Prenatal diagnosis of del(15)(q11q13)

A case of del(15)(q11q13) was detected in amniotic fluid cell cultures and confirmed by cordocentesis in a 27-year-old woman with a low maternal serum alpha-fetoprotein level. The fetus was shown to have a short femoral length on ultrasonography. This structural chromosome abnormality associated with the prenatal ultrasonographic findings and the morphological characteristics visualized after termination of pregnancy strongly suggest Prader-Willi syndrome.     

The 48,XXYY syndrome: A case detected by maternal serum alpha-fetoprotein screening

A 17-year-old woman was referred for amniocentesis due to a low maternal serum alpha-fetoprotein (AFP) concentration in a voluntary screening test. The fetal karyotype was 48,XXYY, and the pregnancy was terminated. Autopsy of the fetus disclosed agenesis of the corpus callosum and unusual facial features.     

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.     

Assessment and management of fetal agenesis of the corpus callosum

Prenatal counselling for fetal agenesis of the corpus callosum is difficult as the prognosis until now has been so uncertain. We have reviewed the current world English literature to provide the best probabilistic information for prospective parents. In total, there are 70 cases where the diagnosis was made prenatally. The diagnosis of apparently isolated agenesis of the corpus callosum (in the absence of other sonographically detectable anomalies) appears to carry an excellent prognosis, with an 85 per cent chance of a normal developmental outcome and a 15 per cent risk of handicap. Fetal karyotyping is recommended as there is a 1 in 10 risk of aneuploidy. If other anomalies are detected prenatally, the outcome is very poor. Termination of pregnancy is advised in these circumstances.     

Prenatal diagnosis of a fetus with terminal deletion of chromosome 1 (q41)

Many authors have suggested that individuals affected by a terminal 1q deletion display a phenotypically definable and recognizable syndrome. In all of the 27 cases reported to date, the breakpoints were at band q42 or distally to it. To our knowledge, we report the first case of a terminal 1q41 deletion. Diagnosis was made prenatally by amniocentesis, following ultrasonographic diagnosis of omphalocele, cerebral ventriculomegaly, and increased nuchal fold thickness in a 19-week female fetus. Multiple facial and extremity features were consistent with the proposed distal 1q deletion syndrome; omphalocele, however, has not been reported previously. The absence of liver herniation into the omphalocele sac in this case supports the previously reported association of this finding with chromosomal anomalies.     

Congenital cervical teratoma,associated with agenesis of corpus callosum and a subarachnoid cyst

Cervical teratoma is a neoplasm composed of embryonic tissues with representation of all three germ layers. We report an extremely rare case of fetal cervical teratoma presenting at 24 weeks of gestation. A submaxillary mass and agenesis of corpus callosum were identified on ultrasonography, associated with agenesis of corpus callosum and a subarachnoid cyst. Copyright © 2005 John Wiley & Sons, Ltd.     

Prenatal diagnosis of trisomy 8 mosaicism in cvs after abnormal ultrasound findings at 12 weeks

We describe a case of trisomy 8 mosaicism in which fetal chromosome analysis was prompted by ultrasound abnormalities, i.e., hygroma colli and dilatation of the renal pelves. Chorionic villus sampling (CVS) was performed, with a false-negative result on direct karyotype analysis, although cultured trophoblasts revealed trisomy 8 mosaicism. Fetal autopsy confirmed the abnormalities found on ultrasound examinations and fetal tissue examination showed different levels of trisomy 8 mosaicism. To our knowledge, this is the first prenatal diagnosis of trisomy 8 made on ultrasound findings.     

Prenatal diagnosis and outcomes of five cases of mosaicism for an isochromosome of 20q

Five cases of mosaicism for an isochromosome of 20q have been detected from a total of 50 000 cases analysed for prenatal diagnosis by amniocentesis. Karyotypes were designated mos 46,X_/46,X_,i(20q). In all cases, the abnormal cell line was detected in more than one primary culture, thus fulfilling the criterion for true (level III) mosaicism. Indications for prenatal diagnosis were parental anxiety (two cases), low maternal serum alpha-fetoprotein (AFP) (two cases), and high maternal serum AFP (one case). Level II ultrasounds on all five fetuses were normal, and the abnormal cell line was never detected in fetal blood and/or cord blood. All five pregnancies were continued and had normal outcomes, with birth weights ranging from 2.4 to 3.8 kg. The development of all five children has been normal, with the oldest child in the study now 4 years of age. We suggest that the abnormal cell line in each case was of extrafetal origin, and that this may be one of the more common examples of this phenomenon, occurring in approximately 1/10000 prenatal diagnoses. Mosaicism i(20q) may have been missed in the past because of the higher resolution necessary to detect this subtle change.     

Peri- and paracentric inversions in chromosome 12: Prenatal diagnosis and family study

Three different types of chromosome 12 inversion were seen in 15 individuals out of 44 individuals examined in one 8 generation family. Type 1: a pericentric inversion inv(12) (p112; q131) was found in 7 individuals and twice at prenatal diagnosis. Type 2: a paracentric inversion inv(12) (p123; p131) was seen in two individuals. Two individuals carried both inversion chromosomes, namely type 1 and type 2. The two inversion chromosomes were transmitted from each of the parents. Type 3: a double pericentric and paracentric inversion (type 3) inv(12) (p123; p131) (p112; q131) was observed in the daughter of one of the carriers of type 1 and 2 inversions and again at prenatal diagnosis in her son. The double inversion most likely arose through crossing-over in between the two inversion loops. A balanced translocation t(7; 13) and the inversion type 1 was observed in one individual, who transmitted the translocation only to an offspring. The frequency of inversions in amniotic fluid cells observed in our laboratory was 1·9 per cent. The clinical implications of these findings are discussed.     

