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Rubinstein-Taybi Syndrome

Synonym: Broad Thumb-Hallux Syndrome

, MD.

Author Information and Affiliations

Initial Posting: ; Last Update: November 9, 2023.

Estimated reading time: 34 minutes


Clinical characteristics.

Rubinstein-Taybi syndrome (RSTS) is characterized by distinctive facial features, broad and often angulated thumbs and halluces, short stature, and moderate-to-severe intellectual disability. Characteristic craniofacial features include downslanted palpebral fissures, low-hanging columella, high palate, grimacing smile, and talon cusps. Prenatal growth is often normal, then height, weight, and head circumference percentiles rapidly drop in the first few months of life. Short stature is typical in adulthood. Obesity may develop in childhood or adolescence. Average IQ ranges between 35 and 50; however, developmental outcome varies considerably. Some individuals with EP300-related RSTS have normal intellect. Additional features include ocular abnormalities, hearing loss, respiratory difficulties, congenital heart defects, renal abnormalities, cryptorchidism, feeding problems, recurrent infections, and severe constipation.


The diagnosis of RSTS is established in a proband with characteristic clinical features. A heterozygous pathogenic variant in CREBBP or EP300 identified by molecular genetic testing confirms the diagnosis if clinical features are inconclusive.


Treatment of manifestations: Early intervention programs, special education, vocational training to address developmental disabilities, referral to behavioral specialists / psychologists, and support groups / resources for family members; standard treatment for eye abnormalities, hearing loss, sleep apnea, cardiac anomalies, renal anomalies, cryptorchidism, and dental anomalies; aggressive management of gastroesophageal reflux and constipation; surgical repair of significantly angulated thumbs or duplicated halluces.

Surveillance: Monitoring of growth and feeding, especially in the first year of life; annual eye and hearing evaluations; routine monitoring for cardiac, renal, and dental anomalies.

Pregnancy management: Preeclampsia or placental abnormalities have been reported in some pregnancies with RSTS.

Genetic counseling.

RSTS is inherited in an autosomal dominant manner. Most individuals diagnosed with RSTS have the disorder as the result of a de novo pathogenic variant and are the only affected member of their families. Rarely, an individual diagnosed with RSTS has the disorder as the result of a CREBBP or EP300 pathogenic variant inherited from a heterozygous or mosaic parent. Each child of an individual with RSTS has a 50% chance of inheriting the RSTS-related pathogenic variant. Once the RSTS-related pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing for RSTS are possible.


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 Figure 1.)
  • 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
Figure 1. . Typical facial appearance in individuals with RSTS.

Figure 1.

Typical facial appearance in individuals with RSTS. Note arched brows, downslanted palpebral fissures, low-hanging columella, and grimacing smile.

Other features (See Figure 2 and Figure 3.)

Figure 2.

Figure 2.

Broad terminal phalanges (A) and broad, radially deviated thumbs (B)

Figure 3.

Figure 3.

Broad, partially duplicated halluces

  • The thumbs and halluces are almost always broad and often angulated.
  • The distal phalanges of the fingers may appear broad.
  • The proximal phalanges may be abnormally shaped. Radiographs of the hands and feet in individuals with RSTS are unusual but not necessarily diagnostic.
  • Most males have undescended testes.
  • Structural abnormalities of the urinary tract are common.
  • Congenital heart defects of various types occur in approximately one third of individuals.


  • While prenatal growth is often normal, height, weight, and head circumference percentiles rapidly drop in the first few months of life. Short stature is typical in adulthood. Absence of the pubertal growth spurt adds to the reduced final height for males and females.
  • Microcephaly is present within the first few months of life and typically persists into adulthood.
  • Obesity may develop, particularly in adolescence or adulthood.

Intellectual disability. The average IQ ranges between 35 and 50; however, developmental outcome varies considerably. Some individuals with EP300-related RSTS have normal intellect.

Neuroimaging findings. The most common feature on brain imaging is a dysmorphic or dysplastic corpus callosum (73.6%).

Family history. Because Rubinstein-Taybi syndrome is typically caused by a de novo pathogenic variant, most probands represent a simplex case (i.e., a single occurrence in a family). Rarely, the family history may be consistent with autosomal dominant inheritance (e.g., affected males and females in multiple generations).

Establishing the Diagnosis

The diagnosis of RSTS is established in a proband with the aforementioned suggestive findings. Identification of one of the following on molecular genetic testing can confirm the diagnosis especially if clinical features are inconclusive (see Table 1):

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 considered diagnostic and can be used for clinical decision making [Richards et al 2015]. Reference to "pathogenic variants" in this GeneReview is understood to include likely pathogenic variants. (2) Identification of a heterozygous variant of uncertain significance does not establish or rule out the diagnosis.

