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Best Practice & Research. Clinical... Aug 2018Atypical genitalia in a boy may have a very wide and diverse aetiology and a definitive diagnosis is often challenging to reach. Detailed clinical evaluation integrated... (Review)
Review
Atypical genitalia in a boy may have a very wide and diverse aetiology and a definitive diagnosis is often challenging to reach. Detailed clinical evaluation integrated with extensive biochemical and genetic studies play an important role in this process. Such care should be undertaken in highly specialized centres that can also provide access to a multidisciplinary team for optimal long-term care.
Topics: Disorders of Sex Development; Female; Humans; Male
PubMed: 30086868
DOI: 10.1016/j.beem.2018.05.013 -
Sexual Development : Genetics,... 2019Ambiguous genitalia affect 1 in 5,000 live births. Diagnostic procedures can be time-consuming, and often the etiology cannot be established in this group of individuals...
Ambiguous genitalia affect 1 in 5,000 live births. Diagnostic procedures can be time-consuming, and often the etiology cannot be established in this group of individuals with differences/disorders of sex development (DSD). We aimed to evaluate the clinical presentation, sex assignment, and diagnostic workup in these patients. In this retrospective observational study, we included infants who presented with ambiguous genitalia from 2006 to 2016 at the Radboudumc (Radboud University Medical Center) DSD expert center. Relevant data were collected from patient records. Sixty-two 46,XY and fourteen 46,XX individuals were included. Sex was assigned in the first days of life and based on the combination of presence or absence of a uterus on ultrasound, AMH level, palpable gonads, and the karyotype (corresponded in 96% of the patients). In 86% of the 46,XX DSD subjects, a diagnosis was made, whereas in only 15/62 (24%) of the 46,XY DSD individuals, etiology was determined. In 52 individuals, genetic testing was performed resulting in a diagnosis in 24 patients (46%). AMH, hCG-stimulated testosterone, and dihydrotestosterone levels contributed to determining etiology, whilst basal testosterone and basal dihydrotestosterone did not. Establishing a diagnosis in infants with ambiguous genitalia is complex and challenging; this study aids to enhance this process and improve current practice.
Topics: Child; Child, Preschool; Disorders of Sex Development; Female; Genetic Testing; Gonadal Dysgenesis, 46,XY; Humans; Infant; Male; Retrospective Studies; Sex Determination Processes
PubMed: 31466074
DOI: 10.1159/000502074 -
Sexual Development : Genetics,... 2018
Topics: Disorders of Sex Development; Humans; Sexual Development
PubMed: 29055947
DOI: 10.1159/000480746 -
African Health Sciences Sep 2021In humans, sex determination and differentiation is genetically controlled. Disorders of sex development (DSD) result in anomalies of the development of the external and...
BACKGROUND
In humans, sex determination and differentiation is genetically controlled. Disorders of sex development (DSD) result in anomalies of the development of the external and internal genitalia. Variants in transcription factors such as SRY, NR5A1 and SOX9, can cause changes in gonadal development often associated with ambiguity of the external genitalia.
OBJECTIVES
This study has been conducted to determine the frequency, types and associated genetic alterations in patients with DSD in the Algerian population.
METHODS
Thirty patients were included. Based on their clinical presentation, thirteen patients presented with ambiguous external genitalia, thirteen patients presented with hypospadias and four patients presented with bilateral undescended testes. Karyotype analysis was performed on peripheral blood lymphocytes using standard R-banding. DNA was isolated from blood leukocytes for PCR reaction and mutational analysis of SRY and NR5A1 was done by direct sequencing.
RESULTS
Most patients with ambiguous genitalia had a 46,XY karyotype. One patient had a deletion of SRY, otherwise no point mutations in SRY or NR5A1 genes were identified. However, a single NR5A1 polymorphism (p.Gly146Ala) in patient with 46,XX DSD has been detected.
CONCLUSIONS
The absence of mutations in these genes suggests that there are others genes playing an important role in sex development and differentiation.
