Clinical Guidance

Pathogenic variants that affect the ATRX zinc finger domain produce severe psychomotor impairment and urogenital anomalies, whereas pathogenic variants in the helicase domains cause milder phenotypes . More severe genital anomalies occur with variants in the plant homeodomain-like domain. A nonsense variant in exon 2 appears to be a common pathogenic variant that results in an overall milder phenotype .

Source: GeneReviews — "Alpha-Thalassemia X-Linked Intellectual Disability Syndrome"

Diagnostic Criteria

Alpha-thalassemia X-linked intellectual disability (ATR-X) syndrome should be suspected in individuals with the following clinical findings, hematologic findings, and family history.

Clinical findings

Source: GeneReviews — "Alpha-Thalassemia X-Linked Intellectual Disability Syndrome"

Differential Diagnosis

Table 3. Genes of Interest in the Differential Diagnosis of Alpha-Thalassemia X-Linked Intellectual Disability Syndrome

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with alpha-thalassemia X-linked intellectual disability (ATR-X) syndrome, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 4.

Recommended Evaluations Following Initial Diagnosis in Individuals with ATR-X Syndrome

System/Concern | Evaluation | Comment

Growth

| Assess height, weight, head circumference | In infants children

Development

| Developmental assessment | • To incl motor, adaptive, cognitive, speech-language eval

• Eval for early intervention/ speech therapy/ PT OT/ special education

Neurologic

| Neurologic eval | • To assess muscle tone, evidence for spasticity ( reflexes, Babinski response)

• To incl EEG MRI if seizures a concern

Gastrointestinal/

Feeding

| Gastroenterology/ nutrition/ feeding team eval | For:

• Nutritional status

• Swallowing difficulties aspiration risk

• GERD /or recurrent vomiting

• Gastric pseudo-obstruction

• Constipation

Genital

abnormalities | Physical exam for evidence of a disorder of genital development such as cryptorchidism, hypospadias, ambiguous genitalia, normal female external genitalia in 46,XY individuals | Consultation w/pediatric urologist if surgical intervention required

Musculoskeletal

| Orthopedics/ physical medicine rehab/ PT OT eval | To incl assessment of:

Source: GeneReviews — "Alpha-Thalassemia X-Linked Intellectual Disability 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 — "Alpha-Thalassemia X-Linked Intellectual Disability Syndrome"

Surveillance Guidelines

Table 6. Recommended Surveillance for Individuals with ATR-X Syndrome

Source: GeneReviews — "Alpha-Thalassemia X-Linked Intellectual Disability Syndrome"