Clinical Guidance

No clear genotype-phenotype correlations have been identified to date in GRIA2-NDD. However, strong correlations have been observed between two specific recurrent pathogenic variants and the phenotypes of the affected individuals .

Source: GeneReviews — "GRIA2-Related Neurodevelopmental Disorder"

Diagnostic Criteria

Formal diagnostic criteria for GRIA2-related neurodevelopmental disorder (NDD) have not been established.

Suggestive Findings

GRIA2-NDD should be considered in a proband with the following clinical and brain MRI findings and family history.

Clinical findings

• Developmental delay (DD) and/or intellectual disability (ID) (present in all individuals)

AND any of the following features presenting in infancy or childhood:

• Body tone abnormalities

Source: GeneReviews — "GRIA2-Related Neurodevelopmental Disorder"

Differential Diagnosis

Because GRIA2-related neurodevelopmental disorder is associated with a broad phenotypic spectrum, all disorders with intellectual disability without other distinctive clinical features or 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. In persons with abnormal developmental milestones, epilepsy, and features resembling MECP2 disorders, the genes listed in may be of specific interest. Table 3. Selected Genes of Interest in the Differential Diagnosis of GRIA2-Related Neurodevelopmental Disorder

Management Guidelines

No clinical practice guidelines for GRIA2-related neurodevelopmental disorder (GRIA2-NDD) have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with GRIA2-NDD and similar disorders.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with GRIA2-NDD, the evaluations summarized (if not performed as part of the evaluation that led to diagnosis) are recommended.

Table 4.

GRIA2-Related Neurodevelopmental Disorder: Recommended Evaluations Following Initial Diagnosis

System/Concern | Evaluation | Comment

Constitutional

| Measure length/height, weight, OFC |

Neurologic

| Neurologic eval | To include:

• Brain MRI

• EEG if history of seizures

• Eval for movement disorders

• Eval for sleep apnea

Development

| Developmental assessment/ physical medicine rehab/ PT OT eval | To include assessment of:

• Motor, adaptive, cognitive, speech-language ability

• Mobility, ADL, need for adaptive devices

• Need for PT (to improve gross motor skills) /or OT (to improve fine motor skills

• Early intervention/ special education

• Speech therapy

Speech language

| Eval by speech-language therapist | Consider need for augmentative alternative communication (AAC)

Neurobehavioral/

Psychiatric

| Neuropsychiatric eval | For persons age 12 mos: screening for behavior concerns including ADHD, ASD

Musculoskeletal

| Orthopedics/ physical medicine rehab/ PT OT eval | To include assessment ...

Source: GeneReviews — "GRIA2-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 — "GRIA2-Related Neurodevelopmental Disorder"

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended.

Table 6.

GRIA2-Related Neurodevelopmental Disorder: Recommended Surveillance

System/Concern | Evaluation | Frequency

Feeding

| • Measurement of growth parameters (incl OFC)

• Eval of nutritional status safety of oral intake

| At each visit

Gastrointestinal

| • Monitor for constipation gastroesophageal reflux disease.

• Monitor feeding needs, esp in early infancy.

Respiratory

| Monitor for evidence of aspiration, respiratory insufficiency, or abnormal respiratory pattern (episodes of hyperventilation).

Neurologic

| • Monitor those w/seizures as clinically indicated.

• Assess for new manifestations such as seizures, changes in tone, or movement disorders.

Development

| Monitor developmental progress educational needs.

Neurobehavioral/

Psychiatric

| Behavioral assessment for anxiety, ADHD, ASD, aggression, self-injury

Musculoskeletal

| Physical medicine, OT/PT assessment of mobility, self-help skills

Ophthalmologic involvement

| Monitor those w/abnormal ocular motility or strabismus. | Per treating ophthalmologist(s)

Respiratory

| Monitor abnormal breathing patterns (irregular breathing hyperventilation episodes). | At each visit

Family/Community

| Assess family need for social work support (e.g., palliative/respite care, home nursing, other local resources), care coordination, or follow-up genetic counseling if new questions arise (e.g., family...

Source: GeneReviews — "GRIA2-Related Neurodevelopmental Disorder"