title: Safe, accurate, prenatal diagnosis of thanatophoric dysplasia using ultrasound and free fetal DNA.
abstract: OBJECTIVE
  To improve the prenatal diagnosis of thanatophoric dysplasia by defining the change in fetal size across gestation and the frequency of sonographic features, and developing non-invasive molecular genetic diagnosis based on cell-free fetal DNA (cffDNA) in maternal plasma.
  
  
  METHODS
  Fetuses with a confirmed diagnosis of thanatophoric dysplasia were ascertained, records reviewed, sonographic features and measurements determined. Charts of fetal size were then constructed using the LMS (lambda-mu-sigma) method and compared with charts used in normal pregnancies and those complicated by achondroplasia. Cases in this cohort referred to our Regional Genetics Laboratory for molecular diagnosis using cffDNA were identified and results reviewed.
  
  
  RESULTS
  Forty-two cases were scanned in our units. Commonly reported sonographic features were very short and sometimes bowed femora, frontal bossing, cloverleaf skull, short fingers, a small chest and polyhydramnios. Limb shortening was obvious from as early as 13 weeks' gestation, with minimal growth after 20 weeks. Analysis of cffDNA in three of these pregnancies confirmed the presence of the c.742C>CT (p.Arg248Cys) or the c.1948A>AG (p.Lys650Glu) mutation in the fibroblast growth factor receptor 3 gene.
  
  
  CONCLUSIONS
  These data should improve the accuracy of the sonographic diagnosis of thanatophoric dysplasia and have implications for reliable and safe targeted molecular confirmation using cffDNA.
authors: Clinical and Molecular Genetics Unit, UCL Institute of Child Health, University College London, UK. l.chitty@ucl.ac.uk
authors: Lyn S
authors: LS
authors: Chitty
authors: Asma
authors: A
authors: Khalil
authors: Angela N
authors: AN
authors: Barrett
authors: Eva
authors: E
authors: Pajkrt
authors: David R
authors: DR
authors: Griffin
authors: Tim J
authors: TJ
authors: Cole
mesh_terms: D000328:Adult; D004247:DNA / Q000032:analysis / Q000097:blood* / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D005269:Femur / Q000196:embryology; D005333:Fetus / Q000196:embryology / Q000378:metabolism; D005865:Gestational Age; D057238:Growth Charts; D006801:Humans; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000009:adverse effects / Q000379:methods*; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D013796:Thanatophoric Dysplasia / Q000097:blood / Q000175:diagnosis* / Q000000981:diagnostic imaging; D016216:Ultrasonography, Prenatal
chemical_list: D004247:DNA; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3