Prenatal diagnosis of complete trisomy 19q

This communication presents the first case of complete trisomy 19q, prenatally detected by ultrasound investigation. Real-time high-resolution ultrasound examination was performed at 19 weeks of gestation. After termination of the pregnancy, autopsy investigation was done. GTG-banding, fluorescence in situ hybridization m-(FISH) analysis, and FISH analysis with a 19q subtelomeric specific probe were used for identification of the fetal karyotype. Sonographic examination revealed an enlarged cisterna magna, cerebellar hypoplasia and aplasia of the inferior part of the vermis, combined and bilateral kidney malformations, significant nuchal fold, absence of fetal nasal bones, and intracardial calcifications. Autopsy confirmed ultrasound findings, but also revealed situs viscerum inversus of the lungs. Fetal karyotype was defined as: 46,XY,der(21)t(19;21)(q11;p13)mat. Our ultrasound and autopsy findings will certainly contribute to better knowledge of phenotype characterization of this rare chromosomal disorder. Copyright © 2007 John Wiley & Sons, Ltd.     

Tetrasomy 12p (Pallister-Killian syndrome): Ultrasound indicators and confirmation by interphase fish

Tetrasomy 12p (Pallister-Killian syndrome) is a mosaic aneuploidy syndrome in which the isochromosome is present in amniocytes with a much greater percentage than fetal lymphocytes. Two new cases identified by prenatal diagnosis are reported. Indications for prenatal diagnosis were advanced maternal age and fetal anomalies. The most consistent reported prenatal ultrasound findings for tetrasomy 12p include polyhydramnios with short femurs and a diaphragmatic hernia. Recognition of congenital malformation patterns prenatally may allow appropriate selection of tissue for chromosome analysis. Molecular cytogenetic analysis using fluorescence in situ hybridization was used retrospectively to confirm the presence of the isochromosome 12p in various formalin-fixed fetal tissues. The levels of mosaicism detected in fetal and placental tissues were lower than those detected prenatally.     

Prenatal detection of monosomy 21 mosaicism

We report a case of chromosomal mosaicism for monosomy 21 revealed in amniotic fluid cell culture. Ultrasound examination at 19 weeks' gestation showed in utero growth retardation and a complex cardiac malformation. A repeated amniocentesis confirmed the presence of monosomy 21 mosaicism. In view of the sonographically detected fetal abnormalities, termination of pregnancy was elected.     

Prenatal counselling and diagnosis in progressively deforming osteogenesis imperfecta: A case of autosomal dominant transmission

A 21 -year-old woman with progressively deforming or type III osteogenesis imperfecta (OI) presented for prenatal counselling and diagnosis at 10 weeks' gestation. Family history was non-contributory. At 14.8 weeks' gestation, ultrasonographic examination revealed fetal skeletal hypomineralization, easily compressible fetal cranium, and thickened long bones, indicating that the fetus was also affected. Confirmation of the prenatal diagnosis of OI type III was made following a Caesarean section birth of a male infant with multiple skeletal deformities and blue sclerae implying, in this case, autosomal dominant inheritance.     

Pre- and perinatal findings in partial trisomy 7q resulting from balanced parental translocations t(7;21) and t(4;7)

We report on a fetus and a newborn, both with partial trisomy 7q21→qter due to different familial translocations, t(7;21)(q21.2;p12) and t(4;7)(q35;q21.2). Postmortem examination of the 19-week-old female fetus disclosed dysmorphic features, cleft palate, anomalies of the great vessels, intestinal malrotation and uterus bicornis. The newborn girl revealed a pattern of minor anomalies, cleft palate, cerebellar hypoplasia, and anomalies of pancreas, gall bladder and appendix. The clinical findings in three other reported fetuses with partial trisomy 7q described so far are reviewed. A duplication 7q21→qter, as found in the propositi, has only been described in 11 patients who all had a concurrent partial monosomy. Patient 1 is particularly interesting since she is, to our knowledge, the first reported case with pure trisomy 7q21/22→qter. We reviewed the phenotype of the previously described patients, compared it with the propositae, and summarized the clinical features of pure trisomy 7q21/22→qter. Copyright © 2001 John Wiley & Sons, Ltd.     

