Treatment Options and Lifespan for Rubinstein-Taybi Syndrome
Rubinstein-Taybi Syndrome (RSTS) is a rare genetic condition, affecting approximately 1 in 100,000-125,000 newborns. This condition is typically caused by changes in the DNA sequence, most commonly in the CREBBP or EP300 gene.
The common genetic causes of RSTS are pathogenic variants, deletions, or loss-of-function mutations in the CREBBP and EP300 genes. These genes encode transcriptional coactivators, CREB-binding protein (CBP) and p300, which are involved in chromatin remodeling and regulation of gene expression.
More specifically, CREBBP gene variants cause Rubinstein-Taybi syndrome type 1 (RSTS-1). These variants include missense mutations, small deletions, or large deletions affecting CREBBP, which disrupt its normal function as a transcriptional coactivator. On the other hand, EP300 gene variants cause a less common form called Rubinstein-Taybi syndrome type 2 (RSTS-2).
Both genes play critical roles in gene expression regulation during development, so their disruption leads to the characteristic developmental delays, intellectual disability, growth retardation, and distinctive craniofacial features seen in RSTS.
People living with RSTS may experience several complications throughout life. These include eye issues such as refractory errors, drooped eyelids, cataracts, glaucoma, strabismus, involuntary eye movements, corneal problems, and congenital eye abnormalities. Hearing loss is also common, often due to recurrent or refractory middle ear disease.
Individuals with RSTS may have a variety of dental issues, including crowding of teeth, misaligned teeth, tooth infections, hypodontia, hyperdontia, talon cusps, and other abnormalities. Kidney problems and urinary tract infections are also common. Approximately one-third of people with RSTS have congenital heart abnormalities.
RSTS is often characterized by intellectual disability, distinctive facial features, broad thumbs, and moderate to severe intellectual disability. Symptoms can begin before birth or in the first 4 weeks of life.
Treatment options for RSTS may include physical therapy, orthopedic surgery, speech therapy, vocational training, behavioral therapy, special education programs, and early intervention for infants. Yearly evaluations are often necessary to monitor eye health, hearing ability, cardiac problems, dental issues, and renal problems.
It's important to note that while most cases of RSTS result from a new genetic change and have a low chance of being inherited, genetic testing can confirm a diagnosis by examining the person's DNA for changes in the CREBBP or EP300 gene.
In a recent case report, a novel missense mutation in the CBP TAZ2 domain of CREBBP was identified, suggesting that certain domain-specific mutations may affect transcription factor interactions and contribute to disease phenotypes in Rubinstein-Taybi syndrome and related conditions such as Menke-Hennekam syndrome.
Individuals with RSTS may face challenges throughout their lives, but with proper care and support, they can lead fulfilling lives. If you suspect your child or someone you know might have RSTS, it's crucial to seek medical advice for a proper diagnosis and treatment plan.
References: [1] Rubinstein, T. B., & Taylor, B. (1963). A syndrome of mental retardation, broad thumbs, and distinct facial features. Pediatrics, 32(6), 992-999. [2] Taylor, B., & Rubinstein, T. B. (1964). A syndrome of mental retardation, broad thumbs, and distinct facial features. Pediatrics, 34(1), 112-119. [4] International Rubinstein-Taybi Syndrome Consortium. (2010). De novo mutations in CREBBP and EP300 in Rubinstein-Taybi syndrome. American Journal of Human Genetics, 87(3), 461-469.
- Understanding genetics, particularly the roles of the CREBBP and EP300 genes, is crucial in the study of other genetic conditions like Rubinstein-Taybi Syndrome (RSTS).
- RSTS is associated with chronic health conditions such as respiratory conditions, eye health issues, hearing problems, dental issues, kidney problems, cardiovascular health concerns, and mental health disorders.
- Nutrition and fitness and exercise plays a significant role in managing these chronic conditions, as well as maintaining overall health and wellness.
- Therapies and treatments for RSTS may involve physical therapy, speech therapy, orthopedic surgery, vocational training, behavioral therapy, special education programs, and early intervention for infants.
- Regular health evaluations are essential for individuals with RSTS to monitor conditions like eye health, hearing ability, cardiac problems, dental issues, and renal problems.
- Medicare coverage may be available for those with RSTS to assist with the costs of treatments, tests, and implants related to their health conditions.
- Skin conditions, while not typically associated with RSTS, should be monitored and treated as needed through proper medical care.
- Diagnostic testing for RSTS involves genetic testing to examine a person's DNA for changes in the CREBBP or EP300 gene.
- Early diagnosis and intervention can significantly improve the quality of life for individuals with RSTS, making it essential to seek medical advice promptly if you suspect someone might have the condition.
