neurojourНеврологический журнал имени Л.О. БадалянаL.O. Badalyan Neurological Journal2686-89972712-794XФГАУ «НМИЦ здоровья детей» Минздрава России10.46563/2686-8997-2020-1-01-29-34neurojour-28Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESКлинико-генетическая характеристика пациентов с синдромом Питта–ХопкинсаClinical and genetic characteristic of patients with Pitt–Hopkins syndromehttps://orcid.org/0000-0002-6316-9992КондаковаОльга БорисовнаKondakovaOlga B.

Канд. мед. наук, зав. отделением медицинской генетики ФГАУ НМИЦ здоровья детей, 119991, Москва.

e-mail: kondakova.ob@nzcd.ru

MD, Ph.D., head of the Department of medical genetics of the National Medical Research Center for Children’s Health, Moscow, 119991, Russian Federation.

e-mail: kondakova.ob@nzcd.ru

kondakova.ob@nzcd.ruhttps://orcid.org/0000-0002-0551-5869ГребенкинД. И.GrebenkinDmitry I.noemail@neicon.ruhttps://orcid.org/0000-0001-5657-7851ЛялинаА. А.LyalinaAnastasiya A.noemail@neicon.ruhttps://orcid.org/0000-0002-4202-863XХрусталеваЕ. В.KrustalevaEvgeniya V.noemail@neicon.ruhttps://orcid.org/0000-0001-5821-9783КанивецИ. В.KanivetsIlya V.noemail@neicon.ruhttps://orcid.org/0000-0003-0928-2131БатышеваТ. Т.BatyshevaTatiana T.noemail@neicon.ruФГАУ «Национальный медицинский исследовательский центр здоровья детей» Минздрава РоссииРоссияNational Medical Research Center for Children's HealthRussian FederationГБУЗ «Научно-практический центр детской психоневрологии ДЗ г. Москвы»РоссияScientific and Practical Center for Child PsychoneurologyRussian FederationГенетический центр «Геномед»РоссияGenetic Center «Genomed»Russian Federation202030032021112934Copyright © Кондакова О.Б., Гребенкин Д.И., Лялина А.А., Хрусталева Е.В., Канивец И.В., Батышева Т.Т., 20212021Кондакова О.Б., Гребенкин Д.И., Лялина А.А., Хрусталева Е.В., Канивец И.В., Батышева Т.Т.Kondakova O.B., Grebenkin D.I., Lyalina A.A., Krustaleva E.V., Kanivets I.V., Batysheva T.T.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.neuro-journal.ru/jour/article/view/28Введение

Введение. Синдром Питта–Хопкинса (СПХ) — редкое наследственное заболевание, характеризующееся грубой задержкой моторного развития, умственной отсталостью, аутистическими чертами, эпизодами гипервентиляции с последующим апноэ, эпилепсией и фенотипическими особенностями. Причинами СПХ является микроделеция длинного плеча 18 хромосомы или точковая мутация гена TCF4. Спектр мутаций представлен в 40% случаев точковыми мутациями, в 30% — мелкими делециями/инсерциями, в 30% —крупными делециями. В настоящее время в мире описано более 500 случаев СПХ.

Материалы и методы

Материалы и методы. В исследование были включены 4 мальчика и 5 девочек с СПХ в возрасте от 1 года 8 месяцев до 12 лет. Диагноз был подтвержден с помощью хромосомного микроматричного анализа или секвенирования нового поколения. 

Результаты

Результаты. У 5 пациентов выявлены микроделеции длинного плеча 18 хромосомы. Размер выявленных микроделеций варьировал от 307 Kb до 11.62 Mb. Точковые мутации обнаружены у 4 детей: 2 пациентов имели мутацию в сайте сплайсинга, 1 — миссенс- и 1 — нонсенс-мутацию. Клиническая картина была проанализирована у всех детей: отмечались грубая задержка моторного и психоречевого развития, мышечная гипотония и специфические стигмы дизэмбриогенеза.

Заключение

Заключение. При сравнительном анализе клинической картины у больных с СПХ, обусловленной микроделецией длинного плеча 18-й хромосомы и точковой мутацией  гена TCF4, значимых различий не выявлено. Основными клиническими критериями, позволяющими заподозрить СПХ, являются грубая задержка развития, специфические особенности фенотипа, нарушения поведения и эпизоды гипервентиляции с последующим апноэ. 

Background

Background. Pitt–Hopkins syndrome (PHS) is the rare inherited disease, caused by a microdeletion on chromosome 18q21 or heterozygous mutation TCF4 gene and characterized by severe mental retardation, abnormal breathing patterns: hyperventilation, apnea, and unusual facial features. 

Material and method

Material and method. We examined 9 children, included 4 boys and 5 girls at the age of 1 year 8 months to 12 years with PHS. All children have clinical symptoms characteristic of this syndrome. The diagnosis was confirmed by Array CGH (deletion of genomic material in chromosomal region 18q21) and new generation sequencing.

Results

Results. Microdeletions chromosome 18 (18q21) were identified in 5 patients. The size of the microdeletions varied from 307 Kb to 11.62 Mb. A point mutation was detected in 4 children: two patients had a mutation in the splicing site, 1 — missense and 1 — nonsense-mutation. The clinical picture was analyzed in all children: psychomotor retardation, severe intellectual disability, poor speech, autistic behavior, hypotonia, and specific phenotype. 

Conclusion

Conclusion. Comparative analysis of the clinical picture in patients with PHS, caused by a microdeletion on chromosome 18q21 and point mutation in the TCF4 gene showed that no significant clinical differences were found. The main clinical criteria for suspecting PHS are gross developmental delay, severe delayed psychomotor development, behavioral disorders, and episodes of  hyperventilation with the subsequent apnea.

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