Epilepsy with faint capillary malformation or reticulated telangiectasia associated with mosaic AKT3 pathogenic variants
Por:
De Bortoli M, Ivars M, Revencu N, Nassogne MC, Lavarino C, Paco-Mercader S, Lammens M, Renders A, Dumitriu D, Helaers R, Boon LM, Baselga E and Vikkula M
Publicada:
1 jun 2024
Ahead of Print:
1 feb 2024
Resumen:
Capillary malformations (CMs) are the most common type of vascular anomalies, affecting around 0.3% of newborns. They are usually caused by somatic pathogenic variants in GNAQ or GNA11. PIK3CA and PIK3R1, part of the phosphoinositide 3-kinase-protein kinase B-mammalian target of rapamycin pathway, are mutated in fainter CMs such as diffuse CM with overgrowth and megalencephaly CM. In this study, we present two young patients with a CM-like phenotype associated with cerebral anomalies and severe epilepsy. Pathogenic variants in PIK3CA and PIK3R1, as well as GNAQ and GNA11, were absent in affected cutaneous tissue biopsies. Instead, we identified two somatic pathogenic variants in the AKT3 gene. Subsequent analysis of the DNA obtained from surgically resected brain tissue of one of the two patients confirmed the presence of the AKT3 variant. Focal cortical dysplasia was also detected in this patient. Genetic analysis thus facilitated workup to reach a precise diagnosis for these patients, associating the vascular anomaly with the neurological symptoms. This study underscores the importance of searching for additional signs and symptoms to guide the diagnostic workup, especially in cases with atypical vascular malformations. In addition, it strongly emphasizes the significance of genotype-phenotype correlation studies in guiding clinicians' informed decision-making regarding patient care.
Filiaciones:
De Bortoli M:
Human Molecular Genetics, de Duve Institute, UCLouvain, Brussels, Belgium
:
Department of Dermatology, VASCERN VASCA European Reference Center, Hospital Sant Joan de Deu, Barcelona, Spain
Revencu N:
Center for Human Genetics, VASCERN VASCA European Reference Center, Cliniques Universitaires Saint Luc, UCLouvain, Brussels, Belgium
Nassogne MC:
Pediatric Neurology Unit, VASCERN VASCA European Reference Center, Cliniques Universitaires Saint Luc, UCLouvain, Brussels, Belgium
Lavarino C:
Laboratory of Molecular Oncology, VASCERN VASCA European Reference Center, Pediatric Cancer Center Barcelona, Hospital Sant Joan de Déu, Barcelona, Spain
Paco-Mercader S:
Laboratory of Molecular Oncology, VASCERN VASCA European Reference Center, Pediatric Cancer Center Barcelona, Hospital Sant Joan de Déu, Barcelona, Spain
Lammens M:
Department of Pathology, Antwerp University Hospital, University of Antwerp, Edegem, Belgium
Service d'anatomopathologie, VASCERN VASCA European Reference Center, Cliniques Universitaires Saint Luc, UCLouvain, Brussels, Belgium
Renders A:
Rehabilitation Department, Cliniques Universitaires Saint Luc, UCLouvain, Brussels, Belgium
Dumitriu D:
Pediatric Radiology Unit, VASCERN VASCA European Reference Center, Cliniques Universitaires Saint Luc, UCLouvain, Brussels, Belgium
Helaers R:
Human Molecular Genetics, de Duve Institute, UCLouvain, Brussels, Belgium
Boon LM:
Human Molecular Genetics, de Duve Institute, UCLouvain, Brussels, Belgium
Center for Vascular Anomalies, Division of Plastic Surgery, VASCERN VASCA European Reference Center, Cliniques Universitaires Saint Luc, UCLouvain, Brussels, Belgium
Baselga E:
Department of Dermatology, VASCERN VASCA European Reference Center, Hospital Sant Joan de Deu, Barcelona, Spain
Vikkula M:
Human Molecular Genetics, de Duve Institute, UCLouvain, Brussels, Belgium
WELBIO department, WEL Research Institute, Wavre, Belgium
Green Submitted, Bronze
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