scholarly journals Report of Fertility in a Woman with a Predominantly 46,XY Karyotype in a Family with Multiple Disorders of Sexual Development

2008 ◽  
Vol 93 (1) ◽  
pp. 182-189 ◽  
Author(s):  
Miroslav Dumic ◽  
Karen Lin-Su ◽  
Natasha I. Leibel ◽  
Srecko Ciglar ◽  
Giovanna Vinci ◽  
...  
Keyword(s):  
Y Chromosome ◽  
Gonadal Dysgenesis ◽  
Ambiguous Genitalia ◽  
Chromosomal Mosaicism ◽  
Normal Male ◽  
Disorders Of Sexual Development ◽  
Cultured Skin ◽  
Family Pedigree ◽  
Mother And Daughter ◽  
Complete Gonadal Dysgenesis

Abstract Context: We report herein a remarkable family in which the mother of a woman with 46,XY complete gonadal dysgenesis was found to have a 46,XY karyotype in peripheral lymphocytes, mosaicism in cultured skin fibroblasts (80% 46,XY and 20% 45,X) and a predominantly 46,XY karyotype in the ovary (93% 46,XY and 6% 45,X). Patients: A 46,XY mother who developed as a normal woman underwent spontaneous puberty, reached menarche, menstruated regularly, experienced two unassisted pregnancies, and gave birth to a 46,XY daughter with complete gonadal dysgenesis. Results: Evaluation of the Y chromosome in the daughter and both parents revealed that the daughter inherited her Y chromosome from her father. Molecular analysis of the genes SOX9, SF1, DMRT1, DMRT3, TSPYL, BPESC1, DHH, WNT4, SRY, and DAX1 revealed normal male coding sequences in both the mother and daughter. An extensive family pedigree across four generations revealed multiple other family members with ambiguous genitalia and infertility in both phenotypic males and females, and the mode of inheritance of the phenotype was strongly suggestive of X-linkage. Conclusions: The range of phenotypes observed in this unique family suggests that there may be transmission of a mutation in a novel sex-determining gene or in a gene that predisposes to chromosomal mosaicism.

Imaging Findings of Septooptic Dysplasia and Joubert's Syndrome in A Patient with Mixed Gonadal Dysgenesis: A New Coexistence?

2020 ◽  
Author(s):  
Merter Keçeli
Keyword(s):  
Gonadal Dysgenesis ◽  
Sex Chromosome ◽  
Karyotype Analysis ◽  
Ambiguous Genitalia ◽  
Total Testosterone ◽  
Resonance Imaging ◽  
Disorders Of Sexual Development ◽  
Laboratory Findings ◽  
Mixed Gonadal Dysgenesis ◽  
Motor Retardation

AbstractAmbiguous genitalia is a common feature in most disorders of sexual development. These disorders can be evaluated within three groups: sex chromosome disorders, 46,XY disorders, and 46,XX disorders. Except for Turner's syndrome, these anomalies are not related to neurological developmental anomalies. A 6-month-old patient presenting with ambiguous genitalia had developmental and motor retardation with nystagmus. In karyotype analysis, 45,X/46,XY sequences were found, compatible with mixed gonadal dysgenesis (GD). Laboratory findings were normal except for low serum total testosterone level. The uterus and left adnexal structures were seen in imaging. There were no gonads in the labial/scrotal regions. Septooptic dysplasia (SOD) and Joubert's syndrome (JS) were detected in cranial magnetic resonance imaging. This presentation reports rare association of SOD and JS in a child with mixed GD.

45,X/46,XY Mosaicism with Male Phenotype: Case Report

2021 ◽  
pp. 1-4
Author(s):  
Angie Carolina Carreño-Martínez ◽  
Victor Clemente Mendoza Rojas ◽  
Julian Arturo Gil Forero ◽  
Victor Hugo Figueroa ◽  
Gustavo Adolfo Contreras-García
Keyword(s):  
Case Report ◽  
Physical Examination ◽  
Aortic Coarctation ◽  
Gonadal Dysgenesis ◽  
Ambiguous Genitalia ◽  
Normal Male ◽  
Corrective Surgery ◽  
Male Phenotype ◽  
Treatment Alternatives

