A patient with Kalman syndrome asks: Is it possible that there is a risk of inheritance regardless of whether treatment is with pump or HCG/HMG, and what is the probability of this risk? How can I avoid it as much as possible? A: IHH is a genetically heterogeneous disease. Less than 50% of patients with IHH have been found to have a genetic defect, and an increasing number of genetic mutations have been found to be associated with IHH. We do not know much about the relationship between the clinical manifestations of the disease and genetic abnormalities. Individuals with detected oligo/mono allelic variants can present with a variety of clinical phenotypes, with most presenting with typical IHH, i.e. complete failure of secondary sexual characteristics at puberty or partial failure of secondary sexual characteristics at puberty, infertility, amenorrhea/sparse menstruation. Others have detectable oligo/mono allelic variants but present with reversible IHH/KS in males (i.e. delayed pubertal secondary sex development, androgen therapy, enlarged testes, but later normal testosterone levels without pharmacological intervention) IHH in males with onset in adulthood (i.e. normal pubertal secondary sex development, past fertility, but central infertility in adulthood) primary or secondary hypothalamic amenorrhea in females, or even oligo/single allele variants detected in individuals, but with completely normal secondary sex development and completely normal hypothalamic pituitary target gland axis function/reproductive function, but may be accompanied by hyposmia. This illustrates the inconsistency of IHH genetic epistasis. That is, more than half of the patients with IHH have not been found to have a known causative gene, and individuals with detectable oligo/single allele variants may also have mild secondary sex development abnormalities or a minority of adolescents with no secondary sex development abnormalities/no infertility. there is an inherited risk for either IHH or Kallmann syndrome, independent of the treatment regimen used, and no statistical reports of risk probabilities are available. We believe that it is feasible to obtain fetal DNA for testing by amniocentesis when a patient with IHH or Kallmann syndrome (or his wife) becomes pregnant to compare the presence of the reported defective gene to help determine whether the fetus may also have the disease, but this program is not routinely performed in the clinic to date and does not identify the unknown causative gene. We are conducting more clinical genetic studies on IHH, working on the discovery and identification of new pathogenic genes and studying the relationship between various pathogenic genes and clinical phenotypes.