Clinical Guidance

No clear clinically relevant genotype-phenotype correlations have been noted; however, all individuals with a pathogenic variant within the C-terminal helicase region of the ATPase domain have severe intellectual disability and epilepsy, a frequency higher than that in individuals with pathogenic variants in other parts of the gene. More than half of all individuals with SMARCA2-NCBRS reported have a pathogenic variant within the C-terminal helicase region .

Source: GeneReviews — "SMARCA2-Related Nicolaides-Baraitser Syndrome"

Diagnostic Criteria

Consensus clinical diagnostic criteria for SMARC2-related Nicolaides-Baraitser syndrome (SMARC2-NCBRS) have not been established.

Suggestive Findings

SMARCA2-NCBRS should be considered in probands with the following clinical and radiographic findings and family history.

Clinical findings

• Developmental delay/ intellectual disability (DD/ID), most commonly in the severe range but with some having either mild or moderate DD/ID

• Sparse scalp hair

• Prominence of the interphalangeal joints and distal phalanges secondary to poor subcutaneous fat distribution (See and .)

• Characteristic facial features (see , Facial features) that can be subtle in the newborn period and in early childhood, with coarsening of the face and increased skin wrinkling over time (See .)

• Microcephaly

• Seizures

Source: GeneReviews — "SMARCA2-Related Nicolaides-Baraitser Syndrome"

Differential Diagnosis

Genetic disorders of interest in the differential diagnosis of SMARCA2-related Nicolaides-Baraitser syndrome (SMARCA2-NCBRS) are listed in .

Table 3.

Genes of Interest in the Differential Diagnosis of SMARCA2-Related Nicolaides-Baraitser Syndrome

Gene(s) | Disorder | MOI | Features Overlapping w/SMARCA2-NCBRS | Features Distinguishing from SMARCA2-NCBRS

ARID1A

ARID1B

ARID2

DPF2

SMARCA4

SMARCB1

SMARCC2

SMARCE1

SOX4

SOX11

| Coffin-Siris syndrome (CSS)1 | AD2 | Coarse facial features that can be similar to those in SMARCA2-NCBRS | • Digital findings are particularly helpful in differentiating these disorders: persons w/SMARCA2-NCBRS uniquely have prominent interphalangeal joints do not have hypoplasia of the 5th digits.

Source: GeneReviews — "SMARCA2-Related Nicolaides-Baraitser Syndrome"

Management Guidelines

No clinical practice guidelines for SMARCA2-related Nicolaides-Baraitser syndrome (SMARCA2-NCBRS) have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with this disorder.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with SMARCA2-NCBRS, the evaluations summarized (if not performed as part of the evaluation that led to diagnosis) are recommended.

Table 4:

SMARCA2-Related Nicolaides-Baraitser Syndrome: Recommended Evaluations Following Initial Diagnosis

System/Concern | Evaluation | Comment

Constitutional

| Measure growth parameters, incl head circumference | To assess for microcephaly short stature

Neurologic

| Neurologic eval | Consider EEG if seizures are a concern.

Development

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

• Eval for early intervention/ special education

Neurobehavioral/

Psychiatric

| Neuropsychiatric eval | For persons age 12 mos: screening for concerns incl behavioral issues /or findings suggestive of ASD

Musculoskeletal

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

• Gross motor fine motor skills

• Mobility, ADL, need for adaptive devices

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

Gastrointestinal/

Feeding

| Gastroenterology/ nutrition/ feeding team eval | • To incl eval of aspiration risk nutritional sta...

Source: GeneReviews — "SMARCA2-Related Nicolaides-Baraitser 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 — "SMARCA2-Related Nicolaides-Baraitser Syndrome"

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. SMARCA2-Related Nicolaides-Baraitser Syndrome: Recommended Surveillance

Source: GeneReviews — "SMARCA2-Related Nicolaides-Baraitser Syndrome"