Topics: Adolescent; Child; Disorders of Sex Development; Humans; Male; Mutation; Polymerase Chain Reaction; Sex-Determining Region Y Protein; Sexual Development; Steroidogenic Factor 1; Transcription Factors
PubMed: 35222615
DOI: 10.4314/ahs.v21i3.61 -
Tidsskrift For Den Norske Laegeforening... Feb 2008Androgen insensitivity is caused by mutations in the androgen receptor gene, and is a common etiological factor to ambiguous genitalia in the newborn. This article... (Review)
Review
BACKGROUND
Androgen insensitivity is caused by mutations in the androgen receptor gene, and is a common etiological factor to ambiguous genitalia in the newborn. This article discusses the role of androgens in sex differentiation, the structure and function of the androgen receptor, the genetic background to androgen insensitivity as well as clinical aspects.
MATERIAL AND METHODS
The article is based on literature retrieved from PubMed, the androgen receptor mutation database and the authors' own research and clinical experience.
RESULTS AND DISCUSSION
Androgen insensitivity encompasses a wide spectrum of clinical manifestations. Besides exclusion of possible differential diagnosis, the diagnostic work-up includes a clinical assessment of the androgen receptor's susceptibility to androgen stimulation as well as molecular genetic analysis of the androgen receptor gene. The condition should be managed with a multidisciplinary approach by teams competent to treat children with disorders of sexual development.
Topics: Adolescent; Adult; Androgen-Insensitivity Syndrome; Child; Diagnosis, Differential; Female; Humans; Infant, Newborn; Male; Mutation; Psychosexual Development; Receptors, Androgen; Sex Differentiation
PubMed: 18311203
DOI: No ID Found -
Journal of Clinical Research in... Dec 2017The newborn infant with atypical genitalia presents a challenging clinical scenario and requires expert input. There have been appreciable advances in our knowledge of... (Review)
Review
The newborn infant with atypical genitalia presents a challenging clinical scenario and requires expert input. There have been appreciable advances in our knowledge of the underlying causes that may lead to a mere difference or a more serious disorder of sex development (DSD), the natural history of conditions, as well as the short and long-term complications of these conditions themselves, together with the clinical interventions that are associated with these conditions. With this information, the DSD expert can be more confident when discussing options with the parents of the newborn infant. By working within a multidisciplinary team, the expert should be able to support the family whilst individualising the management plan so that it is also cognizant of the shifts in societal attitudes and expectations around concepts of diversity and openness. It is, therefore, likely that the practice of assigning sex, especially in those cases where sex assignment is unclear on expert assessment, will continue to show temporal, social and geographical variations. It is imperative that clinical data for rare conditions such as these are collected in a standardized format and shared through a common registry so that any evidence that is used for future shifts in practice has a stronger foundation than that which is currently available.
Topics: Disorders of Sex Development; Female; Humans; Infant; Infant, Newborn; Male
PubMed: 29280745
DOI: 10.4274/jcrpe.2017.S009 -
Hormone Research in Paediatrics 2022Testes were associated with maleness from antiquity, and ancient societies had fanciful myths about the origins of the sexes and about fetal sexual development. 17th... (Review)
Review
Testes were associated with maleness from antiquity, and ancient societies had fanciful myths about the origins of the sexes and about fetal sexual development. 17th century anatomists developed the concept that mammals developed from eggs and discovered sperm in semen; in 1878, Hertwig observed sperm entering eggs (of sea urchins), establishing the cellular basis of sex development. Individuals with atypical genitalia were known clinically in the 17th century, with much debate about their origins, but by the late 19th century it was generally accepted that gonads determined sex, and that sex determined gender role. Testosterone was isolated in 1935, and Alfred Jost showed that both circulating testosterone and diffusible anti-Mullerian hormone were needed for male development. Patients with apparent androgen insensitivity were reported in 1937 and shown to be unresponsive to exogenous androgen by Lawson Wilkins in 1957; androgen receptor mutations were reported in 1989. Steroidogenic errors were associated with differences in sex development (DSDs) starting in the 1940s, and finding mutations in the responsible enzymes explained many forms of hyper- and hypo-androgenism in both sexes. Sex chromosomes were identified in the early 20th century; Y was associated with maleness, and the responsible SRY gene was identified in 1991. Early efforts to manage patients with DSDs were confounded by philosophical perspectives on the relative roles of prenatal biology versus postnatal environment. Approaches to natal sex assignment evolved in the later 20th century and now emphasize a team approach based on data, not guessing, parental involvement, cultural considerations, and the acknowledgement of uncertainty.
Topics: Female; Child; Animals; Pregnancy; Male; Humans; Androgens; Semen; Sexual Development; Disorders of Sex Development; Testosterone; Mammals
PubMed: 36446331
DOI: 10.1159/000527042 -
Frontiers in Endocrinology 2024Differences/disorders of sex development (DSD) comprise a large group of rare congenital conditions. 46,XX DSD, excluding congenital adrenal hyperplasia (CAH), represent... (Review)
Review
Differences/disorders of sex development (DSD) comprise a large group of rare congenital conditions. 46,XX DSD, excluding congenital adrenal hyperplasia (CAH), represent only a small number of these diseases. Due to the rarity of non-CAH 46,XX DSD, data on this sex chromosomal aberration were confined to case reports or case series with small numbers of patients. As the literature is still relatively sparse, medical data on the long-term effects of these pathologies remain scarce. In this review, we aim to provide an overview of current data on the long-term follow-up of patients with non-CAH 46,XX DSD, by covering the following topics: quality of life, gender identity, fertility and sexuality, global health, bone and cardiometabolic effects, cancer risk, and mortality. As non-CAH 46,XX DSD is a very rare condition, we have no accurate data on adult QoL assessment for these patients. Various factors may contribute to a legitimate questioning about their gender identity, which may differ from their sex assigned at birth. A significant proportion of gender dysphoria has been reported in various series of 46,XX DSD patients. However, it is difficult to give an accurate prevalence of gender dysphoria and gender reassignment in non-CAH 46,XX DSD because of the rarity of the data. Whatever the aetiology of non-CAH 46,XX DSD, fertility seems to be impaired. On the other hand, sexuality appears preserved in 46,XX men, whereas it is impaired in women with MRKH syndrome before treatment. Although there is still a paucity of data on general health, bone and cardiometabolic effects, and mortality, it would appear that the 46,XX DSD condition is less severely affected than other DSD conditions. Further structured and continued multi-center follow-up is needed to provide more information on the long-term outcome of this very rare non-CAH 46,XX DSD condition.
Topics: Humans; 46, XX Disorders of Sex Development; Quality of Life; Female; Male; Adrenal Hyperplasia, Congenital; Gender Identity; Disorders of Sex Development; Fertility
PubMed: 38752171
DOI: 10.3389/fendo.2024.1372887 -
Journal of Feline Medicine and Surgery Mar 2022Any congenital or developmental abnormality of any part of the male or female reproductive tract is a 'disorder of sexual development' (DSD). The tricolored male cat... (Review)
Review
PRACTICAL RELEVANCE
Any congenital or developmental abnormality of any part of the male or female reproductive tract is a 'disorder of sexual development' (DSD). The tricolored male cat phenotype, cryptorchidism, gonadal hypoplasia and incidental abnormalities such as cystic remnants or embryonic ducts are well-known feline DSDs.
CLINICAL CHALLENGES
Full characterization of DSDs requires sex chromosome determination and identification of genes related to development of the gonads, internal tubular genitalia and external genitalia. Fortunately, affected cats are seen sporadically and the clinical effects are usually minimal.
CLASSIFICATION
The classification nomenclature has changed. In place of intersex, hermaphrodite, pseudohermaphrodite and sex reversal, the newer standard classification, based on sex chromosomes, designates sex chromosome DSD when there is an abnormality in the sex chromosomes, and XX (female) and XY (male) DSDs where there is not. Identification of the gonadal type (testes, ovaries, ovotestes or gonadal dysgenesis) and documentation of the internal and external genital components completes the classification.
EVIDENCE BASE
The original basis of the DSD classification was a consensus reached in humans. It was quickly accepted in veterinary pathology, courtesy of its logic and ease of application, and it has subsequently begun to appear in peer-reviewed papers and clinical reviews. This article reviewing the various disorders in cats is based on application of the classification and draws on the feline peer-reviewed literature encompassing chromosome analysis and definition of reproductive abnormalities, syndromes and diseases.
Topics: Animals; Cat Diseases; Cats; Disorders of Sex Development; Female; Male; Ovary; Sexual Development; Testis
PubMed: 35209773
DOI: 10.1177/1098612X221079711 -
BMJ (Clinical Research Ed.) Dec 2001
Topics: Attitude of Health Personnel; Clitoris; Disorders of Sex Development; Evidence-Based Medicine; Female; Humans; Infant; Male; Truth Disclosure; Vagina
PubMed: 11731376
DOI: 10.1136/bmj.323.7324.1264