A Rare Cause of Familial Pubertal Delay

Background: Delayed puberty (DP) is described as central or peripheral whether the problem lies in the hypothalamo–pituitary axis or in the gonads respectively.
Idiopathic hypogonadotropic hypogonadism (IHH) is a central cause of DP due to a failure of gonadotrofin releasing hormone (GnRH) secretion impairing the physiological initiation of puberty.

Objective and Methods: We present three intra-familial cases of normosmic IHH (nIHH) related to a new association of two heterozygotic TARC3 mutations.

Case Report: The index case reports to a 16 years-old male with no pubertal development at this age. Later, two of his three sisters also presented complete hypogonadism. All cases had a normal sense of smell. Investigation showed low sex steroid and gonadotropin levels and no evidence of a mass lesion in cerebral MRI. The diagnosis of nIHH was supported by the identification of two heterozygous mutations on TACR3 gene in all subjects.

Conclusion: Congenital IHH is a very rare genetic disorder that if undiagnosed or untreated may lead to infertility associated to complete or partial absence of GnRH.TACR3 mutations have a critical importance on sexual maturation and are an important genetic cause of nIHH. The treatment of nIHH is based on sex steroids replacement, therefore promoting the pubertal development.