The role of ultrasound to evaluate the disorders of sex development: a pictorial essay

2022 ◽  
Author(s):  
Takahiro Hosokawa ◽  
Yutaka Tanami ◽  
Yumiko Sato ◽  
Mayumi Hosokawa ◽  
Eiji Oguma
Keyword(s):  
Disorders Of Sex Development ◽  
Sex Development ◽  
Pictorial Essay

The role of anti-Mullerian and inhibin B hormones in the evaluation of 46,XY disorders of sex development

2014 ◽  
Vol 27 (9-10) ◽  
Author(s):  
Mona Hafez ◽  
Soha M. Abd El Dayem ◽  
Fatma El Mougy ◽  
Abeer Atef ◽  
Manal Kandil ◽  
...  
Keyword(s):  
Disorders Of Sex Development ◽  
Inhibin B ◽  
Sex Development

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

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.

scholarly journals THE ROLE OF UROLOGISTS IN MANAGEMENT OF DISORDERS OF SEX DEVELOPMENT

2012 ◽  
Vol 19 (1) ◽  
Author(s):  
Ilham Wahyudi ◽  
Irfan Wahyudi ◽  
Kanadi Sumadipradja ◽  
Jose RL Batubara ◽  
Arry Rodjani
Keyword(s):  
Multidisciplinary Team ◽  
Disorders Of Sex Development ◽  
Androgen Insensitivity Syndrome ◽  
Therapeutic Management ◽  
Gender Assignment ◽  
Disorder Of Sex Development ◽  
Sex Development ◽  
Diagnostic Management ◽  
One Year

Objective: To evaluate disorder of sex development (DSD) profile at Cipto Mangunkusumo Hospital (RSCM), the management profile, and the role of urologist on diagnostic and therapeutic management. Material & method: We retrospectively collected data from medical record of all DSD cases managed by pediatric endocrinologist, urologist, obstetric gynaecologist at RSCM from January 2002 up to December 2009. 2006 IICP criteria was used as classification. The management profile and the role of urologist were evaluated. Results: there were 133 DSD cases with the majority of cases was congenital adrenal hyperplasia (CAH) followed by androgen insensitivity syndrome (AIS). Most of the cases were diagnosed before one year old and other on pubertal period. Karyotyping, laboratory examination, ultrasonography, genitography, uretrocystoscopy, kolposcopy, diagnostic laparascopy were performed as diagnostic management. Gender assignment was performed by multidisciplinary team. Masculinizing surgery, feminizing surgery, and gonadectomy was done as therapeutic management. Conclusion: The majority case on RSCM’s DSD profile was CAH. The management was performed by multidisciplinary team. Gender assignment decision should be based upon thorough diagnostic evaluation. The urologist has important role on diagnostic and therapeutic management. Keywords: Disorder of sex development, diagnostic management, gender assignment, therapeutic management, urologist.

scholarly journals Clinical and molecular spectrum of 46, XY disorders of sex development that harbour MAMLD1 variations: Case series and review of literature

2020 ◽  
Author(s):  
Li Lele ◽  
Lijun Fan ◽  
Fenqi Gao ◽  
Di Wu ◽  
Chunxiu Gong
Keyword(s):  
Protein Function ◽  
Clinical Manifestations ◽  
Disorders Of Sex Development ◽  
Case Series ◽  
In Silico Analysis ◽  
Causative Role ◽  
Causative Gene ◽  
Sex Development ◽  
Clinical Series

