This panel consists of 39 genes that have been associated with Kallmann syndrome (KS) and normosmic idiopathic hypogonadotropic hypogonadism (nIHH). These conditions are characterized by delayed or absent puberty due to decreased production and/or function of gonadotropin-releasing hormone. The majority of affected individuals are diagnosed at puberty due to the abnormal development of secondary sex characteristics. However, infant males with KS and nIHH often present with cryptorchidism and micropenis. Abnormalities in the sense of smell, including hyposmia or anosmia, is frequently observed in KS. Additional clinical features include renal agenesis, cleft palate, sensorineural hearing loss, dental agenesis, abnormal eye and hand movements, and abnormalities of the bones in the hands and feet.
When left untreated, adult males tend to have decreased bone density, muscle mass and libido, erectile dysfunction, and infertility. Adult females have little or no breast development and primary amenorrhea. Confirmation of pathogenic variants can assist in early detection and hormone replacement treatment to induce puberty, secondary sex development, and fertility in patients with KS and nIHH.