Cardiofaciocutaneous syndrome and immunodeficiency: data from an international multicenter cohort

Cardiofaciocutaneous syndrome and immunodeficiency: data from an international multicenter cohort

IntroductionCardiofaciocutaneous syndrome (CFCS) is a rare syndromic disorder caused by germline mutations affecting the RAS/MAPK pathway. It is characterized by distinctive craniofacial dysmorphism, congenital heart defects, skin abnormalities, gastrointestinal dysfunction, neurocognitive impairmen...

Full description

Saved in:
Bibliographic Details
Main Authors: Benedetta Elena Di Majo, Chiara Leoni, Eleonora Cartisano, Chiara Fossati, Germana Viscogliosi, Valentina Trevisan, Lucia Pia Bruno, Francesca Conti, Mattia Moratti, Emilia Monaco, Donato Rigante, Beatrice Rivalta, Caterina Cancrini, Aleksandra Szczawińska-Popłonyk, Aleksander Jamsheer, Monika Obara-Moszyńska, Viktoria Zakharova, Anna Shcherbina, Julija Rodina, Beyhan Tüysüz, Saumya Shekhar Jamuar, Jiin Ying Lim, Jeannette Goh, Anna Cereda, Teresa Agovino, Ilaria Contaldo, Maria Luigia Gambardella, Adriana Cristina Balduzzi, Alessia Cherubino, Giovanni Antonio Marrocco, Silvia Bellesi, Valentina Carusi, Gabriele Rumi, Andrea Biondi, Giuseppe Zampino, Francesco Saettini
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Immunology
Subjects:
primary immunodeficiency
inborn errors of immunity
cardiofaciocutaneous syndrome
rasopathy
hypogammaglobulinemia
BRAF
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1598896/full
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:IntroductionCardiofaciocutaneous syndrome (CFCS) is a rare syndromic disorder caused by germline mutations affecting the RAS/MAPK pathway. It is characterized by distinctive craniofacial dysmorphism, congenital heart defects, skin abnormalities, gastrointestinal dysfunction, neurocognitive impairment, and epilepsy. Emerging evidence suggests an association with hypogammaglobulinemia, but a comprehensive characterization of immunological abnormalities in CFCS is lacking.MethodsWe conducted a retrospective, multicenter observational study to investigate the immunological phenotype of CFCS. Clinical features, immune-related manifestations, and laboratory parameters were analyzed to delineate the immunological profile of affected individuals.ResultsA total of 56 patients with a confirmed clinical and molecular diagnosis of CFCS were included, with a median age at evaluation of 13 years (range: 1–39 years). Increased susceptibility to infections was reported in 18/56 patients (32%), while autoimmune manifestations were observed in 14/56 patients (25%). Common immunological findings included monocytosis (32%), lymphopenia (21%), and hypogammaglobulinemia, with decreased IgG, IgA, or IgM levels in 21%, 40%, and 35% of patients, respectively. Genotype-phenotype analysis revealed that BRAF mutations were predominantly associated with T-cell lymphopenia, whereas MAP2K1 mutations were linked to monocytosis, reduced naïve and switched-memory B cells, and hypogammaglobulinemia. Immunodeficiency-related treatments, including immunoglobulin replacement therapy, antibiotic prophylaxis, or immunosuppressive therapy, were administered to 6/56 patients (11%).ConclusionsCFCS is associated with recurrent yet heterogeneous immunological abnormalities, including lymphopenia, hypogammaglobulinemia, and increased infection susceptibility. Given these findings, routine immunological assessment should be considered in CFCS patients to facilitate early detection and appropriate management of immune dysfunction.
ISSN:1664-3224

Similar Items