Il faut soupçonner mosaïsm génétique Quand le patient présente :
  • Trouble de croissance asymétrique.
    • Associées à des lésions pigmentaires de la peau à répartition inégale (telles que taches café au lait, naevus, etc.), notamment si elles présentent une répartition suivant les lignes de Blaschko.
    • Combiné avec des malformations vasculaires.
Principaux types de mosaïcisme : Selon la lignée cellulaire atteinte : somatique (a), gonosomale (b), germinale (c). Modèles reconnaissables de mutations en mosaïque dans la peau : lignes de Blaschko étroites (d), lignes de Blaschko larges (e), motif en damier (f), motif phylloïde (g), motif inégal sans séparation sur la ligne médiane (h). 
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1.
Biesecker LG, Spinner NB. Une vision génomique du mosaïcisme et des maladies humaines. Nat Rév Genet [Internet]. Mai 2013 [cité le 2 octobre 2015];14(5):307-20. Disponible à partir de : http://www.nature.com/nrg/journal/v14/n5/abs/nrg3424.html
Mosaïcisme cutané et troubles neurocutanés en mosaïque.
  • La présence d'un mosaïcisme pigmentaire cutané est un facteur de risque de troubles neurodéveloppementaux (jusqu'à 56 % présentent des manifestations extracutanées, qui peuvent être neurologiques, squelettiques, endocrinologiques, etc.).
  • Les maladies mosaïques peuvent avoir plusieurs causes génétiques sous-jacentes, allant des mutations ponctuelles aux réarrangements chromosomiques.
  • Le diagnostic différentiel des différents types de maladies mosaïques est difficile. Ils se caractérisent par la présentation d'un spectre phénotypique très large avec un degré élevé de variabilité clinique, puisque l'essence du mosacisme est la combinaison de plusieurs populations cellulaires avec des codes génétiques différents, et leur distribution et proportion sont aléatoires.
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1.
Kromann AB, Ousager LB, Ali IKM, Aydemir N, Bygum A. Mosaïcisme pigmentaire : une revue de la littérature originale et des recommandations pour une manipulation future. Journal Orphanet des maladies rares [Internet]. 5 mars 2018 [cité le 20 juillet 2019];13(1):39. Disponible à partir de : https://doi.org/10.1186/s13023-018-0778-6
Réarrangements chromosomiques en mosaïque (CNV).
  • Le Hypomélanose Ito Il s'agit d'une maladie neurocutanée classique dans laquelle il existe un réarrangement chromosomique identifiable par biopsie (qui peut affecter plusieurs régions chromosomiques différentes), et qui provoque des modifications pigmentaires en affectant le développement de la crête neurale (neurocristopathie).
Maladies de la mosaïque monogénétique.
  • Ce sont des maladies de transmission autosomique dominante.
  • Certains d'entre eux ne sont pas compatibles avec la vie dans leur présentation constitutionnelle (ils conduisent à l'avortement ou à la mort fœtale, comme le syndrome de l'ENFANT), car le gène affecté a une grande importance évolutive, de sorte que seules les mosaïques avec un phénotype atténué survivent.
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1.
Ruggieri M, Praticò PD, Happle R. Troubles neurocutanés mosaïques et leurs causes. Séminaires en neurologie pédiatrique [Internet]. 13 novembre 2015 [cité le 13 novembre 2015] ; Disponible à partir de : http://www.sciencedirect.com/science/article/pii/S1071909115000765
Mosaïcisme cérébral et malformations cérébrales :
  • Certaines malformations cérébrales sont dues à une mutation en mosaïque.
  • La distribution anatomique de la malformation peut aider à déduire qu'il s'agit d'une maladie mosaïque, la neuroimagerie est donc utile pour planifier l'étude génétique.
Lissencéphalie, hémimégalencéphalie, syndrome du double cortex.
Dysplasie corticale focale.
Le type de malformation cérébrale dépendra du moment de l'apparition de la mutation somatique au cours de l'organogenèse cérébrale.
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1.
Rodin RE, Walsh CA. Mutation somatique dans les maladies neurologiques pédiatriques. Neurologie pédiatrique [Internet]. 2018 [cité le 4 décembre 2018] ; 87 : 20–2. Disponible à partir de : https://linkinghub.elsevier.com/retrieve/pii/S0887899418308580
Techniques de diagnostic du mosaïcisme cérébral.

Le mosaïcisme génétique n'est souvent pas détectable dans le sang périphérique et il est nécessaire de réaliser une étude dans le tissu affecté.

