Comprehensive clinical and genetic characterization of a Spanish cohort of 22 patients with Bainbridge–Ropers Syndrome

Trujillano, Laura ; Valenzuela, Irene ; Costa-Roger, Mar ; Cuscó, Ivon ; Fernandez-Alvarez, Paula ; Cueto-González, Anna ; Lasa-Aranzasti, Amaia ; Masotto, Bárbara ; Abulí, Anna ; Codina-Solà, Marta ; del Campo, Miguel ; Ruiz Moreno, Juan Antonio ; Pardo Domínguez, Cristina ; Palma Milla, Carmen ; Pérez de la Fuente, Rubén ; Quesada-Espinosa, Juan Francisco ; Núñez-Enamorado, Noemí ; Gener, Blanca ; Ballesta-Martínez, María Juliana ; Brea-Fernández, Alejandro J. ; Fernández-Prieto, Montse ; Trujillo-Quintero, Juan Pablo ; Ruiz, Anna ; Santos-Simarro, Fernando ; Rosello, Mónica ; Orellana, Carmen ; Martinez, Francisco ; Martinez-Monseny, Antonio F. ; Casas-Alba, Dídac ; Serrano, Mercedes ; Palomares-Bralo, María ; Rikeros-Orozco, Emi ; Gómez-Cano, María Ángeles ; Tirado-Requero, Pilar ; Pié Juste, Juan ; Ramos, Feliciano J. (Universidad de Zaragoza) ; García-Arumí, Elena ; Tizzano, Eduardo F.

Resumen: Bainbridge–Ropers Syndrome (BRPS) is a genetic condition resulting from truncating variants in the ASXL3 gene. The clinical features include neurodevelopmental and language impairments, behavioral issues, hypotonia, feeding difficulties, and distinctive facial features. In this retrospective study, we analyzed 22 Spanish individuals with BRPS, aiming to perform a detailed clinical and molecular description and establish a genotype–phenotype correlation. We identified 19 ASXL3 variants, nine of which are novel. We documented recurrence in nontwin siblings due to parental mosaicism. The predominant prenatal finding was intrauterine growth restriction (35%) followed, after birth, by feeding difficulties (90.5%), hypotonia (85.7%), and gastroesophageal reflux disease (82.4%). Later in life, intellectual disability, language impairment, autism spectrum disorder (75%), and joint laxity (73.7%) were noted. Individuals with variants in the 3′ mutational cluster region (MCR) of exon 12 exhibited more perinatal feeding problems, and those with variants in the 5′ MCR of exon 11 displayed lower percentiles in height and occipitofrontal circumference, as well as higher frequency of arched eyebrows. This study is the first characterization of a Spanish BRPS cohort, with more than 50 clinical features analyzed, representing the most detailed phenotypic analysis to date.

Idioma: Inglés

DOI: 10.1111/cge.14701

Año: 2025

Publicado en: Clinical genetics (2025), [17 pp.]
ISSN: 0009-9163

Tipo y forma: Artículo (PostPrint)

Área (Departamento): Área Pediatría (Dpto. Microb.Ped.Radio.Sal.Pú.)