Pregnancy‐associated respiratory failure in <i>muscle specific kinase</i> congenital myasthenic syndrome

Wadwekar, Vaibhav; Pillai, Rajit; Sesh, S; Nair, Sruthi S; Nair, Muralidharan

doi:10.1002/mus.26410

Cited by 6 publications

(3 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The size and the number of exons within these genes made them challenging to screen using standard PCR and Sanger sequencing techniques. Next-generation sequencing has greatly facilitated mutation detection within these genes and led to the a broadening of the phenotypic spectrum for CMS due to either AGRN [22,23] or MUSK mutations including variants in MUSK giving rise to a late onset limb girdle CMS [24 ▪ ] isolated vocal cord paralysis [25] or pregnancy-associated respiratory failure [26]. It is likely that there will be increasing pick up of variants within these genes but defining pathogenicity will often require time-consuming and quite complex functional studies.…”

Section: Basal Lamina-associated Syndromesmentioning

confidence: 99%

The congenital myasthenic syndromes: expanding genetic and phenotypic spectrums and refining treatment strategies

Vanhaesebrouck

Beeson

2019

Current Opinion in Neurology

View full text Add to dashboard Cite

Purpose of reviewCongenital myasthenic syndromes (CMS) are a group of heterogeneous inherited disorders caused by mutations in genes encoding proteins whose function is essential for the integrity of neuromuscular transmission. This review updates the reader on the expanding phenotypic spectrum and suggested improved treatment strategies.Recent findingsAs next-generation sequencing is taken into the clinic, its use is both continuing to unearth new causative genes in which mutations underlie CMS and also broadening the phenotypic spectrum for known CMS genes. The number of genes in which mutations may cause neuromuscular transmission defects has now passed 30. The defective transmission may be part of an overall more complex phenotype in which there may be muscle, central nervous system or other involvement. Notably, mutations in series of genes encoding proteins located in the presynatic motor bouton have been identified. Rare cases of mutations in basal laminar proteins of the synaptic cleft are coming to light and additional mutations/phenotypic features have been located in some of the larger neuromuscular junction proteins such as AGRN and MUSK, where previously mutation screening by sanger sequencing was time consuming and costly. Finally, there are more reports of the beneficial effects of treatment with β2-adrenergic receptor agonists in patients, and the study of their action in disease models.SummaryRecent studies of the CMS illustrate the increasing complexity of the genetics and pathophysiological mechanisms involved. With therapy tailored for the underlying disease mechanism treatment, although incomplete, is usually life-transforming. However, treatment for newly identified conditions in which myasthenia is only one component within complex multisystem disorder will prove challenging.

show abstract

Section: Basal Lamina-associated Syndromesmentioning

confidence: 99%

The congenital myasthenic syndromes: expanding genetic and phenotypic spectrums and refining treatment strategies

Vanhaesebrouck

Beeson

2019

Current Opinion in Neurology

View full text Add to dashboard Cite

show abstract

“…Most patients will live into adulthood, and thus questions around the impact of pregnancy in females often arise in the clinical setting. Due to the rarity of CMS, with an estimated prevalence of 1 in 300 000, 1 currently available information is limited to case reports and small case series, which have shown variable outcomes 3–7 . The aim of this study was to assess the pregnancy and fetal outcomes in patients with genetically confirmed CMS to improve advice for patients and specialists involved in their antenatal care.…”

Section: Introductionmentioning

confidence: 99%

Pregnancy outcomes in patients with congenital myasthenic syndromes

et al. 2022

View full text Add to dashboard Cite

Introduction/Aims The congenital myasthenic syndromes (CMS) are a heterogeneous group of inherited disorders that affect neuromuscular junction transmission. Data on pregnancy outcomes in women with CMS are limited due to their infrequency. In this study we explored pregnancy with CMS in a large cohort of women attending a national specialty clinic in England. Methods All women with CMS who had a documented pregnancy were invited to complete a questionnaire assessing clinical status during pregnancy and postpartum, pregnancy outcomes, fetal outcomes, and medication use during pregnancy. Results Among 16 women with CMS (acetylcholine receptor deficiency [CHRNE], slow channel syndrome [CHRNA1], DOK7, RAPSYN and glycosylation [DPAGT1 and GFPT1]), 27 pregnancies were recorded: 26 single pregnancies and 1 twin pregnancy. Symptom worsening was reported in 63% of pregnancies, but recovery to baseline function was seen in all but one patient. Miscarriage and cesarean section occurred in 31% and 33% of the women, respectively. Over half of the patients continued taking their medication during pregnancy, which included pyridostigmine (n = 10), 3,4‐diaminopyridine (n = 9), ephedrine (n = 3), salbutamol (n = 3), and quinidine (n = 1). No fetal malformations were recorded. Discussion Our results show that clinical worsening during pregnancy was common but rarely persistent. The majority of women with CMS can safely plan pregnancy, but close follow‐up is required from their neurology and obstetric teams. Although we identified no safety concerns, continued medication use should be reviewed on a case‐by‐case basis.

show abstract

“…O sequenciamento de nova geração (NGS) facilitou muito a detecção de mutações nos genes que codificam essas proteínas, aumentando o espectro fenotípico de SMC relacionadas a mutações nestes genes. De forma mais marcante podemos falar das síndromes do MUSK, como SMC de cinturas de instalação tardia 51 , paralisia isolada das cordas vocais 52 , ou insuficiência respiratória associada à gravidez 53 .…”

Section: Síndromes Miastênicas Congênitas Pós-sinápticasunclassified

Estudo clínico e molecular das síndromes miastênicas congênitas

Estephan¹

View full text Add to dashboard Cite

Pregnancy‐associated respiratory failure in muscle specific kinase congenital myasthenic syndrome

Cited by 6 publications

References 16 publications

The congenital myasthenic syndromes: expanding genetic and phenotypic spectrums and refining treatment strategies

The congenital myasthenic syndromes: expanding genetic and phenotypic spectrums and refining treatment strategies

Pregnancy outcomes in patients with congenital myasthenic syndromes

Estudo clínico e molecular das síndromes miastênicas congênitas

Contact Info

Product

Resources

About