ADGRG6-related disorder: a novel mutation resulting in distal arthrogryposis and a patchy neuropathy.

Arthrogryposis multiplex congenita (AMC) is associated with >150 genes, including ADGRG6, which codes for an adhesion G protein-coupled receptor. Biallelic loss of function variants in ADGRG6 have been linked to lethal congenital contracture syndrome. Here we present an atypical, milder phenotype associated with a novel ADGRG6 variant. A 22-year-old female, born from non-consanguineous parents, presented with non-progressive, distal arthrogryposis of her limbs since birth. Clinical evaluation showed distal contractures of all four limbs, absent right biceps resulting in elbow flexion weakness and patchily absent reflexes. Sensory examination was normal. Neurophysiology found patchy absence of multiple action potentials. Genetic testing revealed a homozygous deletion-insertion variant in ADGRG6's last exon, predicted to extend the protein. We present a unique phenotype of distal arthrogryposis with a patchy neuropathy in a patient with a novel ADGRG6 mutation. We hypothesize that this variant results in a milder phenotype than previously reported loss-of-function mutations.