Neuromyopathy with congenital cataracts and glaucoma: a distinct syndrome caused by POLG variants

Claudia Castiglioni, Fabiana Fattori, Bjarne Udd, Maria de Los Angeles Avaria, Bernardita Suarez, Adele D'Amico, Alessandro Malandrini, Rosalba Carrozzo, Daniela Verrigni, Enrico Bertini, Giorgio Tasca

Research output: Contribution to journalArticlepeer-review


We identified three non-related patients manifesting a childhood-onset progressive neuromyopathy with congenital cataracts, delayed walking, distal weakness and wasting, glaucoma and swallowing difficulties. Electrophysiology and nerve biopsies showed a mixed axonal and demyelinating neuropathy, while muscle biopsy disclosed both neurogenic and myopathic changes with ragged red fibers, and muscle MRI showed consistent features across patients, with a peculiar concentric disto-proximal gradient of fatty replacement. We used targeted next generation sequencing and candidate gene approach to study these families. Compound biallelic heterozygous variants, p.[(Pro648Arg)]; [(His932Tyr)] and p.[(Thr251Ile),(Pro587Leu)]; [(Arg943Cys)], were found in the three patients causing this homogeneous phenotype. Our report on a subset of unrelated patients, that showed a distinct autosomal recessive childhood-onset neuromyopathy with congenital cataracts and glaucoma, expands the clinical spectrum of POLG-related disorders. It also confirms the association between cataracts and neuropathy with variants in POLG. Early onset cataract is otherwise rare in POLG-related disorders and so far reported only in a few patients with the clinical pattern of distal myopathy or neuromyopathy.

Original languageEnglish
Pages (from-to)367-373
Number of pages7
JournalEuropean Journal of Human Genetics
Issue number3
Publication statusPublished - Mar 2018


  • Adolescent
  • Adult
  • Cataract/genetics
  • DNA Polymerase gamma/genetics
  • Female
  • Glaucoma/genetics
  • Humans
  • Male
  • Mutation, Missense
  • Neuromuscular Diseases/genetics
  • Phenotype
  • Syndrome


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