Mixed gonadal dysgenesis is the most common chromosomal abnormality with ambiguous genitalia, defined as a 45,X/46,XY mosaicism. It can present with a normal male phenotype, ambiguous genitalia, or features of Turner syndrome. A 14-year-old patient was referred to the genetics clinic due to hypospadia, cryptorchidism, and aortic coarctation. During the physical examination, short stature, webbed neck, and Blashko lines on his back were noted. He had a previous karyotype reported as normal. However, due to an inadequate evolution and a low resolution on the previous test, a higher resolution karyotype was performed, identifying a mosaicism 45,X/46,XY. A multidisciplinary board examined the case, and follow-up with tumor markers was carried out to evaluate the presence of gonadoblastoma, one of the main complications in these patients. Treatment should be transdisciplinary and focused on the particular characteristics of each case. Other treatment alternatives include corrective surgery and hormonal therapy.

scholarly journals EARLY-ONSET GONADOBLASTOMA IN A 13-MONTH-OLD INFANT WITH 46,XY COMPLETE GONADAL DYSGENESIS IDENTIFIED WITH PRENATAL TESTING: A CASE OF CHROMOSOME 9p DELETION

2019 ◽  
Vol 5 (6) ◽  
pp. e380-e383
Author(s):  
Meghan E. Fredette ◽  
Katelyn Cusmano ◽  
Chanika Phornphutkul ◽  
Jennifer Schwab ◽  
Anthony Caldamone ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Gonadal Dysgenesis ◽  
Prenatal Testing ◽  
Testicular Development ◽  
Disorders Of Sexual Development ◽  
Current Recommendation ◽  
Fetal Ultrasound ◽  
Dmrt1 Gene ◽  
Chromosome 9P ◽  
Complete Gonadal Dysgenesis

Objective: Individuals with 46,XY complete gonadal dysgenesis (CGD) are at high risk of developing gonadal neoplasms. Chromosome 9p monosomy with deletion of the DMRT1 gene, a key transcription factor in testicular development, is one of the known causes of 46,XY CGD. Noninvasive prenatal testing (NIPT) is being increasingly used, and can identify disorders of sexual development (DSDs). Methods: We report the case of a 46,XY infant with phenotypically female external genitalia, müllerian structures including uterus and fallopian tubes, and bilateral streak gonads who was found to have unilateral gonadoblastoma at 13 months. 46,XY DSD was suggested prenatally when discordance between NIPT and fetal ultrasound was noted. Results: Genetic investigation revealed a deletion of 12.5 million base pairs at chromosome 9p24.3, which includes the doublesex and MAB-3-related transcription factor-1 ( DMRT1) gene. Conclusion: Current guidelines recommend gonadectomy at the time of diagnosis in cases of 46,XY CGD, and our patient had gonadoblastoma at 13 months. 46,XY DSD, including rare disorders such as CGD, will be increasingly identified before birth with more widespread use of NIPT, raising the question about the appropriate timing of gonadectomy in prenatal diagnoses. Our case supports the current recommendation to perform gonadectomy as early as possible after diagnosis.

Clinical and Molecular Cytogenetic Characteristics of Five Cases with Isodicentric Y Chromosome

2021 ◽  
pp. 1-9
Author(s):  
María C. Manotas ◽  
Mary García-Acero ◽  
Daniel M. González ◽  
Olga M. Moreno ◽  
Fernando Suárez-Obando ◽  
...  
Keyword(s):  
Y Chromosome ◽  
Disorders Of Sex Development ◽  
Molecular Cytogenetics ◽  
Ambiguous Genitalia ◽  
Disorders Of Sexual Development ◽  
Sex Development ◽  
Y Chromosomes ◽  
Probable Loss ◽  
Mosaic Form ◽  
X Cells

Isodicentric Y chromosome [idic(Y)] is one of the most common structural abnormalities of the Y chromosome and has been observed in patients with reproductive disorders and in patients with disorders of sexual development. Most idic(Y) chromosomes are found in mosaic form with a 45,X cell line. These chromosomes are highly unstable during mitosis due to the presence of 2 centromers, which explains their probable loss in early mitosis or mitosis of the embryo and therefore the presence of the 45,X line. It has been hypothesized that the proportion of 45,X cells in various tissues probably influences the phenotypic sex of individuals carrying an idic(Y) chromosome, ranging from infertile men, hypospadias, ambiguous genitalia, and Turner syndrome to sex reversal. In this article we present 5 cases of patients with idic(Y) referred for suspected disorder of sex development (DSD), 3 with a male assignment and 2 with a female assignment. All cases have variable clinical characteristics, which were assessed by the transdisciplinary group of Disorders of Sex Development of the Hospital Universitario San Ignacio, Bogotá, Colombia. Patients were analyzed by conventional and molecular cytogenetics using high-resolution G-band and FISH techniques. Our findings highlight the importance of cytogenetic studies in the diagnosis of DSD patients.

