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Kallmann syndrome; hypogonadotropic hypogonadism & anosmia

Pathology: 1) absence of GnRH-producing cells in the hypothalamus 2) developmental abnormality of the olfactory placode 3) GnRH cells that arise in the olfactory placode fail to migrate to the hypothalamus 4) impaired axonal extension of olfactory neurons towards the forebrain 5) absence or hypoplasia of the olfactory bulbs & tracts 6) in some cases, midline cranial anomalies (cleft lip/palate & imperfect fusion) are present & anosmia may be absent or inconspicuous 7) renal agenesis, selective tooth agenesis, & bimanual synkinesis in some cases (not type 3) Epidemiology: 1) occurs in males 2) often familial Genetics: - associated with defects in KAL1 gene (type 1) [1] - associated with defects in FGFR1 (type 2) [2] - associated with defects in PROKR2 (type 3) [3] - associated with defects in PROK2 (type 4) [4] - associated with defects in CHD7 (type 5) [5] - associated with defects in FGF8 (type 6) [6] Clinical manifestations: 1) sexual infantilism 2) testes are prepubertal 3) anosmia or hyposmia (80%) 4) midline defects that may be present a) cleft lip or palate b) color blindness c) cryptorchidism d) skeletal abnormalities Laboratory: 1) decreased serum LH & FSH - other pituitary hormones are normal 2) decreased serum testosterone Radiology: - magnetic resonance imaging (MRI) of the head is normal Management: 1) androgen replacement 2) GnRH or gonadotropin therapy a) necessary for restoration of fertility b) patients may be unresponsive to 1st single dose of GnRH, but repeated stimulation leads to normal LH & FSH response

Related

anosmia Anosmin-1; kallmann syndrome protein; Adhesion molecule-like X-linked (KAL1, ADMLX, KAL, KALIG1) Kallman syndrome gene mutation

General

developmental disorder syndrome (multisystem disorder) genetic syndrome (multisystem disorder)

Database Correlations

OMIM correlations

References

  1. OMIM :accession 308700
  2. OMIM :accession 147950
  3. OMIM :accession 244200
  4. OMIM :accession 610628
  5. OMIM :accession 612370
  6. OMIM :accession 612702
  7. OMIM :accession 308750
  8. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 235, 274, 278