The foot deformities in CMT do not result from absolute weakness of the motor units powering the foot but of their relative imbalance. It in fact encompasses a large number of described genetic defects on different chromosomal loci no product proteins have yet been described. It is found in 10% to 20% of all CMT cases and is associated with defects in yet another myelin constituent protein, connexin 32.ĬMT-4 is an autosomal recessive form of the disease and is quite rare. In general, the course of CMT-2 is more indolent than that of CMT-1.ĬMT-X shows an X-linked inheritance pattern male patients are affected and female patients are either unaffected or mildly affected carriers. Four separate chromosomal loci have been identified, but the product proteins involved remain unknown. It is autosomal dominant like CMT-1 but has dramatically different electrical findings: NCVs are near normal, and there is no evidence of demyelination. The phenotype is associated with a particularly aggressive form of the disease.ĬMT-1C represents the small remainder of CMT-1 patients in whom the genetic defect is still unknown.ĬMT-2 is the second most common general form of the disease and represents 20% of patients. This chromosomal aberration is inheritable in an autosomal dominant fashion, but many cases seem to represent sporadic chromosomal recombination events.ĬMT-1B accounts for 5% to 10% of CMT-1 patients and is associated with a point mutation in the myelin P 0 gene.
Although some cases have been linked to alternative point mutations in PMP-22, the segmental trisomy responsible for most cases indicates CMT can be produced from a gene dosage effect. The area contains the gene for peripheral myelin protein-22 (PMP-22), whose function remains unknown. Curiously, it is usually caused by a segmental trisomy along chromosome 17. CMT-1 can be further subdivided.ĬMT-1A accounts for 80% of CMT-1 cases and is the single most common form of the disease in general. It is autosomal dominant and demonstrates slow nerve conduction velocities (NCVs) in the range of 10 to 30 m/sec as a result of demyelination. Since 1990 there has been an explosion of understanding of the specific genetic defects underlying the CMT disorders, 4 leading to a new and still evolving reclassification of the disease.ĬMT-1 is the most common form and accounts for more than 50% of all cases.
PES CAVUS FOOT SERIES
12 Their scheme refers to a series of seven hereditary motor sensory neuropathies (HMSN-I through HMSN-VII). The archaic term peroneal muscular atrophy (PMA) was supplanted by Dyck and Lambert, who developed an extensive classification of inheritable motor neuropathies based upon their electrodiagnostic patterns in the 1960s and 1970s.
The nomenclature associated with CMT is confusing because of the historical lack of understanding of its cause. The disease is the most common inheritable defect of peripheral nerves, but approximately half of the time it represents a new sporadic chromosomal recombination error. 6, 44 Originally, Charcot attributed the disorder to a spinal defect, and it was Tooth’s subsequent work that correctly classified it as a peripheral nerve disorder. The disorder was described in general terms by the great French neurologist Jean Martin Charcot and his pupil Marie in 1886 and independently by Tooth in England later that year. CMT is not, in fact, a single disease but rather a heterogeneous group of disorders caused by inheritable defects in any of several constituent proteins of the myelin sheath of peripheral nerve. 19Ĭharcot-Marie-Tooth disease (CMT) should at least be considered in every patient who presents with pes cavus. Roughly half of the detectable lesions are variants of Charcot-Marie-Tooth disease, but a host of other less common conditions can also be discovered ( Table 26-1). Most cases of idiopathic pes cavus likely represent a very subtle neurologic lesion that is below clinical detection. Of these, 11 of the 26 patients had a family history of pes cavus, and 7 of the 26 had nonspecific abnormalities upon electromyographic and nerve conduction velocity examination. Neither approach is fully satisfactory a cavus foot is best thought of as an end result that a variety of subtle neurologic lesions can produce.īrewerton et al 5 specifically looked at the cause of pes cavus in a series of 77 patients and found subtle neurologic defects in 66% of them, leaving a large group of “idiopathic” cases. In 1959, Duchenne 9 subsequently proposed that the deformity results from an imbalance between the extrinsics and the intrinsics. Bentzon 2 and Hallgrimsson 16 in 1939 proposed that extrinsic muscle imbalance underlay all deformities. Historical attempts to attribute all forms of cavus foot to a single neurologic lesion have proven overly simplistic. Although the specific etiology of any cavus foot varies with the disease process, all forms result from muscle imbalance.
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