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Background  De novo missense variants in  CDK13  have been described as the cause of syndromic congenital heart defects in seven individuals ascertained from a large congenital cardiovascular malformations cohort. We aimed to further define the phenotypic and molecular spectrum of this newly described disorder.    Methods  To minimise ascertainment bias, we recruited nine additional individuals with  CDK13  pathogenic variants from clinical and research exome laboratory sequencing cohorts. Each individual underwent dysmorphology exam and comprehensive medical history review.    Results  We demonstrate greater than expected phenotypic heterogeneity, including 33% (3/9) of individuals without structural heart disease on echocardiogram. There was a high penetrance for a unique constellation of facial dysmorphism and global developmental delay, as well as less frequently seen renal and sacral anomalies. Two individuals had novel  CDK13  variants (p.Asn842Asp, p.Lys734Glu), while the remaining seven unrelated individuals had a recurrent, previously published p.Asn842Ser variant. Summary of all variants published to date demonstrates apparent restriction of pathogenic variants to the protein kinase domain with clustering in the ATP and magnesium binding sites.    Conclusions  Here we provide detailed phenotypic and molecular characterisation of individuals with pathogenic variants in  CDK13  and propose management guidelines based upon the estimated prevalence of anomalies identified.    Electronic supplementary material  The online version of this article (doi:10.1186/s13073-017-0463-8) contains supplementary material, which is available to authorized users.

genome medicine

Phenotypic and molecular characterisation of CDK13-related congenital heart defects, dysmorphic facial features and intellectual developmental disorders