eMedicine Specialties > Dermatology > Pediatric Diseases

Rubinstein-Taybi Syndrome

Author: Zeljko P Mijuskovic, MD, Dermatovenereologist, Department of Dermatology and Venereology, Military Medical Academy, Serbia
Coauthor(s): Djordjije Karadaglic, MD, DSc, Professor, School of Medicine, University of Podgorica, Podgorica, Montenegro; Ljubomir Stojanov, MD, PhD, Professor, University of Belgrade School of Medicine, Serbia
Contributor Information and Disclosures

Updated: Feb 5, 2009

Introduction

Background

In 1963, Rubinstein and Taybi first described Rubinstein-Taybi syndrome (RSTS) (Mendelian Inheritance in Man [MIM] #180849). Rubinstein-Taybi syndrome is a well-delineated malformation syndrome characterized by facial abnormalities, broad thumbs, broad great toes, short stature, and mental retardation.

For additional information, see eMedicine’s Pediatrics article Rubinstein-Taybi Syndrome.

Pathophysiology

The locus of Rubinstein-Taybi syndrome is located on band 16p13.3, which includes a gene encoding a binding protein for cyclic adenosine monophosphate–response element binding protein (CBP) (CREBBP or CBP gene) that is responsible for the phenotype of Rubinstein-Taybi syndrome. CBP spans approximately 150 kb with 31 exons, and its cDNA is 9 kb in length.1 Genetically based growth retardation and feeding difficulties are the main problems in early life; however, respiratory tract infections and complications from congenital heart disease are primary causes of morbidity and mortality in infancy.

Frequency

International

The prevalence of Rubinstein-Taybi syndrome in the general population is approximately 1 case per 300,000 persons and is as high as 1 case per 10,000 live births. Cantani and Gagliesi2 reported that Rubinstein-Taybi syndrome is not so rare and is present in approximately 1 in 600 patients seen in mental retardation clinics. Most cases of Rubinstein-Taybi syndrome are sporadic, although it has been reported in monozygotic twins.

Mortality/Morbidity

The survival rate is good, with frequent reports of adult patients with Rubinstein-Taybi syndrome. Respiratory tract infections and complications from congenital heart disease are primary causes of morbidity and mortality in infancy.

Race

Rubinstein-Taybi syndrome has no racial predilection.

Sex

Rubinstein-Taybi syndrome has no sexual predilection.

Age

The syndrome can often be recognized in the neonatal period by the typical abnormalities seen in the thumbs, the great toes, and the face.

Clinical

History

  • Patients may present with the following:
    • Characteristic abnormalities of the head, the face, the eyes, and the skin
    • Distinctive abnormalities of the fingers and the toes
    • Developmental delays, growth retardation, speech delays, and/or mental retardation
    • Skeletal malformations

