Orphan disease: features of difficult to diagnose and genetically verified muscular dystrophy based on DNA sequencing results (clinical case)

Currently, orphan diseases are rarely diagnosed due to low patient awareness, heterogeneity of symptoms, low publication activity of specialists who may encounter orphan pathology, and limited availability of molecular genetic technologies for verifying the human genome/exome. The clinical case is presented in the form of a detailed interdisciplinary examination of the patient within the framework of the genetic, neurological, radiological and neurophysiological profiles. At the same time, the work shows the clinical and laboratory-instrumental diversity of signs of a hereditary pathological process with neurogenic and myogenic manifestations. The peculiarity of the clinical case of the orphan disease is the rarity of its occurrence, as a consequence of the impossibility of diagnosing it by routine methods. The patient was diagnosed with myofibrillar myopathy (type 1) taking into account the identified criteria: onset at theageof 20-40, burdenedgenealogical history onthefather’s side, progressive muscle weakness, distal muscle group of the legs, hypotrophy, paresis, initial cardiosclerosis, incomplete right bundle branch block, supraventricular extrasystoles, ischemic episodes (according to Holter), significant restructuring of motor unit potentials according to the myogenic type, a decrease in the average duration to 50 % of the norm in the calf muscles, myotonic discharges according to electroneuromyography, signs of myofibrillar muscular dystrophy of the legs with manifestation of a defect in the proteins desmin and αB-crystallin. During the work, a patient was found to have a pathogenic variant of the nucleotide sequence of the DES gene, encoding the desmin protein, is a structural protein of the cytoskeleton, and forming intermediate filaments of muscle cells. Due to the fact that in most cases there is insufficient information about myofibrillar myopathy and the diagnosis of the disease is untimely without the use of specific methods, including medical genetic ones, the diagnosis is established several years later. The effective use of medical genetic technologies and the correct interpretation of the results depend on the coordinated work of a team of professionals.