Thanatophoric Dysplasia Workup

Updated: Sep 18, 2018
  • Author: Germaine L Defendi, MD, MS, FAAP; Chief Editor: Luis O Rohena, MD, FAAP, FACMG  more...
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Workup

Laboratory Studies

The following studies are indicated in suspected cases of thanatophoric dysplasia (TD):

  • Chromosome analysis (karyotype) to determine the presence or absence of chromosomal abnormalities.

  • DNA molecular testing for FGFR3 using targeted and sequence mutation analyses.

A study published in 2015 by Chitty et al suggested that next-generation sequencing (NGS) is more sensitive than polymerase chain reaction assay and restriction enzyme digest (PCR-RED) in the prenatal diagnostic screening for monogenic disorders, including thanatophoric dysplasia and achondroplasia. In the study, which used cell-free DNA from maternal blood, NGS and PCR-RED were performed to aid in the prenatal diagnosis of thanatophoric dysplasia and achondroplasia, with NGS being 96.2% accurate, compared with 88.6% for PCR-RED. [8]  

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Imaging Studies

During the second or third semester of pregnancy, prenatal ultrasonography and CT scan assessments may be diagnostically helpful, as follows [9, 10, 11] :

  • Two-dimensional (2D) ultrasonography reveals polyhydramnios, growth deficiency, ventriculomegaly, a narrow thorax, flattened vertebrae and micromelia
  • Three-dimensional (3D) ultrasonography may reveal the fetal face, scapular anomalies, and chest hypoplasia better than 2D ultrasonography
  • A study published in 2014 by Wang et al indicated that the prenatal identification of temporal lobe dysplasia by ultrasonography may aid in the identification of thanatophoric dysplasia; the study found that out of 24 cases of thanatophoric dysplasia, 16 (67%) demonstrated ultrasonographic evidence of temporal lobe dysplasia [12]
  • Prenatal 3D CT scanning may complement ultrasonographic findings in cases in which fetal skeletal dysplasia is suspected, but no specific diagnosis can be made using ultrasonography alone; further studies on clinical performance and risk-benefit analysis are needed before 3D CT scanning is incorporated into standard practice guidelines [13]

Postnatal radiography and other imaging studies (CT, MRI) may reveal the following:

  • Enlarged skull and a small foramen magnum with potential evidence of brain stem compression
  • CNS abnormalities such as hydrocephalus, brainstem hypoplasia, temporal lobe malformations, neuronal migration abnormalities
  • Flattened vertebral bodies (platyspondyly) with wide intervertebral spacing
  • Rhizomelic shortening and irregular metaphyses of the long bones and "telephone receiver–shaped" bowed femurs
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Histologic Findings

Histologic evaluation of long bone structure in thanatophoric dysplasia shows disruption of endochondral ossification but not of periosteal ossification.

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