Rubinstein-Taybi syndrome (RTS) is a rare genetic condition that affects multiple body systems and impacts development. It is characterized by distinctive physical features, short stature, and varying degrees of intellectual disability. RTS affects an estimated 1 in 100,000 to 125,000 births worldwide. Individuals with RTS present with a wide range of symptoms, and their severity can differ significantly.
Genetic Origins
Rubinstein-Taybi syndrome results from mutations or deletions in specific genes, most commonly the CREBBP gene on chromosome 16, or the EP300 gene on chromosome 22. These genes produce proteins that regulate cell growth, division, and differentiation. When altered, these proteins may not function correctly, leading to the diverse symptoms of RTS.
Many cases of Rubinstein-Taybi syndrome arise from de novo mutations, meaning the genetic change is new in the affected individual and not inherited from either parent. These spontaneous mutations are the most frequent cause, accounting for about 50-60% of cases involving the CREBBP gene and 3-8% for the EP300 gene. In rare instances, the syndrome can follow an autosomal dominant inheritance pattern, where only one copy of the altered gene is sufficient to cause the condition.
Key Physical and Developmental Characteristics
Individuals with Rubinstein-Taybi syndrome exhibit recognizable physical features. Hallmark features include broad and often angled thumbs and first toes, sometimes due to unusually broad bones at the tips of these digits. Distinctive facial features include highly arched eyebrows, long eyelashes, downward-slanting eyes, a prominent nose with a low-hanging nasal septum, and a high-arched palate. Many also have a unique smile where the eyes almost completely close.
Developmental delays and intellectual disability are commonly associated with RTS, ranging from moderate to severe. Individuals may experience slowed development of motor skills, speech delays, and learning difficulties. Short stature and a smaller-than-average head circumference (microcephaly) are also typical features.
The syndrome can impact various other body systems. Associated medical issues include heart defects (e.g., atrial septal defects) and kidney abnormalities (e.g., missing or extra kidneys). Eye and vision problems, such as cataracts, are also possible. Dental issues like an extra cusp on a front tooth (talon cusps) and an elevated palate are common.
Feeding difficulties are common, particularly in infancy, and constipation may be a lifelong concern. Some individuals experience excessive hair growth (hirsutism) and increased susceptibility to respiratory infections in childhood. Less common symptoms include hypermobile joints, seizures, and behavioral challenges like anxiety or obsessive-compulsive behaviors. There is also an increased risk for developing certain benign and cancerous tumors, linked to the gene mutations affecting cell reproduction.
Diagnosis and Supportive Care
Diagnosis of Rubinstein-Taybi syndrome begins with a clinical evaluation based on characteristic physical features. If RTS is suspected, genetic testing confirms the diagnosis. This often involves chromosomal microarray analysis or gene sequencing to identify mutations or deletions in the CREBBP or EP300 genes. A genetic cause is not identified in approximately 30% of clinically diagnosed cases.
Management of Rubinstein-Taybi syndrome involves a multidisciplinary approach tailored to individual needs. Regular medical monitoring includes evaluations for potential cardiac, renal, ophthalmologic, and hearing issues. Early intervention services are beneficial, including physical therapy for motor skill development, occupational therapy for daily living activities, and speech therapy to address communication challenges.
Special education programs are necessary to provide learning support for individuals with intellectual disabilities. Nutritional management may be required. Behavioral interventions can help address behavioral challenges. The goal of supportive care is to manage symptoms, promote development, and enhance the overall quality of life for individuals with Rubinstein-Taybi syndrome.