Redefining the phenotypic spectrum of de novo heterozygous CDK13 variants: Three patients without cardiac defects

Eur J Med Genet. 2018 May;61(5):243-247. doi: 10.1016/j.ejmg.2017.12.004. Epub 2017 Dec 6.

Abstract

Recently, 7 patients with de novo constitutional non-synonymous mutations in the CDK13 gene were ascertained through a trio exome analysis of a large cohort of 610 patients with congenital cardiac diseases. Despite another report describing 9 additional patients, the clinical spectrum of this condition has yet to be defined. Herein, we report 3 patients with heterozygous constitutional CDK13 mutations, who were ascertained through exome analysis of children with intellectual disability and minor anomalies, who lacked cardiac anomalies. Two patients had a c.2149G > A, p.Gly717Arg mutation, and one had a c.2525A > G, p. Asn842Ser mutation. A review of the previously described patients and those described herein has enabled the following points to be clarified. First, congenital heart diseases are not an essential feature (13/19). Second, nasal features may help syndromic recognition (14/16). Third, widely spaced and peg-shaped teeth may represent a previously unappreciated diagnostic clue for this newly identified syndrome. Here, we show that p.Gly717Arg represents a hotspot in addition to p.Asn842Ser. We suggest that this CDK13-related disorder may represent a clinically recognizable syndrome.

Keywords: CDK13; Congenital cardiac diseases; Intellectual disability; Widely spaced and peg-shaped teeth.

Publication types

  • Case Reports

MeSH terms

  • CDC2 Protein Kinase / genetics*
  • Child
  • Child, Preschool
  • Craniofacial Abnormalities / genetics*
  • Craniofacial Abnormalities / pathology
  • Female
  • Heart Defects, Congenital / genetics*
  • Heart Defects, Congenital / pathology
  • Heterozygote
  • Humans
  • Intellectual Disability / genetics*
  • Intellectual Disability / pathology
  • Male
  • Mutation
  • Phenotype*
  • Syndrome

Substances

  • CDC2 Protein Kinase
  • CDK13 protein, human