Novel autosomal dominant TPM3 mutation causes a combined congenital fibre type disproportion-cap disease histological pattern.

• The novel variant of uncertain significance p.Glu237Lys in TPM3 gene is reported • Muscle biopsy featured a combination of congenital fiber type disproportion with cap disease, and no nemaline rods • Clinically the patient showed moderate myopathic features with disproportionate respiratory involvement • Muscle MRI demonstrated a generalized involvement including the tongue • The clinical, MRI and histological findings demonstrate the mutation's pathogenicity Tropomyosin 3 (TPM3) gene mutations associate with autosomal dominant and recessive nemaline myopathy 1 (NEM1), congenital fiber type disproportion myopathy (CFTD) and cap myopathy (CAPM1), and a combination of caps and nemaline bodies. We report on a 47-year-old man with polyglobulia, restricted vital capacity and mild apnea hypopnea syndrome, requiring noninvasive ventilation. Physical assessment revealed bilateral ptosis and facial paresis, with high arched palate and retrognathia; global hypotonia and diffuse axial weakness, including neck and upper and lower limb girdle and foot dorsiflexion weakness. Whole body MRI showed a diffuse fatty replacement with an unspecific pattern. A 122 gene NGS neuromuscular disorders panel revealed the heterozygous VUS c.709G>A (p.Glu237Lys) on exon 8 of TMP3. A deltoid muscle biopsy showed a novel histological pattern combining fiber type disproportion and caps. Our findings support the pathogenicity of the novel TPM3 variant and widen the phenotypic gamut of TMP3 -related congenital myopathy. [ABSTRACT FROM AUTHOR]