Null variants in AGRN cause lethal fetal akinesia deformation sequence

We present a case of lethal fetal akinesia deformation sequence (FADS) caused by a frameshift variant in trans with a 148 kbp deletion encompassing 3‐36 exons of AGRN. Pathogenic variants in AGRN have been described in families with a form of congenital myasthenic syndrome (CMS), manifesting in the early childhood with variable fatigable muscle weakness. To the best of our knowledge, this is the first case of FADS caused by defects in AGRN gene. FADS has been reported to be caused by pathogenic variants in genes previously associated with CMS including these involved in endplate development and maintenance: MuSK, DOK7, and RAPSN. FADS seems to be the most severe form of CMS. None of the reported in the literature CMS cases associated with AGRN had two null variants, like the case presented herein. This indicates a strong genotype‐phenotype correlation. We present a case of lethal fetal akinesia deformation sequence (FADS) caused by a frameshift variant and a 148 kbp deletion encompassing 3‐36 exons of AGRN. Variants in AGRN have been described in families with a form of congenital myasthenic syndrome, manifesting in the early childhood with variable fatigable muscle weakness. To the best of our knowledge, this is the first case of FADS caused by defects in AGRN gene. FADS seems to be the most severe phenotype associated with AGRN. The case presented herein is the first patient, that had two null variants in AGRN gene. This indicates a strong genotype‐phenotype correlation.