title: Antenatal spectrum of CHARGE syndrome in 40 fetuses with CHD7 mutations.
abstract: BACKGROUND
  CHARGE syndrome is a rare, usually sporadic disorder of multiple congenital anomalies ascribed to a CHD7 gene mutation in 60% of cases. Although the syndrome is well characterised in children, only one series of 10 fetuses with CHARGE syndrome has been reported to date. Therefore, we performed a detailed clinicopathological survey in our series of fetuses with CHD7 mutations, now extended to 40 cases. CHARGE syndrome is increasingly diagnosed antenatally, but remains challenging in many instances.
  
  
  METHODS
  Here we report a retrospective study of 40 cases of CHARGE syndrome with a CHD7 mutation, including 10 previously reported fetuses, in which fetal or neonatal clinical, radiological and histopathological examinations were performed.
  
  
  RESULTS
  Conversely to postnatal studies, the proportion of males is high in our series (male to female ratio 2.6:1) suggesting a greater severity in males. Features almost constant in fetuses were external ear anomalies, arhinencephaly and semicircular canal agenesis, while intrauterine growth retardation was never observed. Finally, except for one, all other mutations identified in our antenatal series were truncating, suggesting a possible phenotype-genotype correlation.
  
  
  CONCLUSIONS
  Clinical analysis allowed us to refine the clinical description of CHARGE syndrome in fetuses, describe some novel features and set up diagnostic criteria in order to help the diagnosis of CHARGE syndrome after termination of pregnancies following the detection of severe malformations.
authors.affiliation: INSERM U-781, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Marine
authors.initials: M
authors.lastname: Legendre
authors.forename: Marie
authors.initials: M
authors.lastname: Gonzales
authors.forename: Géraldine
authors.initials: G
authors.lastname: Goudefroye
authors.forename: Frédéric
authors.initials: F
authors.lastname: Bilan
authors.forename: Pauline
authors.initials: P
authors.lastname: Parisot
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: Perez
authors.forename: Maryse
authors.initials: M
authors.lastname: Bonnière
authors.forename: Bettina
authors.initials: B
authors.lastname: Bessières
authors.forename: Jelena
authors.initials: J
authors.lastname: Martinovic
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Delezoide
authors.forename: Frédérique
authors.initials: F
authors.lastname: Jossic
authors.forename: Catherine
authors.initials: C
authors.lastname: Fallet-Bianco
authors.forename: Martine
authors.initials: M
authors.lastname: Bucourt
authors.forename: Julia
authors.initials: J
authors.lastname: Tantau
authors.forename: Philippe
authors.initials: P
authors.lastname: Loget
authors.forename: Laurence
authors.initials: L
authors.lastname: Loeuillet
authors.forename: Nicole
authors.initials: N
authors.lastname: Laurent
authors.forename: Brigitte
authors.initials: B
authors.lastname: Leroy
authors.forename: Houria
authors.initials: H
authors.lastname: Salhi
authors.forename: Nicole
authors.initials: N
authors.lastname: Bigi
authors.forename: Caroline
authors.initials: C
authors.lastname: Rouleau
authors.forename: Fabien
authors.initials: F
authors.lastname: Guimiot
authors.forename: Chloé
authors.initials: C
authors.lastname: Quélin
authors.forename: Anne
authors.initials: A
authors.lastname: Bazin
authors.forename: Caroline
authors.initials: C
authors.lastname: Alby
authors.forename: Amale
authors.initials: A
authors.lastname: Ichkou
authors.forename: Roselyne
authors.initials: R
authors.lastname: Gesny
authors.forename: Alain
authors.initials: A
authors.lastname: Kitzis
authors.forename: Yves
authors.initials: Y
authors.lastname: Ville
authors.forename: Stanislas
authors.initials: S
authors.lastname: Lyonnet
authors.forename: Ferechte
authors.initials: F
authors.lastname: Razavi
authors.forename: Brigitte
authors.initials: B
authors.lastname: Gilbert-Dussardier
authors.forename: Michel
authors.initials: M
authors.lastname: Vekemans
authors.forename: Tania
authors.initials: T
authors.lastname: Attié-Bitach
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D000328:Adult; D058747:CHARGE Syndrome / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D002648:Child; D004265:DNA Helicases / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005333:Fetus; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D011247:Pregnancy; D011248:Pregnancy Complications; D012189:Retrospective Studies
chemical_list: D004268:DNA-Binding Proteins; D004265:DNA Helicases; C491434:CHD7 protein, human