perinatologyРоссийский вестник перинатологии и педиатрииRossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics)1027-40652500-2228Ltd. “The National Academy of Pediatric Science and Innovation”10.21508/1027-4065-2022-67-6-104-112perinatology-1751Research ArticleКЛИНИЧЕСКИЕ СЛУЧАИCLINICAL CASESПервичный иммунодефицит у пациента с синдромом КабукиPrimary immunodeficiency in a patient with Kabuki syndromehttps://orcid.org/0000-0001-9777-1220ДолгополовИ. С.DolgopolovI. S.

Долгополов Игорь Станиславович - д.м.н., зав. кафедрой педиатрии педиатрического факультет

170100 Тверь, ул. Советская, д. 4

Tver

https://orcid.org/0000-0001-9103-9688ГривцоваЛ. Ю.GrivtsovaL. Yu.

Гривцова Людмила Юрьевна - д.б.н., к.м.н., зав. отделением клинической иммунологии

249031 Калужская область, г. Обнинск, ул. Маршала Жукова, д. 10

Obninsk

https://orcid.org/0000-0002-5160-8409УстиноваО. К.UstinovaO. K.

Устинова Ольга Константиновна - к.м.н., гл. врач

170100 Тверь, ул. Рыбацкая, д. 7

Tver

https://orcid.org/0000-0002-8398-7001РыковМ. Ю.RykovM. Yu.

Рыков Максим Юрьевич - д.м.н., доц., проректор по научной работе и инновационной деятельности, зав. кафедрой онкологии факультета дополнительного профессионального образования

170100 Тверь, ул. Советская, д. 4

Tver

wordex2006@rambler.ruФГБОУ ВО «Тверской государственный медицинский университет» Минздрава РоссииРоссияTver State Medical UniversityRussian FederationМедицинский радиологический научный центр им. А.Ф. Цыба - филиал ФГБУ «Национальный медицинский исследовательский центр радиологии» Минздрава РоссииРоссияA. Tsyb Medical Radiological Research Centre - branch of the National Medical Research Radiological CentreRussian FederationГБУЗ ТО «Детская городская клиническая больница №1»РоссияChildren’s City Clinical Hospital No. 1Russian Federation202208012023676104112Copyright © Ltd. “The National Academy of Pediatric Science and Innovation”, 20232023Ltd. “The National Academy of Pediatric Science and Innovation”Ltd. “The National Academy of Pediatric Science and Innovation”https://www.ped-perinatology.ru/jour/about/submissions#copyrightNoticehttps://www.ped-perinatology.ru/jour/article/view/1751

Синдром Кабуки - хорошо известное заболевание, характеризующееся постнатальной недостаточностью роста, дисморфическими чертами лица, аномалиями скелета и умственной отсталостью, связанное с одним из патогенных вариантов мутации вгенах KMT2D или KDM6A. Не менее чем у 50% лиц с синдром Кабуки имеются склонность к рецидивирующим инфекциям и аномалии иммунитета, прежде всего гипогаммаглобулинемия. В статье описано клиническое течение резистентного инфекционного синдрома у ребенка 18 мес без характерных для синдрома Кабуки дисморфических и дерматоглифических проявлений. Длительное течение резистентной бактериальной инфекции и энтероколита, микроцефалия, аутистические черты поведения, неврологические нарушения по типу гиперкинезов, характерная для гранулематозной лимфоцитарной интерстициальной болезни легких (GLILD) картина на компьютерной томограмме, подтвержденная биопсией легкого, заставили предположить иммунодефицит в рамках наследственного генетически обусловленного синдрома. У пациента не выявлена гипогаммаглобулинемия, характерная для синдрома Кабуки. Наличие удовлетворительного ответа на ранее проведенную вакцинацию иполиклональный состав B-лимфоцитов свидетельствовали об отсутствии нарушений в гуморальном звене иммунитета. При иммунофенотипировании выявлено отсутствие популяции Т-регуляторных клеток (CD4+CD25++CD127–) и эффекторных NK-клеток (CD16+CD56+CD3–) в периферической крови. Значимо снижены уровни Т-лимфоцитов CD4+CD3+ иотсутствует экспрессия молекулы адгезии интегрина-бета (CD18) на клетках гранулоцитарного ряда.Заключение. У детей в возрасте до 2 лет синдром Кабуки может представлять трудности для клинической диагностики в связи с отсутствием у них классически сформированных фенотипических признаков. Наличие у ребенка ментальных нарушений, аномалий развития внутренних органов и нарушения в гуморальном и клеточном звеньях иммунной системы требует использования молекулярно-генетических методов, включая исследование на мутации в генах KMT2D и KDM6A.

Kabuki syndrome is a well-known disease characterized by postnatal growth failure, dysmorphic facial features, skeletal abnormalities, and mental retardation associated with one of the pathogenic mutations in the KMT2D or KDM6A genes. At least 50% of individuals with Kabuki syndrome tend to develop recurrent infections and immune abnormalities, primarily hypogammaglobulinemia. The article describes the clinical course of resistant infectious syndrome in an 18-month-old child without typical dysmorphic and dermatoglyphic manifestations characteristic of Kabuki syndrome. A long history of resistant bacterial infection, enterocolitis, microcephaly, autistic-like behavior, hyperkinetic disorder, CT scan patterns of granulomatous lymphocytic interstitial lung disease (GLILD), suggested the immunodeficiency as part of a hereditary genetically determined syndrome. At the same time, the patient did not experience hypogammaglobulinemia characteristic of Kabuki syndrome. The upper normal response to previously received vaccination and a polyclonal repertoire of B-lymphocytes indicated the absence of disturbances in the humoral immunity. Immunophenotyping revealed the absence of T-regulatory cells (CD4+CD25++CD127–) as well as effector NK cells (CD16+CD56+CD3–) in the peripheral blood. The significant reduction of CD4+CD3+ T-lymphocytes and CD4+/CD8+ index was observed. In addition, no expression of integrin-beta (CD18) on neutrophils revealed.Conclusion. In children under the age of 2, Kabuki syndrome may present difficulties for clinical diagnosis due to the absence of distinctive phenotypic signs. Patients with mental disorders, congenital malformations, recurrent infections suspected of immunodeficiency should be carried out using molecular genetic exploration, including testing for mutations in the KMT2D and KDM6A.

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