Prominent Action Tremor in PHARC Syndrome With a Novel ABHD12 Missense Variant

ABSTRACT

Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract (PHARC) syndrome is a rare autosomal recessive neurodegenerative disorder caused by biallelic pathogenic variants in ABHD12 . We report a 50‐year‐old Japanese man with childhood‐onset hearing loss and retinitis pigmentosa who subsequently developed action tremor, sensorimotor polyneuropathy, cataracts, and cerebellar atrophy. The action tremor caused greater functional impairment than gait ataxia. Genetic testing identified compound heterozygous ABHD12 variants: the previously reported Japanese splice‐site variant c.316+2T>A and a novel missense variant c.374C>G (p.Thr125Arg). His asymptomatic mother carried only c.316+2T>A, supporting a likely in trans configuration of the two variants, and p.Thr125Arg was classified as likely pathogenic. This case adds a novel ABHD12 missense variant to the genetic spectrum of PHARC syndrome and illustrates that disabling action tremor can occur in ABHD12 ‐related disease, even when gait ataxia is not the dominant source of disability.