следует подозревать генетический мозаицизм когда у больного наблюдается:
  • Асимметричное нарушение роста.
    • Сочетающиеся с пигментными поражениями кожи с очаговым распространением (например, пятна цвета кофе с молоком, невусы и др.), особенно если они имеют распространение по линиям Блашко.
    • Сочетается с сосудистыми пороками развития.
Основные виды мозаицизма: В зависимости от пораженной клеточной линии: соматический (а), гоносомный (б), герминативный (в). Узнаваемые закономерности мозаичных мутаций кожи: узкие линии Блашко (г), широкие линии Блашко (д), шахматный рисунок (е), филлоидный рисунок (ж), пятнистый рисунок без разделения по средней линии (з). 
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Бизекер Л.Г., Спиннер Н.Б. Геномный взгляд на мозаицизм и болезни человека. Nat Rev Genet [Интернет]. Май 2013 г. [цитировано 2 октября 2015 г.]; 14(5): 307–20. Доступно: http://www.nature.com/nrg/journal/v14/n5/abs/nrg3424.html
Кожный мозаицизм и мозаичные нейрокожные расстройства.
  • Наличие пигментного мозаицизма кожи является фактором риска нарушений нервно-психического развития (до 56% присутствуют внекожные проявления, которые могут быть неврологическими, скелетными, эндокринологическими и др.).
  • Мозаичные заболевания могут иметь несколько основных генетических причин: от точечных мутаций до хромосомных перестроек.
  • Дифференциальная диагностика различных видов мозаичных заболеваний затруднена. Для них характерно представление очень широкого фенотипического спектра с высокой степенью клинической изменчивости, поскольку сущность мосацизма заключается в сочетании нескольких популяций клеток с разными генетическими кодами, а их распределение и соотношение случайны.
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1.
Кроманн А.Б., Усагер Л.Б., Али ИКМ, Айдемир Н., Бигум А. Пигментный мозаицизм: обзор оригинальной литературы и рекомендации по дальнейшему обращению. Журнал редких заболеваний Orphanet [Интернет]. 5 марта 2018 г. [цитата по 20 июля 2019 г.]; 13(1):39. Доступно: https://doi.org/10.1186/s13023-018-0778-6
Мозаичные хромосомные перестройки (CNV).
  • Отсутствие Ито гипомеланоз Это классическое нейрокожное заболевание, при котором наблюдается хромосомная перестройка, выявляемая биопсией (которая может затрагивать несколько различных хромосомных областей), и она вызывает пигментные изменения, влияя на развитие нервного гребня.нейрокристопатия).
Моногенетические мозаичные заболевания.
  • Это заболевания аутосомно-доминантного наследования.
  • Некоторые из них несовместимы с жизнью по своему конституциональному представлению (приводят к аборту или гибели плода, например синдром CHILD), поскольку пораженный ген имеет высокую эволюционную значимость, поэтому выживают только мозаики с ослабленным фенотипом.
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Руджери М., Пратико П.Д., Хаппл Р. Мозаичные нейрокожные расстройства и их причины. Семинары по детской неврологии [Интернет]. 13 ноября 2015 г. [цитата по 13 ноября 2015 г.]; Доступно: http://www.sciencedirect.com/science/article/pii/S1071909115000765
Мозговой мозаицизм и пороки развития головного мозга:
  • Существуют некоторые пороки развития головного мозга, возникающие из-за мозаичной мутации.
  • Анатомическое распределение порока развития может помочь сделать вывод о том, что это мозаичное заболевание, поэтому нейровизуализация полезна для планирования генетического исследования.
Лиссэнцефалия, гемимегалэнцефалия, синдром двойной коры.
Фокальная кортикальная дисплазия.
Тип порока развития головного мозга будет зависеть от момента появления соматической мутации в ходе органогенеза мозга.
19955111 {19955111:YFH4MG27} 1 Ванкувер 50 по умолчанию 2778 https://neuropediatoolkit.org/wp-content/plugins/zotpress/
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1.
Родин Р.Э., Уолш, Калифорния. Соматические мутации при детских неврологических заболеваниях. Детская неврология [Интернет]. 2018 [цитируется по состоянию на 4 декабря 2018 г.];87:20–2. Доступно: https://linkinghub.elsevier.com/retrieve/pii/S0887899418308580
Методы диагностики церебрального мозаицизма.

Генетический мозаицизм часто не выявляется в периферической крови и необходимо проводить исследование в пораженной ткани.

