Congenital Myasthenic Syndrome From a Single Center: Phenotypic and Genotypic features

Abstract

Background: Congenital myasthenic syndrome is a group of rare genetic disorders affecting transmission across the neuromuscular junction. Patients present with variable ocular, bulbar, respiratory, and extremity weakness that may respond to symptomatic therapies. Methods: We identified 18 patients with congenital myasthenic syndrome from a pediatric neuromuscular center over a decade. Through a retrospective chart review, we characterize demographic profile, clinical features, genetic variants, treatment, and follow-up of these patients. Results: Patients had the following genetic subtypes: CHRNE (6), CHAT (2), MUSK (2), DOK7 (2), COLQ (1), RAPSN (1), PREPL (1), GFPT1 (1), CHRBB1 (1), and CHRNA1 (1). The phenotype varied based on the genetic variants, though most patients have generalized fatigable weakness affecting ocular, bulbar, and extremity muscles. There was a significant delay in the diagnosis of this condition from the onset of symptoms. Although most patients improved with pyridostigmine, some subtypes showed worsening with pyridostigmine and others benefited from albuterol, ephedrine, or 3,4-diaminopyridine treatment. Conclusion: Increasing recognition of this rare syndrome will lead to early diagnosis and prompt treatment. Prompt utilization of genetic testing will identify novel variants and the expanding phenotype of this condition.

Congenital myasthenic syndrome: Correlation between clinical features and molecular diagnosis

“…This strengthens the notion that a pure ocular syndrome is not a usual phenotype of CMS, as was previously suggested [24]. Although it is known that congenital myasthenia patients do not usually have pure ocular symptoms, this phenotype has sometimes been reported [25]. Actually, our patient 7 was previously reported as a pure ocular syndrome at 19 years old [18], and now, aged 23 years, it was possible to see limb weakness.…”

“…This strengthens the notion that a pure ocular syndrome is not a usual phenotype of CMS, as was previously suggested [24]. Although it is known that congenital myasthenia patients do not usually have pure ocular symptoms, this phenotype has sometimes been reported [25].…”

Clinicopathological‐genetic features of congenital myasthenic syndrome from a Chinese neuromuscular centre

“…The frequency of mutant genes in our current study, which is from the southern part of China, is more similar to another cohort from the northern part of China than to frequencies from other countries. AGRN‐CMS is one of the most frequent subtypes of CMS from both the southern and northern parts of China 13 but is ultrarare in other countries, in which CHRNE‐CMS is usually the most frequent subtype 2,4,6,51 . CMS caused by mutations in GFPT1 52 and DPAGT1 53 has been associated with tubular aggregates that are of diagnostic support for certain subtypes of CMS.…”

“…AGRN-CMS is one of the most frequent subtypes of CMS from both the southern and northern parts of China 13 but is ultrarare in other countries, in which CHRNE-CMS is usually the most frequent subtype. 2,4,6,51 CMS caused by mutations in GFPT1 52 and DPAGT1 53 has been associated with tubular aggregates that are of diagnostic support for certain subtypes of CMS. For the therapeutic strategy, acetylcholinesterase inhibitors result in some improvement in the majority of CMS but should be avoided in some mutated CMS genes, such as DOK7 10 and COLQ 54 , and should be carefully prescribed for AGRN-CMS.…”

Rapid genome sequencing identifies a novel de novoSNAP25variant for neonatal congenital myasthenic syndrome

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Congenital myasthenic syndrome (CMS) is a group of 32 disorders involving genetic dysfunction at the neuromuscular junction resulting in skeletal muscle weakness that worsens with physical activity. Precise diagnosis and molecular subtype identification are critical for treatment as medication for one subtype may exacerbate disease in another (Finsterer 2019;Prior et al 2021; Engel et al 2015). The SNAP25-related CMS subtype (congenital myasthenic syndrome 18, CMS18; MIM #616330) is a rare disorder characterized by muscle fatigability, delayed psychomotor development and ataxia.

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