Clinical,cytogenetic, and molecular findings in 45,X/47,XX,+18 mosaicism: Clinical report and review of the literature

We report cytogenetic and molecular findings performed in a patient with double mosaic aneuploidy. Chromosome analysis of amniotic fluid cells from a 17‐week‐old fetus was performed because of advanced maternal age. Two karyotypes were detected: 45,X and 47,XX,+18 (50:50%). The same cell lines were determined in uncultured and cultured amniocytes of a second amniotic fluid sample, in fetal lymphocytes, and in uncultured and cultured cells of achilles tendon by conventional cytogenetics and fluorescence in situ hybridization (FISH). In the different investigated tissues, the percentage of cells with 45,X karyotype ranged from 20–99% and the percentage of cells with 47,XX,+18 ranged from 1–80%. The pregnancy was terminated at 22 + 0 weeks because of a severe cardiac malformation. Pathologic examination showed a fetus with aspects typical for manifestation of trisomy 18 and monosomy X, especially in the internal organs. The parent and cell stage of origin was determined by short tandem repeat typing and revealed a maternal meiotic division error that led to trisomy 18, as well as a somatic loss of a paternal sex chromosome. Only two other patients with the same mosaicism have been reported so far. Genetic counseling and prognosis remains challenging. © 2002 Wiley‐Liss, Inc.     

Turner phenotype in a girl with a 45,X/46,XX/47,XX,+18 mosaicism

We report a girl with Turner syndrome phenotype, whose karyotype on amniocyte culture was 45,X, while cytogenetic analysis on peripheral blood lymphocytes showed the presence of a mosaic chromosome constitution with three different cell lines: 45,X[5]/46,XX[3]/47,XX,+18 [35]. No signs of trisomy 18 were observed and a follow up during childhood revealed normal psychomotor development. Parental origin and mechanism of formation were studied using high polymorphic microsatellites and Quantitative Fluorescent PCR. The 18-trisomic cells showed one paternal allele and two maternal homozygous alleles at different loci of chromosome 18, suggesting a maternal M-II meiotic or a postzygotic error. A biparental origin of the X-alleles in the trisomic cells were determined, being the paternal allele retained in the 45,X cells. The possible mechanism of formation implying meiotic and/or mitotic errors is discussed.     

Ullrich-Turner phenotype with unusual manifestation in a patient with mosaicism 45,X/47,XX,+18

We report on a girl with Ullrich-Turner phenotype and 45,X/47,XX,+18 chromosomal mosaicism. Only two other patients with similar mosaicism have been reported, both girls with XY sex chromosome constitution. The face of the patient was highly asymmetric, the right side being almost normal, the left showing a typical Ullrich-Turner syndrome appearance. This clinical impression was strengthened by photographic doubling of both hemifaces. The patient had normal intelligence and did not show any stigmata of trisomy 18. © 1996 Wiley-Liss, Inc.     

A mildly retarded woman with 46,XX/47,XX,+18 mosaicism

We describe a mildly retarded woman with trisomy 18 mosaicism. The phenotype did not suggest trisomy 18, but the mild mental retardation, asymmetric face with bushy eyebrows and thick lips, short stature, and older maternal age raised the suspicion of a chromosomal cause for her condition.     

