Pathologically, the majority of the muscle fibers appears normal in size or enlarged, and no focal destruction or loss of fibers can be found. The unique feature of the disease is the presence in the central portion of each muscle fiber of a dense, amorphous condensation of myofibrils or myofibrillar material. This altered zone characteristically lacks mitochondria and other organelles and gives a reduced positive PAS reaction and a dark blue coloration with the Gomori trichrome stain, contrasting with the normal blue-green color of the peripheral myofibrils. Within the core, there is a lack of phosphorylase and oxidative enzymes. Most of the cores are in type 1 fibers, which predominate in muscle biopsies. These cores run the length of the muscle fiber, thus differing from the multiple cores or minicores that are seen in oculopharyngeal and multiminicore myopathy.
This disorder also expresses itself by hypotonia and impaired motility in infancy and early childhood, but unlike the case in central core disease, the muscles of the trunk and limbs (proximal greater than distal), as well as the facial, lingual, and pharyngeal muscles, are strikingly thin and hypoplastic. Several forms have been observed. One is congenital, with generalized weakness in the neonatal period, making breathing and feeding difficult. The limbs are flaccid and flexic (again “floppy” infant). Pneumonia and death occur within weeks to months. In forms that permit longer survival, the weakness is less severe, involving mainly the proximal muscles. Tendon reflexes are diminished or absent. The young child with this disease usually suffers from inanition and frequent respiratory infections, which may shorten life. Strength slowly improves with growth, the latter process evidently counteracting the advance of the disease.
A slender appearance, narrow face, open mouth, narrow, arched palate, and kyphoscoliosis are regular but not invariable accompaniments of nemaline myopathy. These dysmorphic features are not typical of the other congenital polymyopathies. Pes cavus or clubfoot may be added. Some of the milder cases reach adulthood, at which time a cardiomyopathy may threaten life. A.G. Engel, as well as W.K. Engel and Reznick, observed individuals who first showed signs of the disease in middle age; the weakness was mainly in proximal muscles and the dysmorphic and skeletal abnormalities of the childhood form were lacking. The EMG is “myopathic,” and serum enzymes are normal or only slightly elevated.
Cases of nemaline myopathy have come to attention during adulthood because of disproportionate involvement of the respiratory muscles, a feature shared with the adult appearance of acid maltase deficiency. Usually these patients have had a history of poor physical performance throughout their earlier life.
An unexplained accompanying monoclonal gammopathy has appeared in case reports of late-onset nemaline myopathy and probably represents a separate process that is more than chance occurrence. In the series of late-onset cases described by Chahin and colleagues, 7 of 14 cases had an abnormal blood protein and these authors suggested that the prognosis may be less favorable than in those lacking the protein. The patients who have been shown with this combination of adult proximal weakness and monoclonal protein had no dysmorphic features, suggesting that these cases are different from the typical genetically determined nemaline myopathy described as follows.