Neurogenic arthrogryposis and the power of phenotyping

Abstract

In this article we review the commonest cause of neurogenic arthrogryposis, termed Spinal Muscular Atrophy Lower Extremity Dominant (SMALED), due to variants in DYNC1H1 and BICD2. We discuss the characteristic clinical and radiological phenotype of this disorder and how this has facilitated the identification of the genetic cause of SMALED2. We also review the similarities and differences between the human SMALED phenotype and mouse models and how this has informed our understanding of the potential mechanisms governing motor neuron loss in these disorders.

Keywords: Arthrogryposis; BICD2; Dynein; Muscle; SMALED.