CDK13-Related Disorder

Clinical characteristics: CDK13-related disorder, reported in 43 individuals to date, is characterized in all individuals by developmental delay / intellectual disability (DD/ID); nearly all individuals older than age one year display impaired verbal language skills (either absent or restricted speech). Other common findings are recognizable facial features in some individuals, behavioral problems (autism spectrum disorder or autistic traits/stereotypies, attention-deficit/hyperactivity disorder), feeding difficulties in infancy, structural cardiac defects, and seizures.

Diagnosis/testing: The diagnosis of CDK13 disorder is established in a proband by identification of a heterozygous pathogenic variant in CDK13 by molecular genetic testing.

Management: Treatment of manifestations: Management of DD/ID is per usual practice with attention to gross and fine motor skills, language and communication skills, and behavioral issues. Some children with feeding difficulties require tube feeding. Structural heart defects are treated in the usual manner by a cardiologist. Seizures are treated in the usual manner with anti-seizure medication.

Surveillance: For infants with feeding difficulties: Assess swallowing, feeding, nutritional status, and weight gain monthly during the first few months of life and then at least annually during childhood. Routine monitoring of developmental progress and educational needs. Annual assessment of behavior to identify new or evolving issues. As indicated by specialists: follow up of structural cardiac defects, seizures, scoliosis, constipation, and renal structural abnormalities.

Genetic counseling: CDK13 disorder is inherited in an autosomal dominant manner. To date all probands whose parents have undergone molecular genetic testing have the disorder as a result of a de novo CDK13 pathogenic variant. Individuals with CDK13 disorder are not known to reproduce, and fertility has not been assessed. Given the estimated recurrence risk to sibs of 1% based on the theoretic possibility of parental germline mosaicism, prenatal testing and preimplantation genetic testing are options for parents of a child with CDK13 disorder.