Penetrance

The penetrance of SETD1B-NDD is predicted to be high. To date, no individuals have been confirmed to have inherited a pathogenic variant from an unaffected parent, and one individual inherited a pathogenic variant from an affected parent .

Source: GeneReviews — "SETD1B-Related Neurodevelopmental Disorder"

Diagnostic Criteria

Suggestive Findings

SETD1B-related neurodevelopmental disorder (SETD1B-NDD) should be considered in individuals with the following clinical findings:

• Developmental delay (especially speech and language delay)

• Intellectual disability (ID)

• Seizures that are frequently refractory to treatment

• Autism spectrum disorder or autism-like behaviors

• Other behavioral concerns (hyperactivity, aggression, anxiety, sleep disorders)

Establishing the Diagnosis

The diagnosis of SETD1B-NDD is established in a proband with and a heterozygous pathogenic (or likely pathogenic) variant in SETD1B identified by molecular genetic testing . Note: (1) Per ACMG/AMP variant interpretation guidelines, the terms "pathogenic variant" and "likely pathogenic variant" are synonymous in a clinical setting, meaning that both are c...

Source: GeneReviews — "SETD1B-Related Neurodevelopmental Disorder"

Differential Diagnosis

Because the phenotypic features associated with SETD1B-related neurodevelopmental disorder 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.

Source: GeneReviews — "SETD1B-Related Neurodevelopmental Disorder"

Management Guidelines

No clinical practice guidelines for SETD1B-related neurodevelopmental disorder (SETD1B-NDD) have been published. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with SETD1B-NDD, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 3. Recommended Evaluations Following Initial Diagnosis in Individuals with SETD1B-Related Neurodevelopmental Disorder

Source: GeneReviews — "SETD1B-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 — "SETD1B-Related Neurodevelopmental Disorder"

Surveillance Guidelines

Table 5.

Recommended Surveillance for Individuals with SETD1B-Related Neurodevelopmental Disorder

System/Concern | Evaluation | Frequency

Feeding

| • Measurement of growth parameters

• Eval of nutritional status safety of oral intake

| At each visit

Development

| Monitor developmental progress educational needs. | • At each visit

• Persons w/SETD1B-NDD may demonstrate developmental regression, even in absence of seizures, normal initial eval should not preclude continued monitoring support during early childhood.

Neurologic

| • Monitor those w/seizures as clinically indicated.

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

| At each visit

Neurobehavioral/

Psychiatric

| Assessment for anxiety, attention, aggressive or self-injurious behavior

Musculoskeletal

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

Sleep

| Assess for sleep disturbance.

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).

OT = occupational therapy; PT = physical therapy

Source: GeneReviews — "SETD1B-Related Neurodevelopmental Disorder"