Rubinstein-Taybi Syndrome

What is Rubinstein-Taybi Syndrome?

Rubinstein-Taybi Syndrome (RTS) can be defined as multi-system disorder develops due to abnormal genetic mutation. The characteristic features of RTS include different multiple developmental disorders. The name of this syndrome is named so because of inventors of this disease are Jack Rubinstein and HooshangTaybi. The disease is first described in 1957, but Jack Rubinstein and HooshangTaybi identified this disease in 1963¹.

Symptoms

Rubinstein-Taybi Syndrome has some typical characteristics, which include

• Short stature
• Moderate to severe intellectual disability
• Distinctive facial features
• Broad thumbs
• First toes²

Other included symptoms rather associated disorders are as follows, which may not see to every individual

• Eye abnormalities
• Cardiac problem
• Renal defects
• Dental troubles
• Obesity²

RTS patients have some characteristic features, which include

• Angulated toes and thumbs
• Delayed bone growth
• Broad nasal bridge
• Beak shaped nose
• Either side of the nose has extra skin folding
• Small sized lower jaw
• Small circumference of head
• Ear malformation
• High dome shaped palate
• Feeding difficulty
• Hyperextensible joints³

The illustration of ocular symptoms of Rubinstein-Taybi Syndrome include following features

• Position of the eye is slightly downward and slanting
• Space between two eyes are wide
• Misalignment of the eye (strabismus)
• Ptosis (droopy eyelid)
• Eyebrows are high arched
• Tear drainage duct become blocked and leads to frequent eye infection⁴

Apart from above mentioned symptoms, some associated eye disease like congenital glaucoma may develop at the RTS, though it is not always associated with RTS. Some characteristic features are uncontrollable tearing of the eyes, large sized eye than normal eyes, and/or cloudy corneas³.

Complications

Rubinstein-Taybi syndrome has some serious complications like cancerous and non-cancerous tumor development, brain tumor growth, leukemia. These complications are very usual findings in patients with Rubinstein-Taybi syndrome.

Rarely, Rubinstein-Taybi syndrome can involve serious complications such as a failure to gain weight and grow at the expected rate (failure to thrive) and life-threatening infections. Infants born with this severe form of the disorder usually survive only into early childhood³.

Causes

A de novo genetic mutation is caused by Rubinstein-Taybi syndrome. This novel genetic mutation has no hereditary involvement, therefore, does not shift from parental source. The effect individual rarely has only 1% risk of a second  affected child.

In the case of inherited in an autosomal dominant pattern responsible for RTS causes 50% risk for development of the same condition (RTS) for each of his/her child.

The most common identified gene involved in the RTS is CREBBP. Mostly the short arm of affected gene chromosome 16 (16p) is get affected. Approximately, 50 to 60% of individuals are affected with the CREBBP gene. Almost 3% to 8% of an affected individual has an abnormal mutation in EP300 gene. The location of the gene is on chromosome 22 (22q13.2)².

Diagnosis

The initial diagnosis is based upon clinical features analysis and that mainly conducted by physical examination. All the typical features of RTS are indicative of the presence of the disease. Different laboratory-based tests also conducted for diagnosis of the disease, which include

X-ray

X-ray images showed that hands and feet bones malformation.

FISH or sequence analysis

FISH test is conducted for genetic analysis and considered as a confirmatory test for RTS. genetic testing can identify the pathogenic variation of CREBBP gene in almost 50% to 60% affected individuals and also able to identify EP300 gene mutation in 3%-8% affected the individual⁴.

Treatment

• The treatment plan is completely dependent upon symptoms of the patient and severity of the symptoms.
• Speech therapy is recommended at the early stage of detection
• Sign language learning is also advantageous for patients who have extremely delayed verbal communication.
• Physical therapies and occupational therapies need for patients suffering from skeletal muscle abnormality
• Multiple deformity and disorders are associated with RTS, therefore, a team of experts in which included doctors like cardiologists for heart abnormality, orthopedists for skeletal abnormalities, audiologists for hearing problems, urologists for urinary tract abnormalities, nephrologists for kidney malformations, as well as dentist for dental problem usually present to handle the patient condition.
• Early intervention and special care can prevent respiratory and feeding difficulties. But patients who already have the above-mentioned condition, then they need special educational training and speech therapy to avoid the problem.
• Parent support groups can provide information which will be beneficial for affected family. Genetic counseling also helps to support family members^1,4.

Prognosis

All the available treatment is symptomatic. The prognosis of this disease is good, but usually, mortality occurs in the first year of life due to different disease-related complications⁴.

Life Expectancy

Life expectancy is normal if the patient survives the first year of his or her life. Because multiple disease-related fetal complications can arise within the first year of lifespan, which includes congenital heart disease, instability of the craniovertebral junction at C1-C2, a fusion of the cervical vertebrae and hypoplasia of the dens. All these conditions can cause the potentially life-threatening outcome. Collapsible airway and susceptibility to succinylcholine have been also considered as perioperative management. Wiley et al have presented a clinical strategy for the management and supervision of RTS patients^2,4.

Pictures

References

1. Rubinstein-Taybi Syndrome; American Association for Pediatric Ophthalmology and Strabismus; Online available at https://www.aapos.org/terms/conditions/96
2. Keith K Vaux, Genetics of Rubinstein-Taybi Syndrome Medication; Medscape; http://emedicine.medscape.com/article/948453-medication
3. Rubinstein-Taybi syndrome; Genetic Home References; Online available at https://ghr.nlm.nih.gov/condition/rubinstein-taybi-syndrome
4. Rubinstein Taybi Syndrome; Natonal Organization for Rare disorders; Online available at https://rarediseases.org/rare-diseases/rubinstein-taybi-syndrome/