GONADAL HISTOLOGY IN PATIENTS WITH MALE PSEUDOHERMAPHRODITISM AND ATYPICAL GONADAL DYSGENESIS: RELATION TO THEORIES OF SEX DIFFERENTIATION

1962 ◽  
Vol 40 (4) ◽  
pp. 493-520 ◽  
Author(s):  
Cesar Bergada ◽  
William W. Cleveland ◽  
Howard W. Jones ◽  
Lawson Wilkins
Keyword(s):  
Gonadal Dysgenesis ◽  
Sex Differentiation ◽  
External Genitalia ◽  
The Other ◽  
Male Pseudohermaphroditism ◽  
Chromosomal Mosaicism ◽  
Normal Male ◽  
Turner's Syndrome ◽  
Turner’S Syndrome ◽  
Gonadal Histology

ABSTRACT The anatomic findings and gonadal histology of 41 patients who had atypical forms of gonadal dysgenesis or of male pseudohermaphroditism are described. Fourteen of these cases were classified as atypical gonadal dysgenesis because there were gross evidences of abnormal gonadal development, differing from those of classical Turner's syndrome. In this group there was no incidence of familial inheritance but there were evidences of chromosomal aberrations. Two patients diagnosed as »gonadal dysplasia« had primitive genital streaks differing from those of typical gonadal aplasia (Turner's Syndrome) only in the presence of masses of Leydig-like cells. That this condition is a variant of gonadal aplasia is suggested by the association of short stature in one case and by the demonstration in the other case of chromosomal mosaicism of XO/XX pattern, with the XO cell type predominant as in chromatin-negative Turner's Syndrome. Ten patients had »asymmetrical gonadal differentiation« with a testis on one side and on the other side either no gonad (2 cases), a primitive genital streak (6 cases) or an undifferentiated gonad (2 cases). Among these mosaicism of XO/XY type was demonstrated in one case and it is suspected that more intensive chromosomal studies in the future may show a high incidence of mosaicism or other chromosomal aberration in this group. In addition 2 cases of true hermaphroditism are described. There were 27 male pseudohermaphrodites who had two testes with no histological evidences of dysgenesis. Eight of these patients had female external genitalia and 19 had genitalia which were ambiguous or resembled the male. In 4 patients of the latter group there were completely developed uterus and Fallopian tubes. Since the testes of all the male hermaphrodites showed good development of the medullary components believed to be responsible for male differentiation, it must be assumed that there was a defect in the biosynthesis of the »male organizing substances« of the foetal testes. Normal male XY chromosomal patterns were found in all of our cases which were studied and have been reported by other workers. The high familial incidence of this disorder suggests that an enzyme defect is transmitted by a mutant gene. In the »syndrome of feminizing testes« the demonstration of oestrogenic manifestations after puberty is further evidence of an abnormality of synthesis of testicular hormones. The correlation of gonadal pathology and the sex differentiation of gonaducts and external genitalia is compatible with the theory of Jost that normal masculinization is dependant upon the production of adequate amounts of masculinizing substances by the foetal testes. Discordances between the degree of masculinization (or feminization) of the gonaducts and the external genitalia can be explained only by postulating that there are at least two substances concerned; one causing masculinization of the Wolffian ducts and external genitalia and the other causing disappearance of the Mullerian ducts.

scholarly journals An N-terminal WT1 mutation (P181S) in an XY patient with ambiguous genitalia, normal testosterone production, absence of kidney disease and associated heart defect: enlarging the phenotypic spectrum of WT1 defects

2004 ◽  
pp. 825-830 ◽  
Author(s):  
B Kohler ◽  
C Pienkowski ◽  
F Audran ◽  
M Delsol ◽  
M Tauber ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Gonadal Dysgenesis ◽  
Molecular Mechanisms ◽  
Kidney Development ◽  
Wilms Tumor ◽  
Ambiguous Genitalia ◽  
Normal Male ◽  
Heterozygous Mutation ◽  
Wt1 Gene ◽  
Heart Defect

