Comprehensive Clinical and Genetic Characterization of a Spanish Cohort of 22 Patients With Bainbridge-Ropers Syndrome.

Autores de IIS La Fe

• Mónica Pilar Roselló Piera

  Autor

• Carmen Orellana Alonso

  Autor

• 

  Francisco Martínez Castellano

  Autor

Participantes ajenos a IIS La Fe

• Trujillano, Laura
• Valenzuela, Irene
• Costa-Roger, Mar
• Cusco, Ivon
• Fernandez-Alvarez, Paula
• Cueto-Gonzalez, Anna
• Lasa-Aranzasti, Amaia
• Masotto, Barbara
• Abuli, Anna
• Codina-Sola, Marta
• Del Campo, Miguel
• Ruiz Moreno, Juan Antonio
• Pardo Dominguez, Cristina
• Palma Milla, Carmen
• Perez de la Fuente, Ruben
• Quesada-Espinosa, Juan Francisco
• Nunez-Enamorado, Noemi
• Gener, Blanca
• Ballesta-Martinez, Maria Juliana
• Brea-Fernandez, Alejandro J
• Fernandez-Prieto, Montse
• Trujillo-Quintero, Juan Pablo
• Ruiz, Anna
• Santos-Simarro, Fernando
• Martinez-Monseny, Antonio F
• Casas-Alba, Didac
• Serrano, Mercedes
• Palomares-Bralo, Maria
• Rikeros-Orozco, Emi
• Gomez-Cano, Maria Angeles
• Tirado-Requero, Pilar
• Pie Juste, Juan
• Ramos, Feliciano J
• Garcia-Arumi, Elena
• Tizzano, Eduardo F

Grupos

• Investigación Traslacional en Genética

  

  Leader

  Francisco Martínez Castellano

Abstract

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.