Prenatal diagnosis and fetal pathology of partial trisomy 20P-monosomy 4P resulting from paternal translocation

Amniocentesis was performed in view of a paternal balanced chromosomal rearrangement t(4;20)(p16;p12), inv(18)(p11q11). The pregnancy was complicated by severe oligohydramnios. The fetal karyotype was unbalanced: 46XX, der(4), t(4;20)(p16;p12), inv(18) (p11q11)pat., thus resulting in partial trisomy 20p and monosomy 4p. In addition, the amniotic fluid alpha-fetoprotein (AFP) became increasingly elevated with gestational age. The pregnancy was terminated at 25 weeks. The fetus presented with typical facial dysmorphic features, unilateral cleft lip and palate, severe renal hypoplasia, consistent with the 4p-(Wolf-Hirschhorn) syndrome.     

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.     

Neuroblastoma in a dysmorphic girl with a partial duplication of 2p caused by an unbalanced translocation

A 1-year-old female child with multiple dysmorphic features including microcephaly, hypertelorism, a short philtrum, low set ears, a narrow high arched palate, micrognathia and growth retardation was found to have a de novo chromosome abnormality including a partial duplication of the short arm of chromosome 2 and a partial deletion of the long arm of chromosome 17. The clinical features of the case shared many similarities to previous reports of trisomy 2p. Three years later, ecchymotic spots appeared around the left ocular region. Further clinical and pathological examination confirmed the diagnosis of a neuroblastoma. This is the first case of an unbalanced translocation, 46, XX, der (17), t (2; 17) (p23; q25), showing the development of a neuroblastoma in addition to the dysmorphic features. We suggest that trisomy 2p including the N-myc proto-oncogene may have predisposed the patient to the development of a neuroblastoma.     

Prenatal diagnosis of partial trisomy 12q: clinical presentations and outcome

We present a pregnant woman with a fetus prenatally diagnosed as 46, XY,der(4) t(4;12) (q35.1; q21.2). This defect resulted from the unbalanced segregation of a paternal balanced translocation, t(4;12) (q35.1; q21.2). Prenatal ultrasound revealed borderline ventriculomegaly, a thick nuchal fold, pericardial effusion, arthrogryposis, a single umbilical artery, and micropenis. Fluorescence in situ hybridization (FISH) with whole chromosome painting probe and microarray-based comparative genomic hybridization analysis further confirmed chromosomal gain of terminal 12q. The woman had her pregnancy terminated at 20 weeks of gestational age. When compared with previously reported cases, the proband had characteristics common to the phenotypes of partial trisomy 12q, including an abnormal facial appearance and multiple anomalies. Additionally, this case had previously unreported phenotypes, such as arthrogryposis, a single umbilical artery, and a micropenis. Regarding the outcome of partial trisomy 12q, the fetuses carrying trisomies distal to 12q24 have a good chance of extended postnatal survival. In contrast, the cases with trisomies involving a larger amount of 12q likely die prenatally or within a few days after birth.     

Prenatal diagnosis of a fetus affected with Down syndrome and deletion 1p36 syndrome by fluorescence in situ hybridization and spectral karyotyping

OBJECTIVE: A fetus having partial trisomy of the distal part of chromosome 21q due to a de novo translocation is reported here. METHOD: A 29-year-old woman received amniocentesis at 18 weeks of gestation because of abnormal ultrasound findings including bilateral choroid plexus cysts, atrioventricular septal defects, rocker-bottom feet, and possible hydrocephalus. RESULTS: Cytogenetic analysis revealed 46,XY, add(1)(p36.3), in which an additional material of unknown origin was attached to one of the terminal short arms of chromosome 1. Parental blood studies showed normal karyotypes in both parents. Spectral karyotyping was then performed and the origin of the additional material locating at chromosome 1p was found to be from chromosome 21. Conventional fluorescence in situ hybridization analysis was also used and confirmed the spectral karyotyping findings by use of a chromosome 21 specific painting probe, a locus specific probe localized within bands 21q22.13-q22.2 and a 21q subtelomeric probe. A hidden Down syndrome caused by a de novo translocation in this fetus was therefore diagnosed and the karyotype was designated as 46,XY, der(1)t(1;21)(p36.3;q22.1).ish der(1)(WCP21+, LSI 21+, 1pTEL-, 21q TEL+) de novo. Clinical features of the 1p36 deletion syndrome are also reviewed and may contribute to some features of this fetus. Termination of pregnancy was performed at 20 weeks of gestation. CONCLUSION: To our knowledge, our case appears to be the first to have partial monosomy 1p and partial trisomy 21q caused by de novo translocation being diagnosed prenatally.     

