Journal of neuromuscular diseases最新文献

Background: Nemaline myopathy type 6 (NEM6) or KBTBD13-related congenital myopathy is the most prevalent type of nemaline myopathy in the Netherlands and is characterised by mild childhood-onset axial, proximal and distal muscle weakness with prominent neck flexor weakness combined with slowness of movements. The most prevalent variant in the Netherlands is the c.1222C > T p.(Arg408Cys) variant in the KBTBD13 gene, also called the Dutch founder variant.

Objective: To provide a comprehensive clinical and functional characterisation of three patients to assess the pathogenicity of a newly identified variant in the KBTBD13 gene.

Results: We present three cases (Patient 1: female, 76 years old; Patient 2: male, 63 years old; and his brother Patient 3: male, 61 years old) with a c.1222C > A p.(Arg408Ser) variant in the KBTBD13 gene. Patient 1 was also included previously in a histopathological study on NEM6. Symptoms of muscle weakness started in childhood and progressed to impaired functional abilities in adulthood. All three patients reported slowness of movements. On examination, they have mild axial, proximal and distal muscle weakness. None of the patients exhibited cardiac abnormalities. Spirometry in two patients showed a restrictive lung pattern. Muscle ultrasound showed symmetrically increased echogenicity indicating fatty replacement and fibrosis in a subset of muscles and histopathological analyses revealed nemaline rods and cores. Slower muscle relaxation kinetics with in vivo functional tests was observed. This was confirmed by in vitro functional tests showing impaired relaxation kinetics in isolated muscle fibres. We found a genealogic link between patient 1, and patient 2 and 3 nine generations earlier.

Conclusions: The c.1222C > A p.(Arg408Ser) variant in the KBTBD13 gene is a likely pathogenic variant causing NEM6.

Background: LAMA2-related dystrophies (LAMA2-RDs) represent one of the most common forms of congenital muscular dystrophy and have historically been classified into two subtypes: complete or partial deficiency of laminin-211 (merosin). Patients with LAMA2-RD with the typical congenital phenotype manifest severe muscle weakness, delayed motor milestones, joint contractures, failure to thrive, and progressive respiratory insufficiency.

Objective: While a comprehensive prospective natural history study has been performed in LAMA2-RD patients over 5 years of age, the early natural history of patients with LAMA2-RD 5 years and younger has not been comprehensively characterized.

Methods: We extracted retrospective data for patients with LAMA2-RD ages birth through 5 years via the Congenital Muscle Disease International Registry (CMDIR). We analyzed the data using a phenotypic classification based on maximal motor milestones to divide patients into two phenotypic groups: "Sit" for those patients who attained that ability to remain seated and "Walk" for those patients who attained the ability to walk independently by 3.5 years of age.

Results: Sixty patients with LAMA2-RD from 10 countries fulfilled the inclusion criteria. Twenty-four patients had initiated non-invasive ventilation by age 5 years. Hospitalizations during the first years of life were often related to respiratory insufficiency. Feeding/nutritional difficulties and orthopedic issues were commonly reported. Significant elevations of creatine kinase (CK) observed during the neonatal period declined rapidly within the first few months of life.

Conclusions: This is the largest international retrospective early natural history study of LAMA2-RD to date, contributing essential data for understanding early clinical findings in LAMA2-RD which, along with the data being collected in international, prospective early natural history studies, will help to establish clinical trial readiness. Our proposed nomenclature of LAMA2-RD1 for patients who attain the ability to sit (remain seated) and LAMA2-RD2 for patients who attain the ability to walk independently is aimed at further improving LAMA2-RD classification.

Background: Myotonic Dystrophy type 2 (DM2) is a dominantly inherited multisystem disease caused by a CCTG repeat expansion in intron 1 of the CNBP gene. Although in the last two decades over 1500 patients with DM2 have been diagnosed worldwide, our clinical impression of a reduced life expectancy in DM2 has not been investigated previously.

Objective: The aim of this observational study was to determine the life expectancy and the causes of death in patients with genetically confirmed DM2.

Methods: We identified the data of all deceased patients with DM2 in the Dutch neuromuscular database between 2000 and 2023. Ages and causes of death and the patients' clinical features during lifetime were determined. Age of death in DM2 was compared to the general population by using life tables with prognostic cohort life expectancy (CLE) and period life expectancy (PLE) data of the Dutch electronic database of statistics (CBS StatLine).

Results: Twenty-six deceased patients were identified in the Dutch DM2 cohort (n = 125). Median age of death in DM2 (70.9 years) was significantly lower compared to sex- and age-matched CLE (78.1 years) and PLE (82.1 years) in the Netherlands. Main causes of death were cardiac diseases (31%) and pneumonia (27%). Seven patients (27%) had a malignancy at the time of death.

Conclusion: These results provide new insights into the phenotype of DM2. Life expectancy in patients with DM2 is reduced, possibly attributable to multiple causes including increased risk of cardiac disease, pneumonia, and malignancies. The occurrence of a significantly reduced life expectancy has implications for clinical practice and may form a basis for advanced care planning, including end-of-life care, to optimize quality of life for patients with DM2 and their family. Research in larger cohorts should be done to confirm these findings and to ascertain more about the natural course in DM2.

Neuromuscular diseases (NMDs), in their phenotypic heterogeneity, share quite invariably common issues that involve several clinical and socio-economical aspects, needing a deep critical analysis to develop better management strategies. From diagnosis to treatment and follow-up, the development of technological solutions can improve the detection of several critical aspects related to the diseases, addressing both the met and unmet needs of clinicians and patients. Among several aspects of the digital transformation of health and care, this congress expands what has been learned from previous congresses editions on applicability and usefulness of technological solutions in NMDs. In particular the focus on new solutions for remote monitoring provide valuable insights to increase disease-specific knowledge and trigger prompt decision-making. In doing that, several perspectives from different areas of expertise were shared and discussed, pointing out strengths and weaknesses on the current state of the art on topic, suggesting new research lines to advance technology in this specific clinical field.