- Volume - Number
- Published: April 29, 2026
Clinical and molecular characterization of 35 Portuguese patients with KBG syndrome
Mariana Tomásio Neves 1, Patrícia Dias 1, Pedro Louro 2, Catarina Rosas 2, Sofia Fernandes 2, María Abreu 3, Susana Ferreira 4, Mafalda Melo 4, Oana Moldovan 1, Juliette Dupont 5, André Travessa 5, João Rodrigues-Alves 1, Ana Medeira 1, Isabel Cordeiro 1, Heloísa Santos 1, Pedro Maia Almeida 2, Joaquim Sá 2, Fabiana Ramos 2, Ana Luísa Carvalho 2, Sérgio Sousa 2, Lina Ramos 2, Ana Rita Soares 3, Célia Soares 6, Gabriela Soares 3, Natália Tkachenko 3, Marta Amorim 4, Marta P. Antunes 7, Diana Antunes 4, João Freixo 8, Ana Maria Fortuna 3, Cláudia Falcão Reis 3, Jorge Saraiva 9, Ana Berta Sousa 5
1 Serviço de Genética Médica, Departamento de Pediatria, Hospital de Santa Maria, Unidade Local de Saúde Santa Maria, Lisboa, Portugal; 2 Serviço de Genética Médica, Hospital Pediátrico, Unidade Local de Saúde de Coimbra, Coimbra, Portugal; 3 Serviço de Genética Médica, Centro de Genética Médica Doutor Jacinto Magalhães, Unidade Local de Saúde Santo António, Porto, Portugal; 4 Serviço de Genética Médica, Hospital Dona Estefânia, Unidade Local de Saúde São José, Lisboa, Portugal; 5 Serviço de Genética Médica, Departamento de Pediatria, Hospital de Santa Maria, Unidade Local de Saúde Santa Maria, Lisboa; Clínica Universitária de Genética Médica, Faculdade de Medicina de Lisboa, Universidade de Lisboa, Lisboa; Portugal; 6 Serviço de Genética Médica, Centro de Genética Médica Doutor Jacinto Magalhães, Unidade Local de Saúde Santo António, Porto; Unit for Multidisciplinary Research in Biomedicine, Instituto de Ciências Biomédicas Abel Salazar/ Universidade do Porto, Porto; Departamento de Ciências Médicas, Universidade de Aveiro, Aveiro; Portugal; 7 Serviço Psiquiatria da Infância e da Adolescência, Centro Hospitalar Universitário do Porto, Porto, Portugal; 8 Centro de Genética Preditiva e Preventiva, Instituto de Biologia Molecular e Celular, i3S, Porto, Portugal; 9 Serviço de Genética Médica, Hospital Pediátrico, Unidade Local de Saúde de Coimbra, Coimbra; Clínica Universitária de Pediatria, Faculdade de Medicina, Universidade de Coimbra, Coimbra; Centro Académico Clínico de Coimbra, Coimbra. Portugal
Mariana Tomásio Neves, Patrícia Dias, Pedro Louro, Catarina Rosas, Sofia Fernandes, María Abreu, Susana Ferreira, Mafalda Melo, Oana Moldovan, Juliette Dupont, André Travessa, João Rodrigues-Alves, Ana Medeira, Isabel Cordeiro, Heloísa Santos, Pedro Maia Almeida, Joaquim Sá, Fabiana Ramos, Ana Luísa Carvalho, Sérgio Sousa, Lina Ramos, Ana Rita Soares, Célia Soares, Gabriela Soares, Natália Tkachenko, Marta Amorim, Marta P. Antunes, Diana Antunes, João Freixo, Ana Maria Fortuna, Cláudia Falcão Reis, Jorge Saraiva, Ana Berta Sousa
La información completa de afiliaciones y autor de correspondencia está disponible en la versión original en PDF.
*Correspondence: Ana Berta Sousa, Email not available
Abstract
Introduction and Objectives: KBG syndrome (MIM #148050; KBGS) is an autosomal dominant syndromic disorder characterized by developmental delay and/or intellectual disability, caused by haploinsufficiency of the ANKRD11 gene. It is typically associated with a distinctive facial gestalt, macrodontia and short stature. KBGS is presumed to be an underdiagnosed cause of syndromic developmental delay and intellectual disability. We present the clinical and molecular characterization of 35 Portuguese patients with KBGS and compare our findings with previously published cohorts. Our aim is to contribute to a better understanding and characterization of the syndrome. Methods: A retrospective review of clinical and molecular data from patients with KBGS diagnosed at Portuguese medical genetics centers was conducted. Results: Overall, the features observed in our cohort are consistent with those described in the literature. We report 15 previously unreported ANKRD11 sequence variants. Our study provides additional clinical details, particularly regarding ophthalmologic, otorhinolaryngologic, cardiac and craniofacial findings. Significantly, we observed a higher prevalence of sensory deficits in our cohort. Additionally, Cornelia de Lange syndrome (CdLS) was the initial suspected diagnosis in 15% of patients, highlighting the need to consider KBGS in the differential diagnosis of CdLS-like phenotypes. Discussion: Although KBGS presents with a clinically recognizable gestalt that can be confirmed through targeted gene sequencing, in current practice, whole exome sequencing (WES) is more commonly used. The syndrome involves multiple comorbidities, underscoring the importance of multidisciplinary clinical follow-up for affected individuals.
