title: Pituitary stalk interruption syndrome in 83 patients: novel HESX1 mutation and severe hormonal prognosis in malformative forms.
abstract: BACKGROUND
  Pituitary stalk interruption syndrome (PSIS) is a particular entity in the population of patients with hypopituitarism. Only rare cases have a known genetic cause.
  
  
  OBJECTIVE
  i) To compare subgroups with or without extra-pituitary malformations (EPM) in a cohort of PSIS patients to identify predictive factors of evolution, ii) to determine the incidence of mutations of the known pituitary transcription factor genes in PSIS. Study design We analyzed features of 83 PSIS patients from 80 pedigrees and screened HESX1, LHX4, OTX2, and SOX3 genes.
  
  
  RESULTS
  PSIS had a male predominance and was rarely familial (5%). Pituitary hypoplasia was observed only in the group with EPM. Multiple hormone deficits were observed significantly more often with versus without EPM (87.5 vs 69.5% respectively). Posterior pituitary location along the stalk was a significant protective factor regarding severity of hormonal phenotype. A novel HESX1 causative mutation was found in a consanguineous family, and two LHX4 mutations were present in familial PSIS.
  
  
  CONCLUSIONS
  PSIS patients with EPM had a more severe hormonal disorder and pituitary imaging status, suggesting an antenatal origin. HESX1 or LHX4 mutations accounted for <5% of cases and were found in consanguineous or familial cases.
authors.affiliation: Pediatric Endocrinology Unit, Department of Pediatrics Department of Endocrinology, Hôpital de la Timone, France. rachel.reynaud@ap-hm.fr
authors.forename: R
authors.initials: R
authors.lastname: Reynaud
authors.forename: F
authors.initials: F
authors.lastname: Albarel
authors.forename: A
authors.initials: A
authors.lastname: Saveanu
authors.forename: N
authors.initials: N
authors.lastname: Kaffel
authors.forename: F
authors.initials: F
authors.lastname: Castinetti
authors.forename: P
authors.initials: P
authors.lastname: Lecomte
authors.forename: R
authors.initials: R
authors.lastname: Brauner
authors.forename: G
authors.initials: G
authors.lastname: Simonin
authors.forename: J
authors.initials: J
authors.lastname: Gaudart
authors.forename: E
authors.initials: E
authors.lastname: Carmona
authors.forename: A
authors.initials: A
authors.lastname: Enjalbert
authors.forename: A
authors.initials: A
authors.lastname: Barlier
authors.forename: T
authors.initials: T
authors.lastname: Brue
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D060850:LIM-Homeodomain Proteins; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D051857:Otx Transcription Factors / Q000235:genetics; D010902:Pituitary Gland / Q000002:abnormalities* / Q000473:pathology; D055748:SOXB1 Transcription Factors / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
chemical_list: C489736:HESX1 protein, human; D018398:Homeodomain Proteins; C486362:LHX4 protein, human; D060850:LIM-Homeodomain Proteins; D051857:Otx Transcription Factors; C527785:SOX3 protein, human; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors