title: Thanatophoric dysplasia. Correlation among bone X-ray morphometry, histopathology, and gene analysis.
abstract: OBJECTIVE
  Documentation through X-ray morphometry and histology of the steady phenotype expressed by FGFR3 gene mutation and interpolation of mechanical factors on spine and long bones dysmorphism.
  
  
  METHODS
  Long bones and spine of eight thanatophoric dysplasia and three age-matched controls without skeletal dysplasia were studied after pregnancy termination between the 18th and the 22nd week with X-ray morphometry, histology, and molecular analysis. Statistical analysis with comparison between TD cases and controls and intraobserver/interobserver variation were applied to X-ray morphometric data.
  
  
  RESULTS
  Generalized shortening of long bones was observed in TD. A variable distribution of axial deformities was correlated with chondrocyte proliferation inhibition, defective seriate cell columns organization, and final formation of the primary metaphyseal trabeculae. The periosteal longitudinal growth was not equally inhibited, so that decoupling with the cartilage growth pattern produced the typical lateral spurs around the metaphyseal growth plates. In spine, platyspondyly was due to a reduced height of the vertebral body anterior ossification center, while its enlargement in the transversal plane was not restricted. The peculiar radiographic and histopathological features of TD bones support the hypothesis of interpolation of mechanical factors with FGFR3 gene mutations.
  
  
  CONCLUSIONS
  The correlated observations of X-ray morphometry, histopathology, and gene analysis prompted the following diagnostic workup for TD: (1) prenatal sonography suspicion of skeletal dysplasia; (2) post-mortem X-ray morphometry for provisional diagnosis; (3) confirmation by genetic tests (hot-spot exons 7, 10, 15, and 19 analysis with 80-90% sensibility); (4) in negative cases if histopathology confirms TD diagnosis, research of rare mutations through sequential analysis of FGFR3 gene.
authors.affiliation: Orthopaedic Clinic, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy, ugo.pazzaglia@spedalicivili.brescia.it.
authors.forename: Ugo E
authors.initials: UE
authors.lastname: Pazzaglia
authors.forename: Carla M
authors.initials: CM
authors.lastname: Donzelli
authors.forename: Claudia
authors.initials: C
authors.lastname: Izzi
authors.forename: Maurizia
authors.initials: M
authors.lastname: Baldi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Gaetano
authors.forename: MariaPia
authors.initials: M
authors.lastname: Bondioni
mesh_terms: D001842:Bone and Bones / Q000000981:diagnostic imaging* / Q000196:embryology / Q000473:pathology*; D020022:Genetic Predisposition to Disease / Q000196:embryology / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011296:Prenatal Diagnosis / Q000379:methods; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics*; D013223:Statistics as Topic; D013796:Thanatophoric Dysplasia / Q000175:diagnosis* / Q000196:embryology / Q000235:genetics*; D014057:Tomography, X-Ray Computed
chemical_list: C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3