Motor neuropathies with conduction slowing or block – beyond inflammatory disease

<h3>Introduction</h3> Neurophysiology demonstrating conduction block (CB) and/or slowing (CS) in motor neuropathies usually prompts investigation for an acquired cause. We present three genetic causes for these ‘acquired’ features. <h3>Methods</h3> Patients were seen at two centres and underwent whole exome or genome sequencing. <h3>Results</h3> Case 1: A 23-year-old male from non-consanguineous parents presented with progressive distal leg weakness since his early teens. Neurophysiology showed a motor neuropathy with CB and dispersion in both ulnar motor nerves in the forearms. He carries homozygous c.757del in <i>SORD</i>. Case 2: A 44-year-old man from consanguineous parents presented with proximal lower limb weakness aged 7. This progressed to upper limbs, and distal extremities. Neurophysiology showed uniform motor CS and CB, with minor sensory involvement. He carries novel homozygous <i>PLEKHG5</i> variant p.(Tyr11*) in the non-canonical transcript. Case 3: A 43-year-old female had falls and walking difficulties since early childhood and progressive distal extremity weakness. Neurophysiology showed a motor neuropathy with widespread CS and CB. She was homozygous for p.Asp876ArgfsTer111 in <i>PIGG</i>. <h3>Conclusions</h3> CS and/or CB in a motor predominant neuropathy does not always signify an acquired neuropathy. A long or slowly progressive history, or lack of treatment response, should prompt consideration of a genetic cause.