Pediatric Nemaline Myopathy: A systematic review using individual patient data

Abstract

Context: Nemaline myopathy (NM) is a skeletal muscle disease that affects 1 in 50,000 live births. Objective: Develop a narrative synthesis of the findings of a systematic review of the latest case descriptions of patients with nemaline myopathy. Data Sources: A systematic search of MEDLINE, Embase, CINAHL, Web of Science, and Scopus was performed using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines using the keywords pediatric, child, nemaline myopathy, nemaline rod, rod myopathy. Study Selection: Case studies focused on pediatric NM and published in English between January 1, 2010 and December 31, 2020 in order to represent the most recent findings. Data Extraction: Information was collected about the age of first signs, earliest presenting neuromuscular signs and symptoms, systems affected, progression, death, pathological description, and genetic changes. Results: Of a total of 385 records, 55 case reports or series were reviewed, covering 101 pediatric patients from 23 countries. We review varying presentations in children ranging in severity despite being caused by the same mutation, in addition to current and future clinical considerations relevant to the care of patients with nemaline myopathy. Limitations: The results are limited by findings shared in the literature, which varied in their detail and sometimes lacked histological or genetic results. Trends and correlations may be altered by information available. Conclusions: This review synthesizes genetic, histopathologic, and disease presentation findings from pediatric nemaline myopathy case reports. These data strengthen our understanding of the wide spectrum of disease seen in nemaline myopathy. Future studies are needed to identify the underlying molecular mechanism of pathology, to improve diagnostics, and to develop better methods to improve quality of life for these patients.

Drosophila Tropomodulin is required for multiple actin-dependent processes in myofiber assembly and maintenance

“…Mutations in sarcomere genes are linked to skeletal muscle diseases such as nemaline myopathy (NM), which presents with defective contraction and muscle weakness (Bonnemann and Laing, 2004, Cassandrini et al, 2017, Tubridy et al, 2001, de Winter and Ottenheijm, 2017. NM is associated specifically with mutations in thin filament genes, including ACTA1, NEB, LMOD3, CFL2, TPM2, TPM3, TNNT1, TNNT3 and MYPN [reviewed in Laitila and Wallgren-Pettersson (2021), Christophers et al (2022)]. In addition to the growing list of mutations identified in human patients, Tmod mutant zebrafish show a NM-like phenotype and muscle weakness (Berger et al, 2014).…”