References

avk

Архивъ внутренней медицины

The Russian Archives of Internal Medicine

2226-67042411-6564

“SINAPS” LLC

10.20514/2226-6704-2021-12-2-93-103

avk-1401

Research Article

ЛЕКЦИИ

LECTURES

Клинические маски нейрофиброматоза 1-го типа

Clinical Masks of Neurofibromatosis Type 1

https://orcid.org/0000-0002-4091-382X

Мустафин

Р. Н.

Mustafin

R. N.

Уфа

Ufa

ruji79@mail.ru

ФГБУЗ «Башкирский государственный медицинский университет»РоссияBashkir State Medical UniversityRussian Federation

2022

28032022

12293103

2022

Мустафин Р.Н.

Mustafin R.N.

Данная работа распространяется под лицензией Creative Commons Attribution 4.0.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://www.medarhive.ru/jour/article/view/1401

Нейрофиброматоз 1-го типа является самым распространенным аутосомно-доминантным опухолевым синдромом, встречающимся с часто- той 1 на 3000 населения. Особенностью клинических проявлений болезни является постепенное появление признаков и выраженный клинический полиморфизм от стертых и атипичных форм до тяжелых классических проявлений. В данном обзоре рассмотрены заболевания, симптомы которых значительно схожи с нейрофиброматозом 1-го типа, в связи с чем важным методом для дифференциальной диагностики является молекулярная диагностика болезни. Поскольку 10% случаев заболевания обусловлены крупными делециями локуса 17q11.2, помимо секвенирования гена NF1 необходимо проведение зависимой от лигирования мультиплексной амплификации зонда. В большинстве случаев начальными проявлениями нейрофиброматоза 1-го типа являются множественные пигментные пятна, которые на протяжении многих лет могут быть единственными внешними признаками болезни. В связи с этим могут быть ошибочно установлены диагнозы, для которых характерны данные пигментные изменения: синдромы Блума, LEOPARD, Карнея, Костелло, Коудена, Легиуса, Ниймеген, Нунан, Пейтца-Егерса, Сильвера-Рассела, кардио-фацио-кожный синдром. Обнаружение подкожных нейрофибром может стать основанием для неверной диагностики схожих по клинике синдромов Легиуса и множественной эндокринной неоплазии. Кроме того, множественные липомы являются специфическими проявлениями липоматозов Маделунга или Деркума, семейного ангиолипоматоза, этиология которых считается неизвестной. Сделано предположение, что эти заболевания являются атипичными формами нейрофиброматоза 1-го типа, поскольку ряд авторов описали идентификацию мутаций в гене NF1 у пациентов со множественным липоматозом. Поэтому важное значение имеет широкое внедрение в клиническую практику возможности молекулярно-генетической идентификации болезни для выявления случаев нейрофиброматоза 1-го типа, не соответствующих принятым NIH (National Institute of Health) критериям диагностики. Наиболее перспективно создание панели с исследованием всех генов, мутации в которых могут вызывать схожие с нейрофиброматозом 1-го типа проявления. Ранняя диагностика заболевания необходима для своевременного начала лечения и предотвращения тяжелых проявлений, поскольку в клиническую практику внедряются эффективные методы противоопухолевой терапии, такие как ингибиторы митоген-активируемой киназы.

Neurofibromatosis type 1 is the most common autosomal dominant tumor syndrome. The prevalence of the disease is 1 in 3000 people. Neurofibromatosis type 1 is characterized by the gradual appearance of signs of the disease and pronounced clinical polymorphism from erased and atypical forms to severe classical manifestations. The review is devoted to the consideration of diseases, the manifestations of which are significantly similar to neurofibromatosis type 1, and therefore, molecular diagnosis of the disease is an important method for differential diagnosis. To make a diagnosis of neurofibromatosis type 1, it is necessary to find mutations in the NF1 gene using sequencing. In 10% of cases, neurofibromatosis type 1 is caused by large deletions of the 17q11.2 locus, therefore, multiplex ligation-dependent probe amplification is also necessary. Typically, the initial manifestations of neurofibromatosis type 1 are multiple café-au-lait spots, which may be the only external signs of the disease for many years. Therefore, patients with neurofibromatosis type 1 may be mistakenly diagnosed with diseases for which these pigmentary changes are characteristic: Bloom, LEOPARD, Carney, Costello, Cowden, Legius, Nijmegen, Noonan, Peitz-Jägers, Silver-Russell, cardio-facio-cutaneous syndromes. The detection of subcutaneous tumors can become the basis for an incorrect diagnosis of the clinically similar Legius syndrome and multiple endocrine neoplasia. In addition, multiple lipomas are specific manifestations of Madelung or Dercum lipomatosis, familial angiolipomatosis, the etiology of which is considered unknown. Therefore, I assume that these diseases are atypical forms of neurofibromatosis type 1, since a number of authors have described the identification of mutations in NF1 gene in patients with multiple lipomatosis. Therefore, it is important to widely introduce into clinical practice the possibility of molecular genetic identification of the disease in order to identify cases of neurofibromatosis type 1 that do not meet the diagnostic criteria adopted by the NIH. It is promising to create a panel for the study of all genes, mutations in which can cause manifestations similar to neurofibromatosis. Early diagnosis of the disease is necessary for timely initiation of treatment and prevention of severe manifestations, since effective methods of antitumor therapy of neurofibromatosis type 1, such as inhibitors of mitogen-activated kinase, are being introduced into clinical practice.

ген NF1дифференциальная диагностикалипоматозмутациинейрофиброматоз 1-го типасеквенирование

NF1 genedifferential diagnosislipomatosismutationsneurofibromatosis type 1sequencing

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The authors declare that there are no conflicts of interest present.