Diagnostic Criteria

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

Suggestive Findings

HNRNPU-NDD should be considered in individuals with the following clinical and brain MRI findings. Clinical findings (presenting in infancy or childhood). Moderate-to-severe developmental delay (DD) or intellectual disability (ID) AND any of the following:

• Generalized hypotonia of infancy

• Infant feeding difficulties

• Speech and language delay and/ or absent speech

• Autism spectrum disorder or autistic traits

• Nonspecific dysmorphic facial features (See .)

• Epilepsy, including generalized tonic-clonic seizures and absence seizures

• Short stature

• Strabismus

Brain MRI findings. The most common brain MRI findings are nonspecific but include:

Source: GeneReviews — "HNRNPU-Related Neurodevelopmental Disorder"

Differential Diagnosis

Because the phenotypic features associated with HNRNPU-related neurodevelopmental disorder are not sufficient to diagnose this condition, all disorders with epileptic encephalopathy and intellectual disability without other distinctive findings should be considered in the differential diagnosis. See OMIM Developmental and Epileptic Encephalopathy Phenotypic Series.

Source: GeneReviews — "HNRNPU-Related Neurodevelopmental Disorder"

Management Guidelines

No clinical practice guidelines for HNRNPU-related neurodevelopmental disorder (HNRNPU-NDD) have been published. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with HNRNPU-NDD, 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 HNRNPU-Related Neurodevelopmental Disorder

Source: GeneReviews — "HNRNPU-Related Neurodevelopmental Disorder"

Clinical Guidance

Avoid activities and agents that may induce seizures, as the majority of affected individuals have a seizure disorder.

Source: GeneReviews — "HNRNPU-Related Neurodevelopmental Disorder"

Therapies Under Investigation

Sustained single-dose gene therapy treatments for genetic forms of epilepsy, including HNRNPU-NDD, are currently being explored. This approach will be based on developing mRNA therapies and/or using a viral vector, such as AAV-9 (adeno-associated vector serotype 9), to deliver therapeutic protein to treat those forms of epilepsy caused by haploinsufficiency of proteins such as HNRNPU. 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.

Source: GeneReviews — "HNRNPU-Related Neurodevelopmental Disorder"

Surveillance Guidelines

Table 5.

Recommended Surveillance for Individuals with HNRNPU-Related Neurodevelopmental Disorder

System/Concern | Evaluation | Frequency

Growth/Feeding

| • Measurement of growth parameters

• Eval of nutritional status safety of oral intake

| At each visit

Gastrointestinal

| Monitor for constipation.

Neurologic

| • Monitor those w/seizures as clinically indicated.

• Assess for new manifestations such as seizures changes in tone.

Development

| Monitor developmental progress educational needs.

Psychiatric/

Behavioral

| Behavioral assessment for anxiety, attention, aggressive or self-injurious behavior

Respiratory

| Monitor for evidence of hyperventilation apnea.

Musculoskeletal

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

Family/

Community

| Assess family need for social work support (e.g., palliative/respite care, home nursing, other local resources) care coordination.

Eyes | Ophthalmologic eval | Annually or as clinically indicated

Hearing

| Audiologic eval

OT = occupational therapy; PT = physical therapy

Source: GeneReviews — "HNRNPU-Related Neurodevelopmental Disorder"