Introduction

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease resulting from loss of motor neurons in the motor cortex, brainstem and spinal cord. Despite a characterised rapidly progressive clinical course with upper and lower motor neuron signs and symptoms in classical ALS, unusual presentations can restrict to a specific spinal or bulbar segment for several years. Flail leg syndrome (FLS) is an atypical variant of ALS characterised by progressive distal onset weakness and atrophy of lower limbs with reduced or absent reflexes. Patients should not present with significant weakness or wasting in upper limbs and bulbar within 12 months after onset.1 Mutations in more than 20 genes have been linked to ALS.2 However, genetic cause familial FLS has never been reported. We have identified a missense mutation in PFN1 gene in a FLS family by whole-exome sequencing (WES).