Clinical Guidance

In general, pathogenic missense variants affecting the atrophin-1 domain of RERE are associated with an increased risk of structural eye defects, congenital heart defects, genitourinary anomalies, and sensorineural hearing loss when compared with loss-of-function variants . This suggests that some changes in this domain may represent dominant negative alleles. The , p.(Leu1438_His1439dup) variant is associated with a unique phenotypic presentation that includes many features commonly seen in individuals with CHARGE syndrome including coloboma, choanal atresia, congenital heart defects, growth deficiency, genitourinary anomalies, and DD/ID.

Source: GeneReviews — "RERE-Related Disorders"

Diagnostic Criteria

No clinical diagnostic criteria have been published.

Suggestive Findings

RERE-related disorders should be considered in individuals presenting with the following clinical and brain MRI findings. Clinical findings. Mild-to-profound developmental delay, intellectual disability, and/or autism spectrum disorder; AND any of the following features presenting in infancy or childhood:

Source: GeneReviews — "RERE-Related Disorders"

Differential Diagnosis

Because the phenotypic features associated with RERE-related disorders 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.

Table 2.

Disorders to Consider in the Differential Diagnosis of RERE-Related Disorders

Disorder | Gene / Genetic Mechanism | MOI | Clinical Features of Differential Diagnosis Disorder

Overlapping w/RERE-related disorders | Distinguishing from RERE-related disorders

CHARGE syndrome

| CHD7 | AD | • Colobomata, congenital heart defects, choanal atresia, ear anomalies, genitourinary anomalies

Source: GeneReviews — "RERE-Related Disorders"

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with RERE-related disorders, 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 RERE-Related Disorders

Source: GeneReviews — "RERE-Related 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 — "RERE-Related Disorders"

Surveillance Guidelines

Table 5. Recommended Surveillance for Individuals with RERE-Related Disorders

Source: GeneReviews — "RERE-Related Disorders"