Clinical Guidance

The type and location of pathogenic variants in CREBBP and EP300 do not correlate with specific physical features, malformations, cognition, or behavior. An exception is missense variants between the end of exon 30 and the beginning of exon 31 in both CREBBP and EP300. This phenotype is distinct from RSTS and is known as Menke-Hennekam syndrome . EP300. In one study examining many variants, no correlation was found between overall phenotype severity and the type of pathogenic variant or location of the pathogenic variant relative to the HAT domain or exon 31. Similar observations were made between genotype and severity of intellectual disability and presence of major organ difference . CREBBP.

Source: GeneReviews — "Rubinstein-Taybi Syndrome"

Diagnostic Criteria

Suggestive Findings

Rubinstein-Taybi syndrome (RSTS) should be suspected in individuals with the following characteristic clinical and neuroimaging findings and family history.

Major features

• Craniofacial appearance (See .)

• Downslanted palpebral fissures

• Convex nasal ridge with low-hanging columella

• High palate

• Grimacing smile

• Talon cusps (an accessory cusp-like structure on the lingual side of the tooth), usually occurring on the maxillary incisors of the permanent dentition

Other features (See and .)

Source: GeneReviews — "Rubinstein-Taybi Syndrome"

Differential Diagnosis

For individuals with the distinctive facial features and hand and foot abnormalities, the diagnosis of Rubinstein-Taybi syndrome (RSTS) is usually straightforward. Broad/angulated thumbs and halluces may be seen in the FGFR-related craniosynostosis syndromes (e.g., Pfeiffer syndrome, Apert syndrome), in Saethre-Chotzen syndrome, and in Greig cephalopolysyndactyly syndrome. The presence of craniosynostosis and the difference in facial features should differentiate these disorders .

Table 3.

Genes of Interest in the Differential Diagnosis of Rubinstein-Taybi Syndrome

Gene(s) | Disorder | MOI | Features of Disorder

Overlapping w/RSTS | Distinguishing from RSTS

FGFR1

FGFR2

FGFR3

| Pfeiffer syndrome Apert syndrome (See FGFR-Related Craniosynostosis Syndromes Overview.) | AD | Broad/angulated thumbs hal...

Source: GeneReviews — "Rubinstein-Taybi Syndrome"

Management Guidelines

Clinical practice guidelines for Rubinstein-Taybi Syndrome (RSTS) have been published by .

Evaluations Following Initial Diagnosis

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

Table 4.

Rubinstein-Taybi Syndrome: Recommended Evaluations Following Initial Diagnosis

System/Concern | Evaluation | Comment

Constitutional

| Measurement of growth | Plot parameters on RSTS growth charts.

Neurologic

| • Neurologic eval

• Ultrasound of spinal canal in neonatal period should be considered to screen for tethered cord.

| • MRI of spinal canal should be performed in older children if symptomatic.

• Consider EEG if seizures are a concern.

Development

| Multidisciplinary developmental /or neuropsychological eval | • 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

Musculoskeletal

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

• Thumbs halluces, joints, spine

• Gross motor fine motor skills

• Contractures, clubfoot, kyphoscoliosis

• 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 | •...

Source: GeneReviews — "Rubinstein-Taybi 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 — "Rubinstein-Taybi 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. Rubinstein-Taybi Syndrome: Recommended Surveillance

Source: GeneReviews — "Rubinstein-Taybi Syndrome"