title: Congenital hypogonadotropic hypogonadism during childhood: presentation and genetic analyses in 46 boys.
abstract: BACKGROUND
  The majority of the patients reported with mutations in isolated hypogonadotropic hypogonadism (HH) are adults. We analysed the presentation and the plasma inhibin B and anti-müllerian hormone (AMH) concentrations during childhood and adolescence, and compared them to the genetic results.
  
  
  METHODS
  This was a retrospective, single-center study of 46 boys with HH.
  
  
  RESULTS
  Fourteen (30.4%) had Kallmann syndrome (KS), 4 (8.7%) had CHARGE syndrome and 28 (60.9%) had HH without olfaction deficit nor olfactive bulb hypoplasia. Eighteen (39%) had an associated malformation or syndromes. At diagnosis, 22 (47.8%) boys were aged <one year, 9 (19%) 1-11 and 15 (32.6%) 11-17.6 years. They presented with micropenis (n = 32, 69.6%, including all those <one year), cryptorchidism (n = 32, 69.6%, unilateral in 8, bilateral in 24), and/or pubertal delay (n = 11). The plasma inhibin B concentrations were normal in 8 (3 KS including one CHARGE and 5 other HH), at the lower limit of the normal in 6 and decreased in 13 (48%) boys. The AMH concentrations were normal in 15 (6 KS including one CHARGE and 9 other HH) and decreased in 12 (44%) boys. In addition to the CHD7 gene mutations in 4 patients with CHARGE, mutations were found in 5/26 other boys analysed including one in KAL1 gene with STS, 2 in FGFR1 gene, one in PROKR2 gene and one in GnRHR gene.
  
  
  CONCLUSIONS
  The presence of micropenis in neonate, particularly if associated with cryptorchidism, is an indication to look for gonadotropin deficiency isolated or associated with other hypothalamic-pituitary deficiencies. Inhibin B and AMH concentrations are suggestive if low, but they may be normal. Despite the high frequency of the associated malformations and excluding the patients with CHARGE or ichtyosis, the 4 patients with mutations had no family history or malformation. This suggests that many other genes are involved.
authors.affiliation: Université Paris Descartes and Fondation Ophtalmologique Adolphe de Rothschild, Pediatric Endocrinology Unit, Paris, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Vizeneux
authors.forename: Aude
authors.initials: A
authors.lastname: Hilfiger
authors.forename: Jérôme
authors.initials: J
authors.lastname: Bouligand
authors.forename: Monique
authors.initials: M
authors.lastname: Pouillot
authors.forename: Sylvie
authors.initials: S
authors.lastname: Brailly-Tabard
authors.forename: Anu
authors.initials: A
authors.lastname: Bashamboo
authors.forename: Ken
authors.initials: K
authors.lastname: McElreavey
authors.forename: Raja
authors.initials: R
authors.lastname: Brauner
mesh_terms: D000293:Adolescent; D000328:Adult; D054304:Anti-Mullerian Hormone / Q000097:blood; D058747:CHARGE Syndrome / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005500:Follow-Up Studies; D005819:Genetic Markers / Q000235:genetics*; D006801:Humans; D007006:Hypogonadism / Q000097:blood / Q000151:congenital / Q000175:diagnosis / Q000235:genetics*; D007223:Infant; D007231:Infant, Newborn; D007265:Inhibins / Q000097:blood; D017436:Kallmann Syndrome / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D007621:Karyotyping; D008297:Male; D011379:Prognosis; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D005819:Genetic Markers; C422364:inhibin B; D007265:Inhibins; D054304:Anti-Mullerian Hormone