vspВопросы современной педиатрииCurrent Pediatrics1682-55271682-5535Издательство «ПедиатрЪ»10.15690/vsp.v21i3.2431vsp-2954Research ArticleКЛИНИЧЕСКОЕ НАБЛЮДЕНИЕCLINICAL OBSERVATIONSПрогерия (синдром Хатчинсона – Гилфорда): обзор литературы и клинический случайProgeria (Hutchinson-Gilford Syndrome): Literature Review and Clinical Casehttps://orcid.org/0000-0002-2335-3023БучинскаяН. В.BuchinskayaNatalia V.

Бучинская Наталья Валерьевна, кандидат медицинских наук, педиатр, ревматолог, врач-генетик консультативного отделения.

194044, Санкт-Петербург, ул. Тобольская, д. 5, тел.: +7 (812) 241-24-84

Saint-Petersburg

nbuchinskaia@gmail.comhttps://orcid.org/0000-0002-8329-4088АхенбековаА. Ж.AkhenbekovaAida Zh.

Алматы

Almaty

https://orcid.org/0000-0002-7767-2900БугыбайА. А.BugybayAliya A.

Алматы

Almaty

https://orcid.org/0000-0002-1180-8086КостикМ. М.KostikMikhail M.

Санкт-Петербург

Saint-Petersburg

Диагностический центр (медико-генетический)РоссияSaint-Petersburg State Medical Diagnostic Center (Genetic medical center)Russian FederationКазахский национальный медицинский университет им. С Д. АсфендияроваКазахстанAsfendiyarov Kazakh National Medical UniversityKazakhstanНаучный центр педиатрии и детской хирургииКазахстанScientific Center of Pediatrics and Pediatric SurgeryKazakhstanСанкт-Петербургский государственный педиатрический медицинский университет; Национальный медицинский исследовательский центр им. В.А. АлмазоваРоссияSaint-Petersburg State Pediatric Medical University; Almazov National Medical Research CentreRussian Federation202214072022213253264Copyright © Бучинская Н.В., Ахенбекова А.Ж., Бугыбай А.А., Костик М.М., 20222022Бучинская Н.В., Ахенбекова А.Ж., Бугыбай А.А., Костик М.М.Buchinskaya N.V., Akhenbekova A.Z., Bugybay A.A., Kostik M.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vsp.spr-journal.ru/jour/article/view/2954

Прогерия, или синдром Хатчинсона – Гилфорда — редкое заболевание из группы ламинопатий, характеризующееся преждевременным старением с поражением кожи, костей и сердечно-сосудистой системы. В основе патогенеза лежат патогенные варианты в гене LMNA, приводящие к аномалии морфологии ядерной мембраны, нарушению экспрессии генов, изменению структуры хроматина, дисфункции митохондрий, дефектам репарации ДНК и альтернативного сплайсинга, ускорению укорочения теломер. Основные проявления болезни — поражения кожи (склеродермоподобный синдром и нарушение пигментации), липодистрофия, позднее прорезывание и скученность зубов, алопеция, дистрофия ногтей, явления остеолизиса концевых фаланг, вальгусная деформация тазобедренных суставов и контрактуры суставов, атеросклероз, тугоухость, ранние инфаркты и инсульты. Склеродермоподобные изменения кожи, остеопороз, сгибательные контрактуры межфаланговых суставов кистей, остеоартрит тазобедренных суставов требуют дифференциальной диагностики с ревматическими заболеваниями. Основой ведения больных с прогерией являются профилактика и лечение сердечно-сосудистых проявлений заболевания (ранних инсультов и инфарктов, артериальной гипертензии и атеросклероза), повышение качества жизни и ежедневной активности пациентов. Изучается эффективность терапии больных с прогерией с применением ингибиторов фарнезилтрансферазы (монотерапия; комбинация с бисфосфонатами или статинами), ретиноидов и 1,25(OH)2 — витамина D3. Настоящий литературный обзор дополнеНописанием клинического случая прогерии у девочки. Диагноз подтвержден секвенированием гена LMNA (по Сэнгеру), выявлен ранее описанный патогенный вариант гена в экзоне 11 (c.1824C>T, rs58596362) в гетерозиготном состоянии (p.Gly608Gly, NM_170707.3).

Progeria, or Hutchinson-Gilford Syndrome is a rare disease from the group of laminopathies characterized by premature aging with skin, bones and cardiovascular system lesions. Pathogenesis is based on pathogenic variants in the LMNA gene leading to anomalies in the nuclear membrane morphology, gene expression disruption, chromatin structure changes, mitochondrial dysfunction, DNA repair and alternative splicing defects, and telomere shortening acceleration. Major manifestations of the disease are: skin lesions (scleroderma-like syndrome and pigmented lesions), lipodystrophy, late teeth eruption, teeth crowding, alopecia, nail dystrophy, osteolysis of distal phalanges, hip joints valgus deformation, joints contractures, atherosclerosis, hearing loss, early heart attacks and strokes. Scleroderma-like skin changes, osteoporosis, flexion contractures of hands’ interphalangeal joints, and hip joints osteoarthritis require differential diagnosis with rheumatic diseases. The basic strategy in management of patients with progeria is the prevention and treatment of its cardiovascular manifestations (early strokes and heart attacks, arterial hypertension, and atherosclerosis), as well as the increase of patients’ quality of life and daily activity. The efficacy of therapy in patients with progeria via the use of farnesyltransferase inhibitors (monotherapy; combination with bisphosphonates or statins), retinoids, and 1,25(OH)2 — vitamin D3 is studied. This literature review is updated with clinical case description of a girl with progeria. The diagnosis was confirmed by sequencing of the LMNA gene (Sanger), and previously described pathogenic variant in exon 11 (c.1824C>T, rs58596362) in the heterozygous state (p.Gly608Gly, NM_170707.3) was revealed.

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