Origin and mechanism of formation of 45,X/47,XX,+21 mosaicism in a fetus

Chromosome analysis of amniotic fluid cells from a 17-week-old fetus with a nuchal cystic hygroma showed a 45,X/47,XX,+21 karyotype. Analyses of cord blood lymphocytes, skin fibroblasts, amniotic membrane, and chorionic villi demonstrated both cell lines in various proportions. We studied the origin and mechanism of formation of the double mosaic aneuploid using Q-banded chromosomal heteromorphisms, and one RFLP, two VNTRs, one tetranucleotide repeat, 28 CA repeat markers, mapped to every member of chromosomes. The heteromorphic markers examined showed no discordant patterns in parent-to-child transmission or between the two cell lines except for those in chromosomes 21 and X. Fetal DNA was extracted from its established monoclonal fibroblast cell lines with 45,X or 47,XX,+21 karyotypes. Genotyping with the DNA markers showed that each cell line was identical at every locus, except for chromosome 21 or X loci, indicating that the fetus was not a chimera but a mosaic. The 21-trisomic cells had one paternal allele and two maternal heterozygous alleles at the D21S270 locus, and the 45,X (21-disomic) cells had two biparental alleles. Alleles at two X chromosomal loci, DXS991 and DXS8057, were biparental in the 47,XX,+21 cells, whereas only the paternal allele was retained in the 45,X cells. Based on these findings, we concluded that the fetus started as a 47,XX,+21 zygote that had resulted from nondisjunction at the maternal first meiotic division and that one each of the maternally derived chromosomes 21 and X was lost during an early mitotic division, leading to the mosaicism. Am. J. Med. Genet. 75:432-437, 1998. © 1998 Wiley-Liss, Inc.     

Turner Phenotype: Mosaic 45,X/47,XY,+18

A 14-year-old girl with Turner phenotype is described, whose lymphocyte and skin fibroblast cultures both revealed a 45,X/47,XY,+18 chromosomal mosaicism. In blood cultures one third and in fibroblasts 7% of the cells had 47 chromosomes. The identity of the Y and the supernumerary 18 were determined by fluorescence and Giemsa banding patterns. The patient is of normal intelligence and does not exhibit any signs of masculinization or stigmata of trisomy 18.     

Pigmentary mosaicism following the lines of Blaschko in a girl with a double aneuploidy mosaicism: (47,XX,+7/45,X)

We report on a 6-year-old girl with linear streaks of apparent hypopigmentation and hyperpigmentation following the Blaschko lines, growth retardation, bupthalmos of the left eye, and mild mental retardation. She had a 45,X karyotype in lymphocytes. In cultured fibroblasts a double aneuploidy mosaicism was detected, consisting of a cell line with trisomy for chromosome 7 and a cell line with monosomy for the X-chromosome and no cell line with a normal karyotype. Cutis tricolor or three levels of pigmentation in different skin areas suggested presence of a third, probably normal cell line. Double aneuploidy mosaicism of a cell line with monosomy X and a cell line with trisomy of an autosome is a rare finding. The combination of monosomy X with trisomy of chromosomes 8, 10, 13, 18, and 21 has been reported, but not the combination with trisomy 7. In the 45,X cell line, microsatellite analysis showed loss of the maternal X-chromosome, and presence of a maternal and paternal chromosome 7. The 47,XX,+7 cell line showed a paternal and a maternal X-chromosome, and a paternal and two identical maternal chromosomes 7. Mechanisms that might explain this double aneuploidy mosaicism are discussed.     

Three cell line mosaicism involving structural and numerical abnormalities of chromosome 18 in a 3.5-year-old girl: 47,XX,+18/47,XX,+del(18)(q22)/46,XX

We report on a 3.5-year-old girl with a mosaic karyotype including full trisomy 18, normal cells and a majority of cells with partial trisomy involving an extra chromosome 18 deleted at band q22. She had cardiac and CNS anomalies, dysmorphic facial features failure to thrive and developmental delay. A gastrostomy tube was placed at 2 years of age. The combination of improved nutrition and optimal developmental therapy has led to her sitting supported, attempting to stand and enhancement of her cognitive and non-verbal communication abilities. Molecular investigation of the patient and her parents using microsatellite analysis has led to the conclusion that, as expected, the additional copy of chromosome 18 constituting the full trisomic cell line is maternal meiosis I in origin. The data, however, indicate that in the trisomic cell line containing the deleted chromosome 18q, the structurally abnormal 18 was of paternal origin. We think this case is the first described with both structural and numerical trisomic mosaicism involving chromosome 18 in a liveborn infant. We propose a mechanism of origin and review the literature, comparing the clinical presentation of this case with individuals having full or partial trisomy 18.     

Triple mosaicism 45,XY,--18/46, XY/47,XY,+18.

A patient with symptoms clinically resembling Edwards's syndrome is presented. Cranial asymmetry, thoracic and lumbar hemivertebrae, and an additional rib were the unusual features. The cytogenetic studies revealed the coexistence of three separate cell lines with 45,XY,--18/46,XY/47,XY,+18 complement.     

