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• In amyopathic MDA5 dermatomyositis histological myositis features can be found. • Clinical symptoms of myositis can be mild or absent. • Tubuloreticular inclusions can be lacking ultrastructurally. • Cutaneous thrombocclusive pathology can occur without overt skin symptoms. • Pulmonary findings are in line with diffuse alveolar damage. Anti-MDA5-positive dermatomyositis (MDA5-DM) often presents with extramuscular, especially pulmonary and skin manifestations, and apparent clinical signs of frank myositis can be missing (so called amyopathic DM). We hereby present two male patients who died from respiratory failure during the course of MDA5-DM. While overt signs of myositis or any skin involvement were absent at admission to hospital we noticed conspicuous inflammatory alterations in various skeletal muscles morphologically, showing different degrees of affection. Furthermore, pathological changes of the lungs compatible with rapid progressive interstitial lung disease and characteristic cutaneous vasculoocclusive features were identified at autopsy. This observation shows that muscles and skin are subclinically affected in a widespread fashion, hence subtle signs of muscle involvement should be sought after in anti-MDA5-positive patients with predominant lung affection to ensure adequate treatment. [ABSTRACT FROM AUTHOR]

• We report a novel splice site mutation in NEB , leading to a severe form of foetal nemaline myopathy with antenatal/foetal developmental disorder and resulting in arthrogryposis/FADS. • NGS disclosed a homozygous mutation in NEB intron122 [chr2:g.152,417,623C> A GRCh37.p11 | c.19,102–1G> T NM_001164508]. • Light microscopic examination revealed immature skeletal muscles (myotubes) with variability of fibre caliber and nuclear size, fibrosis and fatty tissue within the epi- and perimysium were absent. • Ultrastructural analysis including large-scale electron microscopy revealed immature sarcomere structures and "mini"-nemaline bodies within myotubes. • Hence, ultrastructural analysis of foetal skeletal muscle can provide helpful insights and drive further genetic analysis. Nemaline myopathies are a clinically and genetically heterogeneous group of congenital myopathies, mainly characterized by muscle weakness, hypotonia and respiratory insufficiency. Here, we report a male foetus of consanguineous parents with a severe congenital syndrome characterized by arthrogryposis detected at 13 weeks of gestation. We describe severe complex dysmorphic facial and musculoskeletal features by post mortem fetal examination confirming the prenatal diagnosis. Histomorphological and ultrastructural studies of skeletal muscle reveal mini-rods in myotubes caused by a novel homozygous splice-site mutation in NEB (NM_001164508, chr2:g.152,417,623C> A GRCh37.p11 | c.19,102–1G> T ENST00000397345.3). No rods were seen in the myocardium. We discuss the relevance of this mutation in the context of nemaline myopathies associated with early developmental musculoskeletal disorders. [ABSTRACT FROM AUTHOR]