Clinical Guidance

Existing literature supports a genotype-phenotype correlation. Variants predicted to cause protein truncation are associated with a severe neurodevelopmental phenotype. Of 31 individuals with severe or profound ID, 26 were homozygous or compound homozygous for nonsense, frameshift, or splice site variants [, , , , , ]. Two were compound heterozygous for truncating and missense variants and three were homozygous for missense variants that were predicted to disrupt protein binding or folding .

Missense variants

Source: GeneReviews — "GNB5-Related Neurodevelopmental Disorder"

Diagnostic Criteria

No consensus clinical diagnostic criteria for GNB5-related neurodevelopmental disorder (GNB5-NDD) have been published.

Suggestive Findings

GNB5-NDD should be suspected in the following two age groups:

Source: GeneReviews — "GNB5-Related Neurodevelopmental Disorder"

Differential Diagnosis

Because the phenotypic features associated with GNB5-related 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, and Syndromic X-Linked Intellectual Developmental Disorder Phenotypic Series. For children with a phenotype consistent with infantile-onset epileptic encephalopathy, all genes known to be associated with early-infantile epileptic encephalopathy (see OMIM Phenotypic Series) should be included in the differential diagnosis.

Source: GeneReviews — "GNB5-Related Neurodevelopmental Disorder"

Management Guidelines

No clinical practice guidelines for GNB5-related neurodevelopmental disorder (GNB5-NDD) have been published. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with GNB5-related neurodevelopmental disorder, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 3. Recommended Evaluations Following Initial Diagnosis in Individuals with GNB5-Related Neurodevelopmental Disorder

Source: GeneReviews — "GNB5-Related Neurodevelopmental Disorder"

Clinical Guidance

Parasympathomimetics, which should be used with extreme caution because of the potential to cause asystole, are generally only used in the context of general anesthesia or treatment of glaucoma. Access to possible emergent pacing during general anesthesia would be advisable; however, a favorable response to isoprotenerol or epinephrine would be expected . Other drugs that can potentiate bradycardia, particularly beta blockers, are best avoided.

Source: GeneReviews — "GNB5-Related 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 — "GNB5-Related Neurodevelopmental Disorder"

Surveillance Guidelines

Table 5. Recommended Surveillance for Individuals with GNB5-Related Neurodevelopmental Disorder

Source: GeneReviews — "GNB5-Related Neurodevelopmental Disorder"