Rubinstein-Taybi Syndrome
Introduction
Rubinstein-Taybi Syndrome (RTS) is a rare genetic disorder characterized by broad thumbs and toes, intellectual disability, distinctive facial features, and growth retardation. First described by American pediatrician Jack Rubinstein and radiologist Hooshang Taybi in 1963, the syndrome is caused by mutations in the CREBBP (CREB binding protein) or EP300 (E1A binding protein p300) genes.
Genetics
RTS is primarily caused by mutations in the CREBBP or EP300 genes, which are involved in regulating gene activity. These mutations can occur spontaneously or be inherited in an autosomal dominant manner. However, in about 30-40% of cases, the cause of the syndrome remains unknown.
Clinical Features
The clinical features of RTS are quite distinctive and can be observed from birth. They include:
Facial Features
Individuals with RTS often have a distinctive facial appearance, including a beaked nose, down-slanting palpebral fissures (eye slits), a highly arched palate, and a grimacing smile.
Limb Abnormalities
Broad thumbs and toes are a hallmark feature of RTS. Other limb abnormalities may include joint hypermobility and angulated thumbs.
Growth and Development
Growth retardation and developmental delay are common in RTS. Most affected individuals have mild to moderate intellectual disability.
Other Features
Other features may include heart defects, eye abnormalities, hearing loss, and increased risk of certain types of cancer.
Diagnosis
The diagnosis of RTS is primarily based on clinical features. Genetic testing can confirm the diagnosis by identifying a mutation in the CREBBP or EP300 gene.
Management and Treatment
There is no cure for RTS, and treatment is symptomatic and supportive. Management may include physical therapy, special education, and treatment of any associated medical conditions.
Prognosis
The prognosis for individuals with RTS varies. While some individuals may have a normal lifespan, others may have life-threatening complications such as heart defects or cancer.
Epidemiology
RTS is a rare disorder, affecting approximately 1 in 100,000 to 125,000 newborns. It affects males and females equally and is seen in all ethnic groups.
Research Directions
Research is ongoing to better understand the genetic basis of RTS and to develop more effective treatments.