Evaluation of fetal nuchal translucency in 98 pregnancies at risk for severe spinal muscular atrophy: possible relevance of the SMN2 copy number

Abstract

Objective: To study fetal nuchal translucency (NT) thickness as a possible early marker in fetuses at risk for severe spinal muscular atrophy (SMA). To investigate the significance of the survival motor neuron (SMN) 2 gene copy number in affected fetuses. Methods: We performed 2D-ultrasound in 98 pregnancies at risk for SMA, all of which underwent prenatal molecular testing of the SMN1 gene. Crown-rump length (CRL) and NT measurements were obtained in all cases before chorionic villus sampling. Fetuses were diagnosed as healthy, carriers or affected according to the SMN1 molecular testing results. SMN2 copies were also tested in all affected fetuses. Results: Nineteen fetuses were predicted to be affected due to the absence of the SMN1 gene, 18 of which had two SMN2 copies. Mean CRL and NT values did not differ between healthy, carrier and affected fetuses. In the remaining affected case who had only one SMN2 copy, the ultrasound examination showed a NT value of 4.98 mm and findings compatible with hypoplastic left heart. Conclusions: Most affected SMA fetuses have normal NT values. Our findings support the idea that SMN2 copy number in SMA fetuses is relevant for the development of congenital heart defects and increased NT values.

Keywords::

• Congenital heart disease
• nuchal translucency
• prenatal diagnosis
• spinal muscular atrophy
• SMN2 gene

Acknowledgements

We wish to thank the consenting couples who made this study possible.

Declaration of Interest: This work was partially supported by GENAME Project (RM, SB), FIS05-2416 (EA), CIBERER U-705 (LA), and FIS 08-0729, Spain. We are indebted to Ignasi Gich and Josefina Mora for help with statistics and to Carolyn Newey for her contribution in the final edition and revision of this manuscript.