45,X/47,XYY mosaicism.

This paper describes and discusses the clinical and cytogenetic findings in an infant with an unusual sex chromosome abnormality 45X/47XYY.     

Three cell line mosaicism involving structural and numerical abnormalities of chromosome 18 in a 3.5‐Year‐old girl: 47,XX,+18/47,XX,+del(18)(q22)/46,XX

We report on a 3.5‐year‐old girl with a mosaic karyotype including full trisomy 18, normal cells and a majority of cells with partial trisomy involving an extra chromosome 18 deleted at band q22. She had cardiac and CNS anomalies, dysmorphic facial features failure to thrive and developmental delay. A gastrostomy tube was placed at 2 years of age. The combination of improved nutrition and optimal developmental therapy has led to her sitting supported, attempting to stand and enhancement of her cognitive and non‐verbal communication abilities. Molecular investigation of the patient and her parents using microsatellite analysis has led to the conclusion that, as expected, the additional copy of chromosome 18 constituting the full trisomic cell line is maternal meiosis I in origin. The data, however, indicate that in the trisomic cell line containing the deleted chromosome 18q, the structurally abnormal 18 was of paternal origin. We think this case is the first described with both structural and numerical trisomic mosaicism involving chromosome 18 in a liveborn infant. We propose a mechanism of origin and review the literature, comparing the clinical presentation of this case with individuals having full or partial trisomy 18. © 2001 Wiley‐Liss, Inc.     

Hypoplastic left heart in a patient with 45,X/46,XX/47,XXX mosaicism

Recurrence risks for primary congenital heart lesions are well defined. An infant with hypoplastic left heart syndrome is observed to have a short neck with a full skin fold on the right side, unilateral single palmar crease, and whorls on all ten fingers. She was found to have the Ullrich-Turner syndrome with mosaicism 45,X/46,XX/47,XXX. We believe the cardiac malformation was secondary to her aneuploidy. This could have important implications for prediction of recurrence risks to the parents. Chromosomal tests may be indicated for infants were severe congenital cardiac lesions, based on subtle clinical findings.     

45,X/46,X,idic(Yq) mosaicism: Clinical,cytogenetic, and molecular studies in four individuals

45,X/46,X,idic(Yq) mosaicism is associated with a variety of sex phenotypes, including Ullrich-Turner syndrome (UTS), intersexuality, and complete male. It remains unclear whether the phenotypic variability results from a dilutional effect by the 45,X cell line in the primordial gonad or an abnormality of the SRY gene (SRY). We conducted cytogenetic and molecular studies on four patients with such mosaicism, two of whom had a complete male phenotype and two who had UTS. Chromosome analyses showed that the frequency of cells carrying an idic(Yq) chromosome in peripheral blood lymphocytes and skin fibroblasts was not related to the given sex phenotype. The SRY, PABY, and ZFY genes were present in all four patients. A fluorescence in situ hybridization (FISH) study showed that both a patient with a complete male phenotype and another with UTS had duplicate copies of SRY in their idic(Yq) chromosomes, whereas a patient with UTS had a single copy of the gene. These findings suggested that the coexisting 45,X cell line is more influential on the determination of the sex phenotype in individuals with 45,X/46,X,idic(Yq) mosaicism. Am. J. Med. Genet. 78:424–428, 1998. © 1998 Wiley-Liss, Inc.     

Hypoplastic left heart in a patient with 45,X/46,XX/47,XXX mosaicism.

Recurrence risks for primary congenital heart lesions are well defined. An infant with hypoplastic left heart syndrome is observed to have a short neck with a full skin fold on the right side, unilateral single palmar crease, and whorls on all ten fingers. She was found to have the Ullrich-Turner syndrome with mosaicism 45,X/46,XX/47,XXX. We believe the cardiac malformation was secondary to her aneuploidy. This could have important implications for prediction of recurrence risks to the parents. Chromosomal tests may be indicated for infants were severe congenital cardiac lesions, based on subtle clinical findings.