Prenatal diagnosis of Pallister–Killian syndrome: Resolution of cytogenetic ambiguity by use of fluorescent in situ hybridization

We report a case of Pallister-Killian syndrome initially diagnosed prenatally as tetrasomy 21. A 33-year-old primiparous woman was noted at 24 weeks' gestation to have moderate polyhydramnios. Ultrasonography showed diminished fetal stomach filling, hydronephrosis, and prominence of the cisterna magna. Cytogenetic analysis of cultured amniocytes was initially interpreted as mosaic tetrasomy 21: 46,XX/47,XX,+i(21q). The patient was then referred to our centre for genetic counselling. At 34 weeks' gestation, a dysmorphic infant was delivered and died within 30 min. Physical features were consistent with the Pallister-Killian syndrome. Renal, gastrointestinal, and central nervous system anomalies were found at post-mortem examination. Analysis of peripheral lymphocytes revealed 5 per cent of cells with a marker chromosome, while 92 per cent of cultured fibroblasts had this same marker. Fluorescent in situ hybridization (FISH) using an alpha-satellite probe for chromosomes 13 and 21 failed to hybridize to the marker, while a chromosome 12 centromeric probe unequivocally identified it as an i(12p). Use of FISH can provide rapid, specific prenatal diagnosis of ambiguous marker chromosomes and improve prenatal counselling.     

Heterogeneity in fetal akinesia deformation sequence (FADS): autopsy confirmation in three 20–21-week fetuses

Fetal akinesia deformation sequence (FADS) is a rare condition characterized by intrauterine growth retardation (IUGR), congenital limb contractures, pulmonary hypoplasia, hydramnios and craniofacial abnormalities. The present report comprises an autopsy study of three fetuses to illustrate the variable clinical manifestations and neuropathological findings. Fetus 1 had arthrogryposis and no movement on fetal ultrasound examination. Aborted at 21 weeks, the fetus showed micrognathia, bilateral joint contracture with pterygia at the elbow and axilla. Growth retardation and pulmonary hypoplasia were not major features. Neuropathologic examination revealed anterior horn cell loss and lateral corticospinal tract degeneration in spinal cord, with marked muscular atrophy. Fetus 2, 20 weeks' gestation, had fetal akinesia, nuchal thickening, left pleural effusion, and Dandy-Walker malformation on ultrasound examination. Autopsy showed low-set ears, ocular hypertelorism, cleft palate, flexion contractures with pterygia over axilla, elbow and groin, pulmonary hypoplasia, Dandy-Walker malformation, unremarkable spinal cord and skeletal muscle. Fetus 3, 21 weeks' gestation, was aborted for fetal akinesia, neck and limb webbing and severe arthrogryposis. At autopsy, similar facial abnormalities, contracture and pterygia in neck and multiple major joints were found. Borderline pulmonary hypoplasia and severe lumbar scoliosis were also present. The brain, spinal cord and muscle were unremarkable. In these three fetuses, the prenatal ultrasound and autopsy findings were characteristic of FADS. Neurogenic spinal muscular atrophy was the basis of fetal akinesia in Case 1. Dandy-Walker malformation was present in Case 2, but the pathogenetic mechanism of fetal akinesia was not clear as spinal cord and muscle histology appeared normal. The etiology of akinesia was undetermined in Case 3; no extrinsic or intrinsic cause was identified. Copyright © 2002 John Wiley & Sons, Ltd.     

Prenatal diagnosis of a fetus with partial monosomy 7(q34→qter) and partial trisomy 18(q21→qter)

Ultrasound examination of a 31-year-old woman at 27 weeks' gestation revealed fetal growth retardation, a bilateral cleft lip and palate, and the absence of median cerebral structures. Chromosome analysis after cordocentesis showed an abnormal karyotype with a structural abnormality of the long arm of chromosome 7: 46,XX,—7,+der(7), t(7;18) (q34;q21.3)mat. The pregnancy was terminated at week 29. The ultrasound findings were confirmed by post-mortem examination, which also revealed a semilobar holoprosencephaly.     

