Genotype-phenotype correlation in a novel ABHD12 mutation underlying PHARC syndrome

J Peripher Nerv Syst. 2020 Jun;25(2):112-116. doi: 10.1111/jns.12367. Epub 2020 Feb 24.


PHARC syndrome is a rare neurodegenerative disorder caused by mutations in the ABHD12 gene. It is a genetically heterogeneous and clinically variable disease, which is characterized by demyelinating polyneuropathy, hearing loss, cerebellar ataxia, retinitis pigmentosa, and early-onset cataract and can easily be misdiagnosed as other neurologic disorders with a similar clinical picture, such as Charcot-Marie-Tooth disease and Refsum disease. We describe the genotype-phenotype correlation of two siblings with a novel genotype underlying PHARC syndrome. The genotype was identified using next-generation sequencing. We examined both patients by means of thorough history taking and clinical examination, nerve conduction studies (NCS), brain imaging, and optical coherence tomography to establish a genotype-phenotype correlation. We identified a novel homozygous point mutation (c.784C > T, p.Arg262*) in the ABHD12 gene. This mutation was detected in both siblings, who had bilateral hearing loss and cataracts, signs of cerebellar ataxia, and neuropathy with a primarily demyelinating pattern in NCS. In one case, retinitis pigmentosa was also evident. As PHARC syndrome is a rare autosomal recessive disorder, our findings highlight the importance of an interdisciplinary diagnostic workup with clinical and molecular genetic testing to avoid a misdiagnosis as Charcot-Marie-Tooth disease or Refsum disease.

Keywords: Charcot-Marie-Tooth disease; Refsum disease; deafness; hereditary neuropathy; retinitis pigmentosa.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Ataxia / diagnosis
  • Ataxia / genetics*
  • Ataxia / physiopathology*
  • Cataract / diagnosis
  • Cataract / genetics*
  • Cataract / physiopathology*
  • Genetic Association Studies
  • Humans
  • Male
  • Monoacylglycerol Lipases / genetics*
  • Polyneuropathies / diagnosis
  • Polyneuropathies / genetics*
  • Polyneuropathies / physiopathology*
  • Retinitis Pigmentosa / diagnosis
  • Retinitis Pigmentosa / genetics*
  • Retinitis Pigmentosa / physiopathology*
  • Siblings
  • Young Adult


  • ABHD12 protein, human
  • Monoacylglycerol Lipases

Supplementary concepts

  • Polyneuropathy, Hearing Loss, Ataxia, Retinitis Pigmentosa, And Cataract