Rubinstein-Taybi syndrome (RTS) is a rare genetic condition characterized by a specific set of physical features and developmental delays. This syndrome impacts various body systems, making it a complex disorder. Understanding RTS involves recognizing its unique characteristics and the underlying genetic factors that contribute to its manifestation.
Understanding Rubinstein-Taybi Syndrome
Rubinstein-Taybi syndrome is a rare, multi-system genetic disorder. Its estimated prevalence ranges from approximately 1 in 100,000 to 1 in 125,000 live births worldwide.
The syndrome was first described in 1963 by Drs. Jack Rubinstein and Hooshang Taybi, after whom the condition is named. RTS is also sometimes known as broad thumb-hallux syndrome, referencing one of its distinguishing physical characteristics.
Key Features and Health Considerations
Individuals with Rubinstein-Taybi syndrome often present with a recognizable set of physical characteristics. These include broad and often angled thumbs, along with broad first toes. Distinctive facial features frequently observed are highly arched eyebrows, long eyelashes, downward-slanting eyes, a convex nasal ridge, and a small nose with a low-hanging columella.
Beyond these physical traits, developmental challenges are commonly associated with RTS. Intellectual disability, ranging from moderate to severe, is a consistent feature, with reported IQ scores often between 25 and 79. Children with RTS frequently experience delays in physical and motor development, partly due to low muscle tone, which can affect milestones like sitting, walking, and self-care. Speech delays are also prevalent.
Individuals with RTS may experience a range of associated health issues. Heart defects and kidney abnormalities are frequently reported. Feeding difficulties, often stemming from hypotonia and coordination issues, can be a concern, particularly in infancy. Recurrent infections are also more common in this population.
Genetic Origins
Rubinstein-Taybi syndrome arises from genetic alterations, primarily involving mutations in specific genes. The most common cause is a mutation in the CREBBP gene, located on chromosome 16p13. This genetic change accounts for 50-60% of diagnosed cases and is sometimes referred to as RTS Type 1.
A less frequent cause involves mutations in the EP300 gene, found on chromosome 22. Both CREBBP and EP300 genes provide instructions for making proteins that play a role in chromatin remodeling and gene expression. Their disruption leads to the diverse features of RTS.
Most cases of Rubinstein-Taybi syndrome occur spontaneously as new mutations rather than being inherited from a parent. However, in rare instances, the syndrome can be inherited in an autosomal dominant pattern, meaning only one copy of the altered gene is needed to cause the condition. If a parent has RTS, there is a 50% chance their child will inherit the condition.
Diagnosis and Ongoing Care
The diagnosis of Rubinstein-Taybi syndrome often begins with a clinical evaluation. Physicians observe the distinctive facial features, broad thumbs, and broad first toes. This clinical suspicion is then confirmed through genetic testing.
Genetic testing, such as chromosomal microarray analysis or gene sequencing, is used to identify mutations in the CREBBP or EP300 genes. While genetic testing can confirm the diagnosis in many cases, it is important to note that about 30% of individuals with classic RTS features may not have an identified mutation in these specific genes. This means a clinical diagnosis can still be made even without a confirmed genetic mutation.
Ongoing care for individuals with RTS requires a multidisciplinary approach, involving a team of various specialists. Pediatricians oversee general health, while geneticists provide expertise. Cardiologists may address heart defects, and nephrologists manage kidney issues.
Occupational, physical, and speech therapists support developmental progress, address low muscle tone, and improve communication skills. Educational specialists also develop individualized learning programs. Management goals focus on addressing medical concerns, supporting developmental milestones through early intervention, and providing comprehensive educational support throughout the individual’s life.