| Rubinstein–Taybi syndrome |
| Classification and external resources |
Patient with Rubinstein–Taybi syndrome
|
| ICD-10 |
Q87.2 |
| ICD-9 |
759.89 |
| OMIM |
180849 |
| DiseasesDB |
29344 |
| MedlinePlus |
001249 |
| eMedicine |
derm/711 ped/2026 |
| MeSH |
D012415 |
| GeneReviews |
- Rubinstein–Taybi syndrome
|
Rubinstein–Taybi syndrome (RTS), also known as broad thumb-hallux syndrome or Rubinstein syndrome,[1] is a condition characterized by short stature, moderate to severe learning difficulties, distinctive facial features, and broad thumbs and first toes. Other features of the disorder vary among affected individuals. People with this condition have an increased risk of developing noncancerous and cancerous tumors, leukemia, and lymphoma. This condition is sometimes inherited as an autosomal dominant pattern and is uncommon, many times it occurs as a de novo (not inherited) occurrence, it occurs in an estimated 1 in 125,000-300,000 births.
Contents
- 1 Features of Rubinstein–Taybi syndrome
- 2 Genetics
- 3 See also
- 4 References
- 5 External links
Features of Rubinstein–Taybi syndrome[edit source | edit]
Facial features (A), left hand and feet showing broad thumb and big toes (B, C) and X-ray of both hands showing short broad thumbs (D). (Limb Malformations & Skeletal Dysplasia)
A case was described in 1957 by Michail, Matsoukas and Theodorou.[2] In 1963, Jack Herbert Rubinstein (1925–2006) and Hooshang Taybi (born 1919) described a larger series of cases.[3]
Typical features of the disorder include:
- Broad thumbs and broad first toes
- Mental disability
- Small height, bone growth, small head
- Cryptorchidism in males
- Unusual faces involving the eyes, nose, and palate
- Anesthesia may be dangerous in these patients: “According to the medical literature, in some cases, individuals with Rubinstein–Taybi syndrome may have complications (e.g., respiratory distress and/or irregular heart beats [cardiac arrythmias]) associated with a certain muscle relaxant (succinlycholine) and certain anesthesia. Any situations requiring the administration of anesthesia or succinlycholine (e.g., surgical procedures) should be closely monitored by skilled professionals (anesthesiologists).”[4] Primary literature consists mostly of case reports and editorial papers. At least one case series suggests the children may have a higher rate of cardiac physical and conduction abnormalities which may cause unexpected results with cardioactive medications.[5] A further editorial reply in the British Journal of Anaesthesia discusses changes in the face and airway structure making it more difficult to secure the airway under anaesthesia, however, complications appeared in a minority of cases, and routine methods of airway control in the operating room appears to be successful. They recommended close individual evaluation of Rubinstein–Taybi patients for anaesthetic plans.[6]
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, and hypothesized that the identified CREBBP gene impaired motor skills learning.[7] Other research has shown a link with long-term memory (LTM) deficit.[8][9][10]
Genetics[edit source | edit]
Rubinstein–Taybi syndrome is inherited in an autosomal dominant fashion.
Mutations in the CREBBP gene cause Rubinstein–Taybi syndrome.[11] The CREBBP gene makes a protein that helps control the activity of many other genes. The protein, called CREB-binding protein, plays an important role in regulating cell growth and division and is essential for normal fetal development. If one copy of the CREBBP gene is deleted or mutated, cells make only half of the normal amount of CREB binding protein. A reduction in the amount of this protein disrupts normal development before and after birth, leading to the signs and symptoms of Rubinstein–Taybi syndrome.
Mutations in the EP300 gene are responsible for a small percentage of cases of Rubinstein–Taybi syndrome. These mutations result in the loss of one copy of the gene in each cell, which reduces the amount of p300 protein by half. Some mutations lead to the production of a very short, nonfunctional version of the p300 protein, while others prevent one copy of the gene from making any protein at all. Although researchers do not know how a reduction in the amount of p300 protein leads to the specific features of Rubinstein–Taybi syndrome, it is clear that the loss of one copy of the EP300 gene disrupts normal development.
1 out of 100,000 to 125,000 children are born with RTS.
