Supine changes in lung function correlate with chronic respiratory failure in myotonic dystrophy patients

Poussel, Mathias; Kaminsky, P.; Renaud, Pierre; Laroppe, Julien; Pruna, L.; Chenuel, Bruno

doi:10.1016/j.resp.2014.01.006

Cited by 22 publications

(26 citation statements)

References 31 publications

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“…Lung function impairment (respiratory muscle and diaphragmatic weakness, ventilatory restriction, hypoxaemia and hypercapnia) [5] and cardiac dysfunctions [6,7] have been well described and their prognostic value has long been C (%) FVC demonstrated, but the major issues affecting quality of life in DM1 patients are the CNS and cognitive dysfunctions [8,9].…”

Section: Discussionmentioning

confidence: 99%

“…Besides the classical view as a neuromuscular disease (the majority of DM1 research focused on neuromuscular aspects), nowadays DM1 has to be also considered as a brain disorder regarding the central nervous system (CNS) and cognitive dysfunctions. Indeed, if lung function impairment [5] or cardiac conduction diseases [6,7] have been well described and have a clear prognostic value, the major issues affecting quality of life in DM1 patients are the CNS and cognitive dysfunctions [8,9]. The control of breathing has been shown to be affected, with the description of numerous clinical findings such as irregular breathing pattern [10], sleep breathing disorders [11] or excessive daytime sleepiness [12], supporting a dysregulation at the central level.…”

Section: Introductionmentioning

confidence: 99%

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Lack of correlation between the ventilatory response to CO2 and lung function impairment in myotonic dystrophy patients: Evidence for a dysregulation at central level

Poussel

Thil

Kaminsky

et al. 2015

Neuromuscular Disorders

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Lack of correlation between the ventilatory response to CO2 and lung function impairment in myotonic dystrophy patients: Evidence for a dysregulation at central level

Poussel

Thil

Kaminsky

et al. 2015

Neuromuscular Disorders

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“…It is useful to monitor FVC and FEV1 changes from sitting to supine position at clinic visits. 92 The threshold for obtaining polysomnography in this population should be low. Many patients will progress to a point of requiring non-invasive nighttime ventilatory support.…”

Section: Pathogenesismentioning

confidence: 99%

Myotonic Dystrophy

2014

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Myotonic dystrophy (dystrophia myotonica, DM) is one of the most common lethal monogenic disorders in populations of European descent. Myotonic dystrophy type 1 (DM1) was first described over a century ago. DM1 is caused by expansion of a CTG triplet repeat in the 3' non-coding region of DMPK, the gene encoding the DM protein kinase. More recently a second form of the disease, myotonic dystrophy type 2 (DM2) was recognized, which results from repeat expansion in a different gene. The DM2 expansion involves a CCTG repeat in the first intron of Zinc Finger 9 (ZNF9). Both disorders have autosomal dominant inheritance and multisystem features, including myotonic myopathy, cataract, and cardiac conduction disease. Studies suggest that the shared clinical features of DM1 and DM2 involve a novel genetic mechanism in which repetitive RNA exerts a toxic effect. The RNA toxicity stems from the expanded repeat in the transcripts from the mutant DM alleles. This chapter will review the clinical presentation and pathophysiology of DM, and discuss current management and future potential for developing targeted therapies.

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“…Respiratory failure is the most common cause of death in myotonic dystrophy [47]. It has been correlated with CTG repeat size and may even exist in the absence of significant muscle weakness [48]. The respiratory dysfunction likely results from a combination of skeletal muscle weakness and central nervous system dysfunction [49,50].…”

Section: Respiratorymentioning

confidence: 99%

“…Importantly, it has been noted that patients with DM1 may not be aware of their symptoms related to respiratory failure so physicians should be careful in the way questions are posed and monitor respiratory parameters even in the absence of obvious symptomatology [49]. Although respiratory parameters are typically monitored upright, supine evaluation of pulmonary function may be more sensitive at detecting a restrictive ventilatory pattern [48]. With regard to supportive care, noninvasive ventilation for respiratory weakness has been shown to potentially improve survival in DM1 patients, but therapeutic adherence may be poor and requires close follow-up [53].…”

Section: Respiratorymentioning

confidence: 99%

Myotonic Dystrophies: Targeting Therapies for Multisystem Disease

2018

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Myotonic dystrophy is an autosomal dominant muscular dystrophy not only associated with muscle weakness, atrophy, and myotonia but also prominent multisystem involvement. There are 2 similar, but distinct, forms of myotonic dystrophy; type 1 is caused by a CTG repeat expansion in the DMPK gene, and type 2 is caused by a CCTG repeat expansion in the CNBP gene. Type 1 is associated with distal limb, neck flexor, and bulbar weakness and results in different phenotypic subtypes with variable onset from congenital to very late-onset as well as variable signs and symptoms. The classically described adult-onset form is the most common. In contrast, myotonic dystrophy type 2 is adult-onset or late-onset, has proximal predominant muscle weakness, and generally has less severe multisystem involvement. In both forms of myotonic dystrophy, the best characterized disease mechanism is a RNA toxic gain-of-function during which RNA repeats form nuclear foci resulting in sequestration of RNA-binding proteins and, therefore, dysregulated splicing of premessenger RNA. There are currently no disease-modifying therapies, but clinical surveillance, preventative measures, and supportive treatments are used to reduce the impact of muscular impairment and other systemic involvement including cataracts, cardiac conduction abnormalities, fatigue, central nervous system dysfunction, respiratory weakness, dysphagia, and endocrine dysfunction. Exciting preclinical progress has been made in identifying a number of potential strategies including genome editing, small molecule therapeutics, and antisense oligonucleotide-based therapies to target the pathogenesis of type 1 and type 2 myotonic dystrophies at the DNA, RNA, or downstream target level.

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Supine changes in lung function correlate with chronic respiratory failure in myotonic dystrophy patients

Cited by 22 publications

References 31 publications

Lack of correlation between the ventilatory response to CO2 and lung function impairment in myotonic dystrophy patients: Evidence for a dysregulation at central level

Lack of correlation between the ventilatory response to CO2 and lung function impairment in myotonic dystrophy patients: Evidence for a dysregulation at central level

Myotonic Dystrophy

Myotonic Dystrophies: Targeting Therapies for Multisystem Disease

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