RICERCA ITALIANA     

Psychosexual and gender identity development of patients with an intersex condition: relationship to diagnosis, clinical data and genetic data. Elaboration of guidelines for the correct management of such patients

Libera Università "Vita Salute S. Raffaele" - Milano

Abstract

Sex assignment to a newborn with ambiguous genitalia is one of the most challenging tasks for a pediatric endocrinologist. The criteria are currently under re-evaluation, in the light of the future life of the patient and the responsibilities of health operators.
The basis for a correct sex assignment is a precise diagnosis. However, similar clinical phenotypes are expressions of different causes, making a correct diagnosis vary difficult. The high percentage of the cases defined as idiopathic (15 to 30 %) shows the magnitude of the problem. In the last decades we witnessed important progress in the physiology and molecular events that drive sexual differentiation. A number of genes have been discovered that contribute both early and late to the process of sex determination and differentiation. Nevertheless, to date we know the exact function of only a small proportion of them.
The indications for treatment of patients with sex differentiation disorders are highly controversial. This at least in part is due to the lack of knowledge about the medical, surgical and psychosexual outcome of adult patients. The rarity of these disorders, and their heterogeneity in their clinical evolution, add to the difficulty in assembly information in this field.
The aims of this research project (2 years duration, 3 research unit) are the evolution of the medical, surgical and psychosexual outcome of the patients with ambiguous genitalia, the correlation of this >>>

Principal Investigator

Giuseppe CHIUMELLO Libera Università "Vita Salute S.Raffaele" MILANO

Research Objectives

The aims of this project (2 years duration, 3 research units) is the evaluation of the medical, surgical, and psychosexual outcome of patients with genital ambiguity with a multicenter study involving Italian centers with proven experience in the field, and the development of genetic studies on sex differentiation. The results of clinical, psychological and molecular analyses will be used to generate new guidelines for the management of such patients
To achieve these goal
- we will produce and validate a diagnostic multidisciplinary trail for the rapid diagnosis of the disorder responsible for the different clinical forms of genital ambiguity, with the identification of the criteria, modalities, and timing of clinical, hormonal and molecular evaluation.
- we will produce an electronic database for rapid and uniform data collection
- we will produce two specific questionnaires: the first will be targeted to 18-year-older patients and will be focused on items related to the psychosexual development (gender satisfaction, masculinity/femininity, body image, sexual identity, sexual role, sexual orientation, sexual function). The second will be targeted to prepubertal patients, and will be focused mainly on masculinity/femininity, body image, sexual identity, and sexual role.
- we will recruit patients, both newborns with ambiguous genitalia, and patients already known with intersex condition
- we will performe on these patients an >>>

First Results

Elaboration and validation of a multidisciplinary protocol for the rapid and correct diagnosis of the disorder responsible of the different clinical forms of genital ambiguity. The protocol should identify precisely the criteria, modalities, and timing of clinical, hormonal and molecular evaluation.
Elaboration of an electronic database for the uniform collection of data from newborns with genital ambiguity.
Elaboration and validation of questionnaires on the psychosexual outcome and gender identity of patients with intersex conditions.
Study on the clinical, biochemical, and genetic characteristics of patients with intersex conditions.
Identification of specific mechanisms related to sex differentiation.
Mutational screening of candidate genes in patients with intersex conditions.
Possible identification of novel mutations and study on the frequency of already known mutations.
Evaluation of genotype/phenotype correlations.Evaluation of he psychosexual outcome and gender identity of patients with intersex conditions.
Relationship of the he psychosexual outcome and gender identity with diagnosis, clinical presentation, genetic evaluation, clinical history, clinical and therapeutic management, and familial situation.
Evaluation of genotype/phenotype/clinical and psychosexual outcome in the different clinical forms.
Search for SRY genetic modifiers.
Identification of genes involved in testicular >>>

Timescale

24 months

National and international background

Sex differentiation is the result of complex processes, taking place during critical stages of fetal life, involving multiple molecular and hormonal events leading to the sexual dimorphism observed at the birth.
Sex differentiation occurs in three steps.
1. Determination of chromosome sex, which occurs at conception.
2. Determination of gonadal sex: differentiation of the gonad in ovary or testicle.
3. Differentiation of phenotypic sex: differentiation of internal and external genitalia.
Before sex differentiation, testicles and ovaries are not distinct, and thus they are referred to as bipotent or indifferent gonads.The bipotent gonad originates from urogenital ridge; primordial germ cell migrates from allantoid to urogenital ridge. The somatic components of testicle (Sertoli cells and Leyding cells) or the ovary (follicular cells or tecal cells) originate from the primitive gonad. The appearance of differentiated gonadic cells landmark the end of sex determination and the beginning of the sex differentiation phase: the development of internal and external genitalia is accomplished through the action of hormones secreted by gonadal cells just differentiated.
The male gonad differentiates earlier than her feminine counterpart. The first cells to complete differentiation are the Sertoli cells. They produce the anti-müllerian hormone (AMH), which promotes the regression of the müllerian duct that forms the uterus, fallopian tubes and >>>