hypogonadotropic hypogonadism 4
Definition An inherited disorder (OMIM:610628) characterised by hypogonadism* (absent or incomplete sexual maturation by age 18), low circulating gonadotropins and testosterone, and no other hypothalamic-pituitary axis defects. Some patients have non-reproductive system defects–e.g., anosmia (or hyposmia related to absent or hypoplastic olfactory bulbs and tracts), cleft palate, and sensorineural hearing loss.
*Due to deficiency in gonadotropin-releasing hormone, possibly secondary to a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. Idiopathic hypogonadotropic hypogonadism–IHH with anosmia is known as Kallmann syndrome; IHH with a normal sense of smell is termed normosmic idiopathic hypogonadotropic hypogonadism.
Molecular pathology Defects of PROK2, which encodes a protein that may synchronise the circadian clock, and may serve as a chemoattractant for neuronal precursor cells in the olfactory bulb, cause hypogonadotropic hypogonadism type 4
Synonym Idiopathic hypogonadotropic hypogonadism