RESUMO
Disorders of androgen production can occur in all steps of testosterone biosynthesis and secretion carried out by the foetal Leydig cells as well as in the conversion of testosterone into dihydrotestosterone (DHT). The differentiation of Leydig cells from mesenchymal cells is the first walk for testosterone production. In 46,XY disorders of sex development (DSDs) due to Leydig cell hypoplasia, there is a failure in intrauterine and postnatal virilisation due to the paucity of interstitial Leydig cells to secrete testosterone. Enzymatic defects which impair the normal synthesis of testosterone from cholesterol and the conversion of testosterone to its active metabolite DHT are other causes of DSD due to impaired androgen production. Mutations in the genes that codify the enzymes acting in the steps from cholesterol to DHT have been identified in affected patients. Patients with 46,XY DSD secondary to defects in androgen production show a variable phenotype, strongly depending of the specific mutated gene. Often, these conditions are detected at birth due to the ambiguity of external genitalia but, in several patients, the extremely undervirilised genitalia postpone the diagnosis until late childhood or even adulthood. These patients should receive long-term care provided by multidisciplinary teams with experience in this clinical management.
Assuntos
Androgênios/biossíntese , Transtornos do Desenvolvimento Sexual/genética , Disgenesia Gonadal 46 XY/diagnóstico , Disgenesia Gonadal 46 XY/terapia , Hiperplasia Suprarrenal Congênita/fisiopatologia , Adulto , Diferenciação Celular , Criança , Feminino , Glucocorticoides/uso terapêutico , Disgenesia Gonadal 46 XY/patologia , Humanos , Lactente , Recém-Nascido , Células Intersticiais do Testículo/fisiologia , Masculino , Mineralocorticoides/uso terapêutico , Receptores do LH/genética , Síndrome de Smith-Lemli-Opitz/genética , Testosterona/biossínteseRESUMO
The term disorders of sex development (DSD) includes congenital conditions in which development of chromosomal, gonadal or anatomical sex is atypical. Mutations in genes present in X, Y or autosomal chromosomes can cause abnormalities of testis determination or disorders of sex differentiation leading to 46,XY DSD. Detailed clinical phenotypes allow the identification of new factors that can alter the expression or function of mutated proteins helping to understand new undisclosed biochemical pathways. In this review we present an update on 46,XY DSD aetiology, diagnosis and treatment based on extensive review of the literature and our three decades of experience with these patients.
Assuntos
Transtornos do Desenvolvimento Sexual/genética , Disgenesia Gonadal 46 XY/genética , Mutação/genética , Cromossomos Humanos X/genética , Cromossomos Humanos Y/genética , Transtornos do Desenvolvimento Sexual/diagnóstico , Transtornos do Desenvolvimento Sexual/terapia , Feminino , Disgenesia Gonadal 46 XY/diagnóstico , Disgenesia Gonadal 46 XY/terapia , Humanos , Masculino , Testículo/anormalidades , Testosterona/metabolismoRESUMO
La disgenesia gonodal pura 46XY (Síndrome de Swyer) es una entidad rara, caracterizada por la presencia de estrías gonodales indiferenciadas en una paciente de fenotipo femenino que posee genitales femeninos hipoplásticos. La etiología no está muy clara, pero con frecuencia involucra trastornos genéticos a nivel de la región determinante del sexo del cromosoma Y. Se reporta el caso de una paciente abordada por amenorrea primaria a quien se le diagnosticó el sindrome de Swyer y se incluye una breve revisión bibliográfica