Incorporating Clinical and Genetic Approaches in the Diagnosis of 46, XY Gonadal Dysgenesis

This chapter aim to highlights the spectrum of presentation in individuals with discordant genotype and phenotype especially in cases of 46, XY gonadal dysgenesis and to identify the genetic cause and determine the role of genetic testing in such individuals. Disorders of sex development (DSD) refers to a group of conditions in which prenatal sex development is not typical. This usually results in external genitalia that are atypical or ambiguous in appearance. DSD may result from hormonal defects, congenital malformations, chromosomal abnormalities, or molecular defects that alter the differentiation of the bipotential gonad into a testis or ovary during fetal life. Some DSD are associated with defects in kidney or renal development, or inborn errors of metabolism. 46, XY gonadal dysgenesis can have varied genetic etiology and can be the consequence of defects of any gene involved in the process of gonad formation. A retrospective study was conducted and patients with 46, XY with gonadal dysgenesis and female phenotype were studied. A comprehensive clinical examination and in-depth history elicitation were performed. In each case, karyotypic genetic analyses and mutation studies were conducted. Complete gonadal dysgenesis genotypes are known as either 46, XX or 46, XY. Here, we would discuss only 46, XY gonadal dysgenesis, which can be either complete or partial based on its characteristic phenotype and genetic aetiology. This study included 4 patients with 46, XY DSD. We identified mutations in 2 (50%) patients in the WT1 gene. Among them, one patient harboured pathogenic variant, while the other patient had variant of uncertain significance. Despite the clinical and genetic variability of DSD, targeted exome sequencing is an effective technique to increase diagnostic yield. A better knowledge of the disease mechanism, phenotype, and genetic link, as well as patient counseling and therapy, can be achieved by knowing the precise cause in terms of mutation. DNA sequencing technologies have enhanced investigations into specific genetic causes of these disorders and has become crucial for diagnosis, management and prognosis of such disorders caused by gene mutation.