSION: This case provides further evidence of a possible association between chromosomal aberrations in SCTs.     

Prenatal diagnosis of partial monosomy 18p(18p11.2-->pter) and trisomy 21q(21q22.3-->qter) with alobar holoprosencephaly and premaxillary agenesis

A prenatal diagnosis of partial monosomy 18p(18p11.2-->pter) and trisomy 21q(21q22.3-->qter) in a fetus with alobar holoprosencephaly (HPE) and premaxillary agenesis (PMA) but without the classical Down syndrome phenotype is reported. A 27-year-old primigravida woman was referred for genetic counselling at 21 weeks' gestation due to sonographic findings of craniofacial abnormalities. Level II ultrasonograms manifested alobar HPE and median orofacial cleft. Cytogenetic analysis and fluorescence in situ hybridization (FISH) on cells obtained from amniocentesis revealed partial monosomy 18p and a cryptic duplication of 21q,46,XY,der(18)t(18;21)(p11.2;q22.3), resulting from a maternal t(18;21) reciprocal translocation. The breakpoints were ascertained by molecular genetic analysis. The pregnancy was terminated. Autopsy showed alobar HPE with PMA, pituitary dysplasia, clinodactyly and classical 18p deletion phenotype but without the presence of major typical phenotypic features of Down syndrome. The phenotype of this antenatally diagnosed case is compared with those observed in six previously reported cases with monosomy 18p due to 18;21 translocation. The present study is the first report of concomitant deletion of HPE critical region of chromosome 18p11.3 and cryptic duplication of a small segment of distal chromosome 21q22.3 outside Down syndrome critical region. The present study shows that cytogenetic analyses are important in detecting chromosomal aberrations in pregnancies with prenatally detected craniofacial abnormalities, and adjunctive molecular investigations are useful in elucidating the genetic pathogenesis of dysmorphism.     

De novo monosomy 9p24.3-pter and trisomy 17q24.3-qter characterised by microarray comparative genomic hybridisation in a fetus with an increased nuchal translucency

OBJECTIVES: Increased nuchal translucency (NT) during the first trimester of pregnancy is a useful marker to detect chromosomal abnormalities. Here, we report a prenatal case with molecular cytogenetic characterisation of an abnormal derivative chromosome 9 identified through NT. METHODS: Amniocentesis was performed because of an increased NT (4.4 mm) and showed an abnormal de novo 46,XX,add(9)(p24.3) karyotype. To characterise the origin of the small additional material on 9p, we performed a microarray comparative genomic hybridisation (microarray CGH) using a genomic DNA array providing an average of 1 Mb resolution. RESULTS: Microarray CGH showed a deletion of distal 9p and a trisomy of distal 17q. These results were confirmed by FISH analyses. Microarray CGH provided accurate information on the breakpoint regions and the size of both distal 9p deletion and distal 17q trisomy. The fetus was therefore a carrier of a de novo derivative chromosome 9 arising from a t(9;17)(p24.3;q24.3) translocation and generating a monosomy 9p24.3-pter and a trisomy 17q24.3-qter. CONCLUSION: This case illustrates that microarray CGH is a rapid, powerful and sensitive technology to identify small de novo unbalanced chromosomal abnormalities and can be applied in prenatal diagnosis.     

Prenatal findings and molecular cytogenetic analyses of partial trisomy 12q (12q24.32-->qter) and partial monosomy 21q (21q22.2-->qter)

