CSNK2B-Related Neurodevelopmental Disorder

Excerpt

Clinical characteristics: CSNK2B-related neurodevelopmental disorder (CSNK2B-NDD), reported in more than 80 individuals to date, is characterized in most individuals by developmental delay (DD) / intellectual disability (ID) and seizures. Most young children have delays in speech and motor development. The majority of individuals older than age five years at the time of evaluation have ID ranging from borderline/mild to severe/profound. Seizures, present in most individuals, range in type and severity. While many individuals have pharmaco-responsive epilepsy, others have severe epilepsy with recurrent episodes of refractory status epilepticus. Less consistent findings include ataxia or impaired coordination, generalized hypotonia of infancy, neurobehavioral/psychiatric manifestations, and digital anomalies.

Diagnosis/testing: The diagnosis of CSNK2B-NDD is established in a proband with suggestive findings and a heterozygous CSNK2B pathogenic variant identified by molecular genetic testing.

Management: Treatment of manifestations: Supportive care to improve quality of life, maximize function, and reduce complications is recommended. This includes multidisciplinary care by specialists in pediatrics, developmental pediatrics, neurology, physical medicine and rehabilitation, physical therapy, occupational therapy, speech therapy, social work, and medical genetics / genetic counseling.

Surveillance: To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, routinely scheduled evaluations with multidisciplinary care providers are recommended.

Genetic counseling: CSNK2B-NDD is an autosomal dominant disorder typically caused by a de novo pathogenic variant. Almost all probands reported to date whose parents have undergone molecular genetic testing have the disorder as the result of a de novo pathogenic variant. Rarely, individuals diagnosed with CSNK2B-NDD have an affected parent. The risk to the sibs of the proband depends on the genetic status of the proband's parents: if a parent of the proband is known to have the CSNK2B pathogenic variant identified in the proband, the risk to the sibs of inheriting the pathogenic variant is 50%. Once the CSNK2B pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.