Rubinstein–Taybi syndrome

Rubinstein–Taybi syndrome
Patient with Rubinstein–Taybi syndrome
Classification and external resources
Specialty	medical genetics
ICD-10	Q87.2
ICD-9-CM	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.^[2] 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.

Features of Rubinstein–Taybi syndrome

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.^[3] In 1963, Jack Herbert Rubinstein (1925–2006) and Hooshang Taybi (1919–2006) described a larger series of cases.^[4]

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 or Certified Registered Nurse Anesthetists, CRNA's).”^[5] Primary literature suggests the children may have a higher rate of cardiac physical and conduction abnormalities which may cause unexpected results with cardioactive medications.^[6] 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.^[7]

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.^[8] Other research has shown a link with long-term memory (LTM) deficit.^[9]^[10] See also Epigenetics in learning and memory.

Genetics

Rubinstein–Taybi syndrome is inherited in an autosomal dominant fashion.

Rubinstein–Taybi syndrome is a microdeletion syndrome involving chromosomal segment 16p13.3 and is characterized by mutations in the CREBBP gene.^[11]^[12] 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.

References

↑ Online 'Mendelian Inheritance in Man' (OMIM) Rubinstein–Taybi syndrome -180849
↑ 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 (March 2000). "Diagnostic analysis of the Rubinstein-Taybi syndrome: five cosmids should be used for microdeletion detection and low number of protein truncating mutations.". Journal of Medical Genetics 37 (3): 168–76. doi:10.1136/jmg.37.3.168. PMC 1734540. PMID 10699051.
↑ Michail J, Matsoukas J, Theodorou S (1957). "Pouce bot arqué en forte abduction-extension et autres symptômes concomitants" [Arched, clubbed thumb in strong abduction-extension & other concomitant symptoms]. Revue De Chirurgie Orthopédique Et Réparatrice De L'appareil Moteur (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. doi:10.1001/archpedi.1963.02080040590010. PMID 13983033.
↑ http://www.rubinstein-taybi.org/anesthesia.html[]
↑ Stirt JA (July 1981). "Anesthetic problems in Rubinstein-Taybi syndrome". Anesthesia and Analgesia 60 (7): 534–6. doi:10.1213/00000539-198107000-00016. PMID 7195672.
↑ Dearlove OR, Perkins R (March 2003). "Anaesthesia in an adult with Rubinstein-Taybi syndrome". British Journal of Anaesthesia 90 (3): 399–400; author reply 399–400. doi:10.1093/bja/aeg537. 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, et al. (September 2003). "A mouse model of Rubinstein-Taybi syndrome: defective long-term memory is ameliorated by inhibitors of phosphodiesterase 4". Proceedings of the National Academy of Sciences of the United States of America 100 (18): 10518–22. Bibcode:2003PNAS..10010518B. doi:10.1073/pnas.1834280100. JSTOR 3147748. PMC 193593. PMID 12930888.
↑ Alarcón JM, Malleret G, Touzani K, et al. (June 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 (6): 947–59. doi:10.1016/j.neuron.2004.05.021. PMID 15207239.
↑ Wójcik, C; Volz, K; Ranola, M; Kitch, K; Karim, T; O'Neil, J; Smith, J; Torres-Martinez, W (February 2010). "Rubinstein-Taybi syndrome associated with Chiari type I malformation caused by a large 16p13.3 microdeletion: a contiguous gene syndrome?". American journal of medical genetics. Part A 152A (2): 479–83. doi:10.1002/ajmg.a.33303. PMID 20101707.
↑ 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

Wikimedia Commons has media related to Rubinstein–Taybi syndrome.

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
Rubinstein-Taybi syndrome due to 16p13.3 microdeletion on ORPHAnet

Congenital abnormality syndromes (Q87, 759.7)

Craniofacial

Acrocephalosyndactylia Apert syndrome/Pfeiffer syndrome Saethre–Chotzen syndrome Carpenter syndrome Sakati–Nyhan–Tisdale syndrome

other:	Möbius syndrome Goldenhar syndrome Cyclopia Baller–Gerold syndrome

Short stature

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

Overgrowth

Laurence–Moon–Bardet–Biedl

Combined/other,
known locus

2 (Feingold syndrome)
3 (Zimmermann–Laband syndrome)
4/13 (Fraser syndrome)
8 (Branchio-oto-renal syndrome, CHARGE syndrome)
12 (Keutel syndrome, Timothy syndrome)
15 (Marfan syndrome)
19 (Donohue syndrome)
Multiple
- Fryns syndrome

Genetic disorder, protein biosynthesis: Transcription factor/coregulator deficiencies

(1) Basic domains

1.2	Feingold syndrome Saethre–Chotzen syndrome

1.3	Tietz syndrome

(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

(3) Helix-turn-helix domains

3.1	ARX Ohtahara syndrome Lissencephaly X2 MNX1 Currarino syndrome HOXD13 SPD1 Synpolydactyly PDX1 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 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

(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

(0) Other transcription factors

0.6	Kabuki syndrome

Ungrouped

Transcription coregulators

Coactivator:	CREBBP Rubinstein–Taybi syndrome

Corepressor:	HR (Atrichia with papular lesions)

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