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1.
Ye Z, McQuillan L, Poduri A, Green TE, Matsumoto N, Mefford HC et al. Mutation somatique : La génétique cachée des malformations cérébrales et des épilepsies focales. Recherche sur l'épilepsie [Internet]. 2019 [cité le 20 août 2019];155:106161. Disponible à partir de : https://linkinghub.elsevier.com/retrieve/pii/S0920121119301810
Héritage et conseil génétique en mosaïcisme.
Types de mosaïcisme basés sur la génétique.
  • Les maladies mosaïques surviennent en raison d’une mutation postzygotique de novo survenue chez l’individu lui-même et ne sont pas héréditaires (par définition).
  • Ils ne peuvent être transmis que si la personne affectée est porteuse de la mutation germinale (mosaïcisme germinal).
  • Si la maladie est transmise, la présentation clinique chez la progéniture ne sera pas en mosaïque, mais sous la forme d'une mutation constitutionnelle.
Traitement spécifique
  • Il existe des alternatives thérapeutiques spécifiques pour certaines maladies mosaïques, notamment celles qui affectent les gènes de la voie PI3K/AKT et de la voie RAS/RAF.
Protocole de diagnostic

🧠🧬 Algorithme clinique : Mosaïcisme cutané pigmentaire → risque neurodéveloppemental

1️⃣ Confirmez que le motif de la peau est bien blaschkoïde

Clés cliniques:

  • Lignes en « S » sur le tronc, en « V » dans le dos, courbes aux extrémités
  • Respecte les lignes médianes (non dermatomérique, non vasculaire)
  • Hyper- ou hypopigmentation segmentaire

👉 Oui non Blaschko continue → probabilité plus faible de mosaïcisme génétique pertinent.

2️⃣ Stratification initiale du risque neurologique

🔴 Risque élevé (≥1 critère) :

  • Lésions étendues ou bilatérales
  • Atteinte du visage ou du cuir chevelu
  • Associé à :
    • Retard de développement
    • Épilepsie
    • Hypotonie/spasticité
    • Macro/microcéphalie
    • Traits dysmorphiques
    • asymétrie du corps

➡️ Passez directement à l'étude neurologique et génétique élargie.

🟡 Risque intermédiaire :

  • Blessures limitées
  • Enfant asymptomatique ou enfant présentant de légers doutes sur le développement
  • Examen neurologique normal

➡️ Suivi structuré + dépistage neuropsychologique.

🟢 Faible risque :

  • Petite lésion localisée
  • Aucune autre constatation
  • Développement clairement normal

➡️ Suivi clinique, sans tests invasifs initiaux.

3️⃣ Bilan neurologique recommandé

🔹 Toujours

  • Historique de développement détaillé
  • Examen neurologique ciblé
  • Contrôle linguistique et fonctions exécutives

🔹 En cas de suspicion clinique

  • EEG:
    • Crise, régression, TDL avec fluctuation
  • IRM cérébrale (3T si possible):
    • Épilepsie
    • Retard global
    • asymétrie neurologique
    • Malformation corticale suspectée

📌L'IRM peut être normale même avec mosaïcisme cérébral → normalité ≠ exclusion.

4️⃣ Etudes génétiques : quoi commander et dans quel tissu

❌ Ce qui ne suffit PAS

  • Tableau ou exome seulement dans le sang (faux négatifs fréquents)

✔️ Stratégie recommandée (échelonnée)

Niveau 1

  • Array-CGH ou SNP-array dans le sang
    • Détecte les aneuploïdies ou les CNV à pourcentage élevé
    • Utile en cas de dysmorphie ou de retard global

Niveau 2 (si les soupçons persistent)

  • Étude génétique sur la peau affectée
    • Biopsie à l'emporte-pièce
    • Idéalement:
      • NGS ciblé
      • Exome clinique à grande profondeur
      • Comparaison de la peau affectée et du sang

Niveau 3 (phénotype spécifique)

  • Panels dirigés selon la clinique :
    • Épilepsie (PI3K-AKT-mTOR, MTOR, PIK3CA)
    • Troubles pigmentaires/neurocutanés
    • TSA + macrocéphalie

📌 Mosaïcismes <10% nécessite une profondeur >300×.

5️⃣ Modèles cutanés avec une plus grande corrélation neurologique

motif de peauRisque neurologique
Hypomélanose étendue d'Ito🔴 Élevé
Blaschko bilatéral🔴 Élevé
Blessures avec asymétrie corporelle🔴 Élevé
Segmentaire localisé🟡 Variables
Petit coin isolé🟢 Faible

6️⃣ Suivi du neurodéveloppement

Même asymptomatique :

  • Évaluation du développement tous les 6 à 12 mois
  • Langage, attention, coordination
  • Seuil bas pour une intervention précoce

👉 De nombreux phénotypes sont évolutionniste, pas complètement congénital.

7️⃣ Messages clés pour la famille (très important)

  • ❌ N'implique pas de faute ou de relation causale avec la FIV
  • ✔️ C'est une découverte biologique précoce
  • ✔️ La plupart des enfants ne développez pas de handicap grave
  • ✔️ Détection précoce améliore le pronostic fonctionnel
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1.
Kinsler VA. Troubles de la mosaïque affectant la pigmentation – partie 2 : comment poser un diagnostic génétique. Fr. J Dermatol [Internet]. 1er décembre 2025 [cité le 20 décembre 2025];193(6):1047-55. Disponible à partir de : https://doi.org/10.1093/bjd/ljaf224