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

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

Advances in Urology ◽

10.1155/2012/708301 ◽

2012 ◽

Vol 2012 ◽

pp. 1-4 ◽

Cited By ~ 6

Author(s):

Blake W. Palmer ◽

William Reiner ◽

Brad P. Kropp

Keyword(s):

Sexual Development ◽

Disorders Of Sex Development ◽

Hypospadias Repair ◽

Urethral Meatus ◽

Proximal Hypospadias ◽

Sex Development ◽

Disorder Of Sexual Development ◽

Increased Risk ◽

The Mean ◽

Contemporary Study

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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Chromosomal Disorders of Sex Development

10.1093/med/9780199329007.003.0023 ◽

2018 ◽

Author(s):

R. J McKinlay Gardner ◽

David J Amor

Keyword(s):

Sexual Development ◽

De Novo ◽

Chromosome Abnormality ◽

Disorders Of Sex Development ◽

External Genitalia ◽

Sequential Process ◽

Chromosomal Disorders ◽

Sex Development ◽

Development Proceeds

Chromosomal sex is, for the most part, congruently XX female and XY male. The XX and XY embryo are built on a fundamentally similar outline plan, and only as development proceeds do certain modifications evolve. If at any point in this sequential process some genetic instruction is faulty, inappropriate, or cannot be acted on, the direction of anatomical sexual development may proceed imperfectly or completely incongruently. This chapter reviews the conditions of ambiguous/incomplete/indeterminate development of the internal and external genitalia, where the basis of this is a chromosome abnormality, usually of the X or the Y chromosome. The key role of the SRY male-determining gene in a number of these conditions is noted. The de novo or familial origin of these disorders is discussed, with particular reference to possible risks of recurrence.

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