Cystic hygroma: Prenatal diagnosis and genetic counselling

Six cases of cystic hygromas detected during second trimester ultrasound examination are reported: 4 fetuses (67 per cent) had a 45, X karyotype, 1 fetus had trisomy 18, 1 fetus had a normal karyotype (46,XX) and at autopsy multiple anomalies were observed. In the latter case the family history suggested an autosomal recessive pattern of inheritance. In order to reach a definite diagnosis and give proper genetic counselling when a fetus is found to have cystic hygroma, a fetal karyotype as well as a family and reproductive history should be obtained.     

Prenatal diagnosis in monozygotic twins with Down syndrome who had different phenotypes

We report the case of monozygotic (MZ) male twin fetuses with different Down syndrome (DS) phenotypes. Prenatal fetal sonography showed a bichorial biamniotic pregnancy with increased nuchal translucency in twin A and a cervical cystic hygroma and heart defect in twin B. Cytogenetic analysis performed after double amniocentesis showed free and homogeneous trisomy 21 in both twins. Monozygosity was confirmed by molecular analysis. The pregnancy was terminated at 17 weeks of gestation (WG). Postmortem analysis confirmed the phenotypic discordance. To our knowledge, this is the first reported prenatal diagnosis of MZ male twins with different Down syndrome phenotypes but identical karyotypes. We discuss the mechanisms involved in phenotypic discordance of monozygotic twins and particularly the role of environmental factors. Copyright © 2007 John Wiley & Sons, Ltd.     

Prenatal diagnosis of mosaicism for triploidy and trisomy 13

Mosaicism for trisomy 13 and triploidy was detected by amniocentesis performed at 18 weeks' gestation because of fetal anomalies. Pregnancy continued and a live-born male was delivered vaginally at 37 weeks. The infant had features common to both trisomy 13 and triploidy: intrauterine growth retardation (IUGR), small abnormal ears, cleft palate, and a small jaw. In addition, he had complete cutaneous syndactyly of fingers 3 and 4 and partial syndactyly of the toes, as seen in triploidy. Mixoploidy for trisomy 13 and triploidy was confirmed postnatally in blood, skin, and placenta. Examination of chromosome heteromorphisms and DNA markers suggested the presence of two maternal contributions in the triploid cell line. In addition, the extra chromosome 13 in the trisomic cell line was derived from the mother. Copyright © 2001 John Wiley & Sons, Ltd.     

Fetal blood sampling demonstrating chimerism in monozygotic twins discordant for sex and tissue karyotype (46,XY and 45,X)

Fetal blood sampling has been used in the genetic work-up of twin gestations for rapid karotyping. We present a case of twins which on ultrasound evaluation revealed hydrops fetalis in one twin and a normal second twin. Fetal blood sampling revealed the presence of mosaicism for 46,XY/45,X in both twins. HLA antigen testing showed the twins to be identical. The patient elected pregnancy termination. Blood chromosomal analysis after delivery revealed both twins to have 46,XY/45,X mosaicism, but the twin with signs of hydrops fetalis had tissue chromosomes of 45,X and the normal twin had tissue chromosomes of 46,XY. Amniotic fluid chromosomal analysis revealed 46,XY in twin A and 45,X in twin B. This represents a case of identical (monozygotic) twins with sex discordance. In this case, there was the probable occurrence of post-zygotic chromosomal non-disjunction leading to the discordancy of the sex in this set of twins. With the presence of vascular communication in monozygotic twins, there is the possibility of exchange of blood in monozygotic twins and the result of blood chimerism in twins.     

Early prenatal diagnosis of concordant posterior urethral valves in male monochorionic twins

The association between monozygotic twins and posterior urethral valves (PUV) in postnatal life has been thoroughly described. In the fetus, the prenatal recognition of PUV is feasible. However, it has been repeatedly reported in singletons but never in monochorionic twins. We describe two cases of early prenatal diagnosis of concordant PUVs in monochorionic twins. In one of the sets, the expression of the disease was different for each twin. Copyright © 2006 John Wiley & Sons, Ltd.     

Prenatal diagnosis in Coffin-Lowry syndrome demonstrates germinal mosaicism confirmed by mutation analysis

Coffin-Lowry syndrome is a rare X-linked, semi-dominant mental retardation syndrome resulting from mutations of the ribosomal S6 kinase 2 (RSK2) gene. In the present report, a male patient affected with Coffin-Lowry syndrome is shown to have a nonsense mutation of the RSK2 gene. His unaffected mother does not have this mutation in her lymphocytes. In her third pregnancy prenatal diagnosis by mutation analysis has detected gonadal mosaicism. As this is the second report of germinal mosaicism in Coffin-Lowry syndrome, the finding has important implication for genetic counselling. Copyright © 2001 John Wiley & Sons, Ltd.     