Prenatal diagnosis of Apert syndrome: report of two cases

Two de novo cases with Apert Syndrome detected prenatally are presented herein. In the first, fetal ultrasound findings of syndactyly of the hands, craniosynostosis and proptosis resulted in a prenatal diagnosis in the nineteenth week of gestation. This is the earliest prenatal diagnosis of this syndrome in a not-at-risk case. Following counseling, this pregnancy was terminated and subsequent pathological examination and DNA analysis confirmed the diagnosis of Apert Syndrome and coarctation of the aorta. In the second case, fetal ultrasound at 21 weeks' gestation revealed a hypoplastic left heart and clover-leaf skull. Following counseling, this pregnancy was also terminated. Further examination of the fetus and DNA analysis led to a diagnosis of Apert Syndrome. These cases emphasize the need to complete a thorough fetal ultrasound in cases with potentially lethal cardiac abnormality and the importance of incorporating a fetal pathologist, as well as a medical geneticist, in the investigations performed after delivery or pregnancy termination when a fetal abnormality is detected on ultrasound. Copyright © 2003 John Wiley & Sons, Ltd.     

Prenatal diagnosis of a familial complex chromosomal rearrangement involving chromosomes 5, 10, 16 and 18

We report one case of a familial complex chromosomal rearrangement (CCR) involving four different chromosomes 5, 10, 16 and 18. The CCR was detected prenatally at 20 weeks' gestation because of advanced maternal age and history of recurrent miscarriages. Cytogenetic analysis of cultured amniotic fluid cells with GTG banding showed a 46,XX,t(5;16;10;18)(q13;q22;q11.2;q21) karyotype. Parental cytogenetic study revealed that the mother has the same CCR. RBG banding, high-resolution banding and fluorescence in situ hybridization (FISH) were used to characterize further and confirm the conventional banding data. No physical abnormalities were shown in the targeted fetal ultrasonography examination. The parents decided to continue the pregnancy. The child is now 2 years old and has neither congenital anomalies nor evidence of delayed psychomotor development. The fetal targeted ultrasound and FISH analysis helped us reassure fetal status. Copyright © 2002 John Wiley & Sons, Ltd.     

Complete discrepancy between abnormal fetal karyotypes predicted by QF-PCR rapid testing and karyotyped cultured cells in a first-trimester CVS

A chorion villus sample (CVS) biopsied at 11 weeks' gestation for raised nuchal translucency, revealed monosomy X (presumptive 45,X karyotype) by QF-PCR for rapid aneuploidy testing for chromosomes 13, 18, 21, X and Y. Long-term culture gave the karyotype: 47,XY,+ 21[66]/49,XYY,+ 21,+ 21 [22]. This discrepancy prompted redigestion of the combined residual villus fragments from the original QF-PCR assay. The repeat QF-PCR assay identified the presence of trisomy 21 and a Y chromosome consistent with a 47,XY,+ 21 karyotype. A double non-disjunction event early in embryogenesis in a 47,XY,+ 21 conceptus with subsequent cell lineage compartmentalisation of the three observed cell lines (45,X; 47,XY,+ 21 and 49,XYY,+ 21,+ 21) would account for these results. This is the first reported case to describe complete discrepancy at diagnosis between abnormal karyotypes detected by QF-PCR rapid aneuploidy testing and a cultured karyotype in the same CVS. Copyright © 2006 John Wiley & Sons, Ltd.     

Normal karyotype in cultured chorionic villus cells,but mosaicism in amniotic and fetal cells

A case with a normal male karyotype in cultured chorionic villus cells, but 46,XY/45,X/ 46,X,i(Yq) mosaicism in amniotic and fetal tissue is reported. The fetus was a phenotypic male. Pathological examination revealed discrete features, which might indicate a syndrome, and histological examination showed large, bright cells in the tubules of the testes. Possible explanations for discordance between the karyotype of embryonic and extraembryonic tissue are discussed.     

Two unusual chromosome aberrations ascertained by sonographic anomalies

We describe two cases of sonographic abnormalities associated with unusual chromosomal aberrations. Case 1 presented with a cystic hygroma at 12 weeks' gestation. Cytogenetic analysis revealed an unbalanced complex chromosome rearrangement implicating chromosomes 6, 13 and 21 (karyotype: 47,XX,t(6;21;14)(q14;q21;q21)mat,+21) and corresponding to a complete trisomy 21. This anomaly resulted from malsegregation of a maternal balanced three-way translocation. For case 2, an alobar holoprosencephaly was identified by ultrasonography at 23 weeks' gestation. Chromosomal analysis showed a recombinant rec (13), dup q chromosome, secondary to unequal crossing-over of a paternal pericentric inversion of chromosome 13, giving rise to partial trisomy 13q (karyotype: 46,XX,rec(13)dup(13q)inv(13)(p11q21)pat). These two cases illustrate the role of ultrasound in leading to detection not only of foetal chromosomal aberrations but also of rare balanced chromosomal rearrangements presented by one of the two parents. Copyright © 2004 John Wiley & Sons, Ltd.     

