Highlights
- •DOK7-CMS have phenotypic overlap with other causes of ‘unexplained’ LGMW.
- •The minimum prevalence of undiagnosed DOK7-CMS with ‘unexplained’ LGMW is 2.9%.
- •DOK7-CMS should be investigate when manifestation is an ‘unexplained’ LGMW.
Abstract
Congenital myasthenic syndromes (CMS) associated with pathogenic variants in the DOK7 gene (DOK7-CMS) have phenotypic overlap with other neuromuscular disorders associated
with limb-girdle muscular weakness (LGMW). Genetic analysis of the most common mutation
(c.1124_1127dupTGCC) in DOK7 was performed in 34 patients with “unexplained” LGMW associated with non-specific
changes in muscle biopsy. Of the 34 patients, one patient showed the DOK7 c.1124_1127dupTGCC variant in homozygousity. Our study estimates the minimum prevalence
of undiagnosed DOK7-CMS to be 2.9% in southern Brazilian patients from our centre.
Our data confirm that clinicians should look for DOK7-CMS patients when the clinical
manifestation is an ‘unexplained’ LGMW, mainly if associated with non-specific changes
in muscle biopsy.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of Clinical NeuroscienceAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Congenital myasthenic syndrome: a brief review.Pediatr Neurol. 2011; 46: 141-148
- Clinical and research strategies for limb-girdle congenital myasthenic syndromes.Ann N Y Acad Sci. 2018; 1412: 102-112
- Congenital myasthenic syndromes: achievements and limitations of phenotype-guided gene-after-gene sequencing in diagnostic practice: a study of 680 patients.Hum Mutat. 2012; 33: 1474-1484
- Congenital myasthenic syndromes in adult neurology clinic: a long road to diagnosis and therapy.Neurology. 2018; 91: e1770-e1777
- Use of whole-exome sequencing for diagnosis of limb-girdle muscular dystrophy: outcomes and lessons learned.JAMA Neurol. 2015; 72: 1424-1432
- DOK7 mutations presenting as a proximal myopathy in French Canadians.Neuromuscul Dis. 2010; 20: 453-457
- DOK7 congenital Myasthenic syndrome.Ann N Y Acad Sci. 2012; 1275: 49-53
- Delayed diagnosis of DOK7 congenital myasthenic syndrome: case report and literature review.Neurol Clin Pract. 2018; 8: e40-e42
- DOK7 limb-girdle myasthenia syndrome mimicking congenital muscular dystrophy.Neuromuscul Disord. 2013; 23: 36-42
- Beneficial effects of 3,4-diaminopyridine in a 26-year-old woman with DOK7 congenital myasthenic syndrome who was originally diagnosed with facioscapulohumeral dystrophy.Rinsho Shinkeigaku. 2014; 54: 561-564
- Utility of next generation sequencing in genetic diagnosis of early onset neuromuscular disorders.J Med Genet. 2015; 52: 208-216
- A 'limb-girdle muscular dystrophy' responsive to asthma therapy.Pract Neurol. 2017; 17: 327-331
- Congenital myasthenic syndrome and minicore-like myopathy with DOK7 mutation.Muscle Nerve. 2013; 48: 151-152
- Congenital myasthenic syndromes in childhood: diagnostic and management challenges.J Neuroimmunol. 2008; 201–202: 6-12
- Exome sequences versus sequential gene testing in the UK highly specialised Service for Limb Girdle Muscular Dystrophy.Orphanet J Rare Dis. 2017; 12: 151
- The sensitivity of exome sequencing in identifying pathogenic mutations for LGMD in the United States.J Hum Genet. 2017; 62: 243-252
- A first-line diagnostic assay for limb-girdle muscular dystrophy and other myopathies.Hum Genomics. 2016; 10: 32
- Clinical features of the DOK7 neuromuscular junction synaptopathy.Brain. 2007; 130: 1507-1515
- The value of muscle biopsy in neurology: a study of 290 biopsies.Rev Bras Clin Ter. 1981; 10: 2-24
- Congenital Myasthenic syndromes with predominant limb girdle weakness.J Neuromuscul Dis. 2015; 2: S21-S29
- Molecular characterisation of congenital myasthenic syndromes in Southern Brazil.J Neurol Neurosurg Psychiatry. 2010; 81: 973-977
- Phenotypical spectrum of DOK7 mutations in congenital myasthenic syndromes.Brain. 2007; 130: 1497-1506
- Dok-7 Myasthenia: Phenotypic and molecular gnenetic studies in 16 patients.Ann Neurol. 2008; 64: 71-87
- Phenotype genotype analysis in 15 patients presenting a congenitalmyasthenic syndrome due to mutations in DOK7.J Neurol. 2010; 257: 754-766
- Congenital myasthenic syndrome: presentation, electrodiagnosis, and muscle biopsy.J Child Neurol. 2004; 19: 175-182
Article info
Publication history
Published online: March 29, 2020
Accepted:
January 27,
2020
Received:
November 22,
2019
Identification
Copyright
© 2020 Published by Elsevier Ltd.
