Clinical Guidance

The majority of CHD4 variants are missense substitutions that fall in the ATPase / C terminal helicase domain (amino acids 724-1281). Data to date are insufficient to support genotype-phenotype correlations.

Source: GeneReviews — "CHD4 Neurodevelopmental Disorder"

Penetrance

Because the vast majority of individuals with CHD4-NDD reported to date have de novo variants, it is currently thought the penetrance is close to 100%.

Source: GeneReviews — "CHD4 Neurodevelopmental Disorder"

Diagnostic Criteria

Formal diagnostic criteria for CHD4 neurodevelopmental disorder (CHD4-NDD) have not been established.

Suggestive Findings

CHD4-NDD should be considered in individuals with the following clinical and brain MRI findings. Clinical findings. Developmental delay or mild-to-moderate intellectual disability AND any of the following features presenting in infancy or childhood:

Source: GeneReviews — "CHD4 Neurodevelopmental Disorder"

Differential Diagnosis

Because the phenotypic features associated with CHD4 neurodevelopmental disorder are not sufficient to diagnose this condition, all disorders with intellectual disability without other distinctive findings should be considered in the differential diagnosis. See OMIM Autosomal Dominant, Autosomal Recessive, Nonsyndromic X-Linked, and Syndromic X-Linked Intellectual Developmental Disorder Phenotypic Series.

Source: GeneReviews — "CHD4 Neurodevelopmental Disorder"

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with CHD4 neurodevelopmental disorder (CHD4-NDD), 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 CHD4 Neurodevelopmental Disorder

Source: GeneReviews — "CHD4 Neurodevelopmental Disorder"

Clinical Guidance

Avoid activities that involve rapid neck motion and/or possible trauma to the head and neck region (e.g., contact sports or thrill rides at amusement parks) because of the possible increased risk for cervical spine instability.

Source: GeneReviews — "CHD4 Neurodevelopmental Disorder"

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 — "CHD4 Neurodevelopmental Disorder"

Surveillance Guidelines

Table 5. Recommended Surveillance for Individuals with CHD4 Neurodevelopmental Disorder

Source: GeneReviews — "CHD4 Neurodevelopmental Disorder"