What is Rubinstein-Taybi syndrome?

Rubinstein-Taybi syndrome (RSTS) is a disease caused by mutations – or genetic changes – in the CREBBP or EP300 gene. It is characterized by a distinctive shape of the face, broad and often angled thumbs and big toes, dwarfism, and intellectual impairment.

How is Rubinstein-Taybi syndrome diagnosed?

Clinical Diagnosis

The syndrome is generally diagnosed due to the occurrence of specific clinical findings, which include the following anomalies:

  • Distinctive shape of the face

    • Drooping palpebral fissures
    • Low-lying nose bridge
    • High palate
    • Grimacing laugh
    • Growths on the teeth, usually on the inside of the remaining upper incisors
  • Broad, often angled thumbs, broad fingers and toes

  • Undescended testicles in male RSTS patients

  • Changes in the urogenital tract

  • Congenital heart diseases

  • Small stature (dwarfism) during adulthood

  • Obesity during childhood and adolescence

  • Intellectual impairment (IQ between 25 and 79)

Genetic Diagnostics

The diagnosis of “Rubinstein-Taybi syndrome” can also be confirmed by detection of a mutation – or genetic change – in the CREBBP or EP300 gene.

What is the risk of cancer?

To date, various benign and malignant tumors affecting different organs (e.g. liver, nervous system, testicles/ovaries, skin, blood) have been described as part of Rubinstein-Taybi syndrome. However, the risk of malignant diseases is only moderate.

Generally, children with the syndrome are detected at birth or in infancy due to the striking shape of the face and the characteristic changes in the hands and feet. During infancy and early childhood, breathing difficulties, feeding problems, absence of weight gain, frequent infections, and severe constipation may occur.

The symptoms associated with Rubinstein-Taybi syndrome can affect different organ systems and regions, namely the following anomalies and changes:

Region Symptoms
Face Drooping palpebral fissures, low-lying nose bridge, high palate, grimacing laugh
Nervous system Anomalies and structural changes in the area of the head and neck, which can end up constricting the spinal cord, for example.
Eyes Squinting, near and farsightedness, drooping eyelids, a narrowing of the nasolacrimal duct, cataracts, a gap formation in the eye, trembling of the eyes, glaucoma, changes, and the cornea, and retinal defects
Heart Around one third of RSTS patients have congenital heart disease.
Urogenital tract Changes in the kidneys are very common.
Nearly all male RSTS patients have undescended testicles.
Skeleton Broad, often angled thumbs and toes, broad fingers, shifted kneecaps, lax joints, curvature of the spine, death of bone tissue in the head of the femur (Perthes disease), slipping of the head of the femur, and changes in the cervical spine
Sleep apnea Obstructive sleep apnea (periodic interruptions in breathing while asleep) caused by the combination of a constricted palate, a small jaw, muscle weakness, obesity, and a slightly collapsed pharyngeal wall
Skin Small tissue growths and benign, hard skin tumors arising from the hair roots
Teeth Crowded teeth, malocclusion (teeth of the upper and lower jaw not in proper alignment), cavities, excessive or missing teeth, teeth present at birth, growths on the teeth (usually occurring on the inside of the remaining upper incisors)
Growth Normal growth before birth. During infancy, the parameters for growth, weight, and head circumference fall below the 5th percentile. The average height is 153 cm in men and 147 cm in women. Boys often become obese during childhood and girls in adolescence.
Intellect Delays in motor, psychosocial development, and speech. The IQ is between 25 and 79.
Behavior Short attention span, low tolerance for noise and crowds, impulsiveness, and moodiness are frequently observed. In addition, attention deficit problems, hyperactivity, and self-infliction of injuries, aggressive, or autistic behavior may occur.

What causes Rubinstein-Taybi syndrome?

Rubinstein-Taybi syndrome is a disease caused by mutations – or genetic changes – in the CREBBP or EP300 gene. These genes encode for the CREB-binding protein and the EP300 protein, respectively, both of which are necessary for reading and amplifying the DNA – or genetic material – in our body.

Now if the CREBBP or the EP300 gene is altered, the corresponding protein will not be produced correctly, and consequently will not be able to function as a tumor suppressor. This can result in the defective development of various structures in the body.

Rubinstein-Taybi syndrome occurs in approximately one out of 100,000 to 125,000 people and can be passed on by parents to their children. In these cases, it is inherited as an autosomal dominant disease. However, the syndrome is generally due to spontaneous or new mutations, called de novo mutations.

Is there a treatment?

In light of the large number of potential manifestations, treatment should always be symptom-orientated and involve different specialist disciplines working together.

Surveillance Recommendations for the Early Detection of Cancer

Surveillance Recommendations

The following examinations should be conducted for patients with Rubinstein-Taybi syndrome for the purpose of early detection:

  • Close monitoring of body height, especially during the first year of life

  • Annual ophthalmological examination

  • Annual ENT examination, more frequently following multiple middle ear infections (otitis media)

  • Regular examinations to check for changes in the heart or kidneys

  • Regular dental examinations

If any anomalies are detected, other examinations should be conducted as needed and the patient transferred to specialists.

Patients should be informed of their moderately increased risk of cancer. Specific cancer surveillance is not recommended.

Self-Care and Support

What should I pay special attention to?

You should consult a doctor as soon as changes in vision, the skin, perception, or motor skills occur. Moreover, movement restrictions and pain in the bones or joints should be noted and reported to a doctor. You should likewise go to a doctor if new anomalies or complaints such as behavioral disorders develop.

Support Groups and Additional Information