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1.
Йе З., Маккуиллан Л., Подури А., Грин Т.Э., Мацумото Н., Меффорд Х.К. и др. Соматические мутации: скрытая генетика пороков развития головного мозга и фокальных эпилепсий. Исследования эпилепсии [Интернет]. 2019 [цитировано 20 августа 2019 года]; 155: 106161. Доступно: https://linkinghub.elsevier.com/retrieve/pii/S0920121119301810
Наследственное и генетическое консультирование при мозаицизме.
Виды мозаицизма, обусловленные генетикой.
  • Мозаичные заболевания возникают вследствие de novo, постзиготической мутации, возникшей у самого человека, и не наследуются (по определению).
  • Они могут передаваться только в том случае, если больной является носителем мутации зародышевой линии (мозаицизм зародышевой линии).
  • При передаче заболевания клиническая картина у потомства будет не мозаичной, а в виде конституциональной мутации.
Специфическое лечение
  • Существуют конкретные альтернативы лечения некоторых мозаичных заболеваний, особенно тех, которые влияют на гены пути PI3K/AKT и пути RAS/RAF.
Диагностический протокол

🧠🧬 Клинический алгоритм: Пигментный мозаицизм кожи → риск развития нервной системы.

1️⃣ Убедитесь, что рисунок на коже действительно блашковидный.

Клинические ключи:

  • Линии «S» на туловище, «V» на спине, изгибы на конечностях.
  • Соблюдает срединные линии (недерматомерные, несосудистые)
  • Сегментарная гипер- или гипопигментация

👉 Да Нет Блашко продолжает → более низкая вероятность соответствующего генетического мозаицизма.

2️⃣ Первичная стратификация неврологического риска

🔴 Высокий риск (критерий ≥1):

  • Обширные или двусторонние поражения
  • Поражение лица или кожи головы
  • Связано с:
    • Задержка разработки
    • Эпилепсия
    • Гипотония/спастичность
    • Макро/микроцефалия
    • Дисморфические черты
    • асимметрия тела

➡️Переходите сразу на расширенное неврологическое и генетическое исследование.

🟡 Промежуточный риск:

  • Ограниченные травмы
  • Бессимптомный ребенок или ребенок с легкими сомнениями в развитии
  • Нормальное неврологическое обследование

➡️ Структурированное наблюдение + нейропсихологический скрининг.

🟢 Низкий риск:

  • Небольшое, локализованное поражение
  • Никаких других выводов
  • Очевидно, нормальное развитие.

➡️Клиническое наблюдение без первоначальных инвазивных тестов.

3️⃣ Рекомендуемое неврологическое обследование.

🔹 Всегда

  • Подробная история развития
  • Целенаправленное неврологическое обследование
  • Проверка языка и исполнительные функции

🔹При наличии клинического подозрения

  • ЭЭГ:
    • Кризис, регресс, TDL с колебаниями
  • МРТ головного мозга (3Т, если возможно):
    • Эпилепсия
    • Общая задержка
    • неврологическая асимметрия
    • Подозрение на корковую мальформацию

📌МРТ может быть в норме даже при церебральном мозаицизме → норма ≠ исключение.

4️⃣ Генетические исследования: что заказывать и в какой ткани

❌ Чего НЕ хватает

  • Массив или экзом только в крови (частые ложноотрицательные результаты)

✔️ Рекомендуемая стратегия (в шахматном порядке)

Уровень 1

  • Массив-CGH или SNP-массив в крови
    • Обнаруживает анеуплоидию или высокий процент CNV
    • Полезно, если есть дисморфия или глобальная задержка.

Уровень 2 (если подозрение сохраняется)

  • Генетическое исследование пораженной кожи
    • Пункционная биопсия
    • В идеале:
      • Целевой НГС
      • Клинический экзом большой глубины
      • Сравнение пораженной кожи и крови

Уровень 3 (специфический фенотип)

  • Панели направлены по клинике:
    • Эпилепсия (PI3K-AKT-mTOR, MTOR, PIK3CA)
    • Пигментные/нейрокожные нарушения
    • РАС + макроцефалия

📌 Мозаичность <10% требуется глубина >300×.

5. Узоры кожи с большей неврологической корреляцией

рисунок кожиНеврологический риск
Обширный гипомеланоз Ито🔴Высокая
Двусторонний Блашко🔴Высокая
Травмы с асимметрией тела🔴Высокая
Локализованная сегментарная🟡 Переменная
Небольшое изолированное место🟢 Низкий

6️⃣ Мониторинг нейроразвития

Даже если бессимптомно:

  • Оценка развития каждые 6–12 месяцев.
  • Речь, внимание, координация.
  • Низкий порог для раннего вмешательства

👉 Многие фенотипы эволюционный, не полное врожденное.

7️⃣ Ключевые сообщения для семьи (очень важно)

  • ❌ Не предполагает вины или причинно-следственной связи с ЭКО.
  • ✔️ Это раннее биологическое открытие.
  • ✔️Большинство детей не развивать серьезную инвалидность
  • ✔️ Раннее выявление улучшает функциональный прогноз
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Кинслер В.А. Мозаичные нарушения, влияющие на пигментацию – часть 2: как поставить генетический диагноз. Br J Дерматол [Интернет]. 1 декабря 2025 г. [цитировано 20 декабря 2025 г.]; 193 (6): 1047–55. Доступно: https://doi.org/10.1093/bjd/ljaf224