Abstract
SUMMARY: Pathogenic variants in the polymerase γ gene (POLG) cause a diverse group of pathologies known as POLG-related disorders. In this report, we describe brain MR imaging findings and electroencephalogram correlates of 13 children with POLG-related disorders at diagnosis and follow-up. At diagnosis, all patients had seizures and 12 had abnormal MR imaging findings. The most common imaging findings were unilateral or bilateral perirolandic (54%) and unilateral or bilateral thalamic signal changes (77%). Association of epilepsia partialis continua with perirolandic and thalamic signal changes was present in 86% and 70% of the patients, respectively. The occipital lobe was affected in 2 patients. On follow-up, 92% of the patients had disease progression or fatal outcome. Rapid volume loss was seen in 77% of the patients. The occipital lobe (61%) and thalamus (61%) were the most affected brain regions. Perirolandic signal changes and seizures may represent a brain imaging biomarker of early-onset pediatric POLG-related disorders.
ABBREVIATIONS:
- ASL
- arterial spin-labeling
- EEG
- electroencephalogram
- EPC
- epilepsia partialis continua
- MELAS
- mitochondrial encephalomyopath with lactic acidosis and stroke-like episodes
- mtDNA
- mitochondrial DNA
- Polγ
- polymerase γ
- POLG-RD
- DNA polymerase γ–related disorder
Footnotes
G.Z. is the Principal Investigator (P.I.).
This work was funded, in part, by the Mitochondrial Medicine Frontier Program at Children’s Hospital of Philadelphia.
Disclosures: Zarazuela Zolkipli-Cunningham—UNRELATED: Employment: Children’s Hospital of Philadelphia. Marni J. Falk—UNRELATED: Board Membership: United Mitochondrial Disease Foundation, Comments: travel reimbursement for serving on scientific and medical advisory boards and board of trustees of the United Mitochondrial Disease Foundation; Consultancy: several pharma companies, Comments: paid consultant for Mitobridge/Astellas, NeuroVive, Cyclerionc Therapeutics, Reneo Pharmaceuticals, Mission Therapeutics, Stealth BioTherapeutics, and Imel Therapeutics; Grants/Grants Pending: several pharma companies and foundations, Comments: grants from Mitobridge/Astellas, NeurovVive, Cyclerion Therapeutics, Mission Therapeutics (pending), Stealth BioTherapeutics, Minovia Therapeutics (pending)*; Patents (Planned, Pending or Issued): several, Comments: several patents (no current value) at home institution in mitochondrial disease diagnostic and therapeutic development*; Royalties: Elsevier, Comments: editor of book now in press at Elsevier, Mitochondrial Disease Genes Compendium; Stock/Stock Options: Mitocureia, Comments: co-founder and scientific advisory board co-Chair of Mitocureia; Travel/Accommodations/Meeting Expenses Unrelated to Activities Listed: education travel, Comments: reimbursed for travel to speak at meetings on mitochondrial diagnostics and therapeutics including at CardioInfantil, Bogota, Columbia; Pediatric Neurology Society, Mexico; American College of Medical Genetics; Emory/Atlanta Children’s Hospital; New York University; Cornell University; Washington University in St Louis; Seattle Children’s Hospital; scientific and family meetings hosted by United Mitochondrial Disease Foundation; European Society of Human Genetics; Society for the Study of Inborn Errors of Metabolism; Society of Inherited Metabolic Disease; Hebrew University; Asian Society Of Inborn Errors of Metabolism; Wellcome Genome Campus; Cold Spring Harbor Laboratory. Amy Goldstein—UNRELATED: Board Membership: United Mitochondrial Disease Foundation, Comments: Scientific and Medical Advisory Board. *Money paid to the institution.
- © 2020 by American Journal of Neuroradiology