Sex Chromosome Anomalies
Merlin G. Butler, F. John Meaney in Genetics of Developmental Disabilities, 2019
46,XY females with gonadal dysgenesis also have a significantly increased risk of developing tumors in the streak gonads, particularly gonadoblastomas, dysgerminomas, and juvenile granulosa cell tumors. Hamerton (38) reviewed the clinical findings in 20 patients with 46,XY gonadal dysgenesis and reported eight to have some form of gonadal malignancy, most frequently a gonadoblastoma. More recently, Radakovic (181) performed bilateral gonadectomies on 20 patients with 46,XY gonadal dysgenesis, and found 11 with gonadoblastomas or other streak gonad tumors. Based on the high frequency of gonadoblastomas in 46,XY females, the presence of a gonadoblastoma susceptibility gene (GBY) on the Y chromosome has been postulated (182,183). Molecular analysis of the Y chromosome in patients with XY gonadal dysgenesis and gonadal tumors found various deletions, missense mutations, or nucleotide substitutions in SRY in four of six patients (184,185). However, as deletions or mutations of SRY are known to be one of the etiological factors in XY gonadal dysgenesis, it is probable that the association between SRY and a high frequency of gonadoblastoma and other germ cell tumors is indirect. A more promising candidate for GBY may lie in a 4 Mb region in the proximal part of Yq that Salo et al. (186) identified as a region of overlap in two patients with gonadoblastoma who were carrying small marker chromosomes. While the precise molecular basis for their increased risk of gonadal tumors remains unknown, patients with XY gonadal dysgenesis obviously require detailed counseling and should be offered preventative gonadectomy.
Disorders of sexual differentiation
Brice Antao, S Irish Michael, Anthony Lander, S Rothenberg MD Steven in Succeeding in Paediatric Surgery Examinations, 2017
Children with Turner’s syndrome (45,XO) have characteristic clinical findings including short stature, coarctation of the aorta, streak gonads and a shield-shaped chest. These children often present with primary amenorrhoea if not diagnosed at a younger age. A male neonate with 21-hydroxylase deficiency is at risk for salt wasting and may present with vomiting and dehydration. Children suspected of having CAH should always have a basic metabolic panel included in their initial evaluation. A phenotypic female with a 46,XY karyotype, and an absent uterus on pelvic ultrasound has complete androgen insensitivity syndrome and will have a very elevated serum testosterone level. This clinical scenario is in contrast to patients with Swyer’s syndrome who are phenotypically female with a 46,XY karyotype and gonadal dysgenesis, in that patients with Swyer’s syndrome will have müllerian structures present.
Egg and embryo donation
David K. Gardner, Ariel Weissman, Colin M. Howles, Zeev Shoham in Textbook of Assisted Reproductive Techniques, 2017
Non-iatrogenic POI, defined as women <40 years old with persistent amenorrhea and elevated gonadotropins, affects approximately 1% of the female population (13). The majority of cases are idiopathic, but about 20% are suspected of being autoimmune in nature or the result of concomitant glandular autoimmune disease (14). Thus, it is important to ensure that clinical or subclinical failure of the thyroid, parathyroid, and adrenal glands does not coexist, as well as diabetes mellitus and myasthenia gravis. Any of these conditions may adversely affect pregnancy outcome as well as impact upon the general health and well-being of the patient. If POI occurs at <30 years old, a karyotype should also be requested to ascertain the presence of Y-chromosome mosaicism. Patients discovered to be mosaic are at risk of gonadal tumors and require extirpation of the abnormal gonad (15). In addition, a bone density evaluation is helpful to identify patients with osteopenia or osteoporosis, which may be present despite hormonereplacement therapy (16). Turner syndrome is the most common gonadal dysgenesis in women, with a prevalence of 1 in 2000 live-born females. Both spontaneous puberty and spontaneous pregnancy are relatively rare in these patients, occurring in less than 5% of affected individuals (17). Other rare conditions associated with POI include congenital thymic aplasia (e.g., DiGeorge syndrome) (18), galactosemia (19), and ataxia-telangiectasia (20), all of which require a more thorough and specific evaluation.
Sex chromosome DSD individuals with mosaic 45,X0 and aberrant Y chromosomes in 46,XY cells: distinct gender phenotypes and germ cell tumour risks§
Published in Systems Biology in Reproductive Medicine, 2022
Peter H. Vogt, Banu Besikoglu, Markus Bettendorf, Petra Frank-Herrmann, Jutta Zimmer, Urike Bender, Sabine Knauer-Fischer, Daniela Choukair, Peter Sinn, Helmuth-Guenther Doerr, Joachim Woelfle, Peter H. Heidemann, Yun-Fai Chris Lau, Thomas Strowitzki
In human, the 45,X/46,XY karyotype can be associated with Turner syndrome (TS), with mixed gonadal dysgenesis (MGD), earlier also called male pseudohermaphroditism (MPH) and with apparently a normal male phenotype, although infertile (Simpson 1978). Today, these patient groups are summarized under an umbrella coined: “Differences of Sexual Development” (DSD) individuals (Hughes et al. 2006). In the subgroup of “Sex chromosome DSD” individuals with rearrangements or break events on the Y chromosome, sexual gender assignment in the clinic after birth is challenging (Vidal et al. 2010). Current guidelines, therefore, propose child’s/adolescent’s sex assignment first when she/he is able to express autonomously her/his perception of gender identity (Weidler et al. 2019).
Contemporary genetics-based diagnostics of male infertility
Published in Expert Review of Molecular Diagnostics, 2019
Alberto Ferlin, Savina Dipresa, Andrea Delbarba, Filippo Maffezzoni, Teresa Porcelli, Carlo Cappelli, Carlo Foresta
Men with 45,X/46,XY Mixed gonadal dysgenesis may present at birth with ambiguous genitalia or as adults with infertility, gonadal failure and/or short stature [34]. Phenotype is variable and gonads may develop into testicles or undifferentiated streaks, and may be located in the scrotum, intra-abdominally, or along the path of descent in the inguinal canal. Individuals with bilateral scrotal testicles typically present as a male with short stature and gonadal failure, quite invariably azoospermia and very rare chance of sperm retrieval by TESE [35]. About half of them have primary hypogonadism with need for testosterone replacement [36]. This syndrome might present also cardiac and renal malformations, gonadoblastoma, and germ cell tumors.
A case series of patients with gonadal dysgenesis-associated mixed malignant ovarian germ cell tumor
Published in Gynecological Endocrinology, 2020
Wenqing Yang, Lisha Wu, Qiongqiong He, Yi Zhang, Yu Zhang, Yan Tian
Gonadal dysgenesis is a rare condition, which comprises a large group of congenital conditions of the urogenital tract and reproductive system, affecting human gender determination and/or differentiation. In present study, we identified five phenotypic females with gonadal dysgenesis associated ovarian tumors. A previous review showed that up to 5% of patients with dysgerminoma are phenotypic females with 46, XY karyotype [4]. Dysgenetic gonads in the presence of Y chromosomal material confer a rising risk of gonadoblastoma [5]. Due to the increased risk of malignant transformation, possibly related to the rise in androgen exposure from puberty onwards [6], prophylactic gonadectomy is recommended at diagnosis.
Related Knowledge Centers
- Disorders of Sex Development
- Gonad
- Infertility
- Ovary
- Puberty
- Embryo
- Connective Tissue
- Disorders of Sex Development
- Aplasia
- Secondary Sex Characteristic
- Xy Sex-Determination System