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Rubinstein-Taybi Syndrome

Rubinstein Taybi Syndrome

Rubinstein-Taybi syndrome is a rare genetic disease characterized by mental and growth retardation and occurs as a result of chromosomal deletions and point mutations. Because the genes that are affected are involved in the development of numerous organs and tissues, the clinical presentation includes heart, skin, facial and digital anomalies, and the diagnosis is made clinically and by karyotypic analysis. Treatment involves managing symptoms and accompanying comorbidities.


The clinical presentation of Rubinstein-Taybi syndrome involves several organs, but the most prominent features are exhibited in the facial region and the distal extremities. Prominent and beaked nose, hypoplasia of the maxilla, low-set ears, micrognathia, enamel hypoplasia, talon cusps, highly arched eyebrows and long eyelashes are the most common facial abnormalities in these patients [9] [10]. Broad and angulated thumbs, fingers, and great toes are observed in practically all patients, while clinodactyly is seen in some patients as well.

Growth retardation and postnatal growth failure are present in the majority of patients. Infants often fall below the fifth percentile in terms of weight, height, and head circumference, and failure to thrive is frequently reported [11]. Feeding difficulties and dysphagia occur commonly in patients with recurrent respiratory tract infections, and short stature is often established during the physical examination. Microcephaly is also frequently reported.

Severe mental retardation, cognitive impairment, short attention span, sudden mood changes and speech difficulties are readily observed. Defects in motor skills and coordination, sometimes accompanied with hypotonia and hyperreflexia may be seen.

Findings that are somewhat less prevalent in these patients include:

