Double mosaic aneuploidy: 45, X/47,XY,+8 in a male infant

We report on a 13-month-old boy with abnormalities consistent with mosaic trisomy 8 syndrome and male genitalia with partial peno-scrotal transposition without hypospadias, a retractile left testis in inguinal canal, and an absent right testis. A voiding cystourethrogram showed an outpouching close to the lower right side of the bladder (utriculum) and bilateral hydronephrosis secondary to vesicoureteral reflux. Peripheral blood karyotype was 45,X/47,XY,+8. The karyotype of cultured skin fibroblasts was 47,XY,+8 with no 45,X cells detected among 20 cells counted. Tissues removed during surgery documented a 45,X/47,XY,+8 complement in the left testicle and utriculum, but only a 45,X line among 20 cells counted from vas deferens tissue. A possible mechanism for the origin of this previously unreported mosaicism might be an abnormal zygote with a 47,XY,+8 complement with subsequent simultaneous loss of chromosome Y and 8 in a cell at a very early embryonic stage. © 1992 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.     

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/46,XY/47,XY, +21 mosaicism in a hypogonadal phenotypic male.

A phenotypically normal male was found to have a chromosomal complement of 45,X/46,XY/47,XY, +21. This mosaic pattern has been reported only twice before. Although the patient had apparently fathered two children, he now has progressive impotence, absence of sperm in the seminal fluid, atrophic testes, almost complete absence of germ cells in testicular biopsies, high plasma LH and FSH, and a low normal testosterone. There were no physical characteristics of Turner's or Down's syndromes except for dermatoglyphic features commonly associated with the latter. These observations in this patients emphasise the value of chromosomal studies in multiple tissues in cases of mosaicism with atypical clinical features.     

46,XY/48,XXY,+8 in a male with clinical and dermatoglyphic features of mosaic trisomy 8 syndrome

A 15-year-old male was referred for management of scoliosis secondary to congenital vertebral anomalies. Cytogenetic analysis was performed because of multiple congenital malformations. The patient was found to have a mosaic 46,XY/48,XXY, + 8 chromosome complement with the characteristic clinical and dermatoglyphic features of mosaic trisomy 8 syndrome.     

Retrieval of aneuploidy by fish-technique in a case with 46,XX/47,XXX/47,XX,+8

Summary We report on a 46 year old female with a new chromosomal finding [46,XX/47,XXX/47,XX,+8] who was referred for ovarian failure. The clinical presentation was highly unusual and the patient does not exhibit the characteristic phenotype of trisomy 8 syndrome. Interphase cytogenetics using FISH-technique revealed discrepancies with a different population of cells when compared with its metaphase index. Therefore, it is advised that patients with mosaic karyotypes should be evaluated by analyzing metaphase as well as interphase nuclei labeled with chromosome specific molecular tags, especially in the situations where the incidence of a mosaic cell line is very low. Nevertheless, in a cost-conscious environment, we must exercise caution prior to making universal recommendations concerning the usefulness of medical devices which are increasing at a logarithmic rate.     

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.     

Dysgenetic male pseudohermaphroditism in a 45,X/46,X,del(Y)(q11.1) mosaic infant

We describe an infant with dysgenetic male pseudohermaphroditism and the karyotype 45,X/46,X,del(Y)(q11.1). Histologic examination of the resected gonads showed cortical dysplasia indicative of incipient gonadoblastoma.     

Prenatal diagnosis of 45,X/46,XY mosaicism with postnatal confirmation in a phenotypically normal male infant

Prenatal detection of chromosome mosaicism has always been a diagnostic dilemma. In 21 reported cases of chromosomal mosaicism in cultured amniotic fluid cells, only two cases had cytogenetic confirmation of the mosaicism. All 21 pregnancies resulted in either phenotypically normal liveborns or grossly normal abortuses. We report a case of XO/XY mosaicism detected prenatally and confirmed postnatally in a grossly normal male infant. The indication for prenatal cytogenetic diagnosis was advanced maternal age (38 years). A diagnosis of XO/XY mosaicism was made from two separate culture flasks of amniotic fluid cells, with 45,X cells predominating (86.4 % ). The Y chromosome was of normal size but carried no fluorescent band. The parents were counseled and were advised that the phenotype of XO/XY mosaicism can range from relative normality to sexual maldevelopment. They decided to continue this pregnancy. The infant was born at term and was a grossly normal male with normal penis and descended, normal-sized testes. Leukocyte culture from the cord blood and a skin fibroblast culture confirmed the mosaicism of XO/XY. The father's Y chromosome was of identical size and carried a small fluorescent band. It appears that an altered Y chromosome may be predisposed to anaphase lag leading to mosaicism.     

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.     

A 45, X woman with a 47, XY, G+ son

A woman, karyotype 45, X, aged 22, gave birth to a son with Down's syndrome. It is the fourth reported case of childbirth in a woman with monosomy X.     

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.     

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.     

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.     

Cell line segregation in a 45,X/46,XY mosaic child with asymmetric leg growth

Clinical evaluation of a 13 1/2-year-old male revealed a 4.4-cm leg length discrepancy and a small penis with a normal endocrine evaluation. Cytogenetic analysis of peripheral blood lymphocytes and skin fibroblasts derived from the back showed 45,X/46,XY mosaicism with similar percentages of 45,X cells, 36% and 30% respectively. However, two separate skin fibroblast cultures derived from the thigh and calf of the short (right) leg showed significant lack of Y-bearing cells with 100% and 80% 45,X, respectively. In contrast, skin biopsies of the thigh and calf of the normal (left) leg both showed 100% 46,XY. Similar evidence for differences in the percentages of Y-bearing cells in the left versus right leg fibroblast cultures was obtained using densitometric scanning of dot blots following DNA hybridization with a Y-specific probe at the DYZ4 locus. Asymmetric limb growth in cases of X/XY lymphocyte mosaicism warrants further cytogenetic investigation to substantiate possible genotype-phenotype correlations which may help uncover the fundamental growth deficiency in Turner syndrome.     

Male pseudohermaphroditism and gonadal mosaicism in a 47,XY,+22 fetus

Trisomy 22 syndrome manifestations include cranial and facial anomalies. Ambiguous genitalia have been described in some fetus, but histological examination of the gonads has been rarely provided. We report here the first case of a male pseudohermaphrodite fetus with non-mosaic full trisomy 22 in amniocytes and presenting with ambiguous external genitalia, testes, and a uterus. In this case, we have further analyzed cytogenetically gonadal and uterine tissues. FISH analyses on paraffin-embedded gonads and uterus indicated the presence of two cell lines: XY and monosomy X, with 22%-50% of uterine cells having monosomy X, while 85%-100% of right and 77%-96% of left testicular cells were XY. The distribution of sex chromosomes observed in these tissues could explain the sexual differentiation observed in this fetus. On the other hand, this phenotype could also have resulted from cryptic anomalies in one or several genes implicated in sexual differentiation. Further evidence is thus needed before identifying the true cause of pseudohermaphroditism in our patient.