Physical

  • Facial abnormalities (see Media File 1)
    • Hypoplastic maxilla with narrow palate (100%)
    • Prominent beaked nose (90%) (see Media File 2)
    • Antimongoloid palpebral fissures (88%) (see Media File 1)
    • Low-set/malformed ears (84%) (see Media File 2)
    • Strabismus (69%)
    • Large anterior fontanelle (41%)
    • Microcephaly (35%)
    • Small mouth
    • Crowded irregular teeth, high palate, short upper lip, and protuberant lower lip
  • Digital abnormalities
    • Broad great toes (100%) (see Media File 3)
    • Broad thumbs with radial angulation (87%) (see Media File 2)
    • Broad fingers (87%)
    • Persistent fetal finger pads (31%)
    • Duplicated longitudinal bracketed epiphysis (kissing delta phalanx)3
    • Syndactyly, polydactyly, and ulnar deviation of the thumb
  • Ocular abnormalities4
    • Strabismus (60-71%)
    • Nasolacrimal duct problems (38-47%)
    • Congenital or juvenile glaucoma
    • Retinal abnormalities
    • Ptosis (29-32%)
    • Refractive errors (41-56%)
    • Macrocornea, microphthalmos, colobomas (9-11%), congenital cataract, optic nerve atrophy, and corneal keloid
  • Abnormalities of growth and development
    • Mental retardation, with an intelligence quotient (IQ) of 30-79; IQ of less than 50 found in more than 50% of patients
    • Speech difficulties (90%)
    • Hypotonia (67%)
    • Growth retardation (postnatal-onset growth deficiency; average height of men is 153 cm [60 in], and average height of women is 147 cm [58 in], more frequently in patients with no CREBBP mutation)5
    • Feeding problems (85%) and echolalia
  • Skeletal abnormalities
    • Retarded osseous maturation (49%)
    • Vertebral and sternal abnormalities (including instability of C1-C2)
    • Patellar dislocation
    • Patellofemoral instability
    • Fourth cuneiform bones6
    • Joint hypermobility
  • Skin findings
    • Hirsutism (75%)
    • Capillary nevus of the forehead or the nape (>50%)
    • Keloid formation (4.87%)7
    • Multiple pilomatricomas,8 piebaldism, epidermal nevus, keratosis pilaris atrophicans faciei,9 and striate palmoplantar keratoderma10
  • Cardiovascular system11
    • Cardiac anomalies (32.6%)
    • ECG abnormalities (30%)
    • Cardiac arrhythmias with the use of succinylcholine
    • Ventricular septal defect and patent ductus arteriosus (both are most common)
    • Atrial septal defect, coarctation of the aorta, pulmonary artery stenosis, bicuspid aortic valve, hypoplastic left-sided heart, and conduction abnormalities
  • Other conditions
    • Cryptorchidism (78-100% of males)
    • Gastroesophageal reflux (68%)
    • Constipation (40-74%)
    • Laryngeal wall collapsibility (may cause sleeping problems and difficulty during anesthesia)
    • Insomnia (glossoptosis can cause sleep apnea)
    • Mood disorders and obsessive compulsive disorder
    • Abnormal pulmonary lobulation, bilateral vesicoureteral reflux, renal agenesis, polysplenia, thymic hypoplasia, megacolon, multiple meningiomas,12 congenital tracheal stenosis, epilepsy, and congenital hypothyroidism

Causes

CBP is a large nuclear protein involved in transcription regulation, chromatin remodeling, and integration of several signal transduction pathways. During organogenesis, CBP is expressed in specific cell types of the developing heart, vasculature, skin, lungs, and liver. Many of these tissues and organs are known to be affected in mutant mice lacking CBP and in patients with Rubinstein-Taybi syndrome.

Disruption of the human CBP gene, either by gross chromosomal rearrangements or by point mutations, leads to Rubinstein-Taybi syndrome. Translocations and inversions involving band 16p13.3 form the minority of CBP mutations, while microdeletions occur more frequently (approximately 10%). Blough et al13 reported that no phenotypic differences were observed among patients with partial deletion, complete deletion, and nondeletion, supporting a haploinsufficiency model for Rubinstein-Taybi syndrome.

Roelfsema et al14 reported EP300 gene mutations in 3 (3.3%) of 92 patients with either true Rubinstein-Taybi syndrome or different syndromes resembling Rubinstein-Taybi syndrome. The EP300 gene on band 22q13 encodes a protein, p300, that is highly similar to CREBBP. At present, the cause of Rubinstein-Taybi syndrome remains unknown in approximately half the patients. Both CBP and EP300 interact with several cofactors (p/CAF, CITED1, CITED4), which can also be involved in Rubinstein-Taybi syndrome and would indicate further genetic heterogeneity.

More on Rubinstein-Taybi Syndrome

Overview: Rubinstein-Taybi Syndrome
Differential Diagnoses & Workup: Rubinstein-Taybi Syndrome
Treatment & Medication: Rubinstein-Taybi Syndrome
Follow-up: Rubinstein-Taybi Syndrome
Multimedia: Rubinstein-Taybi Syndrome
References
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References

  1. 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. Mar 2000;37(3):168-76. [Medline].

  2. Cantani A, Gagliesi D. Rubinstein-Taybi syndrome. Review of 732 cases and analysis of the typical traits. Eur Rev Med Pharmacol Sci. Mar-Apr 1998;2(2):81-7. [Medline].

  3. Wood VE, Rubinstein J. Duplicated longitudinal bracketed epiphysis "kissing delta phalanx" in Rubinstein-Taybi syndrome. J Pediatr Orthop. Sep-Oct 1999;19(5):603-6. [Medline].

  4. van Genderen MM, Kinds GF, Riemslag FC, Hennekam RC. Ocular features in Rubinstein-Taybi syndrome: investigation of 24 patients and review of the literature. Br J Ophthalmol. Oct 2000;84(10):1177-84. [Medline].