Broad Thumb
  • Rubinstein-Taybi syndrome (RTS), also known as 'broad thumbs syndrome' or 'broad thumb-hallux syndrome', is a malformation syndrome characterized by the triad of broad thumbs or first toes, a peculiar facial expression called 'comical face' and mental[ncbi.nlm.nih.gov]
  • Rubinstein-Taybi syndrome, or broad thumb-hallux syndrome, is a well-defined rare congenital disorder characterised by postnatal growth deficiency, craniofacial dysmorphism, broad thumbs and great toes, and mental retardation (intellectual disability)[ncbi.nlm.nih.gov]
  • However, in the presence of the broad thumb and facial anomalies, we were able to suggest the correct diagnosis.[ncbi.nlm.nih.gov]
  • Rubinstein-Taybi syndrome (RTS) is characterized by mental retardation, broad thumbs and great toes and a recognizable craniofacial phenotype. Causative mutations have been described in the CREBBP and EP300 genes.[ncbi.nlm.nih.gov]
  • The diagnosis of RSTS must be expanded to include patients without broad thumbs or halluces.[ncbi.nlm.nih.gov]
Short Stature
  • Rubinstein-Taybi syndrome (RTS) is a rare congenital disorder characterized by broad thumbs and halluces, dysmorphic facial features, mental retardation, and short stature.[ncbi.nlm.nih.gov]
  • Rubinstein-Taybi syndrome (RTS; MIM# 180849) is a well-known malformation syndrome, characterized by broad thumbs and halluces, a characteristic facies, short stature, and mental retardation.[ncbi.nlm.nih.gov]
  • Rubinstein-Taybi syndrome (RTS) is a well-known disorder characterized by growth and mental retardation, typical facial features, short stature, and broad thumbs and toes.[ncbi.nlm.nih.gov]
  • Rubinstein-Taybi syndrome (RTS) is characterized by typical facies, short stature, mental retardation, broad thumbs and broad great toes.[ncbi.nlm.nih.gov]
Recurrent Infection
  • We conclude that a primary immune deficiency may exist in the remainder of the RTS population and may explain the reason for the propensity for recurrent infections.[ncbi.nlm.nih.gov]
  • Problems that may occur in early life include breathing difficulties, feeding problems, poor weight gain, recurrent infections, and constipation. Developmental delay occurs in most children with RTS.[cafamily.org.uk]
  • Respiratory system - Recurrent infections, sleep apnea, and lung lobulation, while increased susceptibility to the collapse of the larynx and breathing difficulties are also reported.[symptoma.com]
  • Naimi DR, Munoz J, Rubinstein J, et al ; Rubinstein-Taybi syndrome: an immune deficiency as a cause for recurrent infections. Allergy Asthma Proc. 2006 May-Jun27(3):281-4.[patient.info]
Broad Great Toe
  • His facial and clinical features were very typical, including broad thumbs with radial angulation and broad great toes.[ncbi.nlm.nih.gov]
  • Rubinstein-Taybi syndrome (RTS) is characterized by typical facies, short stature, mental retardation, broad thumbs and broad great toes.[ncbi.nlm.nih.gov]
  • Broad great toes in a child with Rubinstein-Taybi syndrome (RSTS).[emedicine.medscape.com]
Single Transverse Palmar Crease
  • transverse palmar crease 0000954 Spina bifida occulta 0003298 Sporadic No previous family history 0003745 Stereotypy Repetitive movements Repetitive or self-injurious behavior [ more ] 0000733 Syndactyly Webbed fingers or toes 0001159 Talon cusp 0011087[rarediseases.info.nih.gov]
High Arched Palate
  • Rubinstein-Taybi syndrome (RTS) is a rare disorder affecting 1 of 300,000 people, characterized by growth, mental and motor retardation, small stature, broad thumbs and toes, characteristic face, high-arched palate, and recurrent respiratory infections[ncbi.nlm.nih.gov]
  • Craniofacial abnormalities including: microcephaly, underdeveloped maxilla, micrognathia, high arched palate, malocclusion, down-slanting palpebral fissures, thick eyelashes and full eyebrows.[ncbi.nlm.nih.gov]
  • Ru·bin·stein-Tay·bi syn·drome ( rū'bĭn-stīn tā'bē ), mental retardation, broad thumb and great toe, antimongoloid slant to the eyes, thin and beaked nose, microcephaly, prominent forehead, low-set ears, high arched palate, and cardiac anomaly; a submicroscopic[medical-dictionary.thefreedictionary.com]
  • Facial features are striking including heavy, arched eyebrows, long eyelashes, downslanting palpebral fissures, beaked nose, broad nasal bridge, narrow, high-arched palate and characteristic grimacing. read more[ctgt.net]
  • Features include 5 : facial appearance high arched eyebrows long eyelashes down-slanting palpebral fissures broad nasal bridge/beaked nose high arched palate mild micrognathia unusual facial expression: the grimacing or at least unusual smile with an[radiopaedia.org]
Poor Oral Hygiene
  • The purpose of this case report was to demonstrate the complicated dental treatment of a 12-year-old, developmentally disabled girl, living with a foster family, who suffered from RTS, extensive caries, and very poor oral hygiene.[ncbi.nlm.nih.gov]
Low Set Ears
  • Ru·bin·stein-Tay·bi syn·drome ( rū'bĭn-stīn tā'bē ), mental retardation, broad thumb and great toe, antimongoloid slant to the eyes, thin and beaked nose, microcephaly, prominent forehead, low-set ears, high arched palate, and cardiac anomaly; a submicroscopic[medical-dictionary.thefreedictionary.com]