Prenatal diagnosis of turner syndrome using cells cultured from cystic hygromas in two pregnancies with normal maternal serum alpha-fetoprotein

In two cases of prenatally detected cystic hygroma with oligohydraminos, successful cytogenetic diagnosis of Turner syndrome was achieved using cells obtained from direct aspiration of the cystic hygroma. Exceptionally high levels of alpha-fetoprotein were found in the cystic hygroma fluid, as might be expected. However, the maternal serum alpha-fetoprotein levels were within normal limits. Elevated alpha-fetoprotein levels in ‘amniotic fluid’ noted previously in the literature may have resulted because of inadvertent tapping of the cystic hygroma. It is clear from our cases that maternal serum levels of alpha-fetoprotein will not necessarily be elevated and will not serve as a screening mechanism for cystic hygromas.     

Pericentric inversion of chromosome 19: prenatal diagnosis and genetic counselling

During prenatal diagnosis for advanced maternal age, a pericentric inversion of a chromosome 19 was detected in a male fetus. The inversion was familial, transmitted to the fetus by the phenotypically normal mother. The pregnancy resulted in a term birth of a phenotypically normal male infant. Inversion 19 appears to be a rare abnormality with only seven families reported thus far including ours. Infants with duplication deficiencies for chromosome 19 have not been reported in these families. This may suggest an apparent suppression of crossing over and recombination within the inverted segment of chromosome 19 during meiosis.     

Robinow's syndrome: Prenatal diagnosis

The prenatal diagnosis of Robinow' s syndrome was accomplished in our case by measuring the length of the long bones and the ulna/humerus ratio. Although the prenatal sonographic appearance did not show the typical 8-week fetal face, pathological findings confirmed this particular feature. In view of the strongly suggestive family history, the authors consider the possible mechanisms of genetic inheritance.     

Prenatal diagnosis of apparently isolated unilateral multicystic kidney: implications for counselling and management

Cases where initial prenatal diagnosis was made of isolated unilateral multicystic kidney (UMCK) were reviewed to determine appropriate counselling and management strategies. For the 73 cases, chromosome abnormalities, pregnancy complications and family histories were reviewed. In addition, subsequently diagnosed birth defects, and pediatric medical and surgical outcomes were available for 54 cases. Of those with outcome information available renal/genital–urinary tract abnormalities were diagnosed subsequently in 33% and non-renal abnormalities in 16% of cases. Of the non-renal abnormalities, congenital heart defects were most frequent (7%). One chromosome abnormality, a trisomy 21, was present among 32 cases where karyotypes were known (3%). Amniotic fluid volume abnormalities were present in 11 cases but not predictive of associated anomalies, with the exception of one case where polyhydramnios accompanied multiple malformations consistent with VATER association. A family history of structural renal anomalies was reported in 11 cases (20%). There were 14 cases of partial or complete involution (25%), including two cases of complete prenatal involution of the cystic kidneys. No long-term associated morbidity such as hypertension or malignancy was present in our cohort. Based on our study and corroborating literature, amniocentesis should be offered to women when a seemingly isolated UMCK is detected on routine prenatal ultrasound. Furthermore, a detailed ultrasound with careful assessment of the fetal heart and contralateral kidney is indicated at diagnosis and during the third trimester to assess for further evidence of structural abnormalities, as well as amniotic fluid volume abnormalities. Careful assessment of the newborn is indicated with appropriate speciality referral as required. Copyright © 2002 John Wiley & Sons, Ltd.     

Strategies for prenatal and preimplantation genetic diagnosis in Marfan syndrome (MFS)

Marfan syndrome (MFS) is an autosomal dominant disorder with a prevalence of 2–3 per 10 000 individuals. Symptoms range from skeletal overgrowth, cutaneous striae to ectopia lentis and aortic dilatation leading to dissection. Prenatal diagnosis was until recently mainly performed in familial cases by linkage analysis. However, mutation detection has become available with thorough screening methods. The phenotypic variability observed in MFS makes reproductive options difficult, as molecular diagnosis cannot predict clinical severity of the disease. Data are presented on 15 prenatal and/or preimplantation genetic diagnoses (PGD) in nine families, originating from Belgium, the Netherlands, Spain and France. In four families data from linkage analysis were used, whereas in five other families the causative FBN1 mutation was characterised. Four PGD cycles in two couples led to one ongoing pregnancy. In addition, two amniocenteses and nine chorionic villus (CV) samplings were performed. In five pregnancies an affected fetus was diagnosed. In one of them, the couple chose to continue the pregnancy and an affected child was born, whereas the other four couples decided to terminate the pregnancy. It is expected that the greater availability of mutation testing of the FBN1 gene will increase requests for prenatal diagnosis. PGD appears to be an acceptable alternative for couples facing ethical reproductive dilemmas. Copyright © 2002 John Wiley & Sons, Ltd.     

Spontaneous resolution of a cystic hygroma in a fetus with Turner syndrome

The prenatal detection of a cystic hygroma (CH) in a fetus with a 45,X karyotype is described. The cystic hygroma underwent spontaneous resolution and a healthy baby with Turner syndrome was subsequently born. The implications for genetic counselling are discussed.