Clinical and Molecular Genetics Unit, UCL Institute of Child Health, University College London, UK.
Prenat Diagn. 2013 May;33(5):416-23. doi: 10.1002/pd.4066. Epub 2013 Feb 14.
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.
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.
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.
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.
通过定义胎儿在妊娠期间的大小变化和超声特征的频率，提高致死性骨发育不良的产前诊断水平，并基于母体外周血游离胎儿 DNA（cffDNA）开发非侵入性分子遗传诊断方法。
确定确诊为致死性骨发育不良的胎儿，回顾病历，确定超声特征和测量值。然后使用 LMS（lambda-mu-sigma）方法构建胎儿大小图表，并与正常妊娠和伴有软骨发育不全的妊娠图表进行比较。本队列中转诊至我们地区遗传实验室进行 cffDNA 分子诊断的病例，对其结果进行回顾。
在我们的单位中扫描了 42 例病例。常报道的超声特征包括非常短且有时弯曲的股骨、额骨突出、三叶形颅骨、短指、小胸部和羊水过多。肢体缩短从 13 周妊娠开始就很明显，20 周后几乎没有生长。对其中 3 例妊娠的 cffDNA 分析证实存在成纤维细胞生长因子受体 3 基因 c.742C>T（p.Arg248Cys）或 c.1948A>G（p.Lys650Glu）突变。
这些数据应提高致死性骨发育不良的超声诊断准确性，并对使用 cffDNA 进行可靠和安全的靶向分子确认具有重要意义。