  • Various facial features, such as the underdeveloped jaw, beaked nose, low-set ears, and long eyelashes, are accompanied with broadening and angulation of thumbs, big toes, and other fingers.[symptoma.com]
  • Sources Occurrence Characteristics short stature moderate to severe intellectual disability underdeveloped bone in midface downward slanted eyes and/or drooping eyelids broad thumbs and big toes heart and kidney defects excess hair on body low set ears[prezi.com]
  • […] development of motor skills accompanied by low muscle tone Other signs and symptoms may include: Absent or extra kidney, and other problems with kidney or bladder An underdeveloped bone in the midface Unsteady or stiff walking gait Downward-slanted eyes Low-set[nicklauschildrens.org]
Hearing Impairment
  • Many children have vision problems and hearing impairments as a result of infections, attributable to an increased sensitivity to infection.[mun-h-center.se]
  • impairment Deafness Hearing defect [ more ] 0000365 Hip dysplasia 0001385 Keloids 0010562 Polyhydramnios High levels of amniotic fluid 0001561 Ptosis Drooping upper eyelid 0000508 Seizures Seizure 0001250 Percent of people who have these symptoms is[rarediseases.info.nih.gov]
  • As part of the underlying condition, our patient had marked nasal speech and mild to moderate right conductive hearing impairment. She had developmental delay and attention deficit hyperactivity disorder.[jmedicalcasereports.com]
  • Clinical findings included mental and motor retardation, patent ductus arteriosus (PDA), undescended testes, hirsutism, broad thumbs with radial angulation and broad toes, and inguinal hernia.[ncbi.nlm.nih.gov]
  • […] of the fifth fingers skull and central nervous system microcephaly mental retardation (IQ 35-50) congenital cardiac abnormalities: reported in up to 33% of affected patients 2 patent ductus arteriosus atrial septal defects ventricular septal defect hirsutism[radiopaedia.org]
  • Symptoms Broadening of the thumbs and big toes Constipation Excess hair on body (hirsutism) Heart defects possibly requiring surgery Intellectual disability Seizures Short stature that is noticeable after birth Slow development of cognitive skills Slow[nicklauschildrens.org]
Cafe-Au-Lait Spots
  • […] inheritance 0000006 Avascular necrosis of the capital femoral epiphysis 0005743 Bifid uterus 0000136 Bimanual synkinesia Hand mirror movements Mirror hand movements Mirror movements [ more ] 0001335 Broad hallux Broad big toe Wide big toe [ more ] 0010055 Cafe-au-lait[rarediseases.info.nih.gov]
Beaked Nose
  • Extra oral features revealed distinctive facial appearance with a broad fore head, hypertelorism, broad nasal bridge and beaked nose.[ncbi.nlm.nih.gov]
  • Ru·bin·stein-Tay·bi syn·drome ( rū'bĭn-stīn tā'bē ), mental retardation, broad thumb and great toe, antimongoloid slant to the eyes, thin and beaked nose, microcephaly, prominent forehead, low-set ears, high arched palate, and cardiac anomaly; a submicroscopic[medical-dictionary.thefreedictionary.com]
  • Facial features are striking including heavy, arched eyebrows, long eyelashes, downslanting palpebral fissures, beaked nose, broad nasal bridge, narrow, high-arched palate and characteristic grimacing. read more[ctgt.net]
  • These include anti-mongoloid slant of eyes, heavy eye brows, low set ears and beaked nose. Clinically, the hallux was broad bilaterally and a skin cleft was noted along the plantar first interspace.[faoj.org]
Poor Coordination
  • However, they displayed some specific behaviors: short attention span, motor stereotypies, poor coordination, and overweight.[ncbi.nlm.nih.gov]
  • The authors concluded that Rubinstein-Taybi patients had specific behaviors including short attention span and poor coordination.) Miller, R, Rubinstein, J. "Tumors in Rubinstein-Taybi syndrome". Am J Med Genet. vol. 56. 1995. pp. 112-115.[clinicaladvisor.com]
  • Short attention span, poor coordination, and sudden mood changes characterize the behavior of RTS patients.[ommbid.mhmedical.com]
  • They recommended close individual evaluation of Rubinstein–Taybi patients for anaesthetic plans. [8] A 2009 study found that children with RTS were more likely to be overweight and to have a short attention span, motor stereotypies , and poor coordination[en.wikipedia.org]
  • coordination 0002370 Postnatal growth retardation Growth delay as children 0008897 Premature thelarche Premature breast development 0010314 Prominent fingertip pads Prominent finger pads 0001212 Proptosis Bulging eye Eyeballs bulging out Prominent eyes[rarediseases.info.nih.gov]
  • Defects in motor skills and coordination, sometimes accompanied with hypotonia and hyperreflexia may be seen.[symptoma.com]
  • In addition, there may be diminished muscle tone (hypotonia), abnormally exaggerated reflexes (hyperreflexia), a stiff, unsteady gait, infrequent bowel movements (constipation), and seizures.[rarediseases.org]
  • Cowlick Frontal Cowlick Upswept frontal hair [ more ] 0002236 Generalized hypotonia Decreased muscle tone Low muscle tone [ more ] 0001290 High axial triradius 0001042 Hirsutism Excessive hairiness 0001007 Hyperactivity More active than typical 0000752 Hyperreflexia[rarediseases.info.nih.gov]