Interstitial deletions without phenotypic effect: Prenatal diagnosis of a new family and brief review

A 39-year-old woman (G4P1SAB2) was referred for amniocentesis for advanced maternal age. An interstitial deletion of the G-dark band 11 pi 2 was found in the fetus. Blood from the mother and her previous son was cultured and the same deletion was found in both. The absence of phenotypic effect in this family further confirms that G-dark euchromatic deletions are compatible with a normal phenotype, and underlines the importance of checking familial karyotypes even when apparently unbalanced structural rearrangements are found at prenatal diagnosis.     

Macroglossia: Prenatal ultrasonographic diagnosis and proposed management

A case in which macroglossia was the sole unusual prenatal sonographic finding in a fetus affected with trisomy 21 is presented. The differential diagnosis of fetal macroglossia is given, emphasizing its strong relationship to fetal aneuploidy, together with the principles for evaluation and management.     

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 of gastrointestinal obstruction: A correlation between prenatal ultrasonic findings and postnatal operative findings

The impact of prenatal sonographic diagnosis of oesophageal and gastrointestinal obstructions has been analysed over a 10-year period. Three groups of patients were evaluated. The first group consisted of 46 newborns with abnormal prenatal sonogratns, 41 of which were confirmed to have intestinal obstruction postnatally. The second group consisted of 17 neonates with normal prenatal sonograms who had intestinal obstruction postnatally. The third group included 56 newborns who did not undergo a prenatal sonogram but who had intestinal obstruction confirmed at surgery. Polyhydramnios without the appearance of a stomach on ultrasound was diagnostic of pure oesophageal atresia. Polyhydramnios with intestinal dilation was diagnostic of intestinal obstruction. Although surgery was performed earlier in the infants diagnosed prenatally with ultrasound, mortality was no less than in the group that did not undergo a prenatal sonogram, probably because of the high incidence of associated anomalies.     

The early prenatal sonographic diagnosis of renal agenesis: Techniques and possible pitfalls

Out of 13 252 cases in which fetal bilateral echogenic kidneys were detected by transvaginal sonography between 12 and 18 weeks' gestation, there were nine fetuses where oval hypoechogenic masses were detected in the renal bed. In five fetuses where hypoechogenic masses in the renal bed were sonographically visualized, postabortal examination was compatible with renal agenesis and the hypoechogenic masses proved to be enlarged adrenals. In three additional cases, unilateral renal agenesis was accompanied by unilateral enlarged adrenals, radiologically confirmed postnatally. In one case, a false-positive sonographic diagnosis of Potter syndrome was made because of bilateral hypoechogenic masses in the renal bed. Postabortal examination detected hypoplastic kidneys, but of normal histology, in a dyskaryotic fetus with trisomy 22. In four cases of renal agenesis, the amniotic fluid was of normal volume until the 17th week. In two of the five cases of Potter syndrome, a cystic structure, compatible with the urinary bladder, was detected in the pelvis at 14 weeks. The diagnostic criteria for renal agenesis in the early fetus differ from those used in the second half of gestation.     

Unusual segregation for 11q;22q parental translocation in a triplet pregnancy: Prenatal diagnosis in chorionic villi and amniotic fluid

The prenatal diagnosis of an 11q;22q translocation in a triplet pregnancy detected at the time of chorionic villus sampling (CVS) because of advanced maternal age is reported. Karyo-types obtained from two apparently different CV samples showed the balanced form of translocation, while the one obtained from a third empty sac showed the unbalanced form: 46, XX, −22, + der(22)t(11;22). Second-trimester amniocentesis confirmed the balanced translocation in one of the two viable fetuses and a normal karyotype in the other. The detected karyotypes derived from two different types of meiotic segregation, alternate and adjacent 1. To our knowledge, this is the first reported case of an unbalanced karyotype not due to a 3:1 meiotic segregation of this specific translocation.     

Prenatal diagnosis of fragile x syndrome: (cgg)n expansion and methylation of chorionic villus samples

Fragile X syndrome is the most common form of inherited mental retardation, due to an expansion of the (CGG)_n trinucleotide repeat in the FMR-1 gene and hypermethylation of its 5′ upstream CpG island. Two major problems remain to be resolved for fragile X prenatal diagnosis: the abnormal methylation patterns of chorionic villus samples (CVS) and the inability to predict the mental status of females with the full mutation. We present here the results of ten prenatal diagnoses of fragile X syndrome using Southern blotting and polymerase chain reaction (PCR) amplification, and the analysis of 50 further CVS to test the methylation status of the CpG island of the FMR-1 gene. In the ten ‘at-risk’ CVS, eight normal (five males and three females) and two affected male fetuses were detected. Absence of methylation in the CVS was observed in two cases, which was not found upon subsequent examination of the newborn or of fetal tissues. In the 50 CVS not ‘at risk’ for fragile X syndrome, abnormal fragment patterns for probe StB12.3 were detected in 32 per cent for female and 24 per cent for male fetuses. This abnormal pattern could be due to absent or partial methylation of the CpG island of the FMR-1 gene in chorionic villus tissues.