Rubinstein-Taybi syndrome (RTS) is a rare, complex genetic condition that affects multiple systems within the body. It is classified as a multisystem disorder because it involves a combination of physical abnormalities, developmental delays, and intellectual differences. The syndrome was named after the pediatrician Dr. Jack Rubinstein and the radiologist Dr. Hooshang Taybi, who published a detailed description of several affected children in 1963. This condition occurs infrequently, with estimates suggesting it affects approximately 1 in 100,000 to 125,000 newborns worldwide.
Defining the Clinical Features
The physical presentation of Rubinstein-Taybi syndrome is characterized by a set of distinctive and recognizable features. A defining characteristic is the presence of broad and often angulated thumbs and great toes, which are sometimes shortened. These limb anomalies are a consistent finding that frequently prompts a clinical suspicion of the syndrome.
Individuals with RTS also display a specific pattern of craniofacial characteristics. These can include a head size that is smaller than average, known as microcephaly, and eyebrows that are noticeably arched. Eye features often involve downward-slanting palpebral fissures, drooping eyelids (ptosis), and issues like strabismus or tearing due to nasolacrimal duct obstruction. The nose may appear prominent or “beaked,” and the palate is often highly arched. Dental anomalies are also commonly seen, sometimes involving crowded teeth or the presence of talon cusps, which are extra projections on the teeth.
These facial and oral features contribute to potential feeding difficulties in infancy and a characteristic “grimacing” smile. Growth and development are significantly affected, with short stature being a common finding that becomes noticeable after birth. Although prenatal growth may be normal, the height and weight percentiles typically drop rapidly within the first few months of life.
Low muscle tone, or hypotonia, is also prevalent, which can contribute to delays in achieving motor milestones such as sitting up and walking. The majority of people with RTS experience some degree of intellectual disability, which generally ranges from mild to moderate. This cognitive difference affects the development of learning, reasoning, and problem-solving skills.
Beyond these primary features, a variety of associated medical issues are commonly reported, including heart defects that may require surgical intervention. Other internal body systems can be affected, as individuals may have kidney or urinary tract abnormalities, such as absent or extra kidneys. Respiratory issues, particularly obstructive sleep apnea, are also a frequent concern due to the combination of a narrow palate, hypotonia, and potential obesity development later in childhood.
The Genetic Basis of RTS
Rubinstein-Taybi syndrome is fundamentally a genetic disorder caused by alterations in one of two specific genes. The primary cause, accounting for approximately 50 to 60% of cases, involves mutations or microdeletions in the CREBBP gene. A smaller number of cases, estimated to be between 3 and 8%, are caused by changes in the EP300 gene.
Both the CREBBP and EP300 genes encode for proteins that act as transcriptional coactivators and crucial regulators of gene expression. These proteins, known as CREB binding protein (CBP) and p300, work by modifying the structure of chromatin, the complex of DNA and protein that makes up chromosomes. Specifically, CBP and p300 are histone acetyltransferases (HATs), which means they add acetyl groups to histone proteins. This acetylation process loosens the chromatin structure, making the genes in that region more accessible for transcription.
The mutations in RTS typically result in a condition called haploinsufficiency, where one functional copy of the gene is not enough to produce the required amount of protein. This deficiency in the CBP or p300 protein disrupts the complex network of gene regulation, leading to the various physical and developmental differences seen in the syndrome. The majority of RTS cases arise from a de novo mutation, meaning the genetic change is new and occurred in the affected individual and was not inherited from either parent.
While most cases are sporadic, RTS follows an autosomal dominant inheritance pattern. This means that a person with the syndrome has a 50% chance of passing the altered gene to their children.
Diagnosis and Comprehensive Management
The initial diagnosis of Rubinstein-Taybi syndrome is typically based on the presence of the characteristic clinical features identified during a physical examination. A healthcare provider will observe the distinctive facial appearance, short stature, and especially the broad thumbs and great toes. A clinical suspicion is then pursued with molecular testing to confirm the diagnosis.
Genetic confirmation involves testing for mutations in the CREBBP and EP300 genes. This is often done through gene sequencing or chromosomal microarray analysis, which can identify point mutations or deletions in the genetic material. Confirming the specific gene variant provides certainty for the family and allows for more informed management planning.
Because RTