Both multifocal, demyelinating features and prednisone responsiveness are rare in Charcot–Marie–Tooth (CMT) disease. We report a mother and son with a prednisone‐responsive, multifocal, demyelinating, predominantly sensory polyneuropathy that was associated with an isoleucine92valine polymorphism of lipopolysaccharide‐induced TNF‐alpha factor (LITAF). The mother had a multifocal, acquired, demyelinating sensory and motor polyneuropathy (MADSAM)‐like presentation. The son developed left peroneal neuropathy during acute Lyme disease with a subsequent relapsing, MADSAM‐like illness, despite antibiotic treatment. Both shared prednisone responsiveness and multifocal, demyelinating features electrophysiologically. MADSAM may be familial (FaDSAM) and respond to prednisone. Muscle Nerve 41: 558–562, 2010