ISSN 2415-3060 (print), ISSN 2522-4972 (online)
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JMBS 2016, 1(2): 37–43

Clinical Polymorphism of 1Аtype Hereditary Motor-Sensory Neuropathy

Govbah I.А.

The article describes the clinical interfamilial polymorphism of 1А type hereditary motor-sensory neuropathy (HMSN). HMSN - is the most common nosology in the structure of monogenic hereditary diseases of the nervous system, since there is no effect on life expectancy it leads to a significant accumulation in families and in populations at whole. The frequency of all HMSN forms in the general population is 1:3000. For nowadays it was quartered over 40 locus, responsible for HMSN; more than 29 genes were identified, the mutations in which leads to the development of the disease, and their search is continuing. Modern HMSN classification is based on the molecular-genetic data, electrophysiological, morphological methods of study, as well as the nature of the peripheral nerves damage. International consortium on the hereditary neuromuscular diseases study as the threshold level of signal (impulse) realization speed (IRS) for motor fibers of the median nerve accepted the rate 38 m/s. On the basis of IRS among motor fibers of the median nerve and the morphological special characteristics of the defect on the structures in peripheral nerves are identify the following clinico-genetic types of HMSN: 1) demielinising (IRS < 38 m/s); 2) axonal (IRS > 38 m/s); 3) intermediate (IRS 25-45 m/s). Like many monogenic diseases of the nervous system, for HMSN inherent pronounced clinical polymorphism. The reason of phonotypical features of hereditary pathology differences is interaction of genetic and environmental factors. The aim of the research was the analysis of 1A type interfamilial polymorphism HMSN on the basis of phenotypic features differences and neurophysiologic indicators of identical genetic pathology bearer – duplication of the gene PMP22 in heterozygous state in a chromosomal zone 17p11.2. The object of the research were involved patients HMSN 1A, who are the members of the same family. This family is under the supervision of the Kharkiv specialized medical genetic center since 1980. The diagnosis of 1 A type hereditary motor-sensory neuropathy was determined among 5 members of this family on the basis of complaints, disease anamnesis, clinical-genealogical analysis, clinical neurological examination, electroneuromyography and molecular - genetic investigation. All the members of this family who were the investigated patients revealed the presence of typical signs of clinical HMSN 1A type: family nature of the disease, hypotrophy and paresis of distal parts muscles of lower limbs; symmetrical damage; sensitivity disorder; foot deformations; gait disorders; decrease of impulse conduction of motor fibers of peripheral nerves. Clinical polymorphism of the disease of the same genetic pathology bearers occurs in the age differences of disease onset; paresis degree of the distal limbs, forms of foot deformities; types of sensitivity disorders; involvement into the pathological process of the upper limbs; pathological changes of the skeletal system; axonopathy signs occur. The majority of patients indicated axonal-demielinising type of damage, the symptom of which is the decrease of the amplitude of M-response. Possible cause of the axons damage with demielinising HMSN can be the pleiotropy of pathological gene, expressed in Schwann cells of the myelin sheath and the neuraxons. Another possible cause of axonopathy may be intergenic interaction, leading to the loss of functional connections between Schwann cells of the myelin sheath and the axons. Further research aimed at the study of the pathogenesis HMSN, will let us to determine the nature of the axonopathy - primary or secondary. The study of the causes underlying the clinical polymorphism, will give us the chance of prediction the severity of the disease and effective pharmacological correction of this pathology.

Keywords: hereditary motor-sensory neuropathy, clinical polymorphism, phenotypic features, neurophysiological indicators

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