Recurrences of trisomy 18 and trisomy 13 after trisomy 21

Summary Between 40 years and 43 years of age, a woman had three consecutive pregnancies with different prenatally diagnosed autosomal trisomies. This is compatible with the view that the predisposition to non-disjunction is not chromosome-specific.     

Reciprocal translocations and full trisomy (trisomy 18 and trisomy 21) in the offspring

In this report, we present examples of trisomy 18 and trisomy 21, both resulting from maternal reciprocal translocations: 46, XX, t(5;18) (q21;q11) and 46, XX, t(5;21) (p11.2;p11), respectively.     

Alpha-fetoprotein and trisomy 21

In 31 affected pregnancies with Down syndrome, the median maternal serum alpha-fetoprotein value was lower than normal, 0.76 MoM, and median amniotic fluid value was quite normal, 0.98 MoM. Selecting an arbitrary cutoff-point of 0.5 MoM, 4.1 percent of normal gestations show values less than 0.5 MoM. Authors discuss problems about screening for fetal Down's syndrome by measuring maternal serum AFP levels.     

Altered placental morphology associated with murine trisomy 16 and murine trisomy 19

The morphology of placentas from trisomy 16 and trisomy 19 mouse conceptuses aged 12 to 18 gestational days was studied at the light microscopic level. Comparisons were made with placentas from normal littermate animals. Trisomy 16 placentas showed marked changes from normal: 1) the junctional zone showed little indication of normal morphologic differentiation throughout gestation; 2) clusters of germinal trophoblast cells persisted in the labyrinth throughout gestation, whereas these cells disappeared by gestational day 16 in the normal littermate placentas; 3) the labyrinth was reduced in size in the trisomic placentas, and the differentiation of the interhemal membranes was delayed. The size of the labyrinths from trisomy 19 placentas appeared to be decreased, but otherwise the placentas appeared to have normal morphology. These observations and others from the literature show that placental development is affected by the presence of a trisomic genome, and that different trisomies influence the development of the placenta differently. For trisomy 16, we propose that the striking changes of the junctional zone may be associated with the trisomy 16-related gene dosage effect for alpha- and beta-interferon cell surface receptors. Because of the homology for this and other genes on mouse chromosome 16 with genes on human chromosome 21, findings related to the altered development of the trisomy 16 mouse may be relevant to understanding some of the phenotypic variations associated with human trisomy 21, the Down syndrome.     

Partial and complete trisomy 9: Delineation of a trisomy 9 syndrome

Summary Two infants with trisomy involving chromosome 9 are described. One had complete trisomy 9 and the other karyotype 47,XX,+der(9),t(7;9)(p22;q32)mat. A trisomy 9 syndrome is delineated, consisting of features of the trisomy 9p syndrome and various other malformations. These include abnormalities of the cardiovascular and urogenital systems, cranial suture anomalies, dislocation of the hips and knees and early death. A possible relationship of some of these findings to regions of 9q involved in cases of partial trisomy 9 is suggested.     

Exomphalos and trisomy 18 syndrome

Summary A large exomphalos was found in two infants with a clinically and cytogenetically typical picture of trisomy 18 syndrome. In addition one infant was a case of male pseudohermaphroditism.     

Incomplete trisomy 22

Summary Two brothers with duplication of the distal segment of 22q inherited from a t(6;22)(q27;13) translocation carrier mother presented with intraurine growth retardation, congenital hydrocephalus, cleft palate, genital hypoplasia with cryptorchidism and hypospadias, and similar facial features including mongoloid position of eyeaxes, hypertelorism, small nose with prominent bridge, prominent upper lip, and small mandible. In addition the second sib revealed renal hypoplasia, arrhinencephaly and pentalogy of Fallot. The patients died at ages eight days and one day, respectively. The two brothers appear to be the first instances of familial trisomy 22q13qter.     

Partial trisomy 21

Summary Cytogenetic analysis of a 6-year-old girl with moderate mental retardation revealed 46 chromosomes with a tandem translocation (21;21) resulting in a partial trisomy 21. Only the terminal band 21q22 was not in triplicate. G-, Q-, R-, and C-banding techniques and silver nitrate staining of the nucleolus organizer regions (NORs) were used to identify this chromosome fully.The phenotype of the patient was not typical for Down's syndrome, providing additional evidence that trisomy of band 21q22 is pathogenetic for the phenotype of Down's syndrome. This is also a new example in human pathology of a stable dicentric chromosome in which one of the centromeric constrictions appears to be nonfunctional.     

Full trisomy 7 and Potter syndrome

Summary A patient with typical Potter's syndrome and full trisomy 7 is described. All previous reports on chromosome 7 abnormalities, whether monosomic or trisomic, p or q, are reviewed and discussed, establishing two 7q trisomy snydromes: 7q227q31 and 7q22, q317qter. Some implications of the finding of full trisomy 7 in a case of Potter's syndrome are discussed.     

Amino acids and trisomy 21]

The relative concentrations of plasmatic and urinary amino acids were analysed in 79 trisomic-21 patients, 322 mentally retarded non-trisomic patients, and 206 controls. No true amino acidopathy was found in 21-trisomy, but in plasma a deficit of serine and an excess of cysteine and lysine are highly significant. Excesses of cysteine, methionine, tyrosine, and methyl-histidine are also typical in urine. The increased activity of superoxide-dismutase, cystathionine-beta-synthase, and purine synthesis enzymes, together with the sensitivity to methotrexate, atropine, and dysthyroidism, are in accordance with this shift of equilibrium. A nutritional compensation seems worth investigating.     

