problendoПроблемы ЭндокринологииProblems of Endocrinology0375-96602308-1430Endocrinology Research Centre10.14341/probl13634problendo-13634Research ArticleДетская эндокринологияPediatric EndocrinologyСиндром Коккейна: особенности клинической манифестации и алгоритм наблюдения в детском возрастеCockayne syndrome: peculiarities of clinical manifestations and algorithm of observation in childhoodhttps://orcid.org/0000-0001-7363-3093КунгурцеваА. Л.KungurtsevaA. L.

Кунгурцева Анастасия Леонидовна,

119991, г. Москва, ул. Трубецкая, д. 8, стр. 2

Anastasiia L. Kungurtseva,

8 Trubetskaya St., bld.2, 119991, Moscow

kungurtseva.al@mail.ruhttps://orcid.org/0000-0002-9660-8795ПоповичА. В.PopovichA. V.

Попович Анастасия Владимировна,

119991, г. Москва, ул. Трубецкая, д. 8, стр. 2

Anastasiia V. Popovich - MD,

8 Trubetskaya St., bld.2, 119991, Moscow

krutova_nastasya@mail.ruhttps://orcid.org/0000-0001-7747-6873ТихоновичЮ. В.TikhonovichYu. V.

Тихонович Юлия Викторовна - к.м.н.,

119991, г. Москва, ул. Трубецкая, д. 8, стр. 2

Yulia V. Tikhonovich - MD, PhD,

8 Trubetskaya St., bld.2, 119991, Moscow

yuliatihonovich@mail.ruhttps://orcid.org/0000-0002-4541-7673ИванниковаТ. Е.IvannikovaT. E.

Иванникова Татьяна Евгеньевна - к.м.н.,

119991, г. Москва, ул. Трубецкая, д. 8, стр. 2

Tatyana E. Ivannikova - MD, PhD,

8 Trubetskaya St., bld.2, 119991, Moscow

ivannikovate@yandex.ruhttps://orcid.org/0000-0002-8728-8574КовальскаяВ. А.KovalskaiaV. A.

Ковальская Валерия Александровна,

Москва

Valeriia A. Kovalskaia,

Moscow

mikhailova.v.a@mail.ruВасильевП. А.VasilievP. A.

Васильев Петр Андреевич,

Москва

Peter A. Vasiliev,

Moscow

vasiluev@med-gen.ruhttps://orcid.org/0000-0001-5689-0194ВитебскаяА. В.VitebskayaA. V.

Витебская Алиса Витальевна - к.м.н.,

119991, г. Москва, ул. Трубецкая, д. 8, стр. 2

Alisa V. Vitebskaya - MD, PhD,

8 Trubetskaya St., bld.2, 119991, Moscow

dr.vitebskaya@gmail.comФГАОУ ВО Первый МГМУ им. И.М. Сеченова Минздрава России (Сеченовский университет)РоссияSechenov First Moscow State Medical UniversityRussian FederationМедико-генетический научный центр им. академика Н.П. БочковаРоссияResearch Centre for Medical GeneticsRussian Federation202607032026721115127Copyright © Кунгурцева А.Л., Попович А.В., Тихонович Ю.В., Иванникова Т.Е., Ковальская В.А., Васильев П.А., Витебская А.В., 20262026Кунгурцева А.Л., Попович А.В., Тихонович Ю.В., Иванникова Т.Е., Ковальская В.А., Васильев П.А., Витебская А.В.Kungurtseva A.L., Popovich A.V., Tikhonovich Y.V., Ivannikova T.E., Kovalskaia V.A., Vasiliev P.A., Vitebskaya A.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.probl-endojournals.ru/jour/article/view/13634ОБОСНОВАНИЕ

ОБОСНОВАНИЕ. Синдром Коккейна — ультраредкое (1:2,5 млн) наследственное заболевание из группы прогероидных синдромов, обусловленное патогенными и вероятнопатогенными вариантами в генах репарации ДНК (ERCC8, ERCC6, XPB (ERCC3), XPD (ERCC2) и XPG (ERCC5)) и характеризующееся аномальной фоточувствительностью, врожденной катарактой, микроцефалией, нейросенсорной тугоухостью, патологией нервной системы и другими мультисистемными изменениями. В данной рукописи, впервые в Российской Федерации, представлены результаты клинико-генетического исследования и наблюдения за российской когортой пациентов.

МАТЕРИАЛЫ И МЕТОДЫ

МАТЕРИАЛЫ И МЕТОДЫ. В течение 2 лет, с 2023 по 2025 гг., под клиническим наблюдением находились 7 пациентов с синдромом Коккейна (4 девочки и 3 мальчика) в возрасте от 3 лет 11 месяцев до 16 лет 3 месяцев, из них у 3 пациентов был диагностирован синдром Коккейна типа А (причинные варианты в гене ERCC8), у 4 пациентов — тип В (причинные варианты в гене ERCC6). Всем пациентам проводилось комплексное мультидисциплинарное обследование с оценкой результатов лабораторных и инструментальных методов исследования.

РЕЗУЛЬТАТЫ

РЕЗУЛЬТАТЫ. По данным наблюдений, нами подтверждена неполная корреляция между генотипом и фенотипом, описанная ранее в литературе. При генотипе синдрома Коккейна типа В, ранее коррелирующего с тяжелым течением заболевания, только у одного пациента наблюдалось тяжелое течение синдрома, у двух — умеренной степени, у одного пациента — легкое течение, что свидетельствует о вариабельности клинической картины в рамках поражения одного гена, а тяжесть течения коррелировала скорее с возрастом дебюта заболевания: раннее начало (до 1 года) ассоциировалось с более быстрым прогрессированием заболевания. Также, вне зависимости от генотипа и степени тяжести течения заболевания, большие диагностические критерии были выявлены у всех пациентов: врожденная катаракта была диагностирована у 5 из 7 наблюдаемых пациентов, нейросенсорная тугоухость — у двух пациентов умеренного и легкого течения заболевания, прогрессирующая патология нервной системы — у 6 пациентов из 7, микроцефалия была диагностирована у всех пациентов.

ЗАКЛЮЧЕНИЕ

ЗАКЛЮЧЕНИЕ. Проведенное исследование расширяет понимание естественного течения синдрома Коккейна и наши знания о вариабельности клинических проявлений и тяжести течения заболевания в рамках поражения одного гена. Своевременная диагностика и персонализированный подход мультидисциплинарной команды специалистов способны замедлить прогрессирование осложнений и улучшить качество жизни пациентов. Работа представляет ценность для врачей различных специальностей, занимающихся диагностикой и лечением орфанных генетических заболеваний, а также исследователей, изучающих механизмы репарации ДНК и преждевременное старение.

BACKGROUND

BACKGROUND: Cockayne syndrome is an ultra-rare (1:2.5 million) hereditary disease from the group of progeroid syndromes caused by pathogenic and probable-pathogenic variants in DNA repair genes (ERCC8, ERCC6, XPB (ERCC3), XPD (ERCC2) and XPG (ERCC5)) and characterized by abnormal photosensitivity, congenital cataract, microcephaly, sensorineural hearing loss, nervous system pathology and other multisystem changes. In this manuscript, for the first time in the Russian Federation, we present the results of a clinical and genetic study and follow-up of a Russian cohort of patients.

MATERIALS AND METHODS

MATERIALS AND METHODS: During 2 years, from 2023 to 2025, 7 patients with Cockayne syndrome (4 girls and 3 boys) aged from 3 years 11 months to 16 years 3 months were under clinical observation, of whom 3 patients were diagnosed with Cockayne syndrome type A (causative variants in ERCC8 gene) and 4 patients with type B (causative variants in ERCC6 gene). All patients underwent a comprehensive multidisciplinary examination with evaluation of the results of laboratory and instrumental methods of investigation.

RESULTS

RESULTS: Based on observational data, we confirmed the incomplete correlation between genotype and phenotype previously described in the literature. With the genotype of Cockayne syndrome type B, previously correlated with severe course of the disease, only one patient had a severe course of the syndrome, two patients had a moderate course, and one patient had a mild course, indicating the variability of the clinical picture within a single gene lesion, and the severity of the course correlated rather with the age of the disease debut: early onset (before 1 year of age) was associated with faster disease progression. Also, regardless of the genotype and severity of the disease course, major diagnostic criteria were identified in all patients: congenital cataract was diagnosed in 5 of 7 observed patients, sensorineural hearing loss in two patients of moderate and mild course of the disease, progressive pathology of the nervous system in 6 of 7 patients, and microcephaly was diagnosed in all patients.

CONCLUSION

CONCLUSION: This study expands our understanding of the natural course of Cockayne syndrome and our knowledge of the variability of clinical manifestations and severity of the disease course within a single gene lesion. Timely diagnosis and personalized approach of a multidisciplinary team of specialists can slow the progression of complications and improve the quality of life of patients. The work is of value for physicians of various specialties involved in the diagnosis and treatment of orphan genetic diseases, as well as researchers studying the mechanisms of DNA repair and premature aging.

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