Genetic diagnosis and clinical evaluation of severe fetal akinesia syndrome

Prenat Diagn. 2020 Dec;40(12):1532-1539. doi: 10.1002/pd.5809. Epub 2020 Sep 10.


Objective: In this retrospective study, we describe the clinical course, ultrasound findings and genetic investigations of fetuses affected by fetal akinesia.

Materials and methods: We enrolled 22 eukaryotic fetuses of 18 families, diagnosed with fetal akinesia between 2008 and 2016 at the Department of Obstetrics and Feto-Maternal Medicine at the Medical University of Vienna. Routine genetic evaluation included karyotyping and chromosomal microarray analysis. Retrospectively, exome sequencing was performed in the index case of 11 families, if stored DNA was available. Confirmation analyses and genetic diagnosis of siblings were performed by using Sanger sequencing.

Results: Whole exome sequencing identified pathogenic variants of CNTN1, RYR1, NEB, GLDN, HRAS and TNNT3 in six cases of 11 families. In three of these families, the variants were confirmed in the respective sibling.

Conclusions: The present study demonstrates a high diagnostic yield of exome sequencing in fetuses affected by akinesia syndrome, especially if family history is positive. Still, in a large part the underlying genetic cause remained unknown, whereas precise clinical evaluation in combination with exome sequencing shows to be the best tool to find the disease causing variants.

MeSH terms

  • Arthrogryposis / genetics*
  • Exome Sequencing
  • Female
  • Humans
  • Microarray Analysis
  • Nuchal Translucency Measurement
  • Pregnancy
  • Pregnancy Outcome
  • Retrospective Studies

Supplementary concepts

  • Pena Shokeir syndrome, type 1