Clinical Guidance

STXBP1 encephalopathy with epilepsy is characterized by developmental delay, intellectual disability or cognitive dysfunction, and epilepsy. To date, about 500 affected individuals have been reported [, , , , , , , , , , , , , , ]. Table 2. STXBP1 Encephalopathy with Epilepsy: Frequency of Select Features

Clinical Guidance

In more than 50 individuals with STXBP1 encephalopathy with epilepsy, no correlation was found between phenotype and the type of pathogenic variant (including splice, nonsense, deletion/duplication, or missense variant) . In 147 individuals, no correlation between the severity of cognitive dysfunction or response to ASM and the type of pathogenic variant (missense or truncating) was identified . In a study of recurrent pathogenic variants (, , , , ) identified in more than ten individuals with STXBP1 encephalopathy with epilepsy, there were no identifiable genotype-phenotype correlations for these variants. Individuals with protein-truncating variants and deletions in STXBP1 showed significant phenotypic similarities.

Source: GeneReviews — "STXBP1 Encephalopathy with Epilepsy"

Penetrance

STXBP1 encephalopathy with epilepsy is expected to be completely penetrant.

Source: GeneReviews — "STXBP1 Encephalopathy with Epilepsy"

Diagnostic Criteria

Suggestive Findings

STXBP1 encephalopathy with epilepsy should be considered in individuals with early-onset refractory seizures, developmental delay, and intellectual disability or cognitive dysfunction, particularly those with the following epilepsy features and seizure types.

Epilepsy features

• Median age of onset six weeks (range: 1 day to 13 years)

• EEG characterized by focal epileptic activity, burst suppression, hypsarrhythmia, or generalized spike-and-slow waves

Seizure types

• Infantile spasms

• Generalized tonic-clonic, clonic, or tonic seizures

• Myoclonic seizures

• Atonic seizures

• Absence seizures

• Focal seizures

Other features

Source: GeneReviews — "STXBP1 Encephalopathy with Epilepsy"

Differential Diagnosis

The phenotypic features (both clinical and electrophysiologic) associated with STXBP1 encephalopathy with epilepsy are not sufficient to diagnose this condition. All genes known to be associated with developmental and epileptic encephalopathy (100 have been identified; see OMIM Phenotypic Series) should be included in the differential diagnosis. Treatable neurometabolic disorders causing early infantile-onset epileptic encephalopathy should be included in the differential diagnosis. These disorders include:

• Vitamin B6-dependent epilepsies (See Pyridoxine-Dependent Epilepsy – ALDH7A1, PNPO Deficiency, and PLPBP Deficiency.)

• Biotinidase deficiency

• Glucose transporter 1 deficiency syndrome

Source: GeneReviews — "STXBP1 Encephalopathy with Epilepsy"

Management Guidelines

No clinical practice guidelines for STXBP1 encephalopathy with epilepsy have been published. Evaluations Following Initial Diagnosis To establish the extent of disease and needs of an individual diagnosed with STXBP1 encephalopathy with epilepsy, the evaluations summarized (if not performed as part of the evaluation that led to diagnosis) are recommended. Table 3. STXBP1 Encephalopathy with Epilepsy: Recommended Evaluations Following Initial Diagnosis

Source: GeneReviews — "STXBP1 Encephalopathy with Epilepsy"

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 — "STXBP1 Encephalopathy with Epilepsy"

Surveillance Guidelines

There are no published guidelines for surveillance of individuals diagnosed with STXBP1 encephalopathy with epilepsy. The following assessments and investigations can be performed as needed .

Table 5.

STXBP1 Encephalopathy with Epilepsy: Recommended Surveillance

System/Concern | Evaluation | Frequency

Development

| Monitor developmental progress educational needs. | At each visit

OT PT assessments to optimize functional outcomes | As needed

Neurologic

| • Monitor those w/seizures as clinically indicated.

• Assess for new manifestations such as seizures,1 changes in tone, or movement disorders.

| At each visit

EEG | As needed

Neurobehavioral/

Psychiatric

| Behavioral assessment for ASD, ADHD, aggression, self-injury, sleep disturbances | At each visit

Feeding

| • Measurement of growth parameters

• Eval of nutritional status safety of oral intake

Gastrointestinal

| Assess for constipation.

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 planning).

ADHD = attention-deficit/hyperactivity disorder; ASD = autism spectrum disorder; OT = occupational therapy; PT = physical therapy

1. 38% of individuals who became seizure-free in childhood or adolescence had seizure recurrence later in life.

Source: GeneReviews — "STXBP1 Encephalopathy with Epilepsy"