title: Incidence, phenotypic features and molecular genetics of Kallmann syndrome in Finland.
abstract: BACKGROUND
  Kallmann syndrome (KS), comprised of congenital hypogonadotropic hypogonadism (HH) and anosmia, is a clinically and genetically heterogeneous disorder. Its exact incidence is currently unknown, and a mutation in one of the identified KS genes has only been found in ~30% of the patients.
  
  
  METHODS
  Herein, we investigated epidemiological, clinical, and genetic features of KS in Finland.
  
  
  RESULTS
  The minimal incidence estimate of KS in Finland was 1:48 000, with clear difference between males (1:30 000) and females (1:125 000) (p = 0.02). The reproductive phenotype of 30 probands (25 men; 5 women) ranged from severe HH to partial puberty. Comprehensive mutation analysis of all 7 known KS genes (KAL1, FGFR1, FGF8, PROK2, PROKR2, CHD7, and WDR11) in these 30 well-phenotyped probands revealed mutations in KAL1 (3 men) and FGFR1 (all 5 women vs. 4/25 men), but not in other genes.
  
  
  CONCLUSIONS
  Our results suggest that Finnish KS men harbor mutations in gene(s) yet-to-be discovered with sex-dependent penetrance of the disease phenotype. In addition, some KS patients without CHD7 mutations display CHARGE-syndrome associated phenotypic features (e.g. ear or eye anomalies), possibly implying that, in addition to CHD7, there may be other genes associated with phenotypes ranging from KS to CHARGE.
authors.affiliation: Children's Hospital, Helsinki University Central Hospital, University of Helsinki, FI-00029 Helsinki, Finland.
authors.forename: Eeva-Maria
authors.initials: EM
authors.lastname: Laitinen
authors.forename: Kirsi
authors.initials: K
authors.lastname: Vaaralahti
authors.forename: Johanna
authors.initials: J
authors.lastname: Tommiska
authors.forename: Elina
authors.initials: E
authors.lastname: Eklund
authors.forename: Mari
authors.initials: M
authors.lastname: Tervaniemi
authors.forename: Leena
authors.initials: L
authors.lastname: Valanne
authors.forename: Taneli
authors.initials: T
authors.lastname: Raivio
mesh_terms: D000293:Adolescent; D000328:Adult; D004252:DNA Mutational Analysis; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D005387:Finland / Q000453:epidemiology; D006801:Humans; D007006:Hypogonadism / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D015994:Incidence; D017436:Kallmann Syndrome / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D000857:Olfaction Disorders / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics*; D055815:Young Adult
chemical_list: C076266:ANOS1 protein, human; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1