Nemaline myopathy-6 is an autosomal dominant skeletal muscle disorder characterized by childhood onset of slowly progressive proximal muscle weakness, exercise intolerance, and slow movements with stiff muscles. Patients are unable to run or correct themselves from falling over. ... Nemaline myopathy-6 is an autosomal dominant skeletal muscle disorder characterized by childhood onset of slowly progressive proximal muscle weakness, exercise intolerance, and slow movements with stiff muscles. Patients are unable to run or correct themselves from falling over. Histopathologic changes seen on skeletal muscle biopsy include nemaline rods, cores devoid of oxidative enzyme activity, and predominance of hypertrophic type 1 fibers. There is no cardiac or respiratory involvement (summary by Sambuughin et al., 2010).
Gommans et al. (2002) reported a 5-generation Dutch family with autosomal dominant nemaline myopathy. The homogeneous clinical phenotype was characterized by normal early motor development followed by onset in childhood of difficulty running, climbing stairs, jumping, and lifting ... Gommans et al. (2002) reported a 5-generation Dutch family with autosomal dominant nemaline myopathy. The homogeneous clinical phenotype was characterized by normal early motor development followed by onset in childhood of difficulty running, climbing stairs, jumping, and lifting above the head, consistent with proximal muscle weakness. The most striking complaint was a feeling of muscle slowness or stiffness, and slow response times to falls. There was no involvement of respiratory or cardiac muscles. There was neck muscle weakness, but no facial weakness or dysphagia. Although there was mild disease progression with age, no patients were wheelchair-bound. Muscle imaging showed fatty infiltration that increased with age. Muscle biopsy showed type 1 fiber predominance, nemaline rods, loss of myofibrillar organization, and some core-like structures. Linkage analysis excluded the TPM3 (191030), ACTA1 (102610), NEB (161650), and TPM2 (190990) genes. Olive et al. (2010) reported a Spanish family in which 4 members had a phenotype similar to that reported by Gommans et al. (2002). After a normal neonatal period and normal motor milestones, affected individuals presented at age 4 to 5 years with slowly progressive proximal muscle weakness in the arms and legs manifest as gait abnormality and difficulties performing sports; they were unable to run or jump, but could walk long distances. All individuals also had distal muscle weakness in the upper and lower limbs, and hypotrophy of the forearm muscles. A particular feature was slowness of movements that appeared as bradykinetic slow-motion behavior and clumsiness. Three of 4 patients remained ambulant into adulthood. Creatine kinase was normal, and EMG studies showed myopathic pattern. There was no cardiac or respiratory involvement or peripheral neuropathy. Muscle biopsy showed marked variation in fiber size, internal nuclei, and aggregates of abnormal fine, granular, or rod-shaped structures in the cytoplasm or in subsarcolemmal regions, as well as core-like areas devoid of oxidative enzyme activity. There was predominance and hypertrophy of type 1 fibers.
In affected members of 4 unrelated families with nemaline myopathy-6 (Gommans et al., 2002; Olive et al., 2010), Sambuughin et al. (2010) identified heterozygous missense mutations in the KBTBD13 gene (613727.0001 and 613727.0002). Another patient with sporadic disease ... In affected members of 4 unrelated families with nemaline myopathy-6 (Gommans et al., 2002; Olive et al., 2010), Sambuughin et al. (2010) identified heterozygous missense mutations in the KBTBD13 gene (613727.0001 and 613727.0002). Another patient with sporadic disease carried a third heterozygous missense mutation (613727.0003).