title: New aids for the non-invasive prenatal diagnosis of achondroplasia: dysmorphic features, charts of fetal size and molecular confirmation using cell-free fetal DNA in maternal plasma.
abstract: OBJECTIVE
  To improve the prenatal diagnosis of achondroplasia by constructing charts of fetal size, defining frequency of sonographic features and exploring the role of non-invasive molecular diagnosis based on cell-free fetal deoxyribonucleic acid (DNA) in maternal plasma.
  
  
  METHODS
  Data on fetuses with a confirmed diagnosis of achondroplasia were obtained from our databases, records reviewed, sonographic features and measurements determined and charts of fetal size constructed using the LMS (lambda-mu-sigma) method and compared with charts used in normal pregnancies. Cases referred to our regional genetics laboratory for molecular diagnosis using cell-free fetal DNA were identified and results reviewed.
  
  
  RESULTS
  Twenty-six cases were scanned in our unit. Fetal size charts showed that femur length was usually on or below the 3(rd) centile by 25 weeks' gestation, and always below the 3(rd) by 30 weeks. Head circumference was above the 50(th) centile, increasing to above the 95(th) when compared with normal for the majority of fetuses. The abdominal circumference was also increased but to a lesser extent. Commonly reported sonographic features were bowing of the femora, frontal bossing, short fingers, a small chest and polyhydramnios. Analysis of cell-free fetal DNA in six pregnancies confirmed the presence of the c.1138G > A mutation in the FGRF3 gene in four cases with achondroplasia, but not the two subsequently found to be growth restricted.
  
  
  CONCLUSIONS
  These data should improve the accuracy of diagnosis of achondroplasia based on sonographic findings, and have implications for targeted molecular confirmation that can reliably and safely be carried out using cell-free fetal DNA.
authors.affiliation: Clinical and Molecular Genetics Unit, University College London Institute of Child Health, London, UK. l.chitty@ich.ucl.ac.uk
authors.forename: L S
authors.initials: LS
authors.lastname: Chitty
authors.forename: D R
authors.initials: DR
authors.lastname: Griffin
authors.forename: C
authors.initials: C
authors.lastname: Meaney
authors.forename: A
authors.initials: A
authors.lastname: Barrett
authors.forename: A
authors.initials: A
authors.lastname: Khalil
authors.forename: E
authors.initials: E
authors.lastname: Pajkrt
authors.forename: T J
authors.initials: TJ
authors.lastname: Cole
mesh_terms: D000130:Achondroplasia / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000235:genetics; D000886:Anthropometry / Q000379:methods; D004247:DNA / Q000097:blood* / Q000235:genetics; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000235:genetics; D006801:Humans; D008431:Maternal-Fetal Exchange; D009154:Mutation / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000097:blood*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D014463:Ultrasonography
chemical_list: D004247:DNA; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3