To identify histological features distinguishing inherited nemaline myopathies (iNM) from sporadic late-onset nemaline myopathy (SLONM). 

iNM are a genetically heterogeneous group of disorders characterised by accumulation of Z-disc derived nemaline rods in muscle fibres and manifesting in infancy to adulthood. Nemaline rods are also a pathological feature of SLONM, an acquired myopathy sometimes associated with monoclonal gammopathies or HIV infection. Identification of pathological parameters distinguishing these two myopathies has significant implications, as SLONM may respond to pharmacological therapy.

We randomly selected 9 patients with iNM and 10 with non-HIV SLONM. Their median ages were 11 and 64 years, respectively. The causative genes in iNM were ACTA1 (3 patients), NEB (1 patient) or unknown (5 patients, aged 2-11). Six SLONM patients had monoclonal gammopathies. The proportion of fibres harbouring nemaline rods was higher in iNM (median 53%, range: 39-99%) than in SLONM (median 11%, range: 1.2-47%). In SLONM, fibres containing nemaline rods had a smaller diameter than fibres devoid of rods (median ratio 0.60), while the opposite was observed in iNM (median ratio 1.12). Atrophic fibres filled with rods occurred in 8/10 SLONM patients and, less conspicuously, in 1/9 iNM patients. In 6/10 SLONM patients, nemaline rods were spread diffusely within the individual fibres, while rods occurred in clusters in 8/9 iNM patients. Necrotic fibres were present in 7/10 SLONM patients, but only in 1/9 iNM patients.

Pathological findings can distinguish SLONM from iNM. These findings, combined with the clinical history, are crucial for differentiating SLONM from adult-onset iNM, particularly when an underlying genetic defect is not detected. This distinction allows the identification of patients amenable to treatment.