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Garde A, Guibaud L, Goldenberg A, et al. Clinical and neuroimaging findings in 33 patients with MCAP syndrome: A survey to evaluate relevant endpoints for future clinical trials. Clin Genet. 2021;99(5):650-661doi: 10.1111/cge.13918.
Garde, A., Guibaud, L., Goldenberg, A., Petit, F., Dard, R., Roume, J., Mazereeuw-Hautier, J., Chassaing, N., Lacombe, D., Morice-Picard, F., Toutain, A., Arpin, S., Boccara, O., Touraine, R., Blanchet, P., Coubes, C., Willems, M., Pinson, L., Van Kien, P. K., Chiaverini, C., Giuliano, F., Alessandri, J. L., Mathieu-Dramard, M., Morin, G., Bursztejn, A. C., Mignot, C., Doummar, D., Di Rocco, F., Cornaton, J., Nicolas, C., Gautier, E., Luu, M., Bardou, M., Sorlin, A., Philippe, C., Edery, P., Rossi, M., Carmignac, V., Thauvin-Robinet, C., Vabres, P., & Faivre, L. (2021). Clinical and neuroimaging findings in 33 patients with MCAP syndrome: A survey to evaluate relevant endpoints for future clinical trials. Clinical genetics, 99(5), 650-661. https://doi.org/10.1111/cge.13918
Garde, Aurore, et al. "Clinical and neuroimaging findings in 33 patients with MCAP syndrome: A survey to evaluate relevant endpoints for future clinical trials." Clinical genetics vol. 99,5 (2021): 650-661. doi: https://doi.org/10.1111/cge.13918
Garde A, Guibaud L, Goldenberg A, Petit F, Dard R, Roume J, Mazereeuw-Hautier J, Chassaing N, Lacombe D, Morice-Picard F, Toutain A, Arpin S, Boccara O, Touraine R, Blanchet P, Coubes C, Willems M, Pinson L, Van Kien PK, Chiaverini C, Giuliano F, Alessandri JL, Mathieu-Dramard M, Morin G, Bursztejn AC, Mignot C, Doummar D, Di Rocco F, Cornaton J, Nicolas C, Gautier E, Luu M, Bardou M, Sorlin A, Philippe C, Edery P, Rossi M, Carmignac V, Thauvin-Robinet C, Vabres P, Faivre L. Clinical and neuroimaging findings in 33 patients with MCAP syndrome: A survey to evaluate relevant endpoints for future clinical trials. Clin Genet. 2021 May;99(5):650-661. doi: 10.1111/cge.13918. Epub 2021 Jan 20. PMID: 33415748.
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Clin Genet. 2021 May;99(5):650-661. doi: 10.1111/cge.13918. Epub 2021 Jan 20.

Clinical and neuroimaging findings in 33 patients with MCAP syndrome: A survey to evaluate relevant endpoints for future clinical trials.

Clinical genetics

Aurore Garde, Laurent Guibaud, Alice Goldenberg, Florence Petit, Rodolphe Dard, Joelle Roume, Juliette Mazereeuw-Hautier, Nicolas Chassaing, Didier Lacombe, Fanny Morice-Picard, Annick Toutain, Stéphanie Arpin, Olivia Boccara, Renaud Touraine, Patricia Blanchet, Christine Coubes, Marjolaine Willems, Lucile Pinson, Philippe Khau Van Kien, Christine Chiaverini, Fabienne Giuliano, Jean-Luc Alessandri, Michèle Mathieu-Dramard, Gilles Morin, Anne-Claire Bursztejn, Cyril Mignot, Diane Doummar, Frederico Di Rocco, Jenny Cornaton, Claire Nicolas, Elodie Gautier, Maxime Luu, Marc Bardou, Arthur Sorlin, Christophe Philippe, Patrick Edery, Massimiliano Rossi, Virginie Carmignac, Christel Thauvin-Robinet, Pierre Vabres, Laurence Faivre

Affiliations

  1. Centre de Référence Anomalies du Développement et Syndromes Malformatifs, FHU TRANSLAD, Hôpital d'Enfants, CHU Dijon, Dijon, France.
  2. Unité Fonctionnelle Innovation en Diagnostic génomique des maladies rares, FHU-TRANSLAD, CHU Dijon Bourgogne, Dijon, France.
  3. Service de Radiologie, Hôpital Femme-Mère-Enfant, Lyon, France.
  4. Unité de Génétique Clinique, CHU de Rouen, Rouen, France.
  5. Service de Génétique Clinique, Centre de Référence Anomalies du Développement CHU, Lille, France.
  6. Département de Génétique, CHI Poissy, St Germain-en-Laye, France.
  7. Département de Dermatologie, Centre de Référence des Maladies Rares de la Peau, CHU de Toulouse, Toulouse, France.
  8. Service de Génétique Médicale, INSERM U543, Hôpital Purpan, CHU de Toulouse, Toulouse, France.
  9. INSERM U1211, Service de Génétique Médicale, CHU de Bordeaux, Bordeaux, France.
  10. Service de génétique, CHRU de Tours, Tours, France.
  11. Département de Dermatologie, Centre de Reference MAGEC, Hopital universitaire Necker-Enfants malades, Paris, France.
  12. Service de Génétique Clinique, Chromosomique et Moléculaire, Centre de Référence des Anomalies du Développement, CHU, de Saint-Etienne, France.
  13. Département de Génétique Médicale, Maladies rares et Médecine Personnalisée, CHRU de Montpellier, Montpellier, France.
  14. UF de Génétique Médicale et Cytogénétique, CHU de Nîmes, Nîmes, France.
  15. Service de Dermatologie, CHU de Nice, Nice, France.
  16. Service de Génétique Médicale, CHU de Nice, Nice, France.
  17. Pôle Enfants, CHU Felix Guyon Saint Denis, Saint Denis, France.
  18. Service de Génétique Clinique, CHU Amiens-Picardie, Amiens, France.
  19. Service de dermatologie et allergologie, CHRU de Nancy, Nancy, France.
  20. Département de Génétique and Centre de Référence Déficiences Intellectuelles de Causes Rares, AP-HP, Sorbonne Université, Paris, France.
  21. Service de Neurologie pédiatrique, Hôpital Armand Trousseau, AP-HP, Paris, France.
  22. Service de neurochirurgie pédiatrique, Hôpital Femme-Mère-Enfant, Lyon, France.
  23. INSERM CIC 1432, Université de Bourgogne, Dijon, France.
  24. UMR1231 GAD, Inserm - Université Bourgogne-Franche Comté, Dijon, France.
  25. Département de Génétique, Hospices Civils de Lyon et GENDEV, INSERM U1028, Lyon, France.
  26. Centre de Référence MAGEC, Service de Dermatologie, Centre Hospitalier Universitaire Dijon Bourgogne, Dijon, France.

PMID: 33415748 DOI: 10.1111/cge.13918

Abstract

Megalencephaly-CApillary malformation-Polymicrogyria (MCAP) syndrome results from somatic mosaic gain-of-function variants in PIK3CA. Main features are macrocephaly, somatic overgrowth, cutaneous vascular malformations, connective tissue dysplasia, neurodevelopmental delay, and brain anomalies. The objectives of this study were to describe the clinical and radiological features of MCAP, to suggest relevant clinical endpoints applicable in future trials of targeted drug therapy. Based on a French collaboration, we collected clinical features of 33 patients (21 females, 12 males, median age of 9.9 years) with MCAP carrying mosaic PIK3CA pathogenic variants. MRI images were reviewed for 21 patients. The main clinical features reported were macrocephaly at birth (20/31), postnatal macrocephaly (31/32), body/facial asymmetry (21/33), cutaneous capillary malformations (naevus flammeus 28/33, cutis marmorata 17/33). Intellectual disability was present in 15 patients. Among the MRI images reviewed, the neuroimaging findings were megalencephaly (20/21), thickening of corpus callosum (16/21), Chiari malformation (12/21), ventriculomegaly/hydrocephaly (10/21), cerebral asymmetry (6/21) and polymicrogyria (2/21). This study confirms the main known clinical features that defines MCAP syndrome. Taking into account the phenotypic heterogeneity in MCAP patients, in the context of emerging clinical trials, we suggest that patients should be evaluated based on the main neurocognitive expression on each patient.

© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Keywords: MCAP syndrome; PIK3CA; PROS; clinical trial

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