Prenatal diagnosis of a fetus with a cryptic translocation 4p;18p and Wolf-Hirschhorn syndrome (WHS)

Wolf-Hirschhorn Syndrome (WHS) is caused by distal deletion of the short arm of chromosome 4 and is characterized by growth deficiency, mental retardation, a distinctive, 'greek-helmet' facial appearance, microcephaly, ear lobe anomalies, and sacral dimples. We report a family with a balanced chromosomal translocation 4;18(p15.32;p11.21) in the father and an unbalanced translocation resulting in partial monosomy 4 and partial trisomy 18 in one living boy and a prenatally diagnosed male fetus. Both showed abnormalities consistent with WHS and had in addition aplasia of one umbilical artery. Karyotyping of another stillborn fetus revealed a supernumerary derivative chromosome der(18)t(4;18)(p15.32;p11.21) of paternal origin and two normal chromosomes 4. The umbilical cord had three normal vessels. A third stillborn fetus with the same balanced translocation as the father had a single umbilical artery and hygroma colli.     

Distal partial trisomy 1q: report of two cases and a review of the literature

We report on two cases with partial trisomy 1q syndrome. One case was a mid-trimester fetus with multiple malformations that was prenatally diagnosed with a de novo distal partial trisomy 1q. Prenatal ultrasound at 24th gestational week demonstrated the presence of cleft lip and palate, increased biparietal diameter and decreased abdominal circumference. Cytogenetic analysis (GTG banding) and subsequent fluorescence in situ hybridization (FISH) using whole chromosome paint 1 and multicolor banding (MCB) demonstrated an aberrant karyotype 46,XY,dup(1)(q31q43 approximately 44). The second case was a newborn male infant with multiple congenital malformations. He had a derivative chromosome 18 as a result of a maternal insertion involving chromosomes 1 and 18. Further analyses including MCB showed his karyotype as 46,XY,ins(18;1)(q22;q23q31.1 approximately 32). The present cases and a review of the literature suggest that partial trisomy of the long arm of chromosome 1 is a distinct clinical entity.     

Chromosomal abnormalities associated with neural tube defects (II): partial aneuploidy

Fetuses with neural tube defects (NTDs) carry a risk of chromosomal abnormalities. The risk varies with maternal age, gestational age at diagnosis, association with other structural abnormalities, and family history of chromosome aberrations. This article provides a comprehensive review of structural chromosomal abnormalities associated with NTDs, such as del(13q), r(13), dup(2p), del(2q), del(1p), del(1q), dup(1q), del(3p), dup(3p), del(3q), dup(3q), del(4p), dup(4p), del(4q), dup(4q), del(5p), del(6p), dup(6q), del(6q), dup(7p), del(7q), dup(8q), del(9p), del(10q), del(11q), dup(11q), dup(12p), dup(14q), del(14q), del(15q), dup(16q), del(18q), r(18), dup(20p), +i(20p), del(22q), del(Xp), and dup(Xq). NTDs may be associated with aneuploidy. Perinatal identification of NTDs should alert one to the possibility of chromosomal abnormalities and prompt a thorough cytogenetic investigation and genetic counseling.     

A patient with de-novo partial deletion of Xp (p11.4-pter) and partial duplication of 22q (q11.2-qter)

We report on a girl with partial deletion of Xp and partial duplication of 22q. Family studies demonstrate that both the patient's mother and her nonidentical twin sister carry the corresponding balanced translocation; 46,X,t(X;22)(p11.4;q11.2). This girl has developmental delay, microcephaly, mild dysmorphisms and hearing loss but otherwise shows few of the features described in individuals with duplications of the long arm of chromosome 22. She does manifest characteristics, such as short stature and biochemical evidence of ovarian failure, which are seen in partial or complete Xp deletions and Turner's syndrome.     

