CHD2-Related Neurodevelopmental Disorders

Clinical characteristics: CHD2-related neurodevelopmental disorders are characterized by early-onset epileptic encephalopathy (i.e., refractory seizures and cognitive slowing or regression associated with frequent ongoing epileptiform activity). Seizure onset is typically between ages six months and four years. Seizure types typically include drop attacks, myoclonus, and rapid onset of multiple seizure types associated with generalized spike-wave on EEG, atonic-myoclonic-absence seizures, and clinical photosensitivity. Intellectual disability and/or autism spectrum disorders are common.

Diagnosis/testing: The diagnosis of a CHD2-related neurodevelopmental disorder is established in a proband with suggestive findings and a heterozygous pathogenic variant in CHD2 identified by molecular genetic testing.

Management: Treatment of manifestations: Seizures should be managed by an experienced pediatric neurologist. At this time, no specific guidelines regarding choice of specific anti-seizure medications exist, as the best regimen for CHD2-related neurodevelopmental disorders is not yet established. Most Individuals remain refractory to treatment and require multiple anti-seizure medications. Support services for those with developmental delay, intellectual disability, and/or associated psychiatric/behavioral disorders.

Surveillance: At each visit assess for new seizures or change in seizures; evaluate developmental progress and educational needs; behavioral assessment for anxiety, attention, and aggressive or self-injurious behavior; assess family need for social work support and care coordination.

Agents/circumstances to avoid: Because clinical photosensitivity may result in injuries due to the consequences of induced seizures, it is recommended that stimuli that may provoke seizures (e.g., intensely flickering lights) be avoided.

Genetic counseling: CHD2-related neurodevelopmental disorders are autosomal dominant disorders typically caused by a de novo pathogenic variant. If the CHD2 pathogenic variant identified in the proband is not identified in either parent, the risk to sibs is low but greater than that of the general population because of the possibility of parental germline mosaicism. Once the CHD2 pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.