Inherited neuromuscular disorder (NMD) is a wide term covering different genetic disorders affecting muscles, nerves, and neuromuscular junctions. Genetic and clinical heterogeneity is the main ...drawback in a routine gene‐by‐gene diagnostics. We present Czech NMD patients with a genetic cause identified using targeted next‐generation sequencing (NGS) and the spectrum of these causes. Overall 167 unrelated patients presenting NMD falling into categories of muscular dystrophies, congenital muscular dystrophies, congenital myopathies, distal myopathies, and other myopathies were tested by targeted NGS of 42 known NMD‐related genes. Pathogenic or probably pathogenic sequence changes were identified in 79 patients (47.3%). In total, 37 novel and 51 known disease‐causing variants were detected in 23 genes. In addition, variants of uncertain significance were suspected in 7 cases (4.2%), and in 81 cases (48.5%) sequence changes associated with NMD were not found. Our results strongly indicate that for molecular diagnostics of heterogeneous disorders such as NMDs, targeted panel testing has a high‐clinical yield and should therefore be the preferred first‐tier approach. Further, we show that in the genetic diagnostic practice of NMDs, it is necessary to take into account different types of inheritance including the occurrence of an autosomal recessive disorder in two generations of one family.
Objectives
The aim of the study was to evaluate the long‐term efficacy and hospitalization rates in children with refractory focal epilepsy treated by vagus nerve stimulation.
Materials and methods
...We retrospectively analyzed 15 children with intractable focal epilepsy treated by vagus nerve stimulation (mean age of 14.6 ± 2.5 years at the time of implantation). We analyzed the treatment effectiveness at 1, 2, and 5 year follow‐up visits. We counted the average number of urgent hospitalizations and number of days of urgent hospitalization per year for each patient before and after the VNS implantation.
Results
The mean seizure reduction was 42.5% at 1 year, 54.9% at 2 years, and 58.3% at 5 years. The number of responders was 7 (46.7%) at 1 year and 9 (60%) at both 2 and 5 years. The mean number of urgent hospitalizations per patient was 1.0 ± 0.6 per year preoperatively and 0.3 ± 0.5 per year post‐operatively (P < 0.0001). The mean number of days of urgent hospitalization per patient was 9.3 ± 6.1 per year preoperatively and 1.3 ± 1.8 per year post‐operatively (P < 0.0001).
Conclusions
Vagus nerve stimulation is an effective method of treating children with refractory focal epilepsy. It leads to a substantial decrease in the number and duration of urgent hospitalizations.
Children with high-grade glioma still have a poor prognosis despite the use of multimodal therapy including surgery, radiotherapy, and chemotherapy. New therapeutic strategies and methods evaluating ...such therapies are needed.
Here we describe a child with anaplastic oligodendroglioma of the spinal cord who was unable to tolerate standard chemoradiotherapy and who had still-vital residual tumour during therapy. A good response was obtained with low-dose metronomic treatment containing vinblastine. The treatment was guided according to gradual response assessed using various positron-emission tomography tracers.
Metronomic treatment guided by positron-emission tomography could be a reasonable option in some high-risk pediatric tumours.
Abstract Congenital muscular dystrophy (CMD) associated with familial junctional epidermolysis bullosa is a rare autosomal recessive disorder caused by mutation in the plectin gene located on ...chromosome 8q24.3. The first clinical symptoms manifest themselves at about 15 days of life, when first blisters and erosions (very often haemorrhagic) develop on patient’s extremities, their back and face. Skin manifestations usually do not progress over time and skin fragility seems to be mild. The first symptoms of muscle weakness tend to manifest at the end of the first decade; gradual progression leads to patient’s disability and being bound to a wheelchair; around the age of 30, patients die because of weak respiratory muscles. Diagnosing of this disease is based on clinical features, findings in skin and muscle biopsies, and results of genetic testing for mutations in the plectin gene. Case report: boy (aged 14) has been monitored from birth at the Department of Paediatric Dermatology at University Hospital Brno for haemorrhagic blisters manifesting especially on his legs. His original diagnosis was epidermolysis bullosa simplex. From the age of 10, he has had difficulties with walking, from the age of 12 he has been using an electric wheelchair. The patient was hospitalized in December 2010 (aged 13) at the Department of Paediatric Neurology, where he underwent detailed examination including brain magnetic resonance, skin and muscle biopsies. The muscle biopsy revealed a severe myogenic lesion, consistent with muscular dystrophy with inflammatory features; the results of morphological testing as well as the analysis of proteins expression in muscle tissue were compatible with the diagnosis of CMD with EB. Subsequently, this diagnosis was also confirmed on a molecular genetic level. Direct sequencing of the plectin gene revealed c.5902_5903delAA and c.9109del17 mutations, disrupting translational reading frame. Both of these pathogenic mutations have not been reported yet.
PDF