Abstract

Noonan syndrome occurs in approximately 1/1,000-1/2,500 live births and is caused by defects in the Ras/mitogen-activated protein kinase pathway. Pubertal development includes syndrome-specific differences which may manifest as delayed puberty in both sexes, as well as cryptorchidism and impaired gonadal function, especially in the males. However gonadal dysgenesis and disorders of sex development have not been previously reported in the literature before. Our patient presented with ambiguous genitalia at two days of age. There was no consanguinity between the parents. On physical examination, the external masculinisation score was 4. Laboratory tests were compatible with gonadal dysgenesis. Echocardiography revealed pulmonary stenosis and a secundum atrial septal defect. Karyotype was 46 XY, SRY (+) and no pathogenic variant was detected in the targeted gene sequencing panel for disorders of sex development. A targeted next-generation seqeuencing (NGS) panel for Noonan syndrome was performed in the patient due to pulmonary stenosis and suggestive facial appearance, identifying a pathogenic c.136 T>G variant in the RIT1 gene. Noonan syndrome may cause gonadal dysfunction leading to delayed puberty and infertility; however, gonadal dysgenesis and ambiguous genitalia have not been previously reported. Noonan syndrome should be investigated in every patient with suggested clinical findings and affected gonadal functions.