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Phenotypical features of two patients diagnosed with PHARC syndrome and carriers of a new homozygous mutation in the ABHD12 gene

  • Marina Frasquet
    Affiliations
    Neuromuscular Research Unit, Instituto de Investigación Sanitaria La Fe, Valencia, Spain
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  • Vincenzo Lupo
    Affiliations
    Unit of Genetics and Genomics of Neuromuscular and Neurodegenerative Disorders and Service of Genomics and Translational Genetics, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain
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  • María José Chumillas
    Affiliations
    Department of Clinical Neurophysiology, Hospital Universitari i Politècnic La Fe, Valencia, Spain

    Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Spain
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  • Juan Francisco Vázquez-Costa
    Affiliations
    Neuromuscular Research Unit, Instituto de Investigación Sanitaria La Fe, Valencia, Spain

    Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Spain
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  • Carmen Espinós
    Affiliations
    Unit of Genetics and Genomics of Neuromuscular and Neurodegenerative Disorders and Service of Genomics and Translational Genetics, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain
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  • Teresa Sevilla
    Correspondence
    Corresponding author at: Hospital Universitari i Politècnic la Fe, Department of Neurology, C/Fernando Abril Martorell, 106, 46026, Valencia, Spain.
    Affiliations
    Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Spain

    Department of Neurology, Hospital Universitari i Politècnic La Fe, Valencia, Spain

    Department of Medicine, University of Valencia, Valencia, Spain
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Published:February 07, 2018DOI:https://doi.org/10.1016/j.jns.2018.02.021

      Highlights

      • In-depth review of neuropathy characteristics in PHARC syndrome
      • PHARC syndrome can be expressed as a typical demyelinating CMT for years.
      • Consider PHARC in demyelinating polyneuropathy with hearing loss and retinopathy

      Abstract

      PHARC (Polyneuropathy, Hearing loss, Ataxia, Retinitis pigmentosa and Cataracts) (MIM# 612674) is an autosomal recessive neurodegenerative disease caused by mutations in the ABHD12 gene. We evaluated two Spanish siblings affected with pes cavus, sensorimotor neuropathy, hearing loss, retinitis pigmentosa and juvenile cataracts in whom the genetic test of ABHD12 revealed a novel homozygous frameshift mutation, c.211_223del (p.Arg71Tyrfs*26). The earliest clinical manifestation in these patients was a demyelinating neuropathy manifested with a Charcot-Marie-Tooth phenotype over three decades. Progressive hearing loss, cataracts and retinitis pigmentosa appeared after the age of 30. We herein describe the complete clinical picture of these two patients, and focus particularly on neuropathy characteristics. This study supports the fact that although PHARC is rare, its phenotype is very characteristic and we should include its study in patients affected with demyelinating polyneuropathy, hearing loss and retinopathy.

      Keywords

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