[Clinical and molecular aspects of congenital isolated hypogonadotropic hypogonadism].
Congenital isolated hypogonadotropic hypogonadism (IHH) is characterized by partial or complete lack of pubertal development due to defects in migration, synthesis, secretion or action of gonadotropin-releasing hormone (GnRH). Laboratory diagnosis is based on the presence of low levels of sex steroids, associated with low or inappropriately normal levels of pituitary gonadotropins (LH and FSH). Secretion of other pituitary hormones is normal, as well magnetic resonance imaging of the hypothalamohypophyseal tract, which shows absence of an anatomical defects. When IHH is associated with olfactory abnormalities (anosmia or hyposmia), it characterizes Kallmann syndrome. A growing list of genes is involved in the etiology of IHH, suggesting the heterogeneity and complexity of the genetic bases of this condition. Defects in olfactory and GnRH neuron migration are the etiopathogenic basis of Kallmann syndrome. Mutations in KAL1, FGFR1/FGF8, PROK2/PROKR2, NELF, CHD7, HS6ST1 and WDR11 are associated with defects in neuronal migration, leading to Kallmann syndrome. Notably, defects in FGFR1, FGF8, PROKR2, CHD7 and WDR11 are also associated with IHH, without olfactory abnormalities (normosmic IHH), although in a lower frequency. Mutations in KISS1R, TAC3/TACR3 and GNRH1/GNRHR are described exclusively in patients with normosmic IHH. In this paper, we reviewed the clinical, hormonal and genetic aspects of IHH.
Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular, Divisão de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, Basil.
Cintia
C
Tusset
Ericka B
EB
Trarbach
Letícia Ferreira Gontijo
LF
Silveira
Daiane
D
Beneduzzi
Luciana
L
Montenegro
Ana Claudia
AC
Latronico
D002465:Cell Movement / Q000235:genetics; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007006:Hypogonadism / Q000151:congenital / Q000235:genetics*; D017436:Kallmann Syndrome / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009474:Neurons / Q000378:metabolism
D007987:Gonadotropin-Releasing Hormone