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Molecular analysis of ring chromosome 20 syndrome reveals two distinct groups of patients
  1. Laura K Conlin1,
  2. Whitney Kramer1,
  3. Anne L Hutchinson1,
  4. Xia Li1,
  5. Harold Riethman2,
  6. Hakon Hakonarson3,
  7. John C Mulley4,5,
  8. Ingrid E Scheffer6,7,
  9. Samuel F Berkovic6,
  10. Syed A Hosain8,
  11. Nancy B Spinner1
  1. 1Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, The University of Pennsylvania School of Medicine, Philadelphia, USA
  2. 2The Wistar Institute, and The University of Pennsylvania School of Medicine, Philadelphia, USA
  3. 3Center for Applied Genomics, and Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, The University of Pennsylvania School of Medicine, Pennsylvania, USA
  4. 4Epilepsy Research Program, SA Pathology at Women's and Children's Hospital, North Adelaide, Australia
  5. 5School of Molecular and Biomedical Sciences, and School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, Australia
  6. 6Epilepsy Research Centre, University of Melbourne, Austin Health, Melbourne, Australia
  7. 7Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Melbourne, Australia
  8. 8Department of Pediatrics, Division of Child Neurology, Robert-Wood Johnson Medical School, UMDNJ, New Brunswick, New Jersey, USA
  1. Correspondence to Nancy B Spinner, Department of Pathology and Laboratory Medicine, 1007A Abramson Research Center, 3615 Civic Center Boulevard, The Children's Hospital of Philadelphia, Philadelphia, The University of Pennsylvania School of Medicine, PA 19104, USA; spinner{at}


Background The ring chromosome 20 syndrome (R20) is a rare genetic disorder associated with a refractory electroclinical epilepsy syndrome and variably expressed comorbidities of intellectual disability and dysmorphism.

Methods To understand the structure and composition of the ring chromosome 20 (r(20)) in this patient cohort, blood specimens from 28 affected individuals were analysed by cytogenetic, fluorescence in situ hybridisation, and/or high resolution whole genome single nucleotide polymorphism array analysis.

Results These studies revealed two distinct groups of patients. Group 1 (N=21) was mosaic for the r(20) and a normal cell line with no detectable deletions or duplications of chromosome 20 in either cell line. The mosaic nature of these rings suggests a postzygotic origin with formation of the ring by fusion of the telomeric regions with no apparent loss of subtelomeric or telomeric DNA. Group 2 (N=7) had non-mosaic ring chromosomes with a deletion at one or both ends of the chromosome, near the ring fusion point. The non-mosaic nature of these rings is consistent with a meiotic origin. The age of onset of seizures was significantly lower in the non-mosaic patients (group 2, median age of onset 2.1 years) than in the mosaic patients (group 1, median age of onset 6.0 years). Patients from group 2 had more extensive comorbidities.

Conclusions These studies demonstrate that r(20) is molecularly heterogeneous and formed by two distinct mechanisms, which, in turn, produce different phenotypic spectrums.

  • Ring chromosome 20 syndrome
  • epilepsy
  • seizures
  • ring chromosomes
  • molecular cytogenetics
  • SNP array
  • clinical genetics

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  • Funding Ring Chromosome 20 Foundation; The Children's Hospital of Philadelphia Research Institute; National Health and Medical Research Council of Australia.

  • Competing interests None

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the Children's Hospital of Philadelphia and the Human Research Ethics Committee of Austin Health (Australia).

  • Provenance and peer review Not commissioned; externally peer reviewed.