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. Copyright © 2001 John Wiley & Sons, Ltd.     

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.     

Prenatal diagnosis of a true mosaic trisomy 20 substantiated by demonstration of a gene dosage effect for adenosine deaminase (ADA)

Fibroblasts from a fetus with the prenatal diagnosis of mosaic trisomy 20 were cloned by dilution plating. Adenosine deaminase (ADA), a biochemical marker for chromosome 20, was assayed in trisomic clones and normal clones as control. The cytogenetic diagnosis was substantiated by demonstration of a triplex gene dosage effect for ADA in the trisomic cells.     

An accessory marker derived from chromosome 20 and its co-existence with a mosaic trisomy 20 cell line

We report a 16-month-old boy with delayed psychomotor development, dysmorphic features, and failure to thrive. He had a mosaic karyotype detected prenatally: mos 46,XY/47,XY,+r(20)/47,XY,+20. After birth, the abnormal cell lines were confirmed in a number of tissues. The small ring chromosome was identified using fluorescence in situ hybridization as derived from chromosome 20. We compared our patient with previously reported cases of mosaic trisomy 20 detected prenatally and associated with an abnormal phenotype. In an attempt to characterize an r(20) syndrome, we also compared our case with two similar reports in the literature.     

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.     

Prenatal diagnosis,fetal pathology,and cytogenetic analysis of mosaic trisomy 14

While true mosaicism occurs in only 0–25 per cent of genetic amniocenteses, nearly 2–5 per cent of amniotic fluid cell cultures contain a second cell line. In the common practice of prenatal diagnosis, an aberrant cell line confined to a single colony is usually disregarded. We present a case of mosaic trisomy 14 which was not detected on initial chromosome analysis. At birth, multiple malformations were apparent. Newborn cytogenetic studies revealed mosaicism [46,XX/46,XX,-14,+i(14q)] with an isochromosome 14 in 37 per cent of lymphocytes. Additional cells from the initial amniotic fluid culture were analysed post-delivery and the isochromosome 14 identified in only one of 12 total colonies. This case illustrates two important lessons in prenatal diagnosis. First, amniotic fluid cell cultures may not accurately reflect the relative distribution of the normal and abnormal cell lines within a mosaic fetus. Second, while it is generally reasonable to disregard mosaicism confined to a single colony, this policy will, on rare occasion, result in diagnostic error. This should be taken into consideration, particularly when dealing with autosomal trisomies potentially compatible with livebirth.     

Normal development in two six-year-old boys born after prenatal diagnosis of trisomy 20 mosaicism

Prenatal diagnosis of trisomy 20 mosaicism was made in two pregnancies by chromosome analysis of cultured amniotic fluid cells. In both cases, the pregnancy continued to term and a healthy male infant was delivered. Regular assessments up to the age of 6-5 years revealed normal physical and intellectual development in both children.