单纯性染色体18p部分三体综合征患儿的产前遗传学诊断和文献回顾

目的探讨单纯性染色体18P部分三体综合征患者的产前诊断特点。方法联合运用传统染色体核型分析和染色体微阵列(chromosome microarray analysis,CMA)基因芯片技术对家系成员行染色体核型分析和基因组拷贝数变异检测。结果胎儿羊水染色体核型结果为46,XY,der(18),父母双方染色体核型均未见异常;胎儿基因芯片检测结果为arr[hg19]18p11.31p11.21(3,521,718-15,099,116)×3,即胎儿基因组18号染色体短臂p11.31p11.21区域存在11.58 Mb的片段重复,父母双方基因芯片结果均为阴性,提示该胎儿的18号染色体结构重排为新发生的。结论在一个有不良生育史家系的胎儿中检出一个罕见新发的单纯性染色体18p部分三体变异,这是世界少见的单纯性染色体18p部分三体综合征的产前病例报道。联合运用传统染色体核型分析和C M A基因芯片技术在预防不良产史家系中胎儿出生缺陷的产前诊断中具有重要的临床应用价值。     

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 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.     

Prenatal diagnosis and molecular cytogenetic characterization of partial dup(18q)/del(18p) due to a paternal pericentric inversion 18 in a fetus with multiple anomalies

ObjectiveWe present prenatal diagnosis of rec(18)dup(18q)inv(18)(p11.2q21.2)pat owing to paternal pericentric inversion in a fetus.Case reportA 37-year-old woman was diagnosed with multiple anomalies on a prenatal ultrasound scan at 17 weeks and 5 days of gestation. She underwent amniocentesis at 20 weeks and 2 days. Conventional karyotyping of amniocyte showed 46, XX, der(18). She was thus referred for genetic counseling; cytogenetic analysis revealed a 46, XY karyotype, inv(18)(p11.2q21.2), of the father. Therefore, based on the results of the father, the fetal karyotype was defined as 46, XX, rec(18)dup(18q)inv(18)(p11.2q21.2)pat. Array comparative genomic hybridization of amniocytes to obtain specific information showed a 3-Mb deletion of 18p11.31p11.32 (136227_3100353)x1 and a 23.7-Mb duplication of 18q21.31-q23 (54222717_77957375) × 3.ConclusionMaternal serum screening produces normal results for 18p-/18q+ syndrome, but it can be diagnosed by fluorescent in situ hybridization, quantitative-fluorescent polymerase chain reaction, or array comparative genomic hybridization test by observing abnormal findings on ultrasound.     

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.     

Prenatal diagnosis of microdeletion 16p13.11 combination with partial monosomy of 2q37.1-qter and partial trisomy of 7p15.3-pter in a fetus with bilateral ventriculomegaly, agenesis of corpus callosum, and polydactyly

ObjectiveTo present a prenatal diagnosis of microdeletion 16p13.11 with partial monosomy of 2q37.1-qter and partial trisomy of 7p15.3-pter in a fetus with bilateral ventriculomegaly, agenesis of corpus callosum, and polydactyly.Case ReportA 41-year-old well-being Taiwanese, nulligravida woman received amniocentesis at a gestational age of 18 weeks for advanced maternal age. The fetus' karyotype showed 46,XY,der(2)t(2;7)(q36.2;p15.1). Both parents also received cytogenetic examinations and the mother's karyotype revealed 46,XX,t(2;7)(2q36.2;p15.1). High-resolution ultrasound showed the fetus had bilateral ventriculomegaly, agenesis of corpus callosum, and polydactyly of the right hand. After the termination of this pregnancy, the whole genome oligonucleotide-base array comparative genomic hybridization (CGH) by using fetal skin cells demonstrated a 8.44-Mb deletion at 2q37.1 (234602276-243041305), a 22.8-Mb duplication (65558-22869338) at 7p15.3, and an additional 1.32-Mb deletion (14968855-16292235) at 16p13.11.ConclusionArray CGH is a useful tool not only to discover the genomic imbalance at the breakpoints as well as to detect unexpectedly complex rearrangements in other chromosomes. Our case also provided evidence that genomic aberration at chromosome 16p13.11 involves in the formation of polydactyly.     

Bilateral renal agenesis and fetal ascites in association with partial trisomy 13 and partial trisomy 16 due to a 3:1 segregation of maternal reciprocal translocation t(13;16)(q12.3; p13.2).

