Proximal Hypospadias Repair Outcomes in Patients with a Specific Disorder of Sexual Development Diagnosis

Boys with undermasculinized external genital and/or 46,XY disorders of sex development (DSD) often receive masculinizing genitoplasty. Such procedures are done to correct ventral curvature of the phallus, reposition a proximally located urethral meatus, and cosmetically correct the appearance of labioscrotal folds. No studies to date have assessed if patients with a specific DSD diagnosis have worse outcomes for severe proximal hypospadias procedures or whether or not these patients require more extensive surgical maneuvers than severe proximal hypospadias patients without a specific DSD diagnosis. We retrospectively reviewed consecutive proximal hypospadias repairs performed at our institution from 1998 to 2010 and compared the anatomy, surgical technique required for repair, and outcomes in patients with and without a definitive DSD diagnosis. Boys with a specific DSD diagnosis do have significantly more atypical anatomy when undergoing proximal hypospadias masculinizing genitoplasties. They are more likely to require associated gonad procedures but do not have an increased risk of complications or number of surgeries when compared to other proximal hypospadias patients without a specific DSD diagnosis. The risk of complications is consistent with reports in the literature, and the mean number of procedures in this contemporary study is fewer than in historic reports.

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Psychological Adjustment and Sexual Development of Adolescents With Disorders of Sex Development

Journal of Adolescent Health ◽

10.1016/j.jadohealth.2010.03.007 ◽

2010 ◽

Vol 47 (5) ◽

pp. 463-471 ◽

Cited By ~ 47

Author(s):

Eva Kleinemeier ◽

Martina Jürgensen ◽

Anke Lux ◽

Pia-Marie Widenka ◽

Ute Thyen

Keyword(s):

Psychological Adjustment ◽

Sexual Development ◽

Disorders Of Sex Development ◽

Sex Development

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Female Hyperandrogenism in Elite Sports and the Athletic Triad

Seminars in Reproductive Medicine ◽

10.1055/s-0041-1736337 ◽

2021 ◽

Author(s):

Angelica Lindén Hirschberg

Keyword(s):

Female Athletes ◽

Polycystic Ovary ◽

Disorders Of Sex Development ◽

Normal Female ◽

Menstrual Disorders ◽

Mineral Density ◽

Energy Deficiency ◽

Sex Development ◽

Endocrine Disturbances ◽

Increased Risk

AbstractEssential hyperandrogenism seems to be overrepresented in female elite athletes. This applies to mild forms such as polycystic ovary syndrome, as well as rare differences/disorders of sex development (DSD). The reason is likely a selection bias since there is increasing evidence that androgens are beneficial for athletic performance by potent anabolic effects on muscle mass and bone mass, and stimulation of erythropoiesis. XY DSD may cause a greatly increased production of testosterone in the male range, that is, 10 to 20 times higher than the normal female range. The established regulations concerning the eligibility of female athletes with severe hyperandrogenism to compete in the female classification remain controversial. The most common cause of menstrual disorders in female athletes, however, is probably an acquired functional hypothalamic disturbance due to energy deficiency in relation to energy expenditure, which could lead to low bone mineral density and increased risk of injury. This condition is particularly common in endurance and esthetic sports, where a lean body composition is considered an advantage for physical performance. It is important to carefully evaluate endocrine disturbances and menstrual disorders in athletes since the management should be specific according to the underlying cause.

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Psychological Problem in Pediatric Disorder of Sex Development Patient and Relatives

Open Access Indonesian Journal of Medical Reviews ◽

10.37275/oaijmr.v1i2.552 ◽

2021 ◽

Vol 1 (2) ◽

pp. 24-27

Author(s):

Erlangga Danu Saputro

Keyword(s):

Sexual Development ◽

Psychosocial Problems ◽

Psychological Problem ◽

Systematic Search ◽

Basic Data ◽

Disorder Of Sex Development ◽

Sex Development ◽

Disorder Of Sexual Development ◽

Counselling Program

Disorder of sexual development (DSD) is one of challenging disorder that has to be done clinically and physiologically. The patients and relatives may experience various psychosocial problems that have an impact on their live. The aim of this study is to look at psychological problem in children with DSD and their relatives. A systematic search was conducted in PubMed for articles representing information on psychological problem to the patient and their relatives. Relevant data were extracted and narratively reviewed. The result of this review can be used as basic data in the development of counselling program for the patients and their relatives.

