Query: dsd female

title: Female fertility preservation in DSD.
abstract: Disorders of sex development (DSD) are a group of complex conditions that can affect chromosomal, gonadal, and/or phenotypical sex with a highly variable fertility potential amongst affected individuals. In this review we discuss fertility issues facing patients affected by DSD and Turner syndrome and summarise the literature on fertility and reproductive outcomes. We will also discuss fertility preservation prior to gonadotoxic treatment in adolescent and prepubertal girls. Future directions in fertility preservation and ethical issues will also be addressed. Fertility preserving options that are established include ovarian tissue and oocyte cryopreservation. However, in many of the DSDs fertility is not possible and the discussion may need to move toward alternative methods of creating a family such as gamete donation or surrogacy.

title: Bilateral Inguinal Hernias in a Phenotypic Female Should Raise the Suspicion for a Disorder of Sexual Development (DSD)
abstract: Disorders of sexual development are rare and carry high potential for medical and psychosocial co morbidities. A 4 year old female presented with non reducible bilateral inguinal masses. Physical exam was consistent with a healthy child with a normal external female genitourinary exam, sexual maturity rating 1. Elective general surgical repair was scheduled. Pre surgical ultrasound imaging revealed isolated loops of bowel in each inguinal canal, no other inguinal masses, a visualized cervix, and non visualized uterus. Further work up was initiated upon recommendations from urology given rare

title: Rare Forms of Disorders of Sex Development (DSD) in Patients with Female Phenotype
abstract: Disorders of Sex development (DSD) belong to uncommon pathologies; in addition, there are especially rare forms, such are ovotesticular disorders (OT) Turner Syndrome and early malignisation of intraabdominal located gonads in the cases of androgen insensitivity syndrome. In this article we present 5 rare cases of DSD in female phenotype patients: 3 cases of ovotesticular DSD with 46,XX and 46,XY karyotypes; 1 familial case of AIS with early malignancy (19 year old) of intraabdominally located testicle in older sibs; and a case of spontaneous menstruation in a patient with Turner syndrome and mosaic karyotype 45,X/47,XXX. Rare cases of DSD are connected with diagnostic and management difficulties and so description of each such case and collection of data in this field is very important from a scientific as well as a practical point of view. Determination of prognosis and adequate management of each individual patient are also essential. Study of this issue is especially sensitive in the case of adolescent patients, in order to avoid physiological stress, to reduce health risks, and to improve the quality of their life.

title: Gonadal Dysgenesis with Special Emphasis on the Molecular Mechanisms of SRY Mutations in Disorders of Sex Development (DSD) Reulting in Female Sex Reversal in 46XY Males
abstract: SRY related high mobility group box (Sox) transcription factors have emerged in the animal kingdom to help cells maintain stemness, commit to a specific lineage, proliferate or die. Encoded by 20 genes in humans and mice they show a highly conserved high mobility group boxdomain, which was originally identified in SRY, the sex determining region on the Y chromosome. This has derived from a high mobility group domain characterized of chromatin associated proteins. HMG (high mobility group) non histone chromosomal proteins include the AT hook, HMGN, and HMG domain families.

title: Natural Selection for Genetic Variants in Sport: The Role of Y Chromosome Genes in Elite Female Athletes with 46,XY DSD
abstract: At present, it is widely assumed that hyperandrogenism in female athletes confers an unfair competitive advantage. This view is perpetuated in current regulations governing eligibility of female athletes with hyperandrogenism to compete, which identify testosterone levels in the male range as the critical factor. Detailed evidence is presented here for the first time that genes for stature (and possibly other genes) on the Y chromosome are responsible for the increased frequency of 46,XY disorder of sex development (46,XY DSD) among elite female athletes identified by eligibility tests. In many cases, androgens are non functional or, alternatively, absent and therefore testosterone cannot be responsible for their athletic success. Genetic variation has a major role in the selection of individuals for training and success in competition; however, this variation is not grounds for determining who should compete in athletic events. There is no convincing evidence to support the view that hyperandrogenism is associated with performance advantage in female athletes. Current time consuming regulations may lead to the unwelcome resurgence of innuendo in the media and coercion of female athletes into accepting gonadectomy and other treatments to which they might otherwise not have been subjected. These regulations should be withdrawn on the grounds that they are not supported scientifically, are discriminatory towards women and place some female athletes at risk of unnecessary and potentially harmful investigations. Improved understanding about genetic factors that lead to selection in sport should offer reassurance that women with hyperandrogenism possess no physical attribute relevant to athletic performance that is neither attainable, nor present in other women.