Abstract Background Mastermind-like domain-containing 1 (MAMLD1) has previously been identified as a causative gene for "46, XY Disorders of Sex Development (DSD)". Recently, there has been some controversy regarding the causative role of MAMLD1 variations in DSDs. Here we describe a clinical series and review the reported cases to evaluate the role of MAMLD1 variants in children with 46, XY DSD. Cases of 46, XY DSD harbouring MAMLD1 variants from unrelated families were recruited from the Beijing Children’s Hospital in China (N = 10) or identified through a literature search (N = 26). The clinical manifestations and genetic variants of all the patients were evaluated.Results Hypospadias was the most prevalent phenotype among our 10 cases (8 out of 10 cases) and in all the previously reported ones. Central precocious puberty and isolated micropenis were observed for the first time. Among the 10 cases, nine variants were identified, including three nonsense (p.A356X, p.G152X, and p.G124X) and six missense (p.P334S, p.S662A, p.A421P,p.T992I, p.P542S, and p.A927L) variants. In silico analysis showed that the variants p.P334S, p.P542S, p.S662A, and p.A927Lmight lead to drastic changes in the interaction force of the amino acid chain and the flexibility of the spatial structure, and such changes may affect protein function.Conclusion Patients with 46, XY DSD harbouring MAMLD1variants manifest a broad spectrum of phenotypes and mostly present with hypospadias. The six novel variants reported here enrich the mutation database and contribute to our understanding of the pathogenesis of 46, XY DSD.

scholarly journals Gender Development in 46,XY DSD: Influences of Chromosomes, Hormones, and Interactions with Parents and Healthcare Professionals

Scientifica ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Amy B. Wisniewski
Keyword(s):  
Healthcare Professionals ◽  
Disorders Of Sex Development ◽  
Gender Development ◽  
Social Variables ◽  
Sex Development ◽  
Genital Ambiguity ◽  
And Gender ◽  
Social Components ◽  
The Impact

Variables that impact gender development in humans are difficult to evaluate. This difficulty exists because it is not usually possible to tease apart biological influences on gender from social variables. People with disorders of sex development, or DSD, provide important opportunities to study gender within individuals for whom biologic components of sex can be discordant with social components of gender. While most studies of gender development in people with 46,XY DSD have historically emphasized the importance of genes and hormones on gender identity and gender role, more recent evidence for a significant role for socialization exists and is considered here. For example, the influence of parents’ perceptions of, and reactions to, DSD are considered. Additionally, the impact of treatments for DSD such as receiving gonadal surgeries or genitoplasty to reduce genital ambiguity on the psychological development of people with 46,XY DSD is presented. Finally, the role of multi-disciplinary care including access to peer support for advancing medical, surgical and psychosexual outcomes of children and adults with 46,XY DSD, regardless of sex of rearing, is discussed.

scholarly journals Clinical and molecular spectrum of 46, XY disorders of sex development that harbour MAMLD1 variations: Case series and review of literature

2020 ◽  
Author(s):  
Li Lele ◽  
Lijun Fan ◽  
Fenqi Gao ◽  
Di Wu ◽  
Chunxiu Gong
Keyword(s):  
Clinical Manifestations ◽  
Disorders Of Sex Development ◽  
Case Series ◽  
In Silico Analysis ◽  
Central Precocious Puberty ◽  
Causative Role ◽  
Causative Gene ◽  
Sex Development ◽  
Clinical Series

Abstract Background Mastermind-like domain-containing 1 (MAMLD1) has previously been identified as a causative gene for "46, XY Disorders of Sex Development (DSD)". Recently, there has been some controversy regarding the causative role of MAMLD1 variations in DSDs. Here we describe a clinical series and review the reported cases to evaluate the role of MAMLD1 variants in children with 46, XY DSD. Cases of 46, XY DSD harbouring MAMLD1 variants from unrelated families were recruited from the Beijing Children’s Hospital in China (N = 10)or identified through a literature search (N = 26). The clinical manifestations and genetic variants of all the patients were evaluated.Results Hypospadias was the most prevalent phenotype among our 10 cases (8 out of 10 cases) and in all the previously reported ones. Central precocious puberty and isolated micropeniswere observedfor the first time. Among the 10 cases, nine variants were identified, including three nonsense (p.A356X, p.G152X, and p.G124X) and six missense (p.P334S, p.S662A, p.A421P,p.T992I, p.P542S, and p.A927L) variants. In silico analysis showed that the variants p.P334S, p.P542S, p.S662A, and p.A927Lmight lead to drastic changes in the interaction force of the amino acid chain and the flexibility of the spatial structure, and such changes may affect protein function.Conclusion Patients with 46, XY DSD harbouring MAMLD1variants manifest a broad spectrum of phenotypes and mostly present with hypospadias. The six novel variants reported here enrich the mutation database and contribute to our understanding of the pathogenesis of 46, XY DSD.