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Disorders of Sex Development in Individuals Harbouring MAMLD1 Variants: WES and Interactome Evidence of Oligogenic Inheritance

Frontiers in Endocrinology ◽

10.3389/fendo.2020.582516 ◽

2020 ◽

Vol 11 ◽

Author(s):

Lele Li ◽

Fenqi Gao ◽

Lijun Fan ◽

Chang Su ◽

Xuejun Liang ◽

...

Keyword(s):

Sexual Development ◽

Disorders Of Sex Development ◽

Specific Gene ◽

Causative Role ◽

Sex Development ◽

Whole Exome ◽

Clinical Series ◽

Oligogenic Inheritance ◽

Mode Of Inheritance

Mastermind-like domain-containing 1 (MAMLD1) has been shown to play an important role in the process of sexual development and is associated with 46,XY disorders of sex development (DSDs). However, the causative role of MAMLD1 variations in DSDs remains disputable. In this study, we have described a clinical series on children from unrelated families with 46,XY DSD harbouring MAMLD1 variants. Whole exome sequencing (WES) was performed for each patient. WES data were filtered using common tools and disease customisation algorithms, including comparison against lists of known and candidate MAMLD1-related and DSD-related genes. Lastly, we investigated the hypothesis that MAMLD1-related DSD may follow an oligogenic mode of inheritance. Forty-three potentially deleterious/candidate variants of 18 genes (RET, CDH23, MYO7A, NOTCH2, MAML1, MAML2, CYP1A1, WNT9B, GLI2, GLI3, MAML3, WNT9A, FRAS1, PIK3R3, FREM2, PTPN11, EVC, and FLNA) were identified, which may have contributed to the patient phenotypes. MYO7A was the most commonly identified gene. Specific gene combinations were also identified. In the interactome analysis, MAMLD1 exhibited direct connection with MAML1/2/3 and NOTCH1/2. Through NOTCH1/2, the following eight genes were shown to be associated with MAMLD1:WNT9A/9B, GLI2/3, RET, FLNA, PTPN11, and EYA1. Our findings provide further evidence that individuals with MAMLD1-related 46,XY DSD could carry two or more variants of known DSD-related genes, and the phenotypic outcome of affected individuals might be determined by multiple genes.

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Predicting Gonadal Germ Cell Cancer in People with Disorders of Sex Development; Insights from Developmental Biology

International Journal of Molecular Sciences ◽

10.3390/ijms20205017 ◽

2019 ◽

Vol 20 (20) ◽

pp. 5017 ◽

Cited By ~ 4

Author(s):

Leendert H. J. Looijenga ◽

Chia-Sui Kao ◽

Muhammad T. Idrees

Keyword(s):

Germ Cell ◽

Y Chromosome ◽

Association Studies ◽

Cell Cancer ◽

Disorders Of Sex Development ◽

Germ Cell Cancer ◽

Genome Wide Association Studies ◽

Sex Development ◽

Stage Of Development ◽

Increased Risk

The risk of gonadal germ cell cancer (GGCC) is increased in selective subgroups, amongst others, defined patients with disorders of sex development (DSD). The increased risk is due to the presence of part of the Y chromosome, i.e., GonadoBlastoma on Y chromosome GBY region, as well as anatomical localization and degree of testicularization and maturation of the gonad. The latter specifically relates to the germ cells present being at risk when blocked in an embryonic stage of development. GGCC originates from either germ cell neoplasia in situ (testicular environment) or gonadoblastoma (ovarian-like environment). These precursors are characterized by presence of the markers OCT3/4 (POU5F1), SOX17, NANOG, as well as TSPY, and cKIT and its ligand KITLG. One of the aims is to stratify individuals with an increased risk based on other parameters than histological investigation of a gonadal biopsy. These might include evaluation of defined susceptibility alleles, as identified by Genome Wide Association Studies, and detailed evaluation of the molecular mechanism underlying the DSD in the individual patient, combined with DNA, mRNA, and microRNA profiling of liquid biopsies. This review will discuss the current opportunities as well as limitations of available knowledge in the context of predicting the risk of GGCC in individual patients.

