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Rubinstein-Taybi syndrome (RTS)

Written2001-06Didier Lacombe
Genetique Medicale-Hopital Pellegrin-Enfants - C.H.U de Bordeaux Place Amélie Raba-Léon 33076 BORDEAUX Cedex, France

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Other namesBroad thumb   hallux syndrome
Atlas_Id 10063
Genes implicated inCREBBP  
Note The Rubinstein-Taybi syndrome is a well-defined entity characterized by growth and mental retardation, broad thumbs and halluces, typical face, and various malformations.
Inheritance The prevalence at birth was estimated to be 1 in 125,000 living newborn infants. RTS is caused by an autosomal dominant mutation.


Phenotype and clinics The main clinical features of RTS are facial dysmorphism, broad thumbs, broad big toes, and growth and mental retardation.
  • The facial appearance is different in the newborn, but the most striking facial features in childhood include microcephaly, downslanting palpebral fissures, prominent and beaked nose with low nasal septum, highly arched palate, and mild micrognathia.
  • Broad thumbs and broad halluces are present in almost all cases. Other extremities abnormalities include angulation deformities of the thumbs and halluces, broad distal phalanges of other fingers, clinodactyly of the 5th finger, persistent fetal fingertip pads and overlapping toes.
  • Growth retardation is generally marked during infancy with feeding problems, and with a tendency to overweight in later childhood and adulthood. Constipation, recurrent upper respiratory infections and conjunctivitis are frequent problems in infancy.
  • Retarded motor and mental development become apparent in the first year of life. The average IQ of the patients is between 35 and 50, but some patients may have a better outcome. The performal IQ is higher than the verbal IQ.
  • Other findings may include eye abnormalities (tear duct obstruction, ptosis, strabismus, glaucoma, coloboma, cataract, refractive error), congenital heart defects (PDA, VSD, ASD), urinary tract malformations, specific dental abnormalities, epilepsy, and skin features (naevus flammeus, hirsutism, keloid scarring).
  • Neoplastic risk An increased risk for different tumors has been noticed. Tumors are reported in about 5 % of RTS patients. The reported tumors include brain tumors as meningioma, acute lymphocytic leukemia, pheochromocytoma, rhabdomyosarcoma (nasopharyngeal), and intraspinal neurilemmoma. An increased frequency of pilomatrixoma is also known in the syndrome.
    Treatment There is no specific treatment in RTS.


    Note Chromosome analysis is usually normal in RTS. Some cytogenetic rearrangements involving chromosome 16p13.3 have been described leading to the identification of the causing gene. An interstitial submicroscopic deletion of this region is found in approximately 12 % of the patients, using two-color FISH and the cosmid RT1 (D16S237).

    Genes involved and Proteins

    Note The gene for the human CREB binding protein, the transcriptional co-activator CREBBP (cAMP Responsive Element Binding Binding Protein), is included in the RT1 cosmid, and mutations in CREBBP have been described in RTS patients.
    Gene NameCREBBP (CREB binding protein)
    Location 16p13.3


    FISH studies in 45 patients with Rubinstein-Taybi syndrome: deletions associated with polysplenia, hypoplastic left heart and death in infancy.
    Bartsch O, Wagner A, Hinkel GK, Krebs P, Stumm M, Schmalenberger B, Böhm S, Balci S, Majewski F
    European journal of human genetics : EJHG. 1999 ; 7 (7) : 748-756.
    PMID 10573006
    Variation in microdeletions of the cyclic AMP-responsive element-binding protein gene at chromosome band 16p13.3 in the Rubinstein-Taybi syndrome.
    Blough RI, Petrij F, Dauwerse JG, Milatovich-Cherry A, Weiss L, Saal HM, Rubinstein JH
    American journal of medical genetics. 2000 ; 90 (1) : 29-34.
    PMID 10602114
    Conjunction dysfunction: CBP/p300 in human disease.
    Giles RH, Peters DJ, Breuning MH
    Trends in genetics : TIG. 1998 ; 14 (5) : 178-183.
    PMID 9613201
    Deletion at chromosome 16p13.3 as a cause of Rubinstein-Taybi syndrome: clinical aspects.
    Hennekam RC, Tilanus M, Hamel BC, Voshart-van Heeren H, Mariman EC, van Beersum SE, van den Boogaard MJ, Breuning MH
    American journal of human genetics. 1993 ; 52 (2) : 255-262.
    PMID 8430692
    Rubinstein-Taybi syndrome with de novo reciprocal translocation t(2;16)(p13.3;p13.3).
    Imaizumi K, Kuroki Y
    American journal of medical genetics. 1991 ; 38 (4) : 636-639.
    PMID 2063911
    Confirmation of assignment of a locus for Rubinstein-Taybi syndrome gene to 16p13.3.
    Lacombe D, Saura R, Taine L, Battin J
    American journal of medical genetics. 1992 ; 44 (1) : 126-128.
    PMID 1519642
    Submicroscopic deletion of chromosome region 16p13.3 in a Japanese patient with Rubinstein-Taybi syndrome.
    Masuno M, Imaizumi K, Kurosawa K, Makita Y, Petrij F, Dauwerse HG, Breuning MH, Kuroki Y
    American journal of medical genetics. 1994 ; 53 (4) : 352-354.
    PMID 7864045
    Diagnostic analysis of the Rubinstein-Taybi syndrome: five cosmids should be used for microdeletion detection and low number of protein truncating mutations.
    Petrij F, Dauwerse HG, Blough RI, Giles RH, van der Smagt JJ, Wallerstein R, Maaswinkel-Mooy PD, van Karnebeek CD, van Ommen GJ, van Haeringen A, Rubinstein JH, Saal HM, Hennekam RC, Peters DJ, Breuning MH
    Journal of medical genetics. 2000 ; 37 (3) : 168-176.
    PMID 10699051
    Petrij F, Giles RH, Breuning MH, Hennekam RC RubinsteinTaybi Syndrome
    In Scriver CR, Beaudet AL, Valle D, Sly WS, editors..
    Broad thumbs and toes and facial abnormalities. A possible mental retardation syndrome.
    American journal of diseases of children (1960). 1963 ; 105 : 588-608.
    PMID 13983033
    Broad thumb-hallux (Rubinstein-Taybi) syndrome 1957-1988.
    Rubinstein JH
    American journal of medical genetics. Supplement. 1990 ; 6 : 3-16.
    PMID 2118774
    Submicroscopic deletion of chromosome 16p13.3 in patients with Rubinstein-Taybi syndrome.
    Taine L, Goizet C, Wen ZQ, Petrij F, Breuning MH, Aymé S, Saura R, Arveiler B, Lacombe D
    American journal of medical genetics. 1998 ; 78 (3) : 267-270.
    PMID 9677064
    Tentative assignment of a locus for Rubinstein-Taybi syndrome to 16p13.3 by a de novo reciprocal translocation, t(7;16)(q34;p13.3).
    Tommerup N, van der Hagen CB, Heiberg A
    American journal of medical genetics. 1992 ; 44 (2) : 237-241.
    PMID 1456298


    This paper should be referenced as such :
    Lacombe, B
    Rubinstein-Taybi syndrome (RTS)
    Atlas Genet Cytogenet Oncol Haematol. 2001;5(3):217-219.
    Free journal version : [ pdf ]   [ DOI ]
    On line version :

    Other genes implicated (Data extracted from papers in the Atlas) [ 2 ]

    Genes CREBBP EP300

    External links

    OrphanetRubinstein-Taybi syndrome
    REVIEW articlesautomatic search in PubMed
    Last year articlesautomatic search in PubMed

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