Clinical approach for evaluation and management of disorders of sex development

"It's a boy" and "It's a girl" are words that are heard every second of every day all around the world. However, it is very distressing when the birth attendants are unable to make such a pronouncement because of disorders of sex development (DSD). DSD are congenital conditions associated with an atypical development of chromosomal, gonadal or anatomical sex. Normal sex development progresses in steps from conception to the complete development of the fetal external genitalia; any disturbance in any of these steps can lead to DSD. Ambiguous genitalia are the most common type of DSD and it is a challenging clinical diagnosis for the pediatric endocrinologist. A newborn baby with ambiguous genitalia is often a surprise for both the medical team and the parents, frequently described as an emergency. The condition needs a special approach in terms of counseling the parents appropriately, evaluation and management. The Chicago Conference (2006) recommended new nomenclature and a classification for DSD, as the old nomenclature was confusing for doctors and parents, and sometimes pejorative. The new classification is based on karyotyping and gonadal structure, improving understanding of the underlying pathogenic mechanisms. The rapid progression of genetic diagnosis of DSD using advanced techniques such as next-generation sequencing (NGS) allows more appropriate diagnosis and genetic counseling for families.
The focus of the article is a review of normal sex development, DSD classification, clinical approach, genetic assessment, sex assignment, surgical management and risk of germ cell tumor development.