Neuromuscular DiseasesNeuromuscular DiseasesНервно-мышечные болезни2222-87212413-0443Publishing House ABV Press54210.17650/2222-8721-2023-13-2-42-55ORIGINAL REPORTSОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯPhenotypic variability in TRPV4-associated neuropathies and neuronopathies: a case seriesФенотипическая вариабельность TRPV4-ассоциированных нейропатий и нейронопатий: серия клинических наблюденийMurtazinaA. F.МуртазинаА. Ф.
Russian Federation

Aysylu Fanzirovna Murtazina

1 Moskvorechye St., Moscow 115522

Айсылу Фанзировна Муртазина

115522 Москва, ул. Москворечье, 1

TsabayP. N.ЦабайП. Н.
Russian Federation

1 Moskvorechye St., Moscow 115522

115522 Москва, ул. Москворечье, 1

RudenskayaG. E.РуденскаяГ. Е.
Russian Federation

1 Moskvorechye St., Moscow 115522

115522 Москва, ул. Москворечье, 1

BessonovaL. A.БессоноваЛ. А.
Russian Federation

1 Moskvorechye St., Moscow 115522

115522 Москва, ул. Москворечье, 1

BostanovaF. M.БостановаФ. М.
Russian Federation

1 Moskvorechye St., Moscow 115522

115522 Москва, ул. Москворечье, 1

GusevaD. M.ГусеваД. М.
Russian Federation

1 Moskvorechye St., Moscow 115522

115522 Москва, ул. Москворечье, 1

SharkovaI. V.ШарковаИ. В.
Russian Federation

1 Moskvorechye St., Moscow 115522

115522 Москва, ул. Москворечье, 1

ShchaginaO. A.ЩагинаО. А.
Russian Federation

1 Moskvorechye St., Moscow 115522

115522 Москва, ул. Москворечье, 1

OrlovaA. A.ОрловаА. А.
Russian Federation

1 Moskvorechye St., Moscow 115522

115522 Москва, ул. Москворечье, 1

RyzhkovaO. P.РыжковаО. П.
Russian Federation

1 Moskvorechye St., Moscow 115522

115522 Москва, ул. Москворечье, 1

MarkovaT. V.МарковаТ. В.
Russian Federation

1 Moskvorechye St., Moscow 115522

115522 Москва, ул. Москворечье, 1

KuchinaA. S.КучинаА. С.
Russian Federation

1 Moskvorechye St., Moscow 115522

115522 Москва, ул. Москворечье, 1

NikitinS. S.НикитинС. С.
Russian Federation

1 Moskvorechye St., Moscow 115522

115522 Москва, ул. Москворечье, 1

DadaliE. L.ДадалиЕ. Л.
Russian Federation

1 Moskvorechye St., Moscow 115522

115522 Москва, ул. Москворечье, 1

N. P. Bochkov Medical Genetic Research CenterФГБНУ «Медико-генетический научный центр им. акад. Н. П. Бочкова» Минобрнауки России1606202313242551506202315062023Copyright ©; 2023, Murtazina A.F., Tsabay P.N., Rudenskaya G.E., Bessonova L.A., Bostanova F.M., Guseva D.M., Sharkova I.V., Shchagina O.A., Orlova A.A., Ryzhkova O.P., Markova T.V., Kuchina A.S., Nikitin S.S., Dadali E.L.Copyright ©; 2023, Муртазина А.Ф., Цабай П.Н., Руденская Г.Е., Бессонова Л.А., Бостанова Ф.М., Гусева Д.М., Шаркова И.В., Щагина О.А., Орлова А.А., Рыжкова О.П., Маркова Т.В., Кучина А.С., Никитин С.С., Дадали Е.Л.2023Murtazina A.F., Tsabay P.N., Rudenskaya G.E., Bessonova L.A., Bostanova F.M., Guseva D.M., Sharkova I.V., Shchagina O.A., Orlova A.A., Ryzhkova O.P., Markova T.V., Kuchina A.S., Nikitin S.S., Dadali E.L.Муртазина А.Ф., Цабай П.Н., Руденская Г.Е., Бессонова Л.А., Бостанова Ф.М., Гусева Д.М., Шаркова И.В., Щагина О.А., Орлова А.А., Рыжкова О.П., Маркова Т.В., Кучина А.С., Никитин С.С., Дадали Е.Л.https://creativecommons.org/licenses/by/4.0https://nmb.abvpress.ru/jour/article/view/542

TRPV4‑associated neuromuscular diseases represent a clinical spectrum of neuropathies and motor neuron disorders. To date, 3 phenotypic forms are distinguished. There are Charcot–Marie–Tooth disease type 2C, distal hereditary motor neuropathy type 8 (DHMN8), scapulo‑peroneal spinal muscular atrophy (SPSMA). Here we report 3 families with DNMN8 and one family with SPSMA. In all cases, DNA‑analysis revealed single nucleotide variants in the TRPV4 gene previously reported as pathogenic. In 3 probands, a combination of signs of both motor and motor‑sensory neuropathies led to difficulties in the establishment of the clinical diagnosis. Patients had mild sensory disturbances in the feet, but in all of these cases nerve conduction study revealed normal sensory nerve action potentials. Considering the prevailing signs of motor neuropathy, these patients were diagnosed with DNMN8. Clinical signs of sensory disturbances are regarded as not  contradicting  the  diagnosis,  since  they  can  be  observed  in  various  forms  of  distal  motor  neuropathies. The clinical features of SPSMA in one patient corresponded to those previously described in the literature. The involvement of the shoulder girdle muscles and the peroneal muscles and neurogenic changes in needle electromyography allow suspecting SPSMA clinically. A distinctive features of TRPV4‑associated neuromuscular diseases are the vocal cords paresis, sensorineural hearing loss and respiratory failure, however they are not obligatory according to our clinical reports.

TRPV4‑ассоциированные нервно‑мышечные болезни представляют собой клинический спектр состояний, в котором выделяют 3 фенотипические формы: болезнь Шарко–Мари–Тута 2С, дистальную наследственную моторную нейропатию 8‑го типа (ДНМН8), скапуло‑перонеальную спинальную мышечную атрофию (СПСМА). В настоящей публикации приводится описание 3 семей с ДНМН8 и 1 семьи с СПСМА, у которых ДНК‑диагностика выявила варианты нуклеотидной последовательности в гене TRPV4, ранее описанные как патогенные. У осмотренных нами 3 пробандов установление клинической формы заболевания вызвало затруднения в связи с сочетанием признаков как моторной, так и моторно‑сенсорной нейропатии. У больных отмечались легкие чувствительные нарушения в стопах, но при этом ни в одном из этих случаев не выявлено признаков вовлечения сенсорных волокон нервов рук и ног при электромиографии. С учетом преобладающих признаков вовлечения моторной порции периферической нервной системы по клиническим и электрофизиологическим данным этим больным установлен диагноз ДНМН8. Клинические признаки нарушения чувствительности расценены как не противоречащие диагнозу, так как известно, что легкие сенсорные нарушения могут отмечаться при разных формах дистальных моторных нейропатий. Клинические признаки СПСМА одной больной соответствовали ранее описанным в литературе. Сочетание поражения мышц плечевого пояса и перонеальной группы при наличии нейрогенного процесса по данным игольчатой электромиографии позволяет заподозрить данную форму болезни на клиническом этапе. Отличительными особенностями TRPV4‑ассоциированных нервно‑мышечных болезней являются парез голосовых связок, нейросенсорная тугоухость и дыхательная недостаточность. Однако, как показали наши наблюдения, эти нарушения не являются облигатными.

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