Mosaic trisomy 15 and hemihypertrophy.

We report a case of mosaic trisomy 15 with mental retardation, facial dysmorphism, and hemihypertrophy, but no manifestations of Prader-Willi or Angelman syndromes. Mosaic trisomy 15 (11%) was discovered at the amniocentesis. Uniparental disomy for chromosome 15 was excluded by molecular analysis. Post-natal blood karyotype and examination were normal. Mosaic was confirmed on skin fibroblasts, placenta and cord. Evolution was marked by progressive right hemi-hypertrophy, and developmental delay. Our case is the first patient reported with hemihypertrophy associated with mosaic trisomy 15. The relevant literature is reviewed.     

Kabuki syndrome and trisomy 10p

Kabuki syndrome (KS) (MIM 147920) is a multiple congenital anomalies/mental retardation syndrome of unknown cause. There is multisystem involvement of anomalies, including 1) unique facial features, 2) postnatal growth retardation, 3) mild-to-moderate mental retardation, 4) skeletal anomalies and 5) dermatoglyphic abnormalities. Kabuki syndrome remains a clinical diagnosis despite significant research on detection of the genetic cause. We present 10 patients with Kabuki syndrome with a brief overview of the syndrome. An additional male patient and his affected aunt, both with trisomy 10p due to unbalanced segregation of a familial translocation, are also discussed for overlapping features and differential clinical diagnosis of the two conditions. Considering a significant overlap in clinical pictures of Kabuki syndrome and trisomy 10p in these two patients, as well as the previous patients with chromosomal abnormalities, we conclude that chromosome analysis is an important step in clinical work-up of patients with Kabuki syndrome.     

Noninvasive prenatal diagnosis of fetal trisomy 18 and trisomy 13 by maternal plasma DNA sequencing

Massively parallel sequencing of DNA molecules in the plasma of pregnant women has been shown to allow accurate and noninvasive prenatal detection of fetal trisomy 21. However, whether the sequencing approach is as accurate for the noninvasive prenatal diagnosis of trisomy 13 and 18 is unclear due to the lack of data from a large sample set. We studied 392 pregnancies, among which 25 involved a trisomy 13 fetus and 37 involved a trisomy 18 fetus, by massively parallel sequencing. By using our previously reported standard z-score approach, we demonstrated that this approach could identify 36.0% and 73.0% of trisomy 13 and 18 at specificities of 92.4% and 97.2%, respectively. We aimed to improve the detection of trisomy 13 and 18 by using a non-repeat-masked reference human genome instead of a repeat-masked one to increase the number of aligned sequence reads for each sample. We then applied a bioinformatics approach to correct GC content bias in the sequencing data. With these measures, we detected all (25 out of 25) trisomy 13 fetuses at a specificity of 98.9% (261 out of 264 non-trisomy 13 cases), and 91.9% (34 out of 37) of the trisomy 18 fetuses at 98.0% specificity (247 out of 252 non-trisomy 18 cases). These data indicate that with appropriate bioinformatics analysis, noninvasive prenatal diagnosis of trisomy 13 and trisomy 18 by maternal plasma DNA sequencing is achievable.     

Gene-rich chromosome regions and autosomal trisomy

Summary Cases of autosomal trisomy and trisomy mosaicism among liveborn infants are reviewed, and a second case of chromosome 3 trisomy mosaicism is described. The occurrence of autosomal trisomy for a particular chromosome is in general negatively correlated with the number of genes which have been localized to that chromosome. It is also positively related to the Q-brightness of the chromosome, which reflects its content of intercalary heterochromatin. Furthermore there are significantly fewer autosomal trisomics for chromosomes which contain hot spots for mitotic chiasmata in Bloom syndrome (chromosomes 1, 3, 6, 11, 12, 17, 19, and 22), compared with similar-sized control chromosomes 2, 4, 7, 9, 10, 18, 20, and 21. This is interpreted as further evidence for the gene richness of the hot spots which, being active, are extended in interphase and are therefore available for mitotic crossing over. The gene richness of these short Q-dark regions is also borne out by the scarcity of trisomic abortions for the chromosomes involved (the embryo dies before the abortion is recognized) and by the higher number of genes localized to these chromosomes compared with the control chromosomes.     

Distal trisomy 14q

Summary Two cases of chromosome 14 rearrangements with partial duplication which occurred de novo were analyzed by Southern blot analysis using IGH, D14S1 and PI probes. In the first case, with a 46,XX,14p+ karyotype, our study confirms that the additional material on chromosome 14p+ results from a duplication of the 14q region containing the IGH, D14S1 and PI loci. In the second case, our study reveals only one 14q32 locus per chromosome 14 indicating that the extra material does not contain the 14q32 region. Our results demonstrate that molecular probes of the 14q32 region are valuable tools for the characterisation of chromosome 14 abnormalities appearing de novo.     

Partial trisomy 14q

Summary A dysmorphic female born with partial trisomy of the proximal segment of the long arm of chromosome 14 had 47 chromosomes. The extra one was acrocentric, smaller than the D group, and bigger than the G-chromosome group. By GTG banding it was identified as a deleted chromosome 14, the karyotype being 47,XX,+del 14(q24). Chromosome analysis of the parents was normal.