Cardioneuromyopathy With Hyaline Masses And Nemaline Rods

Clinical Features

Selcen et al. (2002) described a sister and brother with adult-onset muscle weakness that was greater distally than proximally, as well as respiratory insufficiency, cardiomyopathy, and cervical spine anomalies. Both had lifelong limitation of neck motions, and both developed progressive dyspnea and mild-to-moderately severe limb muscle weakness in the fifth decade of life. The sister was hyporeflexic; the brother was areflexic and had mild distal sensory deficit for pain and light touch. In both patients, radiographs of the cervical spine showed a decreased anteroposterior diameter of the cervical vertebral bodies, fusion of the midcervical facet joints, and widening of the cervical spinal canal. The son of the sister had limited cervical spine motions but no weakness at age 22 years. Electromyography indicated myopathy and findings consistent with neuropathy in both patients. Muscle biopsies revealed that myriad type-1 fibers harbored large, irregularly polygonal, and mostly central hyaline masses, small vacuoles, and nemaline rods flanking the hyaline masses or congregated under the sarcolemma. The hyaline masses were intensely congophilic; reacted strongly for desmin (125660), alpha/beta-crystallin (see 123610), alpha-1-antichymotrypsin (107280), and ubiquitin (191339), and variably for gelsolin (137350) and dystrophin (300377); and were devoid of alpha-actinin (see 102575), nebulin (161650), titin (188840), and slow myosin (see 160760). The constituency of the hyaline masses signaled nonlysosomal protein degradation. Ultrastructurally, the hyaline masses resembled the hyaline structures of myofibrillar myopathy. Selcen et al. (2002) concluded that the pathologic process in this syndrome is one that induces destruction of myofibrillar components, resulting in aggregation of the degraded residues in hyaline masses, and causing replication of Z disks and formation of nemaline rods.

Selcen et al. (2002) considered the disorder in their patients distinct from reported cases of nemaline myopathy (see 161800) with cardiomyopathy because hyaline masses in muscle, evidence of peripheral neuropathy, and cervical spine anomalies were absent in these cases. They also thought it was distinct from reported cases of myopathy with rods and cores (see 117000) and with myofibrillar myopathy.