OBJECTIVE: This study reports the clinical and molecular data of an XY patient with a very unusual phenotype due to a Wilms' tumor-suppressor (WT1) gene mutation. The genotype-phenotype relationship of different WT1 mutations is then discussed. PATIENT: The patient presented at birth with micropenis, severe hypospadias and cryptorchidism. Normal androgen production and an absence of clinical response to a testosterone treatment trial suggested partial androgen resistance. Eventually, female sex of rearing was chosen. At the beginning of puberty, normal male androgen production occurred, and subsequent gonadectomy did not show gonadal dysgenesis. It is notable that the patient, now 20 years of age, has not developed kidney disease. In addition to the genital malformation, the patient displayed an associated congenital heart defect, consisting of a coarctation of the aorta and a patent ductus arteriosis (PDA). RESULTS: No mutations were detected in the androgen receptor or 5alpha-reductase genes. Direct sequencing of the WT1 gene identified a heterozygous proline to serine substitution at position 181 (P181S). The same heterozygous mutation was found in the mother. Interestingly, the mother shows no signs of kidney disease at her present age of 49. CONCLUSION: This is the first germline missense mutation in the N-terminal part of WT1 identified in a patient with the very particular phenotype of ambiguous genitalia with absence of gonadal dysgenesis and kidney disease. The possible molecular mechanisms leading to the patient's phenotype are considered. The high frequency of PDA in newborns and the absence of heart abnormalities in XX females carrying the P181S mutation, however, suggest that the heart defect was most likely a coincidental association. This case enlarges the clinical spectrum of WT1 defects and may provide new insights into the complex functions of WT1 in genital and kidney development.

scholarly journals X/XY Chromosome Mosaicism: Turner Syndrome and Other Clinical Conditions

2009 ◽  
Vol 63 (1-2) ◽  
pp. 1-4
Author(s):  
Irena Andriuškevičiūtė ◽  
Loreta Šalomskienė ◽  
Lina Jurkėnienė ◽  
Algimantas Sinkus
Keyword(s):  
Turner Syndrome ◽  
Y Chromosome ◽  
Wide Spectrum ◽  
Normal Male ◽  
Chromosome Mosaicism ◽  
Lymphocyte Cultures ◽  
Nosological Entity ◽  
The One ◽  
Clinical Conditions ◽  
Pierre Robin

X/XY Chromosome Mosaicism: Turner Syndrome and Other Clinical Conditions The 45,X/46,XY mosaicism shows a wide spectrum of phenotypes ranging from females with Turner syndrome, male or female pseudohermaphroditism, to appearently normal male development. Chromosome anomalies accompanying Turner syndrome were found in lymphocyte cultures of 236 patients. Chromosomal analysis revealed the karyotype 45,X in 118 (50.0%) patients. X monosomy mosaics or structural rearrangements of the X chromosome was established in 112 (47.5%) patients. The Y chromosome was found in six (2.5%) patients with typical features of Turner syndrome. In five mosaics 45,X/46,XY the proportion of the XY clone ranged from 46% to 76%. In one Turner syndrome patient only 47,XYY cells were found (solely blood culture investigated). In most cases of 45,X/46,XY mosaicism, the cause is considered to be the loss of the Y chromosome because of nondisjunction after normal disomic fertilisation. Five other patients with X/XY chromosome mosaicism showed mixed gonadal dysgenesis (two patients), one male pseudohermafroditism, one male with Pierre Robin syndrome, and one normal male phenotype. In two non Turner syndrome patients nondisjunction of the primary clone 46,XY was obvious and resulted in mosaicism 45,X/46,XY/47,XYY, the one patient contained dicentric Y. The similarities between X/XY Turner syndrome and other nosological entity of females possessing Y chromosome — the Swyer syndrome — are discussed.

scholarly journals CLINICAL CASE OF A SUCCESSFUL PREGNANCY WITH THE COMPLETE FORM OF GONADAL DYSGENESIS - SWYER SYNDROME

2019 ◽  
Vol 6 (4) ◽  
pp. 225-228
Author(s):  
Elena V. Timokhina ◽  
N. V Afanas’yeva ◽  
Yu. A Samoylova ◽  
T. M Silayeva ◽  
V. S Belousova ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Gonadal Dysgenesis ◽  
Clinical Case ◽  
Reproductive Technology ◽  
Sry Gene ◽  
Successful Pregnancy ◽  
Pregnancy And Delivery ◽  
Complete Form ◽  
Swyer Syndrome ◽  
Complete Gonadal Dysgenesis

Swyer syndrome (46,XY complete gonadal dysgenesis) is a rare chromosomal pathology. This pathology occurs with a frequency of 1 in 80,000. In genetic analysis, mutations are most often found in the following genes: the SRY gene, the NR5A1 gene, the SOX9 gene, the MAP3K1 gene. Patients with this disease develop phenotypically as women, but due to the absence of gonads and eggs, independent pregnancy is impossible. This article describes a clinical case of a successful onset, course of pregnancy and delivery in a woman with Swyer syndrome using assisted reproductive technology.

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