Horga, A;
Bugiardini, E;
Manole, A;
Bremner, F;
Jaunmuktane, Z;
Dankwa, L;
Rebelo, AP;
Woodward, CE;
Hargreaves, IP;
Cortese, A;
et al.
Horga, A; Bugiardini, E; Manole, A; Bremner, F; Jaunmuktane, Z; Dankwa, L; Rebelo, AP; Woodward, CE; Hargreaves, IP; Cortese, A; Pittman, AM; Brandner, S; Polke, JM; Pitceathly, RDS; Züchner, S; Hanna, MG; Scherer, SS; Houlden, H; Reilly, MM
(2019)
Autosomal dominant optic atrophy and cataract "plus" phenotype including axonal neuropathy.
Neurol Genet, 5 (2).
e322.
ISSN 2376-7839
https://doi.org/10.1212/NXG.0000000000000322
SGUL Authors: Pittman, Alan Michael
Abstract
Objective: To characterize the phenotype in individuals with OPA3-related autosomal dominant optic atrophy and cataract (ADOAC) and peripheral neuropathy (PN). Methods: Two probands with multiple affected relatives and one sporadic case were referred for evaluation of a PN. Their phenotype was determined by clinical ± neurophysiological assessment. Neuropathologic examination of sural nerve and skeletal muscle, and ultrastructural analysis of mitochondria in fibroblasts were performed in one case. Exome sequencing was performed in the probands. Results: The main clinical features in one family (n = 7 affected individuals) and one sporadic case were early-onset cataracts (n = 7), symptoms of gastrointestinal dysmotility (n = 8), and possible/confirmed PN (n = 7). Impaired vision was an early-onset feature in another family (n = 4 affected individuals), in which 3 members had symptoms of gastrointestinal dysmotility and 2 developed PN and cataracts. The less common features among all individuals included symptoms/signs of autonomic dysfunction (n = 3), hearing loss (n = 3), and recurrent pancreatitis (n = 1). In 5 individuals, the neuropathy was axonal and clinically asymptomatic (n = 1), sensory-predominant (n = 2), or motor and sensory (n = 2). In one patient, nerve biopsy revealed a loss of large and small myelinated fibers. In fibroblasts, mitochondria were frequently enlarged with slightly fragmented cristae. The exome sequencing identified OPA3 variants in all probands: a novel variant (c.23T>C) and the known mutation (c.313C>G) in OPA3. Conclusions: A syndromic form of ADOAC (ADOAC+), in which axonal neuropathy may be a major feature, is described. OPA3 mutations should be included in the differential diagnosis of complex inherited PN, even in the absence of clinically apparent optic atrophy.
Item Type: |
Article
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Additional Information: |
Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Journal or Publication Title: |
Neurol Genet |
ISSN: |
2376-7839 |
Language: |
eng |
Dates: |
Date | Event |
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1 April 2019 | Published | 1 February 2019 | Accepted |
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Publisher License: |
Creative Commons: Attribution 4.0 |
Projects: |
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PubMed ID: |
31119193 |
![](http://static.pubmed.gov/portal/portal3rc.fcgi/2745237/img/27842) |
Go to PubMed abstract |
URI: |
https://openaccess.sgul.ac.uk/id/eprint/111329 |
Publisher's version: |
https://doi.org/10.1212/NXG.0000000000000322 |
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