Congenital myasthenic syndrome in a cohort of patients with ‘double’ seronegative myasthenia gravis

Lorenzoni, Paulo José; Ducci, Renata Dal‐Prá; Arndt, Raquel Cristina; Hrysay, Nyvia Milicio Coblinski; Fustes, Otto Jesús Hernández; Töpf, Ana; Lochmüller, Hanns; Werneck, Lineü Cesar; Kay, Cláudia Suemi Kamoi; Scola, Rosana Hermínia

doi:10.1590/0004-282x-anp-2020-0575

Cited by 3 publications

(3 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…First, this may partly be explained by the fact that disease gene discovery is an ongoing process with novel molecular etiologies yet to be identified. Second, there is emerging evidence that hereditary myasthenic syndromes are prone to misdiagnoses and may falsely be classified as (seronegative) autoimmune myasthenia gravis and even be treated with immunosuppressant drugs [ 5 , 12 ]. All the more so, a precise and early molecular diagnosis is of paramount importance to avoid long diagnostic delays and unnecessary treatments with potential side effects.…”

Section: Discussionmentioning

confidence: 99%

The clinical and molecular landscape of congenital myasthenic syndromes in Austria: a nationwide study

et al. 2022

View full text Add to dashboard Cite

Background Congenital myasthenic syndromes (CMS) are a heterogeneous group of disorders caused by genetic defects resulting in impaired neuromuscular transmission. Although effective treatments are available, CMS is probably underdiagnosed, and systematic clinico-genetic investigations are warranted. Methods We used a nationwide approach to collect Austrian patients with genetically confirmed CMS. We provide a clinical and molecular characterization of this cohort and aimed to ascertain the current frequency of CMS in Austria. Results Twenty-eight cases with genetically confirmed CMS were identified, corresponding to an overall prevalence of 3.1 per million (95% CI 2.0–4.3) in Austria. The most frequent genetic etiology was CHRNE (n = 13), accounting for 46.4% of the cohort. Within this subgroup, the variant c.1327del, p.(Glu443Lysfs*64) was detected in nine individuals. Moreover, causative variants were found in DOK7 (n = 4), RAPSN (n = 3), COLQ (n = 2), GMPPB (n = 2), CHAT (n = 1), COL13A1 (n = 1), MUSK (n = 1) and AGRN (n = 1). Clinical onset within the first year of life was reported in one half of the patients. Across all subtypes, the most common symptoms were ptosis (85.7%), lower limb (67.9%), upper limb (60.7%) and facial weakness (60.7%). The majority of patients (96.4%) received specific treatment, including acetylcholinesterase inhibitors in 20, adrenergic agonists in 11 and 3,4-diaminopyridine in nine patients. Conclusions Our study presents the first systematic characterization of individuals with CMS in Austria, providing prevalence estimates and genotype–phenotype correlations that may help to improve the diagnostic approach and patient management.

show abstract

Section: Discussionmentioning

confidence: 99%

The clinical and molecular landscape of congenital myasthenic syndromes in Austria: a nationwide study

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Abnormal muscle fatigue should be differentiated from MG and LEMS. Genetic analysis of 121 patients with MG with no anti-AChR or anti-MuSK antibodies revealed 9 patients with CHNRA1- , CHRNE- , and RAPSN -CMS [ 30 , 31 , 32 ]. Muscle hypoplasia should be differentiated from congenital myopathies and limb-girdle muscular dystrophies.…”

Section: Electrophysiology Muscle Biopsy Laboratory Examinations Diff...mentioning

confidence: 99%

Clinical and Pathologic Features of Congenital Myasthenic Syndromes Caused by 35 Genes—A Comprehensive Review

Ohno

Ohkawara

Shen

et al. 2023

IJMS

View full text Add to dashboard Cite

Congenital myasthenic syndromes (CMS) are a heterogeneous group of disorders characterized by impaired neuromuscular signal transmission due to germline pathogenic variants in genes expressed at the neuromuscular junction (NMJ). A total of 35 genes have been reported in CMS (AGRN, ALG14, ALG2, CHAT, CHD8, CHRNA1, CHRNB1, CHRND, CHRNE, CHRNG, COL13A1, COLQ, DOK7, DPAGT1, GFPT1, GMPPB, LAMA5, LAMB2, LRP4, MUSK, MYO9A, PLEC, PREPL, PURA, RAPSN, RPH3A, SCN4A, SLC18A3, SLC25A1, SLC5A7, SNAP25, SYT2, TOR1AIP1, UNC13A, VAMP1). The 35 genes can be classified into 14 groups according to the pathomechanical, clinical, and therapeutic features of CMS patients. Measurement of compound muscle action potentials elicited by repetitive nerve stimulation is required to diagnose CMS. Clinical and electrophysiological features are not sufficient to identify a defective molecule, and genetic studies are always required for accurate diagnosis. From a pharmacological point of view, cholinesterase inhibitors are effective in most groups of CMS, but are contraindicated in some groups of CMS. Similarly, ephedrine, salbutamol (albuterol), amifampridine are effective in most but not all groups of CMS. This review extensively covers pathomechanical and clinical features of CMS by citing 442 relevant articles.

show abstract

“…Table 2 shows the main differential diagnoses of myasthenia gravis that should be considered when there is no typical clinical or electrophysiological picture, or when the disease course is refractory to treatment. For seronegative patients with no response with corticosteroids and immunosuppressants, it is important to keep in mind congenital myasthenic syndromes 38 . Receptor deficiency due to CHRNE mutations and cases related to RAPSN can be clinically very similar to acquired MG 39 , 40 .…”

Section: Diagnostic Approachmentioning

confidence: 99%

Myasthenia gravis in clinical practice

Estephan

Baima

Zambon

2022

Arq. Neuro-Psiquiatr.

View full text Add to dashboard Cite

Background: Myasthenia gravis is largely a treatable disease, but it can result in significant morbidity and even mortality, which can usually be avoided, or at least mitigated, with timely diagnosis and appropriate treatment of the disease. Objective: this review aims to summarize the main practical aspects of the diagnostic approach, treatment and care of myasthenic patients. Methods: The authors performed a non-systematic critical review summarizing the main practical aspects of myasthenia gravis. Results: Most patients with myasthenia have autoantibodies targeted at acetylcholine receptors or, less commonly, muscle-specific kinase - MuSK. Electrophysiology plays an important role in the diagnosis of neuromuscular junction dysfunction. The central clinical manifestation of myasthenia gravis is fatigable muscle weakness, which can affect eye, bulbar, respiratory, and limb muscles. With rare exceptions, patients have a good response to symptomatic treatment, but corticosteroids and/or immunosuppressants are usually also necessary to obtain good control of the manifestations of the disease. Conclusion: Knowledge of the peculiar aspects of their clinical and electrophysiological presentations is important for the diagnosis. Likewise, specific treatment and response time to each drug are crucial for proper care.

show abstract

Congenital myasthenic syndrome in a cohort of patients with ‘double’ seronegative myasthenia gravis

Cited by 3 publications

References 23 publications

The clinical and molecular landscape of congenital myasthenic syndromes in Austria: a nationwide study

The clinical and molecular landscape of congenital myasthenic syndromes in Austria: a nationwide study

Clinical and Pathologic Features of Congenital Myasthenic Syndromes Caused by 35 Genes—A Comprehensive Review

Myasthenia gravis in clinical practice

Contact Info

Product

Resources

About