Both unrelated individuals described here share a previously unrecognised disorder characterised by GCLJ and giant cell-rich lesions affecting facial/skull bones, skeletal changes and progressive polyneuropathy and carry novel de novo germline TRPV4 variants leading to p.Leu619Pro substitution, expanding the spectrum of TRPV4 channelopathies. Here, TRPV4 is linked to channelopathy.