RT Journal Article
SR Electronic
T1 Clinical, pathological and genetic spectrum in 89 cases of mitochondrial progressive external ophthalmoplegia
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 643
OP 646
DO 10.1136/jmedgenet-2019-106649
VO 57
IS 9
A1 Claudia Rodríguez-López
A1 Luis M. García-Cárdaba
A1 Alberto Blázquez
A1 Pablo Serrano-Lorenzo
A1 Gerardo Gutiérrez-Gutiérrez
A1 Beatriz San Millán-Tejado
A1 Nuria Muelas
A1 Aurelio Hernández-Laín
A1 Juan J. Vílchez
A1 Eduardo Gutiérrez-Rivas
A1 Joaquín Arenas
A1 Miguel A. Martín
A1 Cristina Domínguez-González
YR 2020
UL http://jmg.bmj.com/content/57/9/643.abstract
AB Background Mitochondrial progressive external ophthalmoplegia (PEO) encompasses a broad spectrum of clinical and genetic disorders. We describe the phenotypic subtypes of PEO and its correlation with molecular defects and propose a diagnostic algorithm.Methods Retrospective analysis of the clinical, pathological and genetic features of 89 cases.Results Three main phenotypes were found: ‘pure PEO’ (42%), consisting of isolated palpebral ptosis with ophthalmoparesis; Kearns-Sayre syndrome (10%); and ‘PEO plus’, which associates extraocular symptoms, distinguishing the following subtypes: : myopathic (33%), bulbar (12%) and others (3%). Muscle biopsy was the most accurate test, showing mitochondrial changes in 95%. Genetic diagnosis was achieved in 96% of the patients. Single large-scale mitochondrial DNA (mtDNA) deletion was the most frequent finding (63%), followed by multiple mtDNA deletions (26%) due to mutations in TWNK (n=8), POLG (n=7), TK2 (n=6) or RRM2B (n=2) genes, and point mtDNA mutations (7%). Three new likely pathogenic mutations were identified in the TWNK and MT-TN genes.Conclusions Phenotype–genotype correlations cannot be brought in mitochondrial PEO. Muscle biopsy should be the first step in the diagnostic flow of PEO when mitochondrial aetiology is suspected since it also enables the study of mtDNA rearrangements. If no mtDNA deletions are identified, whole mtDNA sequencing should be performed.