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

• Published in: Ultrasound in obstetrics & gynecology 2011-03, Vol.37 (3), p.283-289
• Main Authors: Chitty, L. S., Griffin, D. R., Meaney, C., Barrett, A., Khalil, A., Pajkrt, E., Cole, T. J.
• Format: Article
• Language: English
• Subjects: Achondroplasia; Achondroplasia - diagnosis; Achondroplasia - diagnostic imaging; Achondroplasia - genetics; Anthropometry - methods; Biological and medical sciences; cell‐free fetal DNA; Chest; Data processing; Diseases of the osteoarticular system; DNA; DNA - blood; DNA - genetics; Female; Femur; Fetal Diseases - diagnosis; Fetal Diseases - diagnostic imaging; Fetal Diseases - genetics; fetal size charts; fetal ultrasound; Fetuses; Finger; Gestation; Gynecology; Gynecology. Andrology. Obstetrics; Human viral diseases; Humans; Infectious diseases; Malformations and congenital and or hereditary diseases involving bones. Joint deformations; Maternal-Fetal Exchange; Medical sciences; Mutation; Mutation - genetics; non‐invasive prenatal diagnosis; Obstetrics; Polymorphism, Single Nucleotide; Pregnancy; Prenatal diagnosis; Prenatal Diagnosis - methods; Receptor, Fibroblast Growth Factor, Type 3 - blood; Reviews; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization - methods; Ultrasonography; Ultrasound; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids
• ISSN: 0960-7692; 1469-0705; 1469-0705
• DOI: 10.1002/uog.8893

Objectives 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 3rd centile by 25 weeks' gestation, and always below the 3rd by 30 weeks. Head circumference was above the 50th centile, increasing to above the 95th 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. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.