Genetic evaluation of children with ambiguous genitalia
Objectives The aim of the study was to conduct a clinical assessment of pediatric patients with ambiguous genitalia, perform molecular genetic studies for SRY and SOX9 genes, and provide genetic counseling for patients and their families. Background Ambiguous genitalia, currently known as disorders of sex development (DSDs) are associated with atypical development of chromosomal, gonadal, or anatomical sexual characteristics, with an incidence of one in 4500 live births. Their early management is crucial for preventing complications, especially psychiatric impacts on the patient and the family, and should be decided after careful consideration of the child's welfare. Materials and methods Sixteen patients aged 1 day to 6 years were selected from the Genetic and Endocrinology Unit, Pediatric Department, Faculty of Medicine, Menoufia University, Egypt. All patients were subjected to detailed history taking, a thorough clinical examination, routine and hormonal investigations, imaging studies, and cytogenetic and molecular studies for SRY and SOX9 genes. Results History revealed seven patients (43.75% with positive consanguinity and five patients with similar conditions in their families. Hormonal study revealed five patients (31.25% above normal ranges for serum 17 OH progesterone levels and two patients (12.5% below normal ranges. Karyotyping revealed six patients with 46, XX DSD, eight with 46, XY DSD, one with 45, X, and another with 45, X/46, XY. On the basis of molecular studies, the SRY gene was positive for six patients with a normal male 46, XY karyotype and for one patient with 45, X karyotype (translocated SRY) SRY was negative for five patients with a normal female 46, XX karyotype and for one patient with 45, X/46, XY karyotype (deleted SRY) All patients were positive for the SOX9 gene and no deletions were detected. Conclusion Early identification of the genetic cause of DSD will in many cases streamline and direct clinical management of the patient with more focused endocrine and imaging studies and better surgical decision.