Clinical Guidance

Truncating pathogenic variants (frameshift or stop-gain) have been reported to span across the length of the gene.

• Truncating pathogenic variants that arise near the N terminus of the protein have been associated with a statistically significant higher risk of developing seizures and scoliosis .

• Similarly, truncating pathogenic variants at the C terminus of the protein are less likely to be associated with the development of seizures or scoliosis.

Missense variants. There are at least ten individuals with clinical features of XGS who have de novo missense variants within AHDC1 that are presumed to be pathogenic .

Source: GeneReviews — "Xia-Gibbs Syndrome"

Diagnostic Criteria

No consensus clinical diagnostic criteria for Xia-Gibbs syndrome (XGS) have been published.

Suggestive Findings

XGS should be considered in individuals with the following clinical and brain MRI findings. Clinical findings. Early-onset moderate-to-profound developmental delay (DD) or intellectual disability (ID) AND any of the following features presenting in infancy or childhood:

• Neurologic issues, including:

• Generalized hypotonia of infancy

• Epilepsy

• Ataxia

• Nystagmus

• Developmental issues, including:

• Delayed motor milestones

• Speech delay

• Autism spectrum disorder (ASD)

• Respiratory issues, including:

• Obstructive sleep apnea

• Tracheomalacia

• Laryngomalacia

• Scoliosis

• Short stature

• Strabismus

• Dysmorphic features (See .)

Brain MRI findings

Source: GeneReviews — "Xia-Gibbs Syndrome"

Differential Diagnosis

Because the clinical presentation of Xia-Gibbs syndrome (XGS) is typically nonspecific developmental delay (DD) and intellectual disability (ID), the phenotypic features alone are not sufficient to diagnose this condition. XGS should be considered as a differential diagnosis for individuals presenting with unexplained ID and DDs. All disorders associated with ID without other distinctive findings and childhood onset behavior disorder (particularly when associated with mild dysmorphic features, sleep apnea, seizures, or scoliosis) 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 — "Xia-Gibbs Syndrome"

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with Xia-Gibbs syndrome (XGS), 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 Xia-Gibbs Syndrome

Source: GeneReviews — "Xia-Gibbs Syndrome"

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 — "Xia-Gibbs Syndrome"

Surveillance Guidelines

Table 5. Recommended Surveillance for Individuals with Xia-Gibbs Syndrome

Source: GeneReviews — "Xia-Gibbs Syndrome"