OBJECTIVES: To present the prenatal findings and molecular cytogenetic analyses of partial trisomy 12q and partial monosomy 21q, and a review of the literature. METHODS: Amniocentesis was performed at 23 gestational weeks in a 33-year-old woman because of abnormal sonographic findings. Amniocentesis revealed a derivative chromosome 21, or der(21), with a deletion on the region of 21q22.2 and an addendum of a small chromosomal segment of unknown origin. The maternal karyotype was subsequently found to be 46,XX,t(12;21)(q24.32;q22.2). Level II ultrasound showed microcephaly, micrognathia, a ventricular septal defect, and rocker-bottom feet. The pregnancy was terminated. A malformed infant was delivered without the phenotype of holoprosencephaly (HPE). Fluorescence in situ hybridization (FISH) and polymorphic DNA markers were used to investigate the involved chromosomal segments. RESULTS: FISH study showed the absence of the signal of 21q subtelomeric probe and the presence of the signal of 12q subtelomeric probe in the der(21).The fetal karyotype was 46,XY,der(21) t(12;21)(q24.32;q22.2)mat. Genetic marker analysis showed a deletion at 21q22.2 and a breakpoint between D21S156 (present) and D21S1245 (absent). The deleted segment was measured about 4.5 Mb encompassing the HPE critical region. CONCLUSIONS: Molecular genetic analyses help in determining the prenatally detected unbalanced cryptic translocation as well as parental balanced subtle translocation. A duplication of 12q24.32-->qter and a deletion of 21q22.2-->qter may be associated with prenatal sonographic findings of microcephaly, borderline ventriculomegaly and cerebellar hypoplasia, micrognathia, a ventricular septal defect, and rocker-bottom feet. Haploinsufficiency of the HPE critical region at 21q22.3 may not cause an HPE phenotype.     

Perinatal findings and molecular cytogenetic analysis of de novo partial trisomy 16q (16q22.1-->qter) and partial monosomy 20q (20q13.3-->qter)

OBJECTIVES: To present the perinatal findings and molecular cytogenetic analysis of de novo partial trisomy 16q and partial monosomy 20q and a review of the literature. CASE AND METHODS: Obstetric ultrasound at 33 weeks' gestation revealed intrauterine growth restriction (IUGR) and dolichocephaly in a 27-year-old primigravid woman. Prenatal cytogenetic diagnosis was not offered because of the late stage of gestation. A 2800-g male baby was delivered at 41 weeks' gestation by cesarean section because of fetal distress. The infant postnatally presented characteristic craniofacial dysmorphism, hypotonia, cleft palate, congenital heart defects, a subependymal cyst, and hypospadia. Cytogenetic analysis revealed an additional material attached to the terminal region of chromosome 20q. The parental karyotypes were normal. Spectral karyotyping (SKY), fluorescence in situ hybridization (FISH), and polymorphic DNA markers were used to investigate the origin of the de novo aberrant chromosome. RESULTS: SKY using 24-color probes, FISH using specific 16p, 16q, 20 centromeric, and 20q telomeric probes, and polymorphic DNA marker analysis confirmed maternal origin of the duplication of distal 16q and the deletion of terminal 20q. Karyotype of the proband was designated as 46,XY.ish der(20)t(16;20)(q22.1;q13.3)(SKY+,16qTEL+,20qTEL-). CONCLUSIONS: Partial trisomy 16q (16q22.1-->qter) and partial monosomy 20q (20q13.3-->qter) may be associated with the perinatal findings of IUGR, dolichocephaly, hypotonia, cleft palate, congenital heart defects, a subependymal cyst, and hypospadia. SKY, FISH, and genetic marker studies help in delineating the parental origin and the regions of the deletion and duplication in the de novo unbalanced translocation.     

Prenatal diagnosis of monosomy 4p14-->pter and trisomy 11q25-->qter: clinical presentations and outcomes

We present the case of a pregnant woman with low free beta-HCG in maternal serum Down syndrome screening that led to prenatal diagnosis of a fetus with 46,XY,der(4)t(4;11)(p14; q25). This chromosomal aneuploidy resulted from unbalanced segregation of a paternal balanced translocation, t(4;11)(p14;q25). Prenatal ultrasound revealed intrauterine growth restriction, cleft lip and palate, a thick nuchal fold, a single umbilical artery, and pyelectasis. Array-based comparative genomic hybridization and short tandem repeat markers further located the exact breakpoint of translocation. The woman had her pregnancy terminated at 23 weeks of gestational age. The proband had general appearance of Wolf-Hirschhorn syndrome and some unique findings, including single umbilical artery, severe immunoglobulin deficiency, scalp defect, and underlying bony defect. Our case underscores the importance of fetal karyotyping when low maternal serum free beta-HCG is found. It also adds information on the fetal presentations of monosomy 4p14-->pter and trisomy 11q25-->qter.     