Molecular genetic testing approaches can include gene-targeted testing (multigene panel, chromosomal microarray analysis) and comprehensive genomic testing (exome sequencing, exome array, genome sequencing) depending on the phenotype.

Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Because the phenotype of RSTS is broad, individuals with the distinctive findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those with a phenotype indistinguishable from other inherited disorders with similar features are more likely to be diagnosed using genomic testing (see Option 2).

Option 1

When the phenotypic and laboratory findings suggest the diagnosis of RSTS, molecular genetic testing approaches can include a multigene panel. Chromosomal microarray analysis can be useful in some situations.

  • A multigene panel that includes CREBBP, EPP300, and other genes of interest (See Differential Diagnosis) is most likely to identify the genetic cause of the condition while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.
    For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
  • Chromosomal microarray analysis (CMA) uses oligonucleotide or SNP arrays to detect genome-wide large deletions/duplications (including CREBBP and EP300) that cannot be detected by sequence analysis.
    Note: (1) Since a significant proportion of CREBBP pathogenic variants are large deletions, RSTS may be diagnosed by CMA performed without prior consideration of a diagnosis of RSTS. (2) Clinical features associated with contiguous gene deletions involving CREBBP that have limited phenotypic overlap with RSTS have been reported (see Genetically Related Disorders).
    For an introduction to CMA click here. More detailed information for clinicians ordering genetic tests can be found here.

Option 2

Comprehensive genomic testing does not require the clinician to determine which gene is likely involved. Exome sequencing is most commonly used; genome sequencing is also possible. To date, the majority of reported CREBBP and EP300 pathogenic variants to date are within the coding region and are likely to be identified on exome sequencing.

For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.

Table 1.

Molecular Genetic Testing Used in Rubinstein-Taybi Syndrome

Gene 1, 2Proportion of RSTS Attributed to Pathogenic Variants in GeneProportion of Probands with a Pathogenic Variant 3 Detectable by Method
Sequence analysis 4Gene-targeted deletion/duplication analysis 5
CREBBP 55%-60% 6~88% 7~12% 7
EP300 8%-10% 8~93% 9~7% 9
Unknown 10~30%

RSTS = Rubinstein-Taybi syndrome


Genes are listed in alphabetic order.


See Molecular Genetics for information on variants detected in these genes.


Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include missense, nonsense, and splice site variants and small intragenic deletions/insertions; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.


Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. Gene-targeted deletion/duplication testing will detect deletions ranging from a single exon to the whole gene; however, breakpoints of large deletions and/or deletion of adjacent genes may not be detected by these methods (see Genetically Related Disorders). Exome and genome sequencing may be able to detect deletions/duplications using breakpoint detection or read depth; however, sensitivity can be lower than gene-targeted deletion/duplication analysis.


Pérez-Grijalba et al [2019]; data also derived from the subscription-based professional view of Human Gene Mutation Database [Stenson et al 2020]


RSTS may be caused by pathogenic variants in other genes in up to 30% of individuals [Fergelot et al 2016].

Clinical Characteristics

Clinical Description

Rubinstein-Taybi syndrome (RSTS) is a multisystem disorder characterized by short stature, variable structural abnormalities, characteristic facial appearance, broad thumbs and halluces, and variable degrees of intellectual disability. The most consistent craniofacial features are microcephaly, highly arched eyebrows, downslanted palpebral fissures, convex nasal ridge, low-hanging columella, and grimacing smile. The thumbs and halluces are broad and often angulated [Hennekam et al 1990, Stevens et al 1990].

RSTS is frequently recognized at birth or in infancy because of the striking facial features and characteristic hand and foot findings. Problems in early life include respiratory difficulties, feeding issues, poor weight gain, recurrent infections, and severe constipation.

To date, at least 600 individuals have been identified with a pathogenic variant in CREBBP or EP300 [Fergelot et al 2016, Pérez-Grijalba et al 2019, Cross et al 2020, Douzgou et al 2022]. The following description of the phenotypic features associated with this condition is based on these reports.

Table 2.

Select Features of Rubinstein-Taybi Syndrome

Feature% of Persons w/FeatureComment
Growth deficiency73%
Eye findings80%
Hearing loss30%Mostly conductive, but can also be sensorineural
Respiratory featuresCommonInfections, aspiration
Cardiac features33%
Genitourinary anomalies27%Cryptorchidism most common (~78%-100% of affected males)
Gastrointestinal features88%Feeding difficulties, constipation
Skeletal abnormalitiesCommon20% scoliosis, 92% thumb/hallux anomalies
Neurologic issues21%
Dental anomalies73%Talon cusps, enamel hypoplasia
Skin findings24%Keloids, pilomatrixomas
Recurrent infections17%Primarily respiratory
Tumors30%Benign and malignant
Developmental delays98%
Behavioral issues41% autism/autistic features, 27%-64% anxiety
Brain MRI abnormalities74%Various findings

Growth. Although prenatal growth is usually normal, growth deficiency begins in the first year of life. There is typically an absence of a growth spurt in adolescence. A higher incidence of microcephaly and growth restriction has been noted in infants with EP300 pathogenic variants, possibly related to the increased incidence of preeclampsia.