See also[edit source | edit]
- Nasodigitoacoustic syndrome
- List of cutaneous conditions
References[edit source | edit]
- ^ Online 'Mendelian Inheritance in Man' (OMIM) Rubinstein–Taybi syndrome -180849
- ^ Michail J, Matsoukas J, Theodorou S (1957). "[Arched, clubbed thumb in strong abduction-extension & other concomitant symptoms.]". Rev Chir Orthop Reparatrice Appar Mot (in French) 43 (2): 142–6. PMID 13466652.
- ^ Rubinstein JH, Taybi H (June 1963). "Broad thumbs and toes and facial abnormalities. A possible mental retardation syndrome". Am. J. Dis. Child. 105: 588–608. PMID 13983033.
- ^ http://www.rubinstein-taybi.org/anesthesia.html
- ^ Stirt, J A (1981). "Anesthetic problems in Rubinstein–Taybi syndrome". Anesthesia & Analgesia. 60 (7): 534–6.
- ^ Dearlove, O R. Perkins, R. (2003). "Anaesthesia in an adult with Rubinstein–Taybi syndrome". British Journal of Anaesthesia 90 (3): 399–400. PMID 12594162.
- ^ Galéra C, Taupiac E, Fraisse S et al. (2009). "Socio-behavioral sharacteristics of children with Rubinstein–Taybi syndrome". J Autism Dev Disord 39 (9): 1252–1260. doi:10.1007/s10803-009-0733-4. PMID 19350377.
- ^ Bourtchouladze R, Lidge R, Catapano R, Stanley J, Gossweiler S, Romashko D, Scott R, Tully T (2003) A mouse model of Rubinstein-Taybi syndrome: defective long-term memory is ameliorated by inhibitors of phosphodiesterase 4. Proc Natl Acad Sci USA 100:10518-10522.
- ^ Alarcon JM, Malleret G, Touzani K, Vronskaya S, Ishii S, Kandel ER, Barco A (2004) Chromatin acetylation, memory, and LTP are impaired in CBP+/– mice: a model for the cognitive deficit in Rubinstein-Taybi syndrome and its amelioration. Neuron 42:947-959.
- ^ Epigenetics in learning and memory
- ^ Petrij F, Giles RH, Dauwerse HG, et al. (July 1995). "Rubinstein–Taybi syndrome caused by mutations in the transcriptional co-activator CBP". Nature 376 (6538): 348–51. Bibcode:1995Natur.376..348P. doi:10.1038/376348a0. PMID 7630403.
External links[edit source | edit]
- RTS – Rubinstein–Taybi Syndrome – Associazione italiana RTS
- RTS – Rubinstein–Taybi Syndrome – a site devoted to the families and people diagnosed with Rubinstein–Taybi syndrome.
- RTS – Rubinstein–Taybi Syndrome Argentina – RTS Argentina – www.rubinsteintaybi.com.ar – Grupo de Apoyo – Historias.
- Dutch RTS-site – RTS the Netherlands
- History of RTS by J.H. Rubinstein.
- GeneReview/UW/NIH entry on Rubinstein-Taybi syndrome
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Congenital abnormality · multiple abnormalities (Q87, 759.7)
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| Craniofacial |
Acrocephalosyndactylia (Apert syndrome/Pfeiffer syndrome, Saethre–Chotzen syndrome, Carpenter syndrome, Sakati–Nyhan–Tisdale syndrome)
other: Möbius syndrome · Goldenhar syndrome · Cyclopia
|
|
| Short stature |
1q21.1 deletion syndrome · Aarskog–Scott syndrome · Cockayne syndrome · Cornelia de Lange Syndrome · Dubowitz syndrome · Noonan syndrome · Robinow syndrome · Silver–Russell syndrome · Seckel syndrome · Smith–Lemli–Opitz syndrome · Turner syndrome
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| Limbs |
Adducted thumb syndrome · Holt–Oram syndrome · Klippel–Trénaunay–Weber syndrome · Nail–patella syndrome · Rubinstein–Taybi syndrome
Gastrulation/mesoderm: Caudal regression syndrome · ectromelia (Sirenomelia) · VACTERL association
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|
| Overgrowth |
Beckwith–Wiedemann syndrome · Sotos syndrome · Weaver syndrome · Perlman syndrome
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| Laurence–Moon–Bardet–Biedl |
