Abstract
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.
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Acknowledgements
We thank the patients’ families for their participation to the study. This work was supported by a grant from Ministry of Health, Ricerca Corrente to EB, FF, and AD, and a grant from Clinica Las Condes PIDA-2014-002 to CC. We are indebted to the technician Margherita Verardo who contributed to the histopathological processing of muscle biopsies.
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Claudia Castiglioni and Fabiana Fattori contributed equally to this work.
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Castiglioni, C., Fattori, F., Udd, B. et al. Neuromyopathy with congenital cataracts and glaucoma: a distinct syndrome caused by POLG variants. Eur J Hum Genet 26, 367–373 (2018). https://doi.org/10.1038/s41431-017-0003-4
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DOI: https://doi.org/10.1038/s41431-017-0003-4
