TY - JOUR
T1 - Familial cardioneuromyopathy with hyaline masses and nemaline rods
T2 - A novel phenotype
AU - Selcen, Duygu
AU - Krueger, Bruce R.
AU - Engel, Andrew G.
PY - 2002
Y1 - 2002
N2 - Two siblings (patients 1 and 2) had adult-onset muscle weakness that was greater distally than proximally, as well as respiratory insufficiency, cardiomyopathy, and cervical spine anomalies. Electromyography studies indicated myopathy and findings consistent with neuropathy in both. In the deltoid muscle of patient 1 and the anterior tibial muscle of patient 2, 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 are intensely congophilic; react strongly for desmin, αB-crystallin, α1-antichymotrypsin, and ubiquitin and variably for gelsolin and dystrophin; and are devoid of α-actinin, nebulin, titin, and slow myosin. The presence of ubiquitin, gelsolin, and fragmented filaments, and the absence of nebulin, titin, α-actinin, and slow myosin in the hyaline masses, signal nonlysosomal protein degradation. Ultrastructurally, the hyaline masses are composed of intermediate-density amorphous material intermingled with fragmented filaments and irregularly branching, pleomorphic, highly electron-dense material, resembling the hyaline structures of myofibrillar myopathy. We conclude that the pathological process in this syndrome is one that induces destruction of myofibrillar components, resulting in aggregation of the degraded residues in hyaline masses, and causes replication of Z disks, resulting in formation of nemaline rods.
AB - Two siblings (patients 1 and 2) had adult-onset muscle weakness that was greater distally than proximally, as well as respiratory insufficiency, cardiomyopathy, and cervical spine anomalies. Electromyography studies indicated myopathy and findings consistent with neuropathy in both. In the deltoid muscle of patient 1 and the anterior tibial muscle of patient 2, 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 are intensely congophilic; react strongly for desmin, αB-crystallin, α1-antichymotrypsin, and ubiquitin and variably for gelsolin and dystrophin; and are devoid of α-actinin, nebulin, titin, and slow myosin. The presence of ubiquitin, gelsolin, and fragmented filaments, and the absence of nebulin, titin, α-actinin, and slow myosin in the hyaline masses, signal nonlysosomal protein degradation. Ultrastructurally, the hyaline masses are composed of intermediate-density amorphous material intermingled with fragmented filaments and irregularly branching, pleomorphic, highly electron-dense material, resembling the hyaline structures of myofibrillar myopathy. We conclude that the pathological process in this syndrome is one that induces destruction of myofibrillar components, resulting in aggregation of the degraded residues in hyaline masses, and causes replication of Z disks, resulting in formation of nemaline rods.
UR - http://www.scopus.com/inward/record.url?scp=0036154431&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036154431&partnerID=8YFLogxK
U2 - 10.1002/ana.10096
DO - 10.1002/ana.10096
M3 - Article
C2 - 11835379
AN - SCOPUS:0036154431
SN - 0364-5134
VL - 51
SP - 224
EP - 234
JO - Annals of neurology
JF - Annals of neurology
IS - 2
ER -