title: Congenital Myasthenic Syndromes with Predominant Limb Girdle Weakness.
abstract: Congenital myasthenic syndromes are a heterogeneous group of genetically determined disorders characterized by impaired neuromuscular transmission. They usually present from birth to childhood and are characterised by exercise induced weakness and fatigability. Genotype-phenotype correlations are difficult. However, in some patients particular phenotypic aspects may point towards a specific genetic defect. The absence of ptosis and ophthalmoparesis in patients with limb-girdle weakness makes the diagnosis of a neuromuscular transmission defect particularly challenging (LG-CMS). This is illustrated by a well-documented case published by Walton in 1956. The diagnosis of LG-CMS is secured by demonstrating a neuromuscular transmission defect with single fibre EMG or repetitive nerve stimulation, in the absence of auto-antibodies. Ultimately, a genetic test is required to identify the underlying cause and assure counselling and optimization of treatment. LG-CMS are inherited in autosomal recessive traits, and are often associated with mutations inDOK7andGFPT1, and less frequently with mutations inCOLQ, ALG2, ALG14andDPAGT. Genetic characterization of CMS is of the upmost importance when choosing the adequate treatment. Some of the currently used drugs can either ameliorate or aggravate the symptoms depending on the underlying genetic defect. The drug most frequently used for the treatment of CMS is pyridostigmine an acetylcholinesterase inhibitor. However, pyridostigmine is not effective or is even detrimental inDOK7- andCOLQ-related LG-CMS, while beta-adrenergic agonists (ephedrine, salbutamol) show some sustained benefit. Standard clinical trials may be difficult, but standardized follow-up of patients and international collaboration may help to improve the standards of care of these conditions.
authors: John Walton Muscular Dystrophy Research Centre, MRC Centre for Neuromuscular Diseases, Newcastle University, Newcastle upon Tyne, UK.
authors: Teresinha
authors: T
authors: Evangelista
authors: UCL MRC Centre for Neuromuscular Disease, Institute of Neurology and National Hospital for Neurology and Neurosurgery, Queen Square, London, United Kingdom.
authors: Mike
authors: M
authors: Hanna
authors: John Walton Muscular Dystrophy Research Centre, MRC Centre for Neuromuscular Diseases, Newcastle University, Newcastle upon Tyne, UK.
authors: Hanns
authors: H
authors: Lochmüller