This syndrome presents with a complex clinical symptomatology, but the distinct facial and digital features, together with findings related to other systems should be indicative of this disease, and the initial diagnosis is made clinically. Once this syndrome is suspected, a full diagnostic workup should be performed, to establish all accompanying findings in these patients. Imaging studies, including X-rays, computed tomography (CT scan) or magnetic resonance imaging (MRI) should be done to evaluate the change in the skeletal system, while echocardiography is indicated to rule out the presence of congenital heart disease. Ophthalmoscopy, ENT examination, ultrasound of the abdomen and lung studies should be performed as well. With supporting evidence obtained from diagnostic procedures, genetic testing can be performed. Karyotype analysis, and in situ hybridization can detect mutations and microdeletions in CREBBP gene and the 16p13.3 segment, respectively. However, CREBBP mutations are established in only 55% of patients [14], which does not exclude the diagnosis, while EP300 gene mutations are established in less than 10% of individuals.

It is important to mention that patients with Rubinstein-Taybi syndrome are prone to develop malignant diseases, including tumors of the nervous system (oligodendroglioma, medulloblastoma, meningioma), as well as lymphomas and leukemias.

Delayed Bone Age
  • Additional observations include maternal pre-eclampsia (2/9), syndactyly (3/9), feeding or swallowing issues (3/9), delayed bone age (2/9) and scoliosis (2/9).[ncbi.nlm.nih.gov]
  • Not every individual has all the characteristics, however, the following is a list of the reported traits: • Broad thumbs and/or toes (sometimes angulated) • Mental retardation (from mild to severe) • Beaked nose • Short stature (delayed bone age) • Broad[aapos.org]
  • bone age, congenital heart disease, recurrent respiratory infections, craniofacial anomalies, breathing and swallowing difficulties, malformations of the kidneys, urogenital system, and skeletal system. [3] , [4] All these features can have an impact[joacp.org]


Treatment of patients with Rubinstein-Taybi syndrome requires a multidisciplinary approach and consists of rehabilitation and supportive therapy together with management of accompanying comorbidities and findings [15]. Mental retardation open link and cognitive difficulties require special forms of education, speech and behavioral therapy, and various other measures of mental rehabilitation, which can present a significant challenge. Growth should be closely monitored, and correction of other findings is necessary. Physical therapy and exercise are indicated in all patients, with an attempt to reduce musculoskeletal changes that may impair the normal functioning of patients.

Congenital heart disease, cryptorchidism, and presence of either benign or malignant tumors, are all indications for surgical treatment, but patients with this syndrome are quite prone to laryngeal and tracheal wall collapse, which can significantly complicate the process of anesthesia and intubation [16]. Management of other findings, such as renal, ocular, and skin manifestations should be done accordingly, and a long-term follow-up of patients is necessary for ensuring a good quality of life.


Overall survival rates are good, patients frequently reach adulthood, but accompanying comorbidities may reduce life expectancy that is estimated to be normal in these patients. Growth and mental retardation present as a significant burden to the patient and the family, and congenital heart disease, recurrent respiratory infections, and other severe complications of this disease can significantly contribute to morbidity and mortality. Additionally, it is established that patients have an increased risk of developing malignant diseases, including lymphomas, leukemias, and tumors of the brain, such as meningioma and medulloblastoma, which can carry a poor prognosis if not diagnosed early [8].


