title: Structural pituitary abnormalities associated with CHARGE syndrome.
abstract: BACKGROUND
  CHARGE syndrome is a multisystem disorder that, in addition to Kallmann syndrome/isolated hypogonadotrophic hypogonadism, has been associated with anterior pituitary hypoplasia (APH). However, structural abnormalities such as an ectopic posterior pituitary (EPP) have not yet been described in such patients.
  
  
  OBJECTIVE
  The aims of the study were: 1) to describe the association between CHARGE syndrome and a structurally abnormal pituitary gland; and 2) to investigate whether CHD7 variants, which are identified in 65% of CHARGE patients, are common in septo-optic dysplasia /hypopituitarism.
  
  
  METHODS
  We describe 2 patients with features of CHARGE and EPP. CHD7 was sequenced in these and other patients with septo-optic dysplasia/hypopituitarism.
  
  
  RESULTS
  EPP, APH, and GH, TSH, and probable LH/FSH deficiency were present in 1 patient, and EPP and APH with GH, TSH, LH/FSH, and ACTH deficiency were present in another patient, both of whom had features of CHARGE syndrome. Both had variations in CHD7 that were novel and undetected in control cohorts or in the international database of CHARGE patients, but were also present in their unaffected mothers. No CHD7 variants were detected in the patients with septo-optic dysplasia/hypopituitarism without additional CHARGE features.
  
  
  CONCLUSIONS
  We report a novel association between CHARGE syndrome and structural abnormalities of the pituitary gland in 2 patients with variations in CHD7 that are of unknown significance. However, CHD7 mutations are an uncommon cause of septo-optic dysplasia or hypopituitarism. Our data suggest the need for evaluation of pituitary function/anatomy in patients with CHARGE syndrome.
authors.affiliation: Developmental Endocrinology Research Group, Clinical and Molecular Genetics Unit, University College London Institute of Child Health, London WC1N 1EH, United Kingdom.
authors.forename: Louise C
authors.initials: LC
authors.lastname: Gregory
authors.forename: Evelien F
authors.initials: EF
authors.lastname: Gevers
authors.forename: Joanne
authors.initials: J
authors.lastname: Baker
authors.forename: Tessa
authors.initials: T
authors.lastname: Kasia
authors.forename: Kling
authors.initials: K
authors.lastname: Chong
authors.forename: Dragana J
authors.initials: DJ
authors.lastname: Josifova
authors.forename: Maria
authors.initials: M
authors.lastname: Caimari
authors.forename: Frederic
authors.initials: F
authors.lastname: Bilan
authors.forename: Mark J
authors.initials: MJ
authors.lastname: McCabe
authors.forename: Mehul T
authors.initials: MT
authors.lastname: Dattani
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D058747:CHARGE Syndrome / Q000150:complications* / Q000453:epidemiology / Q000235:genetics; D002648:Child; D015331:Cohort Studies; D016384:Consensus Sequence; D004265:DNA Helicases / Q000235:genetics; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D006801:Humans; D007018:Hypopituitarism / Q000150:complications* / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D008297:Male; D008954:Models, Biological; D010902:Pituitary Gland / Q000002:abnormalities*; D025962:Septo-Optic Dysplasia / Q000150:complications / Q000453:epidemiology / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D004265:DNA Helicases; C491434:CHD7 protein, human