Clinical and neuroimaging findings in 33 patients with MCAP syndrome: A survey to evaluate relevant endpoints for future clinical trials.
Abnormalities, Multiple
/ diagnostic imaging
Adolescent
Adult
Child
Child, Preschool
Class I Phosphatidylinositol 3-Kinases
/ genetics
Clinical Trials as Topic
Cohort Studies
Female
Forecasting
Humans
Magnetic Resonance Imaging
Male
Megalencephaly
/ diagnostic imaging
Neuroimaging
Skin Diseases, Vascular
/ diagnostic imaging
Telangiectasis
/ congenital
Young Adult
MCAP syndrome
PIK3CA
PROS
clinical trial
Journal
Clinical genetics
ISSN: 1399-0004
Titre abrégé: Clin Genet
Pays: Denmark
ID NLM: 0253664
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
revised:
17
12
2020
received:
18
09
2020
accepted:
04
01
2021
pubmed:
9
1
2021
medline:
1
2
2022
entrez:
8
1
2021
Statut:
ppublish
Résumé
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.
Substances chimiques
Class I Phosphatidylinositol 3-Kinases
EC 2.7.1.137
PIK3CA protein, human
EC 2.7.1.137
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
650-661Informations de copyright
© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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