While body mass index is normal for males at age 21, it is increased for females at this age. Many adults develop obesity of unclear etiology [Stevens et al 2011].

Average height for adult males is 162.6 cm and for adult females is 151.0 cm [Beets et al 2014]. Beets et al [2014] published growth charts for RSTS.

Eye findings include strabismus, refractory errors, ptosis, nasolacrimal duct obstruction, cataracts, coloboma, nystagmus, congenital glaucoma, and corneal and retinal abnormalities.

Hearing loss. Recurrent or refractory middle ear disease can result in conductive hearing loss. Sensorineural hearing loss may also be seen.

Respiratory. Obstructive sleep apnea commonly occurs and may be caused by the combination of a narrow palate, micrognathia, hypotonia, obesity, and easy collapsibility of the laryngeal walls. There are reported incidences of intubation problems due to facial anatomy and laryngo-, tracheo-, and bronchomalacia and anesthesia complications. These include arrhythmias and obstructive symptoms occurring post extubation. Aspiration, asthma, and recurrent upper respiratory infections may also occur. Interstitial lung disease has also been reported in several individuals [Bradford et al 2022].

Cardiac. Approximately one third of affected individuals have congenital heart defects (e.g., atrial septal defect, ventricular septal defect, patent ductus arteriosus, coarctation of the aorta, pulmonary stenosis, bicuspid aortic valve, pseudotruncus arteriosus, aortic stenosis, vascular ring, conduction abnormalities).

Genitourinary. Renal abnormalities, including hydronephrosis and duplications of the renal system, are very common. Other genitourinary complications include hypospadias, vesicoureteral reflux, nephrolithiasis, and urinary tract infections. Most boys have undescended testes.

Gastrointestinal. Feeding problems, gastroesophageal reflux, and constipation are very common. Intestinal malrotation should be suspected if there is bilious vomiting, recurrent abdominal pain, failure to pass stool, or bloody stools [Stevens 2015]. Anorectal malformations have also been reported [Belanger Deloge et al 2023].

Orthopedic. In addition to angulated thumbs and duplicated halluces, orthopedic issues include dislocated patellae, lax joints, spine curvatures, Legg-Perthes disease, increased fracture risk, and cervical vertebral abnormalities.

Neurologic. The most common intracranial malformation involves abnormal structure of the corpus callosum. Occasional craniospinal and posterior fossa abnormalities including Chiari malformation, Dandy-Walker malformation, syringomyelia, os odontoideum, and cervical cord compression have been reported [Marzuillo et al 2013]. There may also be spinal cord tethering or lipoma. Seizures or abnormal EEG findings can occur.

Dental. Dental problems include crowding of teeth, malocclusion, multiple caries, hypodontia, hyperdontia, natal teeth, and talon cusps (most commonly on the upper incisors of the secondary dentition).

Skin. Keloids may occur with only minimal trauma to the skin. Pilomatrixomas (sometimes multiple) are relatively common [Boot et al 2018]. Ingrown nails are common, especially in the partially duplicated thumbs and halluces.

Recurrent infection is reported in some individuals; infections include otitis media, pneumonia, and other respiratory infections. There are reports of individuals with humoral or cellular immunodeficiency.

Tumors. There are early reports of various benign and malignant tumors in individuals with RSTS including neuroblastoma, rhabdomyosarcoma, medulloblastoma, and hematologic malignancies. A study of Dutch individuals with RSTS did not confirm an increased risk for malignancies. However, the incidence of meningiomas and pilomatrixomas was significantly elevated [Boot et al 2018]. There are currently no recommendations for additional surveillance for malignancy before the age of 40 years.

Endocrine. Persistent hyperinsulinemic hypoglycemia has been reported in a few children with RSTS, primarily in those with EP300 pathogenic variants [Welters et al 2019].

Puberty. Puberty and sexual development are typically normal.

Development and intellect. Delayed development is typical in children with RSTS. In one study, the average age of walking was 30 months, first words 25 months, and toilet training 62 months [Stevens et al 1990]. Speech delay occurs in 90% of children and some remain largely nonverbal. Waite et al [2016] noted deficits in verbal and visuospatial working memory.

The average IQ of affected individuals in one study was 51 and in another study 36 [Stevens et al 1990, Hennekam et al 1992]. IQ scores range from 25 to 79. Performance IQ is usually higher than verbal IQ [Stevens et al 1990, Hennekam et al 1992]. Some individuals with EP300-related RSTS have normal intellect [Fergelot et al 2016].