Role of Genetic Counseling for Patients with Hypospadias and Their Families

2021 ◽  
Vol 31 (06) ◽  
pp. 492-496
Author(s):  
Agneta Nordenskjöld ◽  
Gundela Holmdahl
Keyword(s):  
Genetic Counseling ◽  
Disorders Of Sex Development ◽  
Recurrence Risk ◽  
Penile Curvature ◽  
Clinical Value ◽  
Complex Disorder ◽  
Sex Development ◽  
Genetic And Environmental Factors ◽  
Current Guidelines

AbstractCongenital malformations often have a genetic background associated with a recurrence risk and may be part of a syndrome. Therefore, for children with a congenital malformation, the parents should be offered genetic counseling, and the child should also be offered the same when they reach adulthood. Hypospadias is a common malformation in boys that arises during genital development in weeks 8 to 16. This results in an underdevelopment of the ventral aspect of the penis with a misplacement of the urethral opening somewhere along the penis, scrotum, or in the perineum and with different degrees of penile curvature. The cause can be monogenic, but generally it is regarded as a complex disorder caused by both genetic and environmental factors. Severe hypospadias and familial cases should be genetically investigated, as for other forms of disorders of sex development, according to current guidelines with sequencing of relevant genes. Hypospadias associated with another independent malformation may be part of a syndrome and should be investigated. Fortunately, boys born with milder hypospadias generally have a good outcome and thus the clinical value of finding a disease-causing mutation appears to be limited especially in light of the present cost of genetic analysis. However, all men born with hypospadias should be advised on the recurrence risk and risk for reduced fertility.

scholarly journals New findings in disorders of sex development: role of DMRT3 and OAS3

2020 ◽  
Vol 114 (1) ◽  
pp. 71-72
Author(s):  
Adriana Rojas ◽  
María Carolina Manotas
Keyword(s):  
Disorders Of Sex Development ◽  
Sex Development ◽  
New Findings

Ovotesticular disorders of sex development in FGF9 mouse models of human synostosis syndromes

2020 ◽  
Vol 29 (13) ◽  
pp. 2148-2161
Author(s):  
Anthony D Bird ◽  
Brittany M Croft ◽  
Masayo Harada ◽  
Lingyun Tang ◽  
Liang Zhao ◽  
...  
Keyword(s):  
Disorders Of Sex Development ◽  
Gonadal Development ◽  
Testis Development ◽  
Sex Development ◽  
Mouse Mutants ◽  
Skeletal Defects ◽  
Xy Sex Reversal

Abstract In mice, male sex determination depends on FGF9 signalling via FGFR2c in the bipotential gonads to maintain the expression of the key testis gene SOX9. In humans, however, while FGFR2 mutations have been linked to 46,XY disorders of sex development (DSD), the role of FGF9 is unresolved. The only reported pathogenic mutations in human FGF9, FGF9S99N and FGF9R62G, are dominant and result in craniosynostosis (fusion of cranial sutures) or multiple synostoses (fusion of limb joints). Whether these synostosis-causing FGF9 mutations impact upon gonadal development and DSD etiology has not been explored. We therefore examined embryonic gonads in the well-characterized Fgf9 missense mouse mutants, Fgf9S99N and Fgf9N143T, which phenocopy the skeletal defects of FGF9S99N and FGF9R62G variants, respectively. XY Fgf9S99N/S99N and XY Fgf9N143T/N143T fetal mouse gonads showed severely disorganized testis cords and partial XY sex reversal at 12.5 days post coitum (dpc), suggesting loss of FGF9 function. By 15.5 dpc, testis development in both mutants had partly recovered. Mitotic analysis in vivo and in vitro suggested that the testicular phenotypes in these mutants arise in part through reduced proliferation of the gonadal supporting cells. These data raise the possibility that human FGF9 mutations causative for dominant skeletal conditions can also lead to loss of FGF9 function in the developing testis, at least in mice. Our data suggest that, in humans, testis development is largely tolerant of deleterious FGF9 mutations which lead to skeletal defects, thus offering an explanation as to why XY DSDs are rare in patients with pathogenic FGF9 variants.

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