Clinical Guidance

SATB2 pathogenic variants

• More severe clinical phenotype. Using a clinical scoring rubric developed for SAS, individuals with the following types of SATB2 pathogenic variants have a more severe clinical phenotype [; Y Zarate, unpublished data] (see also satb2-portal.broadinstitute.org):

• Null pathogenic variants located after amino acid 350 (the start of the CUT1 domain)

• The recurrent missense pathogenic variant

• The and pathogenic variants

• Intragenic deletions

• Milder clinical phenotype. Missense pathogenic variants located outside the CUT1 or CUT2 domains lead to milder clinical presentations.

Source: GeneReviews — "SATB2-Associated Syndrome"

Diagnostic Criteria

No formal clinical diagnostic criteria have been established for SATB2-associated syndrome (SAS).

Suggestive Findings

SAS should be suspected in individuals with the following clinical and family history findings.

Clinical findings

• Typically moderate-to-profound developmental delay or intellectual disability, including severe speech delay and, in some, absence of speech; however, individuals with milder developmental delay affecting predominantly speech have been reported.

AND

Source: GeneReviews — "SATB2-Associated Syndrome"

Differential Diagnosis

In early infancy SATB2-associated syndrome (SAS) can be particularly difficult to diagnose when developmental delay, hypotonia, feeding difficulties, and palatal issues are the only observable features. During infancy and early childhood, many children with SAS are tested for Angelman syndrome and related disorders. Over time, the emergence of dental issues and distinctive behavioral issues along with lack of speech progression should lead clinicians to consider the diagnosis of SAS. Other syndromes that include developmental delay and dental abnormalities, such as KBG syndrome, can also be considered.

Table 3.

Disorders to Consider in the Differential Diagnosis of SATB2-Associated Syndrome

Source: GeneReviews — "SATB2-Associated Syndrome"

Management Guidelines

No consensus clinical practice guidelines for SATB2-associated syndrome (SAS) have been published. Some broad recommendations have been published , and dedicated neurologic and skeletal surveillance recommendations have been proposed based on two large cohort studies . In the absence of published consensus 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 SAS, the evaluations summarized (if not performed as part of the evaluation that led to diagnosis) are recommended.

Table 4.

SATB2-Associated Syndrome: Recommended Evaluations Following Initial Diagnosis

System/Concern | Evaluation | Comment

Constitutional

| Measurement of weight, length/height, growth velocity, head circumference | • To evaluate for poor growth

• SAS-specific growth charts are available.1

Neurologic

| Neurologic eval | • Consider head MRI to evaluate for brain malformations if clinical seizures are present.2

• Baseline EEG, preferably incl sleep stages to evaluate for ESES3

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 sleep disturbances, ADHD, anxiety, /or findings suggestive of ASD

ENT/Mouth

| Assess for palatal anomalies. | Referr...

Source: GeneReviews — "SATB2-Associated 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 — "SATB2-Associated 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. SATB2-Associated Syndrome: Recommended Surveillance

Source: GeneReviews — "SATB2-Associated Syndrome"