In one study of adults with RSTS, families reported a decline in developmental abilities over time in 32%, including decreased social interaction, more limited speech, and worsening stamina and mobility [Stevens et al 2011].

Behavior. Impulsivity, distractibility, instability of mood, and stereotypies are frequently observed [Verhoeven et al 2010]. Other abnormal behaviors include attention problems, hyperactivity, overfriendliness, increased pain threshold, self-injurious behaviors, and aggressive behaviors. Approximately 62% of adults with RSTS were reported to have autistic-like behaviors and one third had unreasonable fears or anxiety [Stevens et al 2011]. There may be an insistence on sameness and repetitive questioning [Waite et al 2015]. Crawford et al [2017] noted higher levels of panic attack, agoraphobia, and obsessive-compulsive disorder.

Brain MRI findings. The most common feature on brain imaging is a dysmorphic or dysplastic corpus callosum (73.6%) with or without minor dysplasia of the cerebellar vermis, periventricular posterior white matter hyperintensity, and other less common anomalies. Other infrequent findings include Chiari malformation, Dandy-Walker malformation, and underdeveloped pituitary gland.

Prognosis. More than 90% of individuals with RSTS survive into adulthood [Milani et al 2015].

It is unknown whether life span in RSTS is abnormal. One reported individual is alive at age 67 years [Stevens et al 2011], demonstrating that survival into adulthood is possible. Since many adults with disabilities have not undergone advanced genetic testing, it is likely that adults with this condition are underrecognized and underreported.

Phenotype Correlations by Gene

EP300 pathogenic variants cause a phenotype that resembles CREBBP-related RSTS. However, except for the low-hanging columella, the facial features in EP300-related RSTS are less marked. Keloids are also less frequent. Maternal preeclampsia, intrauterine growth restriction, and microcephaly are more common in individuals with EP300 pathogenic variants. Although the thumbs and halluces are broad, angulation is very uncommon. Intellectual disability is variable but is usually less severe and occasionally normal [Fergelot et al 2016].

Genotype-Phenotype Correlations

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 (see Genetically Related Disorders).

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 [Cohen et al 2020].

CREBBP. Deletions of variable sizes involving CREBBP have been reported in many individuals with RSTS to date. Stef et al [2007] and Pérez-Grijalba et al [2019] did not observe a difference in phenotype based on CREBBP deletion size. Rusconi et al [2015] described 14 individuals with CREBBP deletions ranging from single exons to the whole gene and flanking regions. They noted that individuals with deletions extending beyond CREBBP did not always have a more severe phenotype than individuals with CREBBP pathogenic missense variants.

Spena et al [2015] noted that pathogenic variants outside the histone acetyltransferase domain may be associated with a mild phenotype. Pérez-Grijalba et al [2019] did not find a correlation of pathogenic variant type, location, or involvement of the HAT domain with disease severity. Somatic mosaicism may result in a milder phenotype [Gervasini et al 2007, Chiang et al 2009].

Mosaic microdeletions of CREBBP have been reported by Gervasini et al [2007] and Schorry et al [2008]; these individuals tended to have a less severe phenotype than those with nonmosaic deletions.

See Genetically Related Disorders for a discussion of other copy number abnormalities involving CREBBP.


The birth prevalence RSTS in the Netherlands has been estimated to be between 1:100,000 and 1:125,000 [Hennekam et al 1990].

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 (see Table 3).

Table 3.

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

Gene(s)DisorderMOIFeatures of This Disorder:
Overlapping w/RSTSDistinguishing from RSTS
Pfeiffer syndrome & Apert syndrome (See FGFR-Related Craniosynostosis Syndromes Overview.)ADBroad/angulated thumbs & halluces
  • Bicoronal craniosynostosis or cloverleaf skull
  • Distinctive facial features
GLI3 1Typical Greig cephalopolysyndactyly syndrome (GCPS)ADBroad/angulated thumbs & halluces
  • Preaxial polydactyly or mixed pre- & postaxial polydactyly, widely spaced eyes, & macrocephaly
  • Persons w/mild GCPS may have subtle craniofacial findings.
  • Persons w/severe GCPS may have seizures, hydrocephalus, & ID.
GPC4 Keipert syndrome (OMIM 301026)XLBroad thumbs & halluces
  • Hearing loss
  • Characteristic facial features
HOXD13 Brachydactyly type D (OMIM 113200)ADUnilateral or bilateral shortening of distal phalanx of thumbAbsence of other features suggestive of RSTS (i.e., broad thumbs seen as an isolated finding)
SRCAP 2 Floating-Harbor syndrome AD
  • Facial features (e.g., low-hanging columella)
  • Short thumbs & broad fingertips
  • Short stature
  • Normal OFC
  • Absence of downslanting palpebral fissures
  • Thumbs not usually deviated & halluces not broad
TWIST1 Classic Saethre-Chotzen syndromeADBroad/angulated thumbs & halluces
  • Coronal synostosis (unilateral or bilateral), facial asymmetry, ptosis, & characteristic appearance of ear (small pinna w/prominent crus)
  • Syndactyly of digits 2 & 3 of hand variably present
  • Mild-to-moderate DD & ID reported; normal intelligence is more common.
Cornelia de Lange syndrome AD
Short stature, facial dysmorphism, IDLimb reduction defects
KMT2A Wiedemann-Steiner syndrome ADShort stature, facial dysmorphism, IDHypertrichosis cubiti, absence of typical hand/foot findings