The cause of Rubinstein-Taybi syndrome involves the chromosomal segment 16p13.3, and point mutations, translocations, or microdeletions of CREBBP, and the E1A-binding protein p300 (also known as EP300) [4]. The proteins of these genes act as co-activators of the process of transcription, and their roles are bridging of RNA polymerase II and DNA-binding transcription factors, chromatin rearrangements through performing the function of histone acetyltransferases, and other processes in gene expression. EP300 mutations and deletions have been established in patients with malformations of the skeletal system, such as broadening and angulation of fingers and toes, as well as facial abnormalities, which are the hallmarks of this disease [5]. It is understood that because these proteins are present in numerous cells, and perform some of the most important functions in the process of gene expression, several organs may be affected, including the heart, lungs, kidneys, the skin, testes, and the eyes.


The estimated prevalence for Rubinstein-Taybi syndrome vary, and is somewhere between 1 per 100,000-125,000 live births [6]. The majority of cases occur sporadically. Familial cases are extremely rare, and neither gender nor ethnic predilection has been documented.

Sex distribution
Age distribution


It is not completely understood why the changes in the 16p13.3 segment and involvement of CREBBP and EP300 genes occur. It is assumed that the majority of mutations, microdeletions, or simple translocations occur de novo, while familial occurrence is extremely rare. As a result, defects in these regions lead to dysfunctional transcription process, because the proteins derived from these genes are co-activator of this process.

It is established that patients with Rubinstein-Taybi syndrome have some form of immune deficiency, which could be the primary reason why about 75% of patients have recurrent respiratory infections [7].


Although mutations that are presumed to be responsible for Rubinstein-Taybi syndrome have been identified, prevention of this syndrome is currently not possible. It is important to establish the diagnosis as early as possible, so that the development of complications, which can be life-threatening, can be reduced to a minimum. Proper therapy may significantly improve the life of the patient, and reduce the burden that this disease carries.


Rubinstein-Taybi syndrome is a very rare genetic disorder which includes several congenital anomalies such as mental retardation, growth abnormalities, broad and angulated thumbs and toes, and a variety of other symptoms. It was initially described in the 1960s [1], and the cause is presumed to be microdeletions, point mutations, or other types of changes in the chromosome 16p13.3 and cyclic adenosine-monophosphate-response element binding protein (CBP or CREBBP). This protein is active in numerous cells and organs and is involved in various metabolic and proliferative processes, such as chromatin remodeling, signal transduction pathway integration, and regulation of transcription [2]. As a result, its mutations lead to significant impairment of normal cellular functioning, leading to diverse symptoms involving multiple organs. The majority of cases are sporadic, but reports of Rubinstein-Taybi syndrome in monozygotic twins have been documented [3]. The prevalence of this genetic disease is estimated to be 1 per 100,000-125,000 live births, and the most prominent features of this syndrome include mental and growth retardation. Intellectual disability, short stature, feeding problems during the first months and years of life as well as growth failure are essential components of this syndrome and can be quite debilitating for the patient and the family. Facial and digital abnormalities are also characteristic features of this syndrome, including malformations of the ears, nose, lips, and other parts as well; abnormally broad and angulated fingers and toes are some of the most commonly encountered features. Other organs may be involved, including the testes, skin, heart, the skeletal system, and the kidneys, while more than 70% of patients experience recurrent respiratory infections, presumably because of defects in the immune response. The diagnosis is made by clinical criteria, and molecular analysis is shown to reveal mutations in approximately 55% of cases, which does not exclude the diagnosis. Goals of treatment are to reduce the burden of the disease by managing symptoms individually, through physical and mental rehabilitation, genetic counseling, and correction of accompanying findings, such as congenital heart disease, recurrent respiratory infections, and cryptorchidism.

