Genetics of Rubinstein-Taybi Syndrome

Updated: Sep 12, 2016
  • Author: Keith K Vaux, MD; Chief Editor: Luis O Rohena, MD, FAAP, FACMG  more...
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Overview

Practice Essentials

Consistent features of Rubinstein-Taybi syndrome (RSTS) include intellectual disability, broad great toes, broad thumbs, and maxillary abnormality. Other features include characteristic facies, ie, high, arched eyebrows; beaked nose with short columella; abnormal palpebral fissure slant for race; and micrognathia. The syndrome was first described by Rubenstein and Taybi, in 1963. [1, 2]

Most cases arise from sporadic, fresh mutations (1% recurrence risk) in the cAMP response element-binding protein (CREB)–binding protein (CBP) gene or from EP300 mutations. [3, 4]

Patients with RSTS are susceptible to frequent infections (pulmonary and otitis media), have a high anesthesia risk, demonstrate an ineffective response to vaccines (polysaccharide), and have dental abnormalities.

Primary care involves management of the following:

  • Infections
  • Dental abnormalities (crowding, abscesses)
  • Scoliosis
  • Obesity
  • Obstructive sleep apnea
  • Intellectual disability

Screening echocardiogram should be performed if murmur or cyanosis is present. Tumor surveillance (central nervous system neoplasms and rhabdomyosarcoma) is important as well. 

Medications to avoid in RSTS include the following:

  • Muscle relaxants 
  • Succinylcholine
  • Strong warning about out-of-hospital anesthesia
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Pathophysiology

Three main genetic etiologies for RSTS have been identified, accounting for approximately half of all cases. They include the following [5, 6, 7] :

  • 16p13 deletion syndrome - A submicroscopic, proximal deletion on chromosome 16p13.3, which includes the CREB-binding protein ( CBP) gene, DNASE1, and TRAP1
  • Rubenstein-Taybi syndrome 1 (RSTS-1) - A point mutation or deletion in  CBP (OMIM 180849); 50% of cases [4]
  • Rubenstein-Taybi syndrome 2 (RSTS-2) - A point mutation or deletion in EP300 (OMIM 602700);  3% of cases [3]

Mutation of the CBP gene has been detected in approximately 50% of affected individuals with RTST. Mutations in EP300 on 22q13.2 account for a small number of cases. Epigenetic alterations have been suggested as a possible cause for the remaining cases, as approximately 50% of individuals with clinical features consistent with RTST do not have a detectable deletion or mutation in CBP or EP300.

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Epidemiology

Frequency

International

Beets et al stated that the birth prevalence of RSTS is 1 in 100,000-125,000. [8]

Mortality/Morbidity

Respiratory infections and complications from congenital heart disease are major causes of morbidity and mortality in the first years of life. Instability of the craniovertebral junction at C1-C2, hypoplasia of the dens, and fusion of the cervical vertebrae have been described as potentially life-threatening abnormalities. Issues with perioperative management, including collapsible airway and susceptibility to succinylcholine, have also been described. Wiley et al have provided guidelines for the clinical management and surveillance of patients with RSTS. [9]

Race

No known race predilection has been noted.

Sex

Males and females appear to be equally affected.

Age

RSTS is often identified in the newborn period when the characteristic physical features are noted (eg, prominent nose, broad thumb, broad great toe).

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Prognosis

Patients with RSTS can have a normal lifespan. Major causes of morbidity and mortality in the first years of life include the following:

  • Respiratory infections
  • Complications from congenital heart disease
  • Instability of the craniovertebral junction at C1-C2
  • Hypoplasia of the dens
  • Fusion of the cervical vertebrae
  • Perioperative management - Collapsible airway, susceptibility to succinylcholine
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Patient Education

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