AD = autosomal dominant; DD = developmental delay; ID = intellectual disability; MOI = mode of inheritance; OFC = occipital frontal circumference; RSTS = Rubinstein-Taybi syndrome


Greig cephalopolysyndactyly syndrome is associated with either a heterozygous pathogenic variant of GLI3 or a deletion of chromosome 7p14.1 involving GLI3.


Floating-Harbor syndrome is caused by a pathogenic variant in SRCAP, which encodes an SNF2-related chromatin-remodeling factor that serves as a coactivator for CREB-binding protein. This likely accounts for the phenotypic overlap with RSTS.


Clinical practice guidelines for Rubinstein-Taybi Syndrome (RSTS) have been published by Wiley et al [2003].

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with RSTS, the evaluations summarized in Table 4 (if not performed as part of the evaluation that led to diagnosis) are recommended.

Table 4.

Rubinstein-Taybi Syndrome: Recommended Evaluations Following Initial Diagnosis

Constitutional Measurement of growthPlot parameters on RSTS growth charts.
  • 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
Neuropsychiatric evalFor persons age >12 mos: screening for behavior concerns incl sleep disturbances, ADHD, anxiety, &/or findings suggestive of ASD
Musculoskeletal Orthopedics / physical medicine & rehab / PT & OT evalTo 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)
Gastroenterology / nutrition / feeding team eval
  • To incl eval of aspiration risk & nutritional status
  • Assess for gastroesophageal reflux as warranted.
  • Consider eval for gastrostomy tube placement in persons w/dysphagia &/or aspiration risk.
  • Assess for constipation.
  • Upper GI study if symptoms of malrotation
Eyes Ophthalmologic evalTo assess for strabismus, refractive errors, ptosis, nasolacrimal duct obstruction, cataracts, coloboma, nystagmus, glaucoma, & corneal abnormalities that may require referral for subspecialty care &/or low vision services
Hearing Audiologic eval
Cardiovascular Cardiac eval
  • Eval by cardiologist for structural heart defects
  • Echocardiogram
Respiratory Pulmonary evalEval for obstructive sleep apnea by polysomnography if indicated by snoring, particular sleeping posture, night wakefulness, & excessive daytime sleepiness
Genitourinary Nephrology & urology evals
  • Renal ultrasound exam
  • Consider VCUG.
  • Assess for presence of cryptorchidism in males.
  • Refer to urologist for undescended testes by age 6-12 mos.
Dental/Orthodontic Dental & orthodontic evalsAssess palate, tooth number & position, talon cusps, caries, & periodontal disease.
Endocrine Endocrinology evalEval for hyperinsulinemia if there are symptoms of hypoglycemia such as jitteriness, muscle weakness, or seizures
Genetic counseling By genetics professionals 1To inform affected persons & their families re nature, MOI, & implications of RSTS to facilitate medical & personal decision making
Family support
& resources
By clinicians, wider care team, & family support organizationsAssessment of family & social structure to determine need for:

ADHD = attention-deficit/hyperactivity disorder; ADL = activities of daily living; ASD = autism spectrum disorder; GI = gastrointestinal; MOI = mode of inheritance; OT = occupational therapy; PT = physical therapy; RSTS = Rubinstein-Taybi syndrome; VCUG = voiding cystourethrogram


Medical geneticist, certified genetic counselor, certified advanced genetic nurse

Treatment of Manifestations

There is no cure for RSTS.

Supportive care to improve quality of life, maximize function, and reduce complications is recommended. This ideally involves multidisciplinary care by specialists in relevant fields (see Table 5).

Table 5.

