Cardiomyopathy in limb girdle muscular dystrophy <scp>R9</scp>, <scp><i>FKRP</i></scp> related

Libell, Eric M; Richardson, Julia A; Lutz, Katie; Ng, Benton; Mockler, Shelley R.H.; Laubscher, Katie M.; Stephan, Carrie M.; Zimmerman, Bridget; Edens, Erik; Reinking, Benjamin E.; Mathews, Katherine D.

doi:10.1002/mus.27052

Cited by 12 publications

(3 citation statements)

References 35 publications

(102 reference statements)

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“…Patients with LGMD develop progressive muscle weakness in the shoulder and pelvic girdle associated with a variable degree of disability, ranging from patients with mild difficulties walking to patients who are full-time wheelchair users. Cardiac and respiratory muscles can also be affected in some of these conditions, as has been reported in previous singular cohorts of patients with pathogenic variants in the Fkrp , 6 , 7 sarcoglycan, 8 , 9 and Capn3 10 , 11 genes. However, data on the progression of cardiac and respiratory dysfunction over time are lacking for most of these conditions.…”

supporting

confidence: 60%

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Longitudinal Analysis of Respiratory Function of Different Types of Limb Girdle Muscular Dystrophies Reveals Independent Trajectories

Muni-Lofra,

Juanola-Mayos,

Schiava

et al. 2023

Neurol Genet

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Background and ObjectivesThe prevalence and progression of respiratory muscle dysfunction in patients with limb girdle muscular dystrophies (LGMDs) has been only partially described to date. Most reports include cross-sectional data on a limited number of patients making it difficult to gain a wider perspective on respiratory involvement throughout the course of the disease and to compare the most prevalent LGMD subtypes.MethodsWe reviewed the results of spirometry studies collected longitudinally in our cohort of patients in routine clinical visits from 2002 to 2020 along with additional clinical and genetic data. A linear mixed model was used to investigate the factors associated with the progression of respiratory dysfunction.ResultsWe followed up 156 patients with 5 different forms of LGMDs for a median of 8 years (range 1–25 years). Of them, 53 patients had pathogenic variants in theCapn3gene, 47 patients in theDysfgene, 24 patients in theFkrpgene, 19 in theAno5gene, and 13 in one of the sarcoglycan genes (SCG). At baseline, 58 patients (37.1%) had a forced vital capacity percentage predicted (FVCpp) below 80%, while 14 patients (8.9%) had peak cough flow (PCF) values below 270 L/min. As a subgroup,FKRPwas the group with a higher number of patients having FVC <80% and/or PCF <270 L/min at initial assessment (66%). We observed a progressive decline in FVCpp and PCF measurements over time, being age, use of wheelchair, and LGMD subtype independent factors associated with this decline.Fkrpand sarcoglycan patients had a quicker decline in their FVC (Kaplan–Meier curve, F test,p< 0.001 andp= 0.02, respectively). Only 7 of the 58 patients with low FVCpp values reported symptoms of respiratory dysfunction, which are commonly reported by patients with FVCpp below 50%–60%. The number of patients ventilated increased from 2 to 8 during follow-up.DiscussionRespiratory dysfunction is a frequent complication of patients with LGMDs that needs to be carefully studied and has direct implications in the care offered in daily clinics. Respiratory dysfunction is associated with disease progression because it is especially seen in patients who are full-time wheelchair users, being more frequent in patients with mutations in theFkrpand sarcoglycan genes.

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confidence: 60%

“…There are only a few published studies assessing respiratory muscle function using spirometry in patients with LGMD 6 – 11 and with limited analysis of change over time. Our results are consistent with much of the published literature.…”

Section: Discussionmentioning

confidence: 99%

Longitudinal Analysis of Respiratory Function of Different Types of Limb Girdle Muscular Dystrophies Reveals Independent Trajectories

Muni-Lofra,

Juanola-Mayos,

Schiava

et al. 2023

Neurol Genet

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“…Gender was also analysed in two previous studies looking at cardiac involvement in LGMDR9, albeit in genotypically heterogenous cohorts. In one study an increased tendency for cardiomyopathy was found in males [19] , while in another study no association with gender was identified [17] .…”

Section: Article In Pressmentioning

confidence: 91%

Epidemiology and natural history in 101 subjects with FKRP-related limb-girdle muscular dystrophy R9. The Norwegian LGMDR9 cohort study (2020)

Jensen¹,

Müller²,

Mellgren³

et al. 2023

Neuromuscular Disorders

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Insomnia and sleep-disordered breathing in FKRP-related limb-girdle muscular dystrophy R9. The Norwegian LGMDR9 cohort study (2020)

Jensen,

Abeler,

Friborg

et al. 2023

J Neurol

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Limb-girdle muscular dystrophy R9 (LGMDR9) is a progressive and disabling genetic muscle disease. Sleep is relevant in the patient care as it impacts on health, functioning, and well-being. LGMDR9 may potentially affect sleep by physical or emotional symptoms, myalgia, or sleep-disordered breathing (SDB) through cardiorespiratory involvement. The objective was to investigate the occurrence of insomnia and unrecognized or untreated SDB in LGMDR9, associated factors, and relationships with fatigue and health-related quality of life (HRQoL). All 90 adults in a Norwegian LGMDR9 cohort received questionnaires on sleep, fatigue, and HRQoL. Forty-nine of them underwent clinical assessments and 26 without mask-based therapy for respiration disorders additionally underwent polysomnography (PSG) and capnometry. Among 77 questionnaire respondents, 31% received mask-based therapy. The prevalence of insomnia was 32% of both those with and without such therapy but was significantly increased in fatigued respondents (54% vs 21%). Insomnia levels correlated inversely with mental HRQoL. Among 26 PSG candidates, an apnea–hypopnea index (AHI) ≥ 5/h was observed in 16/26 subjects (≥ 15/h in 8/26) with median 6.8 obstructive apneas and 0.2 central apneas per hour of sleep. The AHI was related to advancing age and an ejection fraction < 50%. Sleep-related hypoventilation was detected in one subject. Fatigue severity did not correlate with motor function or nocturnal metrics of respiration or sleep but with Maximal Inspiratory Pressure (r = − 0.46). The results indicate that insomnia and SDB are underrecognized comorbidities in LGMDR9 and associated with HRQoL impairment and heart failure, respectively. We propose an increased attention to insomnia and SDB in the interdisciplinary care of LGMDR9. Insomnia and pulmonary function should be examined in fatigued patients.

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Cardiomyopathy in limb girdle muscular dystrophy R9, FKRP related

Cited by 12 publications

References 35 publications

Longitudinal Analysis of Respiratory Function of Different Types of Limb Girdle Muscular Dystrophies Reveals Independent Trajectories

Longitudinal Analysis of Respiratory Function of Different Types of Limb Girdle Muscular Dystrophies Reveals Independent Trajectories

Epidemiology and natural history in 101 subjects with FKRP-related limb-girdle muscular dystrophy R9. The Norwegian LGMDR9 cohort study (2020)

Insomnia and sleep-disordered breathing in FKRP-related limb-girdle muscular dystrophy R9. The Norwegian LGMDR9 cohort study (2020)

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