A pathogenic missense variant, c.2149G>A (p.Gly717Arg), in CDK13 in a female patient with CDK13-related disorder: A case report and literature review of 112 cases

Abstract

Background

CDK13 (OMIM 603309), a cyclin-dependent kinase, phosphorylates RNA polymerase II and plays a role in various biological processes, including transcriptional regulation, alternative mRNA splicing, and axonal elongation. Patients with CDK13-related disorder present with facial abnormalities; hypotonia; congenital cardiac, renal, and skeletal abnormalities; and psychoneurological manifestations, including developmental delays, intellectual disabilities, and epilepsy.

Case presentation

We present the case of a 7-year-old female patient with CDK13-related disorder. The patient had peculiar facial features, such as microcephaly, hypertelorism, broad nasal root and alar, frontal hypertrichosis, small jaw and low auricle, and atrial septal defect. Additionally, she presented with hypotonia and developmental delays. Her developmental delay was remarkable with her age and her total developmental quotient on the Kyoto Scale of Psychological Development 2020 was 38 (postural-motor, 40; cognitive-adaptive, 41; and language-social, 34) at 7 years and 8 months of age. Her cognitive development was progressing slowly at her own pace, with support from social interactions, physiotherapy, and occupational therapy. Moreover, facial dysmorphism, developmental delays, and intellectual disabilities were highly frequent even among the 15 patients with the CDK13 c.2149G>A (p.Gly717Arg) variant through the literature review.

Conclusion

Patients with CDK13-related disorder typically exhibit facial dysmorphism, developmental delays, and intellectual disabilities, with the possibility of additional manifestations emerging in adulthood. This patient also presented the same manifestations as those of other patients with CDK13-related disorder. Clinical outcomes should be followed up for a long duration in this patient, as various clinical manifestations and problems may be expected.