Rubinstein-Taybi Syndrome: Treatment of Manifestations

Developmental delay /
Intellectual disability /
Neurobehavioral issues
See Developmental Delay / Intellectual Disability Management Issues.
Poor weight gain /
Failure to thrive
  • Feeding therapy
  • Gastrostomy tube placement may be required for persistent feeding issues.
Low threshold for clinical feeding eval &/or radiographic swallowing study when showing clinical signs or symptoms of dysphagia
Epilepsy Standardized treatment w/ASM by experienced neurologist
  • Many ASMs may be effective; none has been demonstrated effective specifically for this disorder.
  • Education of parents/caregivers 1
Musculoskeletal Orthopedics / physical medicine & rehab / PT & OT incl stretching to help avoid contractures & falls
  • Consider need for positioning & mobility devices, disability parking placard.
  • For significantly angulated thumbs or duplicated halluces, surgical repair per orthopedist. Recurrence of deviation may occur after surgery. Decision reg surgery may need to be postponed until function of hands can be accurately evaluated (typically age 3-4 yrs).
Gastrointestinal Standard treatment by gastroenterologist/dietician
  • Standard mgmt of gastroesophageal reflux & constipation
  • Consider tube feeding as needed for failure to thrive.
  • Stool softeners, prokinetics, osmotic agents, dietary changes, or laxatives as needed
Eyes OphthalmologistRefractive errors, strabismus
Ophthalmic subspecialistMore complex findings (e.g., cataract, retinal dystrophy, glaucoma)
Low vision services
  • Children: through early intervention programs and/or school district
  • Adults: low vision clinic &/or community vision services/occupational therapy/mobility services
Hearing Hearing aids may be helpful per otolaryngologist.Community hearing services through early intervention or school district
Cardiac Standard treatment per cardiologist
  • Monitoring by echocardiagram; surgery if necessary
  • The frequency of hypertension is not ↑ in adults.
  • Treatment as in general population
ENT Standard treatment of obstructive sleep apnea / recurrent otitisConsider polysomnogram, CPAP, removal of tonsils/adenoids, tympanostomy tubes as clinically indicated.
Genitourinary Standard treatment per nephrologist &/or urologist
  • Standard treatment of cryptorchidism
  • Provide developmentally appropriate sex education/contraception as needed.
Dental Standard treatment per dentist &/or orthodontistTreatment for talon cusps if interfering w/occlusion, mouth closure, or causing caries
Skin Monitor for keloids/pilomatrixomas.
  • No treatment protocols for keloids but options incl steroid injection, laser, radiation, cryotherapy, & surgery.
  • Pilomatrixomas can be surgically removed if symptomatic.
  • Ensure appropriate social work involvement to connect families w/local resources, respite, & support.
  • Coordinate care to manage multiple subspecialty appointments, equipment, medications, & supplies.
  • Ongoing assessment of need for home nursing support
  • Consider involvement in adaptive sports or Special Olympics.

ASM = anti-seizure medication; CPAP = continuous positive airway pressure; OT = occupational therapy; PT = physical therapy


Education of parents/caregivers regarding common seizure presentations is appropriate. For information on non-medical interventions and coping strategies for children diagnosed with epilepsy, see Epilepsy Foundation Toolbox.

Developmental Delay / Intellectual Disability Management Issues

The following information represents typical management recommendations for individuals with developmental delay / intellectual disability in the United States; standard recommendations may vary from country to country.

Ages 0-3 years. Referral to an early intervention program is recommended for access to occupational, physical, speech, and feeding therapy as well as infant mental health services, special educators, and sensory impairment specialists. In the US, early intervention is a federally funded program available in all states that provides in-home services to target individual therapy needs.

Ages 3-5 years. In the US, developmental preschool through the local public school district is recommended. Before placement, an evaluation is made to determine needed services and therapies and an individualized education plan (IEP) is developed for those who qualify based on established motor, language, social, or cognitive delay. The early intervention program typically assists with this transition. Developmental preschool is center based; for children too medically unstable to attend, home-based services are provided.

All ages. Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies (US) and to support parents in maximizing quality of life. Some issues to consider:

  • IEP services:
    • An IEP provides specially designed instruction and related services to children who qualify.
    • IEP services will be reviewed annually to determine whether any changes are needed.
    • Special education law requires that children participating in an IEP be in the least restrictive environment feasible at school and included in general education as much as possible, when and where appropriate.
    • Vision and hearing consultants should be a part of the child's IEP team to support access to academic material.
    • PT, OT, and speech services will be provided in the IEP to the extent that the need affects the child's access to academic material. Beyond that, private supportive therapies based on the affected individual's needs may be considered. Specific recommendations regarding type of therapy can be made by a developmental pediatrician.
    • As a child enters the teen years, a transition plan should be discussed and incorporated in the IEP. For those receiving IEP services, the public school district is required to provide services until age 21.
  • A 504 plan (Section 504: a US federal statute that prohibits discrimination based on disability) can be considered for those who require accommodations or modifications such as front-of-class seating, assistive technology devices, classroom scribes, extra time between classes, modified assignments, and enlarged text.
  • Developmental Disabilities Administration (DDA) enrollment is recommended. DDA is a US public agency that provides services and support to qualified individuals. Eligibility differs by state but is typically determined by diagnosis and/or associated cognitive/adaptive disabilities.
  • Families with limited income and resources may also qualify for supplemental security income (SSI) for their child with a disability.