title: The effect of hormone therapy on biochemical and ultrasound parameters associated with atherosclerosis in 46,XY DSD individuals with female phenotype
abstract: The aim of this study was to evaluate the effect of hormone therapy (HT) in the endothelial function of 46,XY disorders of sexual development (DSD) patients with female phenotype. Biochemical and ultrasound measurements were performed in 20 patients at initiation of oral 2 mg 17b estradiol/1 mg norethisterone acetate, and after 6 months of therapy. Lipid profile, including total cholesterol (TC) LDL, HDL, triglycerides (TG) and Atherogenic Index of Plasma (AIP) as well as levels of VE Cadherin, E Selectin, Thrombomodulin and vWf were determined. Ultrasonographic examinations included evaluation of flow mediated dilatation (FMD) and measurement of Carotid and Femoral Intima Media Thickness (IMT) HT raised HDL (35.4 mg/dl versus 40.1 mg/dl, p 0.019) while lowering TG (166 mg/dl versus 109 mg/dl, p 0.026) and AIP (0.24 versus 0.04, p 0.007) No changes were noted in TC and LDL (215.7 mg/dl versus 192.25 mg/dl and 87.46 mg/dl versus 76.35 mg/dl, respectively) There was significant reduction of VE Cadherin (4.05 ng/ml versus 2.20 ng/ml, p 0.002) and E selectin (73.98 ng/ml versus 56.73 ng/ml, p 0.004) No change was observed in Thrombomodulin and vWf (11.76 ng/ml versus 13.90 ng/ml and 80.75% versus 79.55% respectively) FMD improved significantly (5.4% versus 8.15% p 0.003) while only carotid bulb IMT decreased significantly (0.65 mm versus 0.60 mm, p 0.018) Overall, HT was found to improve biochemical and ultrasound markers of endothelial function in 46,XY DSD patients with female phenotype.  Ben Shi Yan Zhi Zai Ping Gu Ji Su Zhi Liao (HT)Dui Xing Fa Yu Yi Chang Nu Xing Biao Xing Huan Zhe (46,XY)Nei Pi Gong Neng De Ying Xiang Dui 20Ming Huan Zhe Jin Xing Sheng Hua He Chao Sheng Ce Liang ,Zhi Liao De Chu Shi Kou Fu Ji Liang Wei 2mg 17b Ci Er Chun /1mgCu Suan Gui Nuo Tong ,Zhi Liao 6Ge Yue Hou ,Ce Ding Qi Zhi Lei Dai Xie (Bao Gua Zong Dan Gu Chun [TC] LDL, HDL, Gan You San Zhi [TG] Xie Jiang Zhi Dong Mai Zhou Yang  Shi Jiang Di TG(166mg/dlHe 109mg/dl,p=0.026)He AIP(0.24He 0.04, p=0.007) TCHe LDLWei Jian Dao Ming Xian Bian Hua (Fen Bie Wei 215.7 mg/dlHe 192.25 mg/dl,87.46 mg/dlHe 76.35 mg/dl) Xie Guan Nei Pi Gai Nian Dan Bai (4.05 ng/mlHe 2.20 ng/ml, p=0.002) He EXuan Ze Su (73.98 ng/mlHe 56.73 ng/ml, p=0.004)Xian Zhu Jiang Di Xie Shuan Diao Jie Dan Bai He vWFYin Zi Wei Jian Ce Dao Ming Xian Bian Hua (Fen Bie Wei 11.76 ng/mlHe 13.90 ng/ml and 80.75%He 79.55% FMD Xian Zhu Ti Gao (5.4%He 8.15% p=0.003) Er Zhi You Jing Dong Mai Dou Bu IMTXian Zhu Jiang Di (0.65mm He 0.60 mm, p=0.018) Zong Zhi ,HTBei Fa Xian Ke Yi Ti Gao Xing Fa Yu Yi Chang Nu Xing Biao Xing Huan Zhe (46,XY)Nei Pi Gong Neng De Sheng Hua He Chao Sheng Jian Ce Biao Ji

title: Rare association in a female DSD case of phallus, accessory phallic urethra, perineal lipoma and anterior ectopic anus.
abstract: Disorders of sex differentiation (DSD) are a heterogeneous and broad spectrum group of diseases with a varied appearance. Presence of an accessory phallus with a phallic urethra in association with a normal vagina in a female is an extremely uncommon anomaly. We present a rare case of a genotypically female child with a normal urethra and vagina in association with a phallus, accessory phallic urethra, perineal lipoma and anterior ectopic anus.

