Diagnosis of muscle diseases presenting with early respiratory failure

Abstract

Here we describe a clinical approach and differential diagnosis for chronic muscle diseases which include early respiratory failure as a prominent feature in their presentation (i.e. respiratory failure whilst still ambulant). These patients typically present to neurology or respiratory medicine out-patient clinics and a distinct differential diagnosis of neuromuscular aetiologies should be considered. Amyotrophic lateral sclerosis and myasthenia gravis are the important non-muscle diseases to consider, but once these have been excluded there remains a challenging differential diagnosis of muscle conditions, which will be the focus of this review. The key points in the diagnosis of these disorders are being aware of relevant symptoms, which are initially caused by nocturnal hypoventilation or diaphragmatic weakness; and identifying other features which direct further investigation. Important muscle diseases to identify, because their diagnosis has disease-specific management implications, include adult-onset Pompe disease, inflammatory myopathy, and sporadic adult-onset nemaline myopathy. Cases which are due to metabolic myopathy or muscular dystrophy are important to diagnose because of their implications for genetic counselling. Myopathy from sarcoidosis and colchicine each has a single reported case with this presentation, but should be considered because they are treatable. Disorders which have recently had their genetic aetiologies identified include hereditary myopathy with early respiratory failure (due to TTN mutations), the FHL1-related syndromes, and myofibrillar myopathy due to BAG3 mutation. Recently described syndromes include oculopharyngodistal muscular dystrophy that awaits genetic characterisation.

Adult-onset respiratory insufficiency, scoliosis, and distal joint hyperlaxity in patients with multiminicore disease due to novel Megf10 mutations

“…Electrical myotonia has not been reported in patients with multiminicore disease . This feature, in combination with the classical phenotype of multiminicore disease (early axial weakness, scoliosis, spine rigidity, and myopathic respiratory distress), may resemble late‐onset Pompe disease (LOPD) . Scoliosis was reported in nearly 25% of patients with LOPD, but rigid spine, a feature of multiminicore disease as seen in patient 1, is not typical in Pompe patients.…”

Diaphragm involvement in immune checkpoint inhibitor‐related myositis

“…In the present case, severe diaphragm involvement was confirmed by EMG and US. Respiratory muscle involvement is an uncommon manifestation of ICI‐naive polymyositis/dermatomyositis . However, Haddox and colleagues recently reported a pathologically confirmed fatal case of ICI‐induced necrotizing autoimmune myopathy of the diaphragm .…”

“…Respiratory muscle involvement is an uncommon manifestation of ICI-naive polymyositis/dermatomyositis. 5,6 However, Haddox and colleagues recently reported a pathologically confirmed fatal case of ICI-induced necrotizing autoimmune myopathy of the diaphragm. 3 Distinguishing respiratory dysfunction due to myositis from that due to myasthenia gravis is difficult when elevation of both CK and anti-AChR antibody are present; an electrodiagnostic study is important.…”

Expanding importance of HMERF titinopathy: new mutations and clinical aspects

“…Hereditary myopathy with early respiratory failure (HMERF, OMIM #603689) is characterized by proximal and/or distal muscle weakness, and early and severe diaphragmatic insufficiency [1][2][3][4][5]. In HMERF, respiratory failure can be a presenting symptom in an ambulant adult patient, which is not a common feature in other genetic myopathies [5][6][7]. Typical MRI pattern has been reported with fatty degeneration of semitendinosus and obturator muscles and anterolateral compartment of lower legs early in the disease course [4,5,8,9,10].…”