Partial trisomy 22q12→qter in prenatal diagnosis

Ultrasound examination of a 27-year-old primigravida at 26 weeks' gestation revealed fetal growth retardation, malformation of the ventricular septum, and a neck fold. Chromosome analysis of the amniotic fluid showed an abnormal 46,XY karyotype with an obvious meta-centric chromosome 17. Chromosome analysis of the mother revealed a balanced t (17;22) (p13;q12) translocation. The fetus thus has a rare familial duplication 22q12→qter. Eight live-born and severely malformed infants with this duplication have been reported in the literature.     

Prenatal diagnosis of familial ring 21 chromosome

Ring chromosome 21 is a rare chromosome anomaly often associated with mental retardation and dysmorphic features. Less commonly, the ring chromosome can be familial and associated with a normal phenotype. Phenotypically normal female carriers, however, are at increased risk of having children with Down syndrome, mosaic monosomy 21, and variable duplication or deletion of chromosome 21. Because of the relative mitotic and meiotic instability of ring chromosomes, abnormal cytogenetic findings encountered during prenatal diagnosis may not reflect the true genetic status of the fetus. This is a report of a phenotypically normal female carrier of a familial ring 21 chromosome. Prenatal diagnosis on her twin pregnancy revealed a mosaic 46,XX,r(21)(p13;q22) (77 per cent)/45,XX, – 21 in one fetus and a normal male karyotype in the second. The pregnancy was carried to term. Both infants are completely normal, with a non-mosaic ring 21 karyotype from the lymphocytes of one twin. The diagnostic uncertainty and problematic genetic counselling related to fetal cytogenetic abnormalities are the subjects of this report.     

First trimester diagnosis of Gaucher disease in a fetus with trisomy 21

A 38-year-old lady, who had a previous infant with type 2 Gaucher disease, underwent prenatal diagnosis by chorionic villus sampling at 9 weeks' gestation. Results on the fresh villus revealed a 47,XY,+21 karyotype and a marked deficiency (2 per cent of control) of β-glucosidase activity. Following termination, villus material was cultured which initially revealed only a partial enzyme deficiency and a normal female karyotype, i.e., maternal cells. A subsequent culture contained 47,XY, + 21 cells which were deficient in β-glucosidase activity, thus confirming the diagnosis. The results in this interesting case illustrate the potential dangers of maternal cell contamination in cultured villus cells.     

Cystic hygromata in trisomy 18 and 21

Prenatal diagnosis of cystic hygromata by means of ultrasound examination is possible and highly accurate. Although this is usually associated with Turner's syndrome especially if there is co-existent hydrops fetalis we report three cases in which cystic hygromata were associated with trisomies; two cases of trisomy 21 and one of trisomy 18.     

False-negative amniotic fluid acetylcholinesterase in a case of meningo-encephalocele

We describe a patient with a significantly elevated serum alphafetoprotein (AFP) concentration at 17 weeks of gestation, who showed only a marginally increased amniotic fluid AFP and lacked the second rapidly migrating band of acetylcholinesterase electrophoresis. Ultrasound examination revealed an encephalocele and ventriculomegaly. Autopsy showed that the encephalocele was not covered by skin.     

Prenatal diagnosis of autosomal recessive osteopetrosis,infantile type,by X-ray evaluation

Prenatal diagnosis for infantile osteopetrosis was attempted during the third pregnancy of a first-cousin marriage whose family history revealed an affected previous child. At the 25th week of pregnancy, fetal X-ray evaluation revealed marked sclerosis of osteopetrotic bone and metaphyseal splaying and clubbing of both femurs. The pregnancy was terminated and repeated X-rays and histopathological examination of fetal bone (femur) confirmed the diagnosis.     

Achondrogenesis type 2 diagnosed by transvaginal ultrasound at 12 weeks' gestation

Ultrasound examination at 12 weeks' gestation revealed severe generalised subcutaneous oedema in a pregnancy at risk for achondrogenesis type II. Transvaginal scanning confirmed the oedema and suggested abnormal limb development. The prenatal diagnosis was confirmed by X-ray examination after transvaginal termination.