Clinical Guidance

No genotype-phenotype correlation has been observed between the location/nature of the pathogenic variant and clinical outcome.

Source: GeneReviews — "CHD2-Related Neurodevelopmental Disorders"

Penetrance

Penetrance for CHD2-related neurodevelopmental disorders is unknown but assumed to be complete. There are a small number of instances where the CHD2 variant is inherited from a presumably unaffected parent or a parent with a milder phenotype . In such instances it is important to evaluate the parent for somatic mosaicism.

Source: GeneReviews — "CHD2-Related Neurodevelopmental Disorders"

Diagnostic Criteria

Suggestive Findings

CHD2-related neurodevelopmental disorders should be suspected in individuals with the following:

• Early-onset developmental and epileptic encephalopathy (i.e., refractory seizures and cognitive slowing or regression associated with frequent ongoing epileptiform activity ), particularly those with:

• Seizure onset between ages six months and four years

• Drop attacks and rapid onset of multiple seizure types associated with generalized spike-wave on EEG

• Atonic-myoclonic-absence seizures (See .)

• Clinical photosensitivity

Source: GeneReviews — "CHD2-Related Neurodevelopmental Disorders"

Differential Diagnosis

Phenotypic features associated with CHD2 pathogenic variants are not sufficient to diagnose CHD2-related neurodevelopmental disorders. For children with a phenotype consistent with early-onset epileptic encephalopathy, all genes known to be associated with epileptic encephalopathy (~90 have been identified; see OMIM Phenotypic Series) should be included in the differential diagnosis. For children with intellectual disability and epilepsy, all genes associated with juvenile myoclonic epilepsy (see OMIM Phenotypic Series), idiopathic generalized epilepsy (see OMIM Phenotypic Series), and generalized epilepsy with febrile seizures plus (see OMIM Phenotypic Series) should be included in the differential diagnosis.

Source: GeneReviews — "CHD2-Related Neurodevelopmental Disorders"

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with a CHD2-related neurodevelopmental disorder, the evaluations summarized (if not performed as part of the evaluation that led to diagnosis) are recommended. Table 3. Recommended Evaluations Following Initial Diagnosis in Individuals with CHD2-Related Neurodevelopmental Disorders

Source: GeneReviews — "CHD2-Related Neurodevelopmental Disorders"

Clinical Guidance

Because clinical photosensitivity may result in injuries due to the consequences of induced seizures, the following are recommended:

• Avoid flickering lights that may provoke seizures.

• Advise affected individuals and families that exposure to intensely flickering lights may provoke seizures including eyelid myoclonias, absence seizures, and generalized tonic-clonic seizures. Of note, most televisions do not transmit in the frequency range that is particularly provocative.

Source: GeneReviews — "CHD2-Related Neurodevelopmental Disorders"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "CHD2-Related Neurodevelopmental Disorders"

Surveillance Guidelines

Table 5.

Recommended Surveillance for Individuals with CHD2-Related Neurodevelopmental Disorders

System/Concern | Evaluation | Frequency

Neurologic

| Monitor those w/seizures as clinically indicated assess for new-onset seizures. | At each visit

Development

| Monitor developmental progress educational needs.

Psychiatric/

Behavioral

| Assess behavior for anxiety, attention, aggressive or self-injurious behavior.

Family/

Community

| Assess family need for social work support (e.g., palliative/respite care, home nursing, other local resources) care coordination.

Source: GeneReviews — "CHD2-Related Neurodevelopmental Disorders"