title: Recognition of 5a reductase 2 deficiency in an adult female 46XY DSD clinic.
abstract: The late presentation of steroid 5a reductase 2 (SRD5A2) deficiency in females is poorly characterised. The ratios of 5a/5b reduced metabolites of adrenal steroids in a urine steroid profile (USP) can give an indication of SRD5A2 deficiency, although the diagnostic cut off for 5a/5b ratios are not clearly defined in genetically confirmed cases.  The aim of this study was to establish the frequency of SRD5A2 deficiency in an adult clinic for disorders of sexual development (DSD) focussing on 46XY partially virilised adult female subjects. We investigated the relationship between USP results and SRD5A2 genetic sequence and determined the cut off for USP 5a/5b reduced steroid ratios compared with gene sequencing for the identification of SRD5A2 deficiency.  USP and SRD5A2 genetic analyses were performed in 23 adult females, aged 19 57 years, with 46XY DSD and in four males with confirmed SRD5A2 deficiency. 5a Reductase activity was assessed using the USP ratio of androsterone to aetiocholanolone (A/Ae) 5a tetrahydrocortisol (5a THF)/tetrahydrocortisol (THF) and 5a tetrahydrocorticosterone to tetrahydrocorticosterone (5a THB/THB)  The SRD5A2 gene mutations were found in 10/23 (43% females and in all four males. Totally, four novel mutations were identified. All mutation positive subjects had A/Ae and 5a THB/THB ratios below the lower limit of normal (100% sensitivity) while the sensitivity of 5a THF/THF ratio was 90% CONCLUSION SRD5A2 deficiency is more prevalent than expected in the adult female 46XY DSD population. The clinical spectrum of this disorder may extend to a more female phenotype than previously considered to include individuals with little or no virilisation.

title: A 46,XY Female DSD Patient with Bilateral Gonadoblastoma, a Novel SRY Missense Mutation Combined with a WT1 KTS Splice Site Mutation
abstract: Patients with Disorders of Sex Development (DSD) especially those with gonadal dysgenesis and hypovirilization are at risk of developing malignant type II germ cell tumors/cancer (GCC) (seminoma/dysgerminoma and nonseminoma) with either carcinoma in situ (CIS) or gonadoblastoma (GB) as precursor lesion. In 10 15% of 46,XY gonadal dysgenesis cases (i.e. Swyer syndrome) SRY mutations, residing in the HMG (High Mobility Group) domain, are found to affect nuclear transport or binding to and bending of DNA. Frasier syndrome (FS) is characterized by gonadal dysgenesis with a high risk for development of GB as well as chronic renal failure in early adulthood, and is known to arise from a splice site mutation in intron 9 of the Wilms' tumor 1 gene (WT1) Mutations in SRY as well as WT1 can lead to diminished expression and function of SRY, resulting in sub optimal SOX9 expression, Sertoli cell formation and subsequent lack of proper testicular development. Embryonic germ cells residing in this unfavourable micro environment have an increased risk for malignant transformation. Here a unique case of a phenotypically normal female (age 22 years) is reported, presenting with primary amenorrhoea, later diagnosed as hypergonadotropic hypogonadism on the basis of 46,XY gonadal dygenesis with a novel missense mutation in SRY. Functional in vitro studies showed no convincing protein malfunctioning. Laparoscopic examination revealed streak ovaries and a normal, but small, uterus. Pathological examination demonstrated bilateral GB and dysgerminoma, confirmed by immunohistochemistry. Occurrence of a delayed progressive kidney failure (focal segmental glomerular sclerosis) triggered analysis of WT1, revealing a pathogenic splice site mutation in intron 9. Analysis of the SRY gene in an additional five FS cases did not reveal any mutations. The case presented shows the importance of multi gene based diagnosis of DSD patients, allowing early diagnosis and treatment, thus preventing putative development of an invasive cancer.

title: Rare cases of disorders of sex development (DSD) in adolescents with female phenotype
abstract: Disorders of sex development (DSD) belong to uncommon pathologies; in addition, there are especially rare forms, such are ovotesticular disorders (OT) Turner syndrome and early malignisation of intraabdominal located gonads in the cases of androgen insensitivity syndrome.  In this article we present four rare cases of DSD in female phenotype adolescents: two cases of ovotesticular DSD with 46,XX and 46,XY karyotypes; one familial case of androgen insensitivity syndrome (AIS) with early malignancy (19 year old) of intra abdominally located testicle in older siblings, and a case of spontaneous menstruation in a patient with Turner syndrome and mosaic karyotype 45,X/47,XXX. Rare cases of DSD are connected with diagnostic and management difficulties and so description of each such case and collection of data in this field is very important from a scientific, as well as a practical, point of view. Determination of prognosis and adequate management of each individual patient are also essential. Study of this issue is especially sensitive in the case of adolescent patients in order to avoid physiological stress, to reduce health risks and to improve quality of life.