Definition

Rubinstein-Taybi syndrome is a condition characterized by short stature, intellectual disability, distinctive facial features, and broad thumbs and toes. This rare syndrome affects approximately 1 in 100,000 to 125,000 newborns.

Causes

Mutations in the CREBBP gene account for about half of all cases of Rubinstein-Taybi syndrome. The CREBBP gene provides instructions for the production of a protein that helps regulate the activity of numerous other genes. This protein, known as CREB-binding protein, plays a crucial role in controlling cell growth and division, as well as ensuring proper development before birth.

Due to the loss or mutation of one copy of the CREBBP gene in individuals with Rubinstein-Taybi syndrome, their cells produce only half the normal amount of CREB-binding protein. This deficiency disrupts normal developmental processes both before and after birth.

Abnormal brain development is believed to underlie the intellectual disability seen in individuals with Rubinstein-Taybi syndrome. Researchers are still unclear on how mutations in the CREBBP gene result in the other signs and symptoms associated with the syndrome.

Mutations in the EP300 gene cause a small percentage of Rubinstein-Taybi syndrome cases. Like CREBBP, this gene provides instructions for making a protein that regulates the activity of other genes. Mutations in the EP300 gene result in the loss of one functional copy of the gene in each cell, which impairs normal development and leads to the features of Rubinstein-Taybi syndrome.

Cases caused by mutations in the EP300 gene tend to have milder symptoms compared to those caused by mutations in CREBBP.

Severe cases of Rubinstein-Taybi syndrome can result from the loss of genetic material on the short arm of chromosome 16. Many genes, including CREBBP, are missing due to this loss of genetic material. Researchers believe that the deletion of several genes in this region may contribute to serious complications associated with the syndrome.

In nearly 30 to 40 percent of cases, individuals with Rubinstein-Taybi syndrome do not have mutations in CREBBP or EP300, nor do they exhibit chromosomal deletions. The cause of the condition in these cases remains unknown, though researchers suspect mutations in other genes may be responsible.

Risk Factor

This condition is thought to follow an autosomal dominant inheritance pattern, meaning that a single copy of the mutated gene in each cell is sufficient to cause the disorder. Although Rubinstein-Taybi syndrome can be inherited in an autosomal dominant manner, most cases arise from new mutations in the gene without a family history of the disorder.

Studies suggest that couples who have had one child with Rubinstein-Taybi syndrome have a 0.5% chance of having another child with the same condition. If a person with the syndrome has offspring, there is a 50% risk of passing the condition to their children.

Symptoms

Rubinstein-Taybi Syndrome is characterized by:

• Short stature
  

Height significantly below the expected range for age and gender.

• Feeding difficulties in infants

Infants may exhibit weak and ineffective sucking, frequent short sucking periods, and a tendency to fall asleep while feeding. Chewing difficulties may also be present.

• Global developmental delay
  

A delay in reaching developmental milestones across multiple areas, including motor skills, speech, cognitive abilities, and social-emotional development. This term is typically used to describe children under the age of 5.

• Moderate to severe intellectual disability
  

Impaired intellectual functioning, previously referred to as mental retardation, defined by an IQ score below 70.

• Constipation
• Frequent respiratory infections, especially in infants and young children
• Failure to thrive during infancy
• Excess weight gain, particularly in late childhood or early adolescence

Additionally, individuals with Rubinstein-Taybi syndrome may exhibit distinctive physical features, such as:

• Short fingers compared to the hands or feet.
• Broad thumbs and toes.
• Curved pinky fingers.
• A convex nasal bridge.
• Downward slanting palpebral fissures (the imaginary line drawn between the inner and outer corners of the eyes).
• Increased space between the eyes (hypertelorism).
• High intraocular pressure (glaucoma).
• High arched palate.
• Widely spaced nipples.
• Hypermobile joints, capable of moving beyond the normal range.
• Low-set ears.
• Heart and major blood vessel anomalies.
• Dental abnormalities, such as cavities.
• Skin irregularities, like keloid formation.

Psychological issues associated with Rubinstein-Taybi syndrome include:

• Anxiety, tension, or panic often triggered by interpersonal stress.
• Worry about negative outcomes from past unpleasant experiences or future uncertainties, accompanied by feelings of fear or threat.
• Sudden mood swings.
• Obsessive-compulsive disorder (OCD).
• Attention deficit hyperactivity disorder (ADHD)
  • Easily distracted
  • Impulsive
  • Restless
  • Difficulty in organizing tasks and projects
  • Trouble sleeping.
  • Social interaction challenges, sometimes leading to aggression or noisy behavior.

The severity of these signs and symptoms varies among individuals.

Diagnosis

Diagnosis of Rubinstein-Taybi syndrome typically involves clinical or physical examinations. X-rays may be conducted to detect abnormalities in the bones, especially in the hands and feet. Other radiological assessments may be used to monitor brain activity.

Genetic testing can confirm the presence of chromosomal mutations responsible for Rubinstein-Taybi syndrome.

Management

Treatment for Rubinstein-Taybi syndrome depends on the specific symptoms presented by each individual. A growth chart specifically designed for the syndrome will be used to monitor the child’s growth rate. Annual vision and hearing tests should be conducted, along with long-term monitoring of the heart, kidneys, and teeth.

If skeletal abnormalities are present, surgery, supportive therapy, and physical therapy may be employed to manage these conditions. Surgical intervention can also be performed on the hands or feet if there are abnormal digits. Other treatments include special educational programs, behavioral therapy, and speech therapy.

Complications

People with Rubinstein-Taybi syndrome have an increased risk of developing certain benign brain and skin tumors. However, life expectancy for individuals with the syndrome is generally not significantly different from that of the general population.

Prevention

Prenatal ultrasound is unlikely to provide an accurate diagnosis. If a couple has had a previous child with Rubinstein-Taybi syndrome, prenatal testing using chorionic villus sampling (CVS) may be considered in future pregnancies, if feasible. Testing may also be done if there are suspicions during the first pregnancy.

When to See a Doctor?

If you have concerns about your child's development or complications related to Rubinstein-Taybi syndrome, it is advisable to consult with a doctor.

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