Patient Information

Rubinstein-Taybi syndrome is a rare genetic disease that involves various organs, but primarily exhibits changes in the face and fingers, and virtually all patients have growth retardation and intellectual disability. It occurs in approximately 1 individual per 100,000, and it caused by mutations in genes and parts of chromosomes that are involved in the process of gene expression. These mutations are in extremely rare cases hereditary, and occur spontaneously in the vast majority of patients, for unknown reasons. These mutations lead to defective cellular functioning in numerous organs and systems, and the most prominent pathological findings include growth failure in infants and severe intellectual disability, which presents as a significant burden to patients and their families. Various facial features, such as the underdeveloped jaw, beaked nose, low-set ears, and long eyelashes, are accompanied with broadening and angulation of thumbs, big toes, and other fingers. Additionally, patients may have congenital heart disease, which is diagnosed in a significant number of patients, as well as recurrent respiratory and urinary infections, vision problems, and various other changes. The diagnosis is primarily made upon clinical examination, and mutations of the involved genes are detected in about 50% of patients, which does not exclude the diagnosis. Treatment of patients with Rubinstein-Taybi syndrome is complex and necessitates both mental and physical rehabilitation, but also the management of accompanying comorbidities that may significantly influence the quality and duration of the patients' life. Special education, speech therapy, and physical rehabilitation are indicated for all patients, while surgery may be necessary to correct other defects. Patients with this syndrome carry a good prognosis in general, but significant intellectual disability, as well as the presence of other comorbidities, require long-term monitoring, which is a significant challenge.



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  2. Petrij F, Dauwerse HG, Blough RI, et al. Diagnostic analysis of the Rubinstein-Taybi syndrome: five cosmids should be used for microdeletion detection and low number of protein truncating mutations. J Med Genet. 2000;37(3):168-76.
  3. Baraitser M, Preece MA. The Rubinstein-Taybi syndrome: occurrence in two sets of identical twins. Clin Genet. 1983;23(4):318-20.
  4. Tsai AC, Dossett CJ, Walton CS, et al. Exon deletions of the EP300 and CREBBP genes in two children with Rubinstein-Taybi syndrome detected by aCGH. Eur J Hum Genet. 2011;19(1):43-9.
  5. White SM, Morgan A, Da Costa A, et al. The phenotype of Floating-Harbor syndrome in 10 patients. Am J Med Genet A. 2010;152A:821–9.
  6. Roelfsema JH, White SJ, Ariyürek Y, et al. Genetic heterogeneity in Rubinstein-Taybi syndrome: mutations in both the CBP and EP300 genes cause disease. Am J Hum Genet. 2005;76(4):572-80.
  7. Naimi DR, Munoz J, Rubinstein J, et al. Rubinstein-Taybi syndrome: an immune deficiency as a cause for recurrent infections. Allergy Asthma Proc. 2006;27(3):281-4.
  8. Miller RW, Rubinstein JH. Tumors in Rubinstein–Taybi syndrome. Am J Med Genet. 1995;56:112–115.
  9. Bloch-Zupan A, Stachtou J, Emmanouil D, et al. Oro-dental features as useful diagnostic tool in Rubinstein-Taybi syndrome. Am J Med Genet A. 2007;143A(6):570-3.
  10. Tirali RE, Sar C, Cehreli B. Oro-facio-dental findings of rubinstein-taybi syndrome as a useful diagnostic feature. J Clin Diagn Res. 2014; 8(1):276-8.
  11. Beets L, Rodríguez-Fonseca C, Hennekam RC. Growth charts for individuals with Rubinstein-Taybi syndrome. Am J Med Genet A. 2014 Sep;164A(9):2300-9.
  12. Stevens CA, Bhakta MG. Cardiac abnormalities in the Rubinstein-Taybi syndrome. Am J Med Genet. 1995;59(3):346-8.
  13. van Genderen MM, Kinds GF, Riemslag FC, et al. Ocular features in Rubinstein-Taybi syndrome: investigation of 24 patients and review of the literature. Br J Ophthalmol. 2000;84(10):1177-84.
  14. Roelfsema JH, Peters DJ. Rubinstein-Taybi syndrome: clinical and molecular overview. Expert Rev Mol Med. 2007;9(23):1-16.
  15. Hennekam RC. Rubinstein-Taybi syndrome. Eur J Hum Genet. 2006;14:981–5.
  16. Kumar S, Suthar R, Panigrahi I, Marwaha RK. Rubinstein-Taybi syndrome: Clinical profile of 11 patients and review of literature. Indian J Hum Genet. 2012;18(2):161-166.

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Last updated: 2018-06-21 21:58