Bardet–Biedl syndrome · Laurence–Moon syndrome
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Combined/other,
known locus |
3 (Zimmerman–Laband syndrome) · 4/13 (Fraser syndrome) · 8 (Branchio-oto-renal syndrome) · 12 (Keutel syndrome, Timothy syndrome) · 15 (Marfan syndrome) · 19 (Donohue syndrome)
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Genetic disorder, protein biosynthesis: Transcription factor/coregulator deficiencies
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| (1) Basic domains |
1.2: Feingold syndrome · Saethre–Chotzen syndrome
1.3: Tietz syndrome
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(2) Zinc finger
DNA-binding domains |
2.1 (Intracellular receptor): Thyroid hormone resistance · Androgen insensitivity syndrome (PAIS, MAIS, CAIS) · Kennedy's disease · PHA1AD pseudohypoaldosteronism · Estrogen insensitivity syndrome · X-linked adrenal hypoplasia congenita · MODY 1 · Familial partial lipodystrophy 3 · SF1 XY gonadal dysgenesis
2.2: Barakat syndrome · Tricho–rhino–phalangeal syndrome
2.3: Greig cephalopolysyndactyly syndrome/Pallister–Hall syndrome · Denys–Drash syndrome · Duane-radial ray syndrome · MODY 7 · MRX 89 · Townes–Brocks syndrome · Acrocallosal syndrome · Myotonic dystrophy 2
2.5: Autoimmune polyendocrine syndrome type 1
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| (3) Helix-turn-helix domains |
3.1: ARX (Ohtahara syndrome, Lissencephaly X2) · HLXB9 (Currarino syndrome) · HOXD13 (SPD1 Synpolydactyly) · IPF1 (MODY 4) · LMX1B (Nail–patella syndrome) · MSX1 (Tooth and nail syndrome, OFC5) · PITX2 (Axenfeld syndrome 1) · POU4F3 (DFNA15) · POU3F4 (DFNX2) · ZEB1 (Posterior polymorphous corneal dystrophy 3, Fuchs' dystrophy 3) · ZEB2 (Mowat–Wilson syndrome)
3.2: PAX2 (Papillorenal syndrome) · PAX3 (Waardenburg syndrome 1&3) · PAX4 (MODY 9) · PAX6 (Gillespie syndrome, Coloboma of optic nerve) · PAX8 (Congenital hypothyroidism 2) · PAX9 (STHAG3)
3.3: FOXC1 (Axenfeld syndrome 3, Iridogoniodysgenesis, dominant type) · FOXC2 (Lymphedema–distichiasis syndrome) · FOXE1 (Bamforth–Lazarus syndrome) · FOXE3 (Anterior segment mesenchymal dysgenesis) · FOXF1 (ACD/MPV) · FOXI1 (Enlarged vestibular aqueduct) · FOXL2 (Premature ovarian failure 3) · FOXP3 (IPEX)
3.5: IRF6 (Van der Woude syndrome, Popliteal pterygium syndrome)
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(4) β-Scaffold factors
with minor groove contacts |
4.2: Hyperimmunoglobulin E syndrome
4.3: Holt–Oram syndrome · Li–Fraumeni syndrome · Ulnar–mammary syndrome
4.7: Campomelic dysplasia · MODY 3 · MODY 5 · SF1 (SRY XY gonadal dysgenesis, Premature ovarian failure 7) · SOX10 (Waardenburg syndrome 4c, Yemenite deaf-blind hypopigmentation syndrome)
4.11: Cleidocranial dysostosis
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| (0) Other transcription factors |
0.6: Kabuki syndrome
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| Ungrouped |
TCF4 (Pitt–Hopkins syndrome) · ZFP57 (TNDM1) · TP63 (Rapp–Hodgkin syndrome/Hay–Wells syndrome/Ectrodactyly–ectodermal dysplasia–cleft syndrome 3/Limb–mammary syndrome/OFC8)
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| Transcription coregulators |
coactivator: CREBBP (Rubinstein–Taybi syndrome)
corepressor: HR (Atrichia with papular lesions)
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see also transcription factors
- B structural
- perx
- skel
- cili
- mito
- nucl
- sclr
- DNA/RNA/protein synthesis
- membrane
- transduction
- trfk
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