Prenatal diagnosis and molecular cytogenetic analysis of partial monosomy 10q (10q25.3-->qter) and partial trisomy 18q (18q23-->qter) in a fetus associated with cystic hygroma and ambiguous genitalia

OBJECTIVES: To present the prenatal diagnosis and molecular cytogenetic analysis of a fetus with nuchal cystic hygroma and ambiguous genitalia. CASE AND METHODS: Amniocentesis was performed at 16 weeks' gestation because of the abnormal fetal sonographic finding of a large septated nuchal cystic hygroma. Genetic amniocentesis revealed a terminal deletion in the long arm of chromosome 10. The paternal karyotype was subsequently found to be 46,XY,t(10;18)(q25.3;q23). The maternal karyotype was normal. The pregnancy was terminated. A hydropic fetus was delivered with a septated nuchal cystic hygroma and ambiguous genitalia. Fluorescence in situ hybridization (FISH), microarray-based comparative genomic hybridization (CGH), and polymorphic DNA markers were used to investigate the involved chromosomal segments. RESULTS: FISH study showed absence of the 10q telomeric probe and presence of the 18q telomeric probe in the derivative chromosome 10. Microarray-based CGH analysis showed loss of distal 10q and gain of distal 18q. Polymorphic DNA marker analysis determined the breakpoints. The fetal karyotype was 46,XY,der(10)t(10;18)(q25.3;q23)pat. The chromosome aberration resulted in partial monosomy 10q (10q25.3-->qter) and partial trisomy 18q (18q23-->qter). CONCLUSIONS: The present case provides evidence that partial monosomy 10q (10q25.3-->qter) with partial trisomy 18q (18q23-->qter) can be a genetic cause of fetal cystic hygroma and ambiguous genitalia. Cytogenetic analysis for prenatally detected structural abnormalities may detect unexpected inherited chromosome aberrations.     

Molecular cytogenetic characterization of a de novo unbalanced translocation leading to trisomy 17q25-->qter and monosomy 18p11.3-->pter in a girl with dysmorphic features

An 18-year-old, gravida 1 underwent percutaneous umbilical blood sampling (PUBS) because of positive triple screen, oligohydramnios and markedly short fetal bones. Chromosome analysis showed an abnormal chromosome 18 with unidentified chromatin at the end of the p-arm. Parental karyotypes were normal. FISH analyses with wcp18 showed additional material of unknown origin on the derivative chromosome 18. Further FISH analysis with subtelomeric probes showed normal signals for the long arm of chromosome 18 (18q23) while no signals were observed for the short arm (18p11.32). These findings were confirmed using a YAC probe from the short arm of 18. The infant was delivered at 30 weeks of gestation. At age 3 months, she was developmentally delayed and has multiple dysmorphic features. Further molecular cytogenetic studies including M-FISH and subtelomere probes showed that the additional material on chromosome 18 consisted of the distal 17q25-->qter region. Based on these studies the karyotype has been interpreted as 46,XX,der(18)t(17;18)(q25;p11.32). To the best of our knowledge, this is the first report of partial monosomy 18p and partial trisomy 17q in a patient with no major CNS malformations. This case shows the importance of molecular cytogenetic techniques in detailed characterization of de novo chromosome rearrangements.     

Unbalanced translocation 6p/16q (partial monosomy 6p and trisomy 16q): prenatal diagnosis and cytogenetics

Unbalanced translocation 6p/16q in one fetus is a very rare event and the prenatal sonographic findings have never been published before. We will give a short overview of the literature along with a case report focussing on prenatal ultrasound features and molecular cytogenetic analysis.