Motor Dysfunction

Gross motor dysfunction

  • Physical therapy is recommended to maximize mobility and to reduce the risk for later-onset orthopedic complications (e.g., contractures, scoliosis, hip dislocation).
  • Consider use of durable medical equipment and positioning devices as needed (e.g., wheelchairs, walkers, bath chairs, orthotics, adaptive strollers).
  • For muscle tone abnormalities including hypertonia or dystonia, consider involving appropriate specialists to aid in management of baclofen, tizanidine, Botox®, anti-parkinsonian medications, or orthopedic procedures.

Fine motor dysfunction. Occupational therapy is recommended for difficulty with fine motor skills that affect adaptive function such as feeding, grooming, dressing, and writing.

Oral motor dysfunction should be assessed at each visit and clinical feeding evaluations and/or radiographic swallowing studies should be obtained for choking/gagging during feeds, poor weight gain, frequent respiratory illnesses, or feeding refusal that is not otherwise explained. Assuming that the child is safe to eat by mouth, feeding therapy (typically from an occupational or speech therapist) is recommended to help improve coordination or sensory-related feeding issues. Feeds can be thickened or chilled for safety. When feeding dysfunction is severe, an NG-tube or G-tube may be necessary.

Communication issues. Consider evaluation for alternative means of communication (e.g., augmentative and alternative communication [AAC]) for individuals who have expressive language difficulties. An AAC evaluation can be completed by a speech-language pathologist who has expertise in the area. The evaluation will consider cognitive abilities and sensory impairments to determine the most appropriate form of communication. AAC devices can range from low-tech, such as picture exchange communication, to high-tech, such as voice-generating devices. Contrary to popular belief, AAC devices do not hinder verbal development of speech, but rather support optimal speech and language development.

Neurobehavioral/Psychiatric Concerns

Children may qualify for and benefit from interventions used in treatment of autism spectrum disorder, including applied behavior analysis (ABA). ABA therapy is targeted to the individual child's behavioral, social, and adaptive strengths and weaknesses and typically performed one on one with a board-certified behavior analyst.

Consultation with a developmental pediatrician may be helpful in guiding parents through appropriate behavior management strategies or providing prescription medications, such as medication used to treat attention-deficit/hyperactivity disorder, when necessary.

Concerns about serious aggressive or destructive behavior can be addressed by a pediatric psychiatrist.


To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in Table 6 are recommended.

Table 6.

Rubinstein-Taybi Syndrome: Recommended Surveillance

Growth Monitor weight & linear growth w/RSTS growth charts.
  • Frequently during 1st yr of life & at regular checkups.
  • If growth differs from expected, assess for growth hormone deficiency.
Neurologic Monitor those w/seizures as clinically indicated.At each visit
Assess for new manifestations such as seizures, changes in tone, & movement disorders.
Development Monitor developmental progress & educational needs.
Behavioral assessment for anxiety, ADHD, ASD, aggression, & self-injury
  • Physical medicine, OT/PT assessment of mobility, self-help skills
  • Eval of gait
  • Bone density study if recurrent fractures
  • Measurement of growth parameters
  • Eval of nutritional status & safety of oral intake
Gastrointestinal Monitor for constipation.
Respiratory Monitor for evidence of aspiration, respiratory insufficiency, & sleep apnea.
Ophthalmologic involvement Ophthalmologic evalAnnually or as necessary
Low vision servicesPer treating clinicians
Hearing loss Audiologic evalAnnually (more frequently if person has history of recurrent otitis media)
Cardiovascular Cardiac evalAt diagnosis & then per cardiologist
Genitourinary Renal & urologic evalAt diagnosis & then monitor for symptoms at each visit
Dental anomalies Dental & orthodontic evalBeginning at age 1 yr; continue every 6 mos or per dentist/orthodontist
Endocrine Eval for hypoglycemiaAt each visit
  • Vaccinations per general population
  • If recurrent infections, baseline immune workup
At each visit
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; RSTS = Rubinstein-Taybi syndrome

Evaluation of Relatives at Risk

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Pregnancy Management

Preeclampsia was reported in 12/52 mothers whose fetus had EP300-related RSTS and 2/59 of those with CREBBP-related RSTS [Fergelot et al 2016]. In another study, 4/12 individuals with EP300-related RSTS had pregnancies complicated by preeclampsia or placental abnormalities including one report of uteroplacental malperfusion. Polyhydramnios was noted in two pregnancies [Cohen et al 2020].

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.

Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members; it is not meant to address all personal, cultural, or ethical issues that may arise or to substitute for consultation with a genetics professional. —ED.

Mode of Inheritance

Rubinstein-Taybi syndrome (RSTS) is inherited in an autosomal dominant manner.

Risk to Family Members

Parents of a proband

Sibs of a proband. The risk to the sibs of the proband depends on the clinical/genetic status of the proband's parents:

Offspring of a proband. Each child of an individual with RSTS has a 50% chance of inheriting the RSTS-related pathogenic variant [Hennekam et al 1989, Marion et al 1993, Petrij et al 2000, Bartsch et al 2010].

Other family members. The risk to other family members of a proband depends on the genetic status of the proband's parents: if a parent has the pathogenic variant, the parent's family members may be at risk.

Related Genetic Counseling Issues

Family planning

  • The optimal time for determination of genetic risk and discussion of the availability of prenatal/preimplantation genetic testing is before pregnancy.
  • It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who have had a child with RSTS.

DNA banking. Because it is likely that testing methodology and our understanding of genes, pathogenic mechanisms, and diseases will improve in the future, consideration should be given to banking DNA from probands in whom a molecular diagnosis has not been confirmed (i.e., the causative pathogenic mechanism is unknown). For more information, see Huang et al [2022].

Prenatal Testing and Preimplantation Genetic Testing

Once the RSTS-related pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing for RSTS are possible.

A priori low-risk pregnancies. RSTS is not usually diagnosed by prenatal ultrasound. However, routine prenatal ultrasound examination may identify findings such as growth restriction, polyhydramnios, broad thumbs, and brain abnormalities that raise the possibility of RSTS in a fetus not known to be at increased risk [Van-Gils et al 2019].

Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing. While most centers would consider use of prenatal testing to be a personal decision, discussion of these issues may be helpful.


GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.

Molecular Genetics

Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.

Table A.

Rubinstein-Taybi Syndrome: Genes and Databases

Data are compiled from the following standard references: gene from HGNC; chromosome locus from OMIM; protein from UniProt. For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click here.

Table B.

OMIM Entries for Rubinstein-Taybi Syndrome (View All in OMIM)

602700E1A-BINDING PROTEIN, 300-KD; EP300

CREBBP and EP300 encode histone acetyltransferases (HAT) that act as transcriptional coactivators. The CREB-binding protein (CREBBP) is ubiquitously expressed and is involved in transcriptional coactivation of many different transcription factors. It has intrinsic HAT activity and acts as a scaffold to stabilize additional protein interactions with the transcription complex via chromatin remodeling. CREBBP regulates the expression of many genes affecting cellular pathways such as cell growth control, cellular differentiation, apoptosis, and tumor suppression [Negri et al 2016]. Germline pathogenic variants in CREBBP may lead to a truncated CREBBP or one with an amino acid substitution. Pathogenic variants in the HAT domain interfere with the acetylation of histones, which is an important step in transcription activation. CREBBP also acetylates p53, a tumor suppressor pathway known to be deregulated in many human cancers.

EP300 encodes the p300 transcriptional coactivator protein, which shares 63% homology with CREBBP at the amino acid level. It functions as a HAT, regulating transcription via chromatin remodeling and playing an important role in cell proliferation and differentiation. Pathogenic variants result in truncated p300 protein or absence of allele expression, which may lead to loss of HAT activity.

Mechanism of disease causation. Loss of function (haploinsufficiency)

Chapter Notes

Author Notes

The Rubinstein-Taybi Syndrome Program at Cincinnati Children's is one of the country's leading programs for the care of children with Rubinstein-Taybi syndrome (RSTS) and provides expert confirmation of diagnosis as well as the latest treatments and support.

Brittany Simpson, MD (moc.liamg@4321nospmisnb), is actively involved in clinical research regarding individuals with RSTS. Dr Jane Waite (ku.ca.notsa@etiaw.j) in the United Kingdom is collecting data on the behavioral phenotype in RSTS. They would be happy to communicate with persons who have any questions regarding diagnosis of RSTS or other considerations.

Dr Simpson is also interested in hearing from clinicians treating families affected by RSTS in whom no causative pathogenic variant has been identified through molecular genetic testing of the genes known to be involved in RSTS.

Contact Dr Simpson to inquire about review of CREBBP and EP300 variants of uncertain significance.

Revision History

  • 9 November 2023 (gm) Comprehensive update posted live
  • 22 August 2019 (sw) Comprehensive update posted live
  • 7 August 2014 (me) Comprehensive update posted live
  • 16 April 2009 (me) Comprehensive update posted live
  • 2 October 2006 (me) Comprehensive update posted live
  • 22 July 2004 (me) Comprehensive update posted live
  • 30 August 2002 (tk,me) Review posted live
  • 5 April 2002 (cs) Original submission


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