A female fetus with bilateral renal agenesis and fetal ascites was found to have partial trisomy 13 (pter-q12.3) and partial trisomy 16 (p13.2-pter), 47,XX,+der(13)t(13;16)(q12.3; p13.2)mat. The chromosomal aberration was due to a 3:1 segregation with tertiary trisomy transmitted from a maternal reciprocal translocation 13;16. Prenatal ultrasound of a 29-year-old, gravida 2, para 0 woman at 22 gestational weeks showed fetal ascites, severe oligohydramnios and non-visualization of fetal urinary bladder and kidneys. The pregnancy was terminated. At delivery, the proband displayed dysmorphic features of hypertelorism, a prominent glabella, epicanthic fold, a stubby nose with a depressed nasal bridge, anteverted nares, thin lips, micrognathia, low-set ears, a short neck and a distended abdomen. Necropsy confirmed bilateral renal agenesis and ascites. A cytogenetic study performed on fibroblasts obtained from the proband's skin revealed an extra supernumerary chromosome. The mother was later found to have a reciprocal translocation. Fluorescence in situ hybridization for a submicroscopic deletion in chromosome 22q11 in the proband was negative. The parents had no urological anomalies. Our observation further extends the clinical spectrum associated with proximal trisomy 13q and distal trisomy 16p. We suggest prenatal cytogenetic analysis in fetuses with urological anomalies, including renal agenesis, to uncover underlying genetic disorders.     

Prenatal diagnosis of partial trisomy 3p (3p21-->pter) and partial monosomy 11q (11q23-->qter) associated with abnormal sonographic findings of holoprosencephaly, orofacial clefts, pyelectasis and a unilateral duplex renal system

Patients with partial trisomy 3p seldom present major dysmorphic features, and holoprosencephaly occurs in only 10% of the cases with partial trisomy 3p. It has been suggested that multiple genetic hits or environmental exposures are required for the clinical expression of holoprosencephaly. At 16 weeks of gestation, prenatal sonography identified a fetus with holoprosencephaly, orofacial clefts, pyelectasis, and a unilateral duplex renal system. Amniocentesis revealed the karyotype of 46,XX,der(11)t(3;11)(p21;q23)pat with partial trisomy 3p (3p21-->pter) and partial monosomy 11q (11q23-->qter). The pregnancy was subsequently terminated. Postnatally, the proband showed hypotelorism, a depressed nasal bridge, orofacial clefts and holoprosencephaly-premaxillary agenesis. The present case provides evidence that partial trisomy 3p/monosomy 11q can be a genetic cause of holoprosencephaly and del(11)(q23-->qter) is associated with a duplex renal system.     

Prenatal diagnosis of partial trisomy 4q26-qter and monosomy for the Wolf-Hirschhorn critical region in a fetus with split hand malformation

We describe the results of prenatal analyses and postnatal findings in a male fetus with a partial trisomy for the long arm and a small terminal monosomy for the short arm of chromosome 4 with the following karyotype: 46,XY,add(4)(p16.3).ish dup(4)(q26qter)(wcp4+, D4S2336x3,AFMb280xa5x2,4ptel-,WHCR-). G-banding did not identify the origin of the additional chromosomal segment, but this was achieved prenatally by application of RxFISH and whole chromosome painting probes. Subsequent FISH analysis with region-specific YAC clones was used to relate the phenotypic findings such as bilateral split hand formation, specific cardiac and kidney anomalies, microtia, and hypoplastic thorax more exactly to the partial trisomy of the segment 4q26-qter.     

Prenatal diagnosis of a fetus with pure partial trisomy 1q32-44 due to a familial balanced rearrangement

We diagnosed a pure partial trisomy of the long arm of chromosome 1 in a fetus with multiple malformations detected prenatally. The father was a carrier of a balanced rearrangement involving 46,XY,inv(1)(qter-->p36::q32-->qter::p36-->q32). The fetus had preaxial polydactyly, low-set ears, macrocephaly, a prominent forehead, a broad and flat nasal bridge, a small mouth, an arched palate, micrognathia and unilateral renal agenesis. The couple had previously an infant with the same phenotypic abnormalities. The aberration was initially detected on amniocentesis with GTG banding and was confirmed by fluorescence in situ hybridization (FISH). Our case and other published pure trisomy 1q32-44 cases showed similarities, which allowed the further delineation of the trisomy 1q syndrome.     

Prenatal morphology of partial monosomy 18q

Prenatal diagnosis, performed in a woman with reciprocal translocation (9:18), disclosed partial monosomy 18q in a fetus. Morphologic studies of this fetus revealed dysplastic face and ears, a high palate, hypomotility of joints, an accessory spleen and anomalous dermatoglyphics. Biochemical examination detected a decrease of most amino acids, which is typical for many chromosomal syndromes.