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Disorders of gender and fertility

Endocrinology (Oxford Desk Reference) ◽

10.1093/med/9780199672837.003.0009 ◽

2018 ◽

pp. 263-282

Author(s):

Helen E. Turner ◽

Richard Eastell ◽

Ashley Grossman

Keyword(s):

Sexual Development ◽

Treatment Options ◽

Management Strategies ◽

Disorders Of Sex Development ◽

Physical Symptoms ◽

Sex Development ◽

Psychosocial Therapy ◽

Wide Range ◽

Genetic Assessment ◽

Testicular Disease

This chapter discusses disorders of sex development, listing terminology, proper communication, family history, hormonal assessment, genetic assessment, and management strategies like surgery and psychosocial therapy. Disorders of sex development are a wide range of conditions with diverse pathophysiology that most often present in the newborn or the adolescent. Affected newborns usually present with atypical genitalia, whereas adolescents present with atypical sexual development during the pubertal years. The chapter also describes gender dysmorphia, its physical symptoms, hormonal causes, and drug-related or surgical treatment options. It finally discusses the epidemiology, clinical features, and management of infertility in both sexes, and the causes behind infertility, like hypogonadism, endometriosis, intrauterine factors, autoimmunity, primary testicular disease, varicocele, and ejaculatory disorders.

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Delayed Recognition of Disorders of Sex Development (DSD): A Missed Opportunity for Early Diagnosis of Malignant Germ Cell Tumors

International Journal of Endocrinology ◽

10.1155/2012/671209 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 17

Author(s):

Remko Hersmus ◽

Hans Stoop ◽

Stefan J. White ◽

Stenvert L. S. Drop ◽

J. Wolter Oosterhuis ◽

...

Keyword(s):

Germ Cell ◽

Early Recognition ◽

Metastatic Cancer ◽

Germ Cell Tumors ◽

Disorders Of Sex Development ◽

Ambiguous Genitalia ◽

Normal Male ◽

Testicular Dysgenesis Syndrome ◽

Sex Development ◽

Increased Risk

Disorders of sex development (DSD) are defined as a congenital condition in which development of chromosomal, gonadal or anatomical sex is atypical. DSD patients with gonadal dysgenesis or hypovirilization, containing part of the Y chromosome (GBY), have an increased risk for malignant type II germ cell tumors (GCTs: seminomas and nonseminomas). DSD may be diagnosed in newborns (e.g., ambiguous genitalia), or later in life, even at or after puberty. Here we describe three independent male patients with a GCT; two were retrospectively recognized as DSD, based on the histological identification of both carcinomain situand gonadoblastoma in a single gonad as the cancer precursor. Hypospadias and cryptorchidism in their history are consistent with this conclusion. The power of recognition of these parameters is demonstrated by the third patient, in which the precursor lesion was diagnosed before progression to invasiveness. Early recognition based on these clinical parameters could have prevented development of (metastatic) cancer, to be treated by systemic therapy. All three patients showed a normal male 46,XY karyotype, without obvious genetic rearrangements by high-resolution whole-genome copy number analysis. These cases demonstrate overlap between DSD and the so-called testicular dysgenesis syndrome (TDS), of significant relevance for identification of individuals at increased risk for development of a malignant GCT.

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Genetic Analysis for the Diagnosis of Disorders of Sexual Development in Indonesia

Journal of Biomedicine and Translational Research ◽

10.14710/jbtr.v2i2.622 ◽

2016 ◽

Vol 2 (2) ◽

pp. 44

Author(s):

Sultana MH Faradz

Keyword(s):

Sexual Development ◽

Disorders Of Sex Development ◽

External Genitalia ◽

Gonadal Development ◽

Androgen Insensitivity Syndrome ◽

Medical Professionals ◽

Adrenal Hyperplasia ◽

Disorders Of Sexual Development ◽

Sex Development

Disorders of sex development (DSD) is defined by congenital conditions in which development of chromosomal, gonadal, or anatomical sex is atypical, while in clinical practice this term means any abnormality of the external genitalia. DSD patients have been managed by a multidisciplinary gender team in our center as collaboration between Dr. Kariadi province referral hospital and Faculty of Medicine Diponegoro University. Diagnosis should be established by specific physical examination hormonal, chromosomal and DNA studies; and imaging for most of the cases depending on indication.Since 2004 the involvement of molecular and cytogenetic analysis so far can diagnosed many of the DSD cases. Most of the genetically proven cases were Congenital Adrenal hyperplasia, Androgen Insensitivity syndrome and sex chromosomal DSD that lead abnormal gonadal development. Many of them remain undiagnosed, further testing such as advanced DNA study should be carried out in collaboration with other center in overseas.The novel genes were found in some cases that contributed for the management of DSD. Information for medical professionals, patients, family members and community about the availability and necessity of DSD diagnosis should be delivered to improve DSD management and patient quality of life.

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