  5. Schorry EK, Keddache M, Lanphear N, et al. Genotype-phenotype correlations in Rubinstein-Taybi syndrome. Am J Med Genet A. Oct 1 2008;146A(19):2512-9. [Medline].

  6. Sener RN. Bilateral extra tarsal bones in Rubinstein-Taybi syndrome: the fourth cuneiform bones. Eur Radiol. 1999;9(3):483-4. [Medline].

  7. Siraganian PA, Rubinstein JH, Miller RW. Keloids and neoplasms in the Rubinstein-Taybi syndrome. Med Pediatr Oncol. 1989;17(6):485-91. [Medline].

  8. Bayle P, Bazex J, Lamant L, Lauque D, Durieu C, Albes B. Multiple perforating and non perforating pilomatricomas in a patient with Churg-Strauss syndrome and Rubinstein-Taybi syndrome. J Eur Acad Dermatol Venereol. Sep 2004;18(5):607-10. [Medline].

  9. Gomez Centeno P, Roson E, Peteiro C, Mercedes Pereiro M, Toribio J. Rubinstein--Taybi syndrome and ulerythema ophryogenes in a 9-year-old boy. Pediatr Dermatol. Mar-Apr 1999;16(2):134-6. [Medline].

  10. Nakai K, Yoneda K, Moriue T, Kubota Y. Striate palmoplantar keratoderma in a patient with Rubinstein-Taybi syndrome. J Eur Acad Dermatol Venereol. Jul 9 2008;[Medline].

  11. Stevens CA, Bhakta MG. Cardiac abnormalities in the Rubinstein-Taybi syndrome. Am J Med Genet. Nov 20 1995;59(3):346-8. [Medline].

  12. Verstegen MJ, van den Munckhof P, Troost D, Bouma GJ. Multiple meningiomas in a patient with Rubinstein-Taybi syndrome. Case report. J Neurosurg. Jan 2005;102(1):167-8. [Medline].

  13. Blough RI, Petrij F, Dauwerse JG, et al. Variation in microdeletions of the cyclic AMP-responsive element-binding protein gene at chromosome band 16p13.3 in the Rubinstein-Taybi syndrome. Am J Med Genet. Jan 3 2000;90(1):29-34. [Medline].

  14. 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. Apr 2005;76(4):572-80. [Medline].

  15. Wiley S, Swayne S, Rubinstein JH, Lanphear NE, Stevens CA. Rubinstein-Taybi syndrome medical guidelines. Am J Med Genet A. Jun 1 2003;119A(2):101-10. [Medline].

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Further Reading

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Keywords

Rubinstein-Taybi syndrome, RSTS, broad thumb-hallux syndrome, mental retardation, broad big toes, prominent nose, growth retardation, feeding difficulties, congenital heart disease, developmental abnormalities

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Contributor Information and Disclosures

Author

Zeljko P Mijuskovic, MD, Dermatovenereologist, Department of Dermatology and Venereology, Military Medical Academy, Serbia
Zeljko P Mijuskovic, MD is a member of the following medical societies: European Academy of Dermatology and Venereology, European Society for Dermatological Research, International Society of Dermatology, and Serbian Association of DermatoVenereologists
Disclosure: Nothing to disclose.

Coauthor(s)

Djordjije Karadaglic, MD, DSc, Professor, School of Medicine, University of Podgorica, Podgorica, Montenegro
Djordjije Karadaglic, MD, DSc is a member of the following medical societies: American Academy of Dermatology, European Academy of Dermatology and Venereology, and Serbian Association of DermatoVenereologists
Disclosure: Nothing to disclose.

Ljubomir Stojanov, MD, PhD, Professor, University of Belgrade School of Medicine, Serbia
Disclosure: Nothing to disclose.

Medical Editor

Mark A Crowe, MD, Assistant Clinical Instructor, Department of Medicine, Division of Dermatology, University of Washington School of Medicine
Mark A Crowe, MD is a member of the following medical societies: American Academy of Dermatology and North American Clinical Dermatologic Society
Disclosure: Nothing to disclose.

Pharmacy Editor

David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic
David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Managing Editor

Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi
Disclosure: Nothing to disclose.

CME Editor

Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University
Catherine Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

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