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Best Practice & Research. Clinical... Apr 2018Normal sex development depends on the precise spatio-temporal sequence and coordination of mutually antagonistic activating and repressing factors. These factors... (Review)
Review
Normal sex development depends on the precise spatio-temporal sequence and coordination of mutually antagonistic activating and repressing factors. These factors regulate the commitment of the unipotential gonad into the binary pathways governing normal sex development. Typically, the presence of the SRY gene on the Y chromosome triggers the cascade of molecular events that lead to male sex development. Disorders of sex development comprise a heterogeneous group of congenital conditions associated with atypical development of internal and external genitalia. These disorders are generally attributed to deviations from the typical progression of sex development. Disorders of sex development can be classified into several categories including chromosomal, gonadal, and anatomic abnormalities. Genetic tools such as microarray analyses and next-generation sequencing techniques have identified novel genetic variants among patients with disorders of sexual development. Most importantly, patient management needs to be individualized, especially for decisions related to sex of rearing, surgical interventions, hormone treatment, and potential for fertility preservation.
Topics: Child; Disease Management; Disorders of Sex Development; Female; Humans; Male
PubMed: 29503125
DOI: 10.1016/j.bpobgyn.2017.11.005 -
Frontiers in Endocrinology 2020Disorders of Sex Development (DSD) are congenital anomalies in which there is a discordance between chromosomal, genetic, gonadal, and/or internal/external genital sex.... (Review)
Review
Disorders of Sex Development (DSD) are congenital anomalies in which there is a discordance between chromosomal, genetic, gonadal, and/or internal/external genital sex. In XY individuals, the process of fetal sex differentiation can be disrupted at the stage of gonadal differentiation, resulting in gonadal dysgenesis, a form of early fetal-onset primary hypogonadism characterized by insufficient androgen and anti-Müllerian hormone (AMH) production, which leads to the development of ambiguous or female genitalia. The process of sex differentiation can also be disrupted at the stage of genital differentiation, due to isolated defects in androgen or AMH secretion, but not both. These are forms of fetal-onset hypogonadism with dissociated gonadal dysfunction. In this review, we present a perspective on impaired testicular endocrine function, i.e., fetal-onset male hypogonadism, resulting in incomplete virilization at birth.
Topics: Disorders of Sex Development; Humans; Hypogonadism; Male
PubMed: 32351452
DOI: 10.3389/fendo.2020.00211 -
Nature Reviews. Endocrinology Jul 2018The term differences of sex development (DSDs; also known as disorders of sex development) refers to a heterogeneous group of congenital conditions affecting human sex... (Review)
Review
The term differences of sex development (DSDs; also known as disorders of sex development) refers to a heterogeneous group of congenital conditions affecting human sex determination and differentiation. Several reports highlighting suboptimal physical and psychosexual outcomes in individuals who have a DSD led to a radical revision of nomenclature and management a decade ago. Whereas the resulting recommendations for holistic, multidisciplinary care seem to have been implemented rapidly in specialized paediatric services around the world, adolescents often experience difficulties in finding access to expert adult care and gradually or abruptly cease medical follow-up. Many adults with a DSD have health-related questions that remain unanswered owing to a lack of evidence pertaining to the natural evolution of the various conditions in later life stages. This Consensus Statement, developed by a European multidisciplinary group of experts, including patient representatives, summarizes evidence-based and experience-based recommendations for lifelong care and data collection in individuals with a DSD across ages and highlights clinical research priorities. By doing so, we hope to contribute to improving understanding and management of these conditions by involved medical professionals. In addition, we hope to give impetus to multicentre studies that will shed light on outcomes and comorbidities of DSD conditions across the lifespan.
Topics: Child; Child, Preschool; Consensus; Disease Management; Disorders of Sex Development; Europe; Female; Humans; Infant; Interdisciplinary Communication; Male; Needs Assessment; Practice Guidelines as Topic; Precision Medicine; Psychology; Psychosexual Development; Risk Assessment
PubMed: 29769693
DOI: 10.1038/s41574-018-0010-8 -
Hormone Research in Paediatrics 2016The goal of this update regarding the diagnosis and care of persons with disorders of sex development (DSDs) is to address changes in the clinical approach since the... (Review)
Review
The goal of this update regarding the diagnosis and care of persons with disorders of sex development (DSDs) is to address changes in the clinical approach since the 2005 Consensus Conference, since knowledge and viewpoints change. An effort was made to include representatives from a broad perspective including support and advocacy groups. The goal of patient care is focused upon the best possible quality of life (QoL). The field of DSD is continuously developing. An update on the clinical evaluation of infants and older individuals with ambiguous genitalia including perceptions regarding male or female assignment is discussed. Topics include biochemical and genetic assessment, the risk of germ cell tumor development, approaches to psychosocial and psychosexual well-being and an update on support groups. Open and on-going communication with patients and parents must involve full disclosure, with the recognition that, while DSD conditions are life-long, enhancement of the best possible outcome improves QoL. The evolution of diagnosis and care continues, while it is still impossible to predict gender development in an individual case with certainty. Such decisions and decisions regarding surgery during infancy that alters external genital anatomy or removes germ cells continue to carry risk.
Topics: Disorders of Sex Development; Female; Humans; Male; Quality of Life; Sexual Development
PubMed: 26820577
DOI: 10.1159/000442975 -
Archives of Disease in Childhood Jul 2006Management of intersex disorders
Management of intersex disorders
Topics: Culture; Disorders of Sex Development; Female; Gender Identity; Gonadal Steroid Hormones; Humans; Male; Patient Care Team; Prognosis; Psychotherapy; Stereotyping; Terminology as Topic
PubMed: 16624884
DOI: 10.1136/adc.2006.098319 -
Genome Biology Nov 2016Disorders of sex development (DSD) are congenital conditions in which chromosomal, gonadal, or phenotypic sex is atypical. Clinical management of DSD is often difficult...
BACKGROUND
Disorders of sex development (DSD) are congenital conditions in which chromosomal, gonadal, or phenotypic sex is atypical. Clinical management of DSD is often difficult and currently only 13% of patients receive an accurate clinical genetic diagnosis. To address this we have developed a massively parallel sequencing targeted DSD gene panel which allows us to sequence all 64 known diagnostic DSD genes and candidate genes simultaneously.
RESULTS
We analyzed DNA from the largest reported international cohort of patients with DSD (278 patients with 46,XY DSD and 48 with 46,XX DSD). Our targeted gene panel compares favorably with other sequencing platforms. We found a total of 28 diagnostic genes that are implicated in DSD, highlighting the genetic spectrum of this disorder. Sequencing revealed 93 previously unreported DSD gene variants. Overall, we identified a likely genetic diagnosis in 43% of patients with 46,XY DSD. In patients with 46,XY disorders of androgen synthesis and action the genetic diagnosis rate reached 60%. Surprisingly, little difference in diagnostic rate was observed between singletons and trios. In many cases our findings are informative as to the likely cause of the DSD, which will facilitate clinical management.
CONCLUSIONS
Our massively parallel sequencing targeted DSD gene panel represents an economical means of improving the genetic diagnostic capability for patients affected by DSD. Implementation of this panel in a large cohort of patients has expanded our understanding of the underlying genetic etiology of DSD. The inclusion of research candidate genes also provides an invaluable resource for future identification of novel genes.
Topics: Chromosome Aberrations; Cohort Studies; Disorders of Sex Development; Female; Genetic Association Studies; Genetic Predisposition to Disease; Genetic Variation; Gonads; High-Throughput Nucleotide Sequencing; Humans; Male; Mutation; Ovary; Pedigree; Phenotype; Testis
PubMed: 27899157
DOI: 10.1186/s13059-016-1105-y -
Lakartidningen Oct 2019
Review
Topics: Adolescent; Age of Onset; Autism Spectrum Disorder; Child; Comorbidity; Disorders of Sex Development; Feeding and Eating Disorders; Gender Dysphoria; Humans; Interdisciplinary Communication; Legislation, Medical; Patient Care Team; Sex Reassignment Surgery; Sweden; Transsexualism; Young Adult
PubMed: 31613370
DOI: No ID Found -
La Clinica Terapeutica 2022Disorders of sex development (DSD) are a heterogeneous group of pathologies that result in an alteration in sex determination or differentiation. DSD are estimated to... (Review)
Review
Disorders of sex development (DSD) are a heterogeneous group of pathologies that result in an alteration in sex determination or differentiation. DSD are estimated to affect 1: 4,500 newborns and according to the 2006 Chicago Consensus classification, DSD can be divided into three categories: those with a 46 XX karyotype, those with a 46 XY karyotype and those relating to sex chromosomes. It is crucial to correctly identify the pathology already in the first days of life to direct the patient and his family to the best path of care. For this reason, the role of the pediatrician is fundamental in the correct identification of the clinical picture and in supporting the family during the long process that involves the management of these patients. To make a diagnosis, it is necessary to follow a path led by a multidisciplinary team that includes several steps such as the execution of the genetic analysis, the evaluation with diagnostic imaging methods and laboratory evaluations. The therapeutic management, on the other hand, is still very complex even if in recent years we have moved from an attitude of early gender reassignment to an approach of watchful waiting to let the patient choose when she/he is mature enough to do so, which gender she/he feels to belong. It should not be forgotten that throughout this process the pediatrician must be both supportive and clinically active in the management of the child and his family.
Topics: Child; Developmental Disabilities; Disorders of Sex Development; Family; Female; Gender Identity; Humans; Infant, Newborn
PubMed: 36155734
DOI: 10.7417/CT.2022.2466 -
Ugeskrift For Laeger Mar 2017Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a congenital anomaly characterized by uterovaginal agenesis in females with normal secondary sex characteristics and... (Review)
Review
Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a congenital anomaly characterized by uterovaginal agenesis in females with normal secondary sex characteristics and normal karyotype (46,XX). The prevalence of MRKH syndrome is one in 5,000 live female births as recently confirmed by a nationwide population-based study in Denmark. This review kaleidoscopically summarizes the current knowledge of the history, genetics, diagnostics, treatment of vaginal agenesis, psychosexual aspects, and fertility options in MRKH syndrome.
Topics: 46, XX Disorders of Sex Development; Congenital Abnormalities; Female; Humans; Infertility, Female; Magnetic Resonance Imaging; Mullerian Ducts
PubMed: 28397650
DOI: No ID Found -
European Journal of Medical Genetics Sep 2020The term chimera has been borrowed from Greek mythology and has a long history of use in biology and genetics. A chimera is an organism whose cells are derived from two... (Review)
Review
The term chimera has been borrowed from Greek mythology and has a long history of use in biology and genetics. A chimera is an organism whose cells are derived from two or more zygotes. Recipients of tissue and organ transplants are artificial chimeras. This review concerns natural human chimeras. The first human chimera was reported in 1953. Natural chimeras can arise in various ways. Fetal and maternal cells can cross the placental barrier so that both mother and child may become microchimeras. Two zygotes can fuse together during an early embryonic stage to form a fusion chimera. Most chimeras remain undetected, especially if both zygotes are of the same genetic sex. Many are discovered accidently, for example, during a routine blood group test. Even sex-discordant chimeras can have a normal male or female phenotype. Only 28 of the 50 individuals with a 46,XX/46,XY karyotype were either true hermaphrodites or had ambiguous genitalia. Blood chimeras are formed by blood transfusion between dizygotic twins via the shared placenta and are more common than was once assumed. In marmoset monkey twins the exchange via the placenta is not limited to blood but can involve other tissues, including germ cells. To date there are no examples in humans of twin chimeras involving germ cells. If human chimeras are more common than hitherto thought there could be many medical, social, forensic, and legal implications. More multidisciplinary research is required for a better understanding of this fascinating subject.
Topics: Chromosome Disorders; Disorders of Sex Development; Humans; Karyotype; Mosaicism; Phenotype
PubMed: 32565253
DOI: 10.1016/j.ejmg.2020.103971