Neuromyopathy with congenital cataracts and glaucoma: A distinct syndrome caused by POLG variants /692/308 /692/699 article

C. Castiglioni, F. Fattori, B. Udd, M. De Los Angeles Avaria, B. Suarez, A. D'Amico, A. Malandrini, R. Carrozzo, D. Verrigni, E. Bertini, G. 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. © 2018 European Society of Human Genetics.
Original languageEnglish
Pages (from-to)367-373
Number of pages7
JournalEuropean Journal of Human Genetics
Issue number3
Publication statusPublished - 2018


  • immunoglobulin
  • DNA directed DNA polymerase gamma
  • POLG protein, human, adolescent
  • adult
  • Article
  • blindness
  • cachexia
  • case report
  • cataract extraction
  • child
  • clinical article
  • closed angle glaucoma
  • congenital cataract
  • demyelinating neuropathy
  • developmental delay
  • distal myopathy
  • dysphagia
  • electrophysiology
  • exophthalmos
  • female
  • gastrostomy
  • gene
  • glaucoma
  • human
  • human tissue
  • hypogonadotropic hypogonadism
  • infant
  • male
  • mitochondrial myopathy
  • molecular genetics
  • motor neuropathy
  • muscle atrophy
  • muscle biopsy
  • muscle hypotonia
  • nerve biopsy
  • neuromuscular disease
  • next generation sequencing
  • nuclear magnetic resonance imaging
  • ophthalmoplegia
  • phenotype
  • polg gene
  • priority journal
  • quadriplegia
  • recurrent infection
  • respiratory failure
  • school child
  • secondary sexual characteristics
  • sensorimotor neuropathy
  • tracheostomy
  • weakness
  • young adult
  • cataract
  • genetics
  • missense mutation
  • pathology
  • syndrome, Adolescent
  • Adult
  • Cataract
  • DNA Polymerase gamma
  • Female
  • Glaucoma
  • Humans
  • Male
  • Mutation, Missense
  • Neuromuscular Diseases
  • Phenotype
  • Syndrome


Dive into the research topics of 'Neuromyopathy with congenital cataracts and glaucoma: A distinct syndrome caused by POLG variants /692/308 /692/699 article'. Together they form a unique fingerprint.

Cite this