CDK13‐Related Disorder: Novel Insights From A Series of 27 Cases and Recommendations for Clinical Management

• Published in: Clinical genetics Vol. 108; no. 2; pp. 146 - 155
• Main Authors: Contrò, Gianluca, Baroni, Maria Chiara, Caraffi, Stefano Giuseppe, Napoli, Manuela, Artuso, Rosangela, Giliberti, Annarita, Bargiacchi, Sara, Mancano, Giorgia, Traficante, Giovanna, Mucciolo, Mafalda, Radio, Francesca Clementina, Cordeddu, Viviana, Mancini, Cecilia, Bottillo, Irene, Pirro, Federica Anna, Bonati, Maria Teresa, Becker, Cord‐Christian, Carli, Diana, Mussa, Alessandro, Gonzalez, Maria Isis Atallah, Ruiz‐Arana, Inge Lore, Kumps, Camille, Maystadt, Isabelle, Moortgat, Stephanie, Peker, Alp, Piccione, Maria, Grammatico, Paola, Rostomashvili, Nino, Lévy, Jonathan, Scala, Marcello, Capra, Valeria, Torella, Annalaura, Eyk, Clare, Isidor, Bertrand, Cogne, Benjamin, Srivastava, Siddharth, Quinlan, Aisling, Vaisfeld, Alessandro, Licchetta, Laura, Frattini, Daniele, Graziano, Claudio, Severi, Giulia, Bacchi, Isabelle, Soliani, Luca, Sherr, Elliott H., Argilli, Emanuela, Goel, Himanshu, De Luca, Chiara, Leonardi, Silvia, Brancati, Francesco, Faletra, Flavio, Mio, Catia, Braibanti, Silvia, Gargano, Giancarlo, Fusco, Carlo, Novelli, Antonio, Tartaglia, Marco, Garavelli, Livia
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.08.2025
• Subjects: Adolescent; CDC2 Protein Kinase; CDK13; CDK13‐related disorder; CHDFIDD; Child; Child, Preschool; Congenital diseases; Craniosynostosis; Cyclin-Dependent Kinases - genetics; cyclin‐dependent kinase; Differential diagnosis; Disease Management; Female; Genetic Association Studies; Genetic Predisposition to Disease; Glaucoma; Heart Defects, Congenital - diagnosis; Heart Defects, Congenital - genetics; Heart Defects, Congenital - pathology; Humans; Infant; Intellectual disabilities; Intellectual Disability - diagnosis; Intellectual Disability - genetics; Intellectual Disability - pathology; Male; Mutation; Original; Phenotype; Phenotypes; syndromic intellectual disability; cyclin‐dependent kinase; CDK13; CDK13‐related disorder; syndromic intellectual disability; CHDFIDD
• ISSN: 0009-9163; 1399-0004; 1399-0004
• DOI: 10.1111/cge.14726

ABSTRACT In 2016, Sifrim and colleagues described the first group of patients carrying heterozygous pathogenic variants in CDK13 and sharing major clinical features mainly consisting of congenital heart defects, intellectual disability and peculiar facial features (Congenital Heart Defects, Dysmorphic Facial Features, and Intellectual Developmental Disorder; CHDFIDD, OMIM # 617360). This condition is generally referred to as CDK13‐related disorder, and since then other reports have provided further clinical and molecular information. Here we describe a group of 27 previously unreported patients to more accurately profile the clinical spectrum associated with CDK13 variants, disclosing novel associated findings, such as complex craniosynostosis and variable skeletal features (e.g., cranio‐cervical anomalies). We also focused on the ocular phenotype that appears to include bilateral congenital glaucoma, posterior embriotoxon, buphthalmos and Duane anomaly. Finally, we observed two cases of mother‐to‐daughter transmission. Our work clarifies some novel features of CHDFIDD, defines the differential diagnosis of this disorder, and provides recommendations for its clinical management. This report described 27 novel subject with CDK13‐related disorders. Collecting the clinical and radiological data, we better define the phenotypic spectrum of this condition and we suggest a comprehensive clinical management.