Pediatric CIDP: Diagnosis and Management. A Single-Center Experience.

Background: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare acquired polyneuropathy that especially among youngest children should be differentiated with hereditary neuropathies. Even though upon diagnosis treatment options are similar in children and adults, diagnostic challenges are faced in the pediatric population. Methods: We conducted a retrospective analysis of clinical symptoms, nerve conduction study results, modes of treatment, and final outcome in 37 children aged 3.5-17 years with a final diagnosis of CIDP (18 girls, 19 boys). We established three groups of patients based on age at onset of CIDP: 0-4, 4-13, and 13-18 years. Follow-up ranged from 10 to 222 months. Results: In our analysis, 19/37 patients (51.4%) had an atypical presentation: distal variant of CIDP in 12/37 patients (32.4%) and pure motor variant of CIDP in 5/37 patients (13.5%), and one patient had a pure sensory variant (1/37, 2.7%). Furthermore, 3/37 patients (8.1%) had additional concurring symptoms, including involuntary movements of face muscles (1/37, 2.7%) or hand tremor (2/37, 5.4%). During the follow-up, 23/37 patients (62.2%) received intravenous immunoglobulin (IVIg); 22/37 patients (59.5%) received steroids, 6/37 patients (16.2%) received IVIg and steroids, and 12/37 patients (32.4%) received immunosuppressive drugs, mostly azathioprine, but also methotrexate and rituximab. One patient was treated with plasmapheresis. Complete remission was achieved in 19/37 patients (51.4%) with CIDP in its typical form. Remission with residual symptoms or minimal deficit was observed in 4/37 patients (10.8%), whereas 14/37 patients (37.8%) remain on treatment with gradual improvement. Conclusion: Childhood CIDP may occur in its typical form, but even ~50% of children can present as an atypical variant including distal, pure motor, or pure sensory. Most children have a good prognosis; however, many of them may require long-term treatment. This highlights the importance of an early diagnosis and treatment for childhood CIDP.

Floppy infant syndrome as a first manifestation of LMNA-related congenital muscular dystrophy.

LMNA-related congenital muscular dystrophy (L-CMD) is the most severe phenotypic form of skeletal muscle laminopathies. This paper reports clinical presentation of the disease in 15 Polish patients from 13 families with genetically confirmed skeletal muscle laminopathy. In all these patients floppy infant syndrome was the first manifestation of the disease. The genetic diagnosis was established by next generation sequencing (targeted panel or exome; 11 patients) or classic Sanger sequencing (4 patients). In addition to known pathogenic LMNA variants: c.116A > G (p.Asn39Ser), c.745C > T (p.Arg249Trp), c.746G > A (p.Arg249Gln), c.1072G > A (p.Glu358Lys), c.1147G > A (p.Glu383Lys), c.1163G > C (p.Arg388Pro), c.1357C > T (p.Arg453Trp), c.1583C > G (p.Thr528Arg), we have identified three novel ones: c.121C > G (p.Arg41Gly), c.1127A > G (p.Tyr376Cys) and c.1160T > C (p.Leu387Pro). Eleven patients had de novo mutations, 4 - familial. In one family we observed intrafamilial variability of clinical course: severe L-CMD in the male proband, intermediate form in his sister and asymptomatic in their mother. One asymptomatic father had somatic mosaicism. L-CMD should be suspected in children with hypotonia in infancy and delayed motor development, who have poor head control, severe hyperlordosis and unstable and awkward gait. Serum creatine kinase may be high (~1000IU/l). Progression of muscle weakness is fast, leading to early immobilization. In some patients with L-CMD joint contractures can develop with time. MRI shows that the most frequently affected muscles are the serratus anterior, lumbar paraspinal, gluteus, vastus, adductor magnus, hamstrings, medial head of gastrocnemius and soleus. Ultra-rare laminopathies can be a relatively common cause of generalized hypotonia in children. Introduction of wide genome sequencing methods was a breakthrough in diagnostics of diseases with great clinical and genetic variability and allowed approach "from genotype do phenotype". However target sequencing of LMNA gene could be considered in selected patients with clinical picture suggestive for laminopathy.

Pathogenic Mutations and Putative Phenotype-Affecting Variants in Polish Myofibrillar Myopathy Patients.

Myofibrillar myopathies (MFM) are heterogeneous hereditary muscle diseases with characteristic myopathological features of Z-disk dissolution and aggregates of its degradation products. The onset and progression of the disease are variable, with an elusive genetic background, and around half of the cases lacking molecular diagnosis. Here, we attempted to establish possible genetic foundations of MFM by performing whole exome sequencing (WES) in eleven unrelated families of 13 patients clinically diagnosed as MFM spectrum. A filtering strategy aimed at identification of variants related to the disease was used and included integrative analysis of WES data and human phenotype ontology (HPO) terms, analysis of muscle-expressed genes, and analysis of the disease-associated interactome. Genetic diagnosis was possible in eight out of eleven cases. Putative causative mutations were found in the DES (two cases), CRYAB, TPM3, and SELENON (four cases) genes, the latter typically presenting with a rigid spine syndrome. Moreover, a variety of additional, possibly phenotype-affecting variants were found. These findings indicate a markedly heterogeneous genetic background of MFM and show the usefulness of next generation sequencing in the identification of disease-associated mutations. Finally, we discuss the emerging concept of variant load as the basis of phenotypic heterogeneity.

Corrigendum: Pediatric CIDP: Diagnosis and Management. A Single-Center Experience.

[This corrects the article DOI: 10.3389/fneur.2021.667378.].

ANO5 mutations in the Polish limb girdle muscular dystrophy patients: Effects on the protein structure.

LGMD2L is a subtype of limb-girdle muscular dystrophy (LGMD), caused by recessive mutations in ANO5, encoding anoctamin-5 (ANO5). We present the analysis of five patients with skeletal muscle weakness for whom heterozygous mutations within ANO5 were identified by whole exome sequencing (WES). Patients varied in the age of the disease onset (from 22 to 38 years) and severity of the morphological and clinical phenotypes. Out of the nine detected mutations one was novel (missense p.Lys132Met, accompanied by p.His841Asp) and one was not yet characterized in the literature (nonsense, p.Trp401Ter, accompanied by p.Asp81Gly). The p.Asp81Gly mutation was also identified in another patient carrying a p.Arg758Cys mutation as well. Also, a c.191dupA frameshift (p.Asn64LysfsTer15), the first described and common mutation was identified. Mutations were predicted by in silico tools to have damaging effects and are likely pathogenic according to criteria of the American College of Medical Genetics and Genomics (ACMG). Indeed, molecular modeling of mutations revealed substantial changes in ANO5 conformation that could affect the protein structure and function. In addition, variants in other genes associated with muscle pathology were identified, possibly affecting the disease progress. The presented data indicate that the identified ANO5 mutations contribute to the observed muscle pathology and broaden the genetic spectrum of LGMD myopathies.

Comparison of LI-RADS v.2017 and ESGAR Guidelines Imaging Criteria in HCC Diagnosis Using MRI with Hepatobiliary Contrast Agents.

PURPOSE: The purpose of this study was to assess and compare diagnostic ability of LI-RADS (LR) v. 2017 and ESGAR guidelines in hepatocellular carcinoma (HCC) diagnosis using MRI with hepatobiliary contrast agents. METHODS: Seventy pathologically confirmed lesions in 32 patients (24 males and 8 females) who had MRI with hepatobiliary contrast done before surgery or biopsy were reviewed retrospectively. Six lesions were <10mm, 31 lesions 10-19mm, and 33 lesions ≥20mm. Two readers assessed all lesions according to LI-RADS v.2017 criteria and ESGAR consensus statement on liver MR imaging and clinical use of liver-specific contrast agents. Statistical analysis was performed to compare diagnostic ability of both guidelines including receiver operative curves (ROC) and area under curve (AUC). RESULTS: For LR ≥ 4 sensitivity, specificity, accuracy, and AUC were 96%, 75%, 88.6%, and 85.5, respectively. For LR5 they were 74%, 95%, 80%, and 84.5, respectively. For ESGAR criteria with major and additional features, they were 88%, 75%, 84.3%, and 81.5, respectively. For ESGAR criteria only with major features they were 78%, 80%, 78.6%, and 79, respectively. AUC analysis revealed that overall diagnostic ability of LI-RADS was higher than ESGAR but the results did not show statistical significance. CONCLUSIONS: Both LI-RADS and ESGAR guidelines presented high diagnostic ability in HCC diagnosis of MRI studies with hepatobiliary contrast agents. More complex LI-RADS criteria performed better than ESGAR guidelines and it may justify extra effort that needs to be put in the report. However, the results were not statistically different and the simplicity of the ESGAR guidelines should also be taken into consideration.

CT/MRI LI-RADS v2017 - review of the guidelines.

The Liver Imaging-Reporting and Data System (LI-RADS or LR) is a classification system for reading and reporting imaging studies in patients with high risk for hepatocellular carcinoma (HCC). One of its main goals is to improve communication between specialties, especially radiologists, hepatologists, surgeons, and pathologists. LI-RADS defines imaging features of the lesions and stratifies the risk of HCC into categories. It is the most comprehensive and highly specific system; however, its seeming complexity prevents many radiologists from using it in everyday practice. This article is a detailed review of the latest version of LI-RADS (v. 2017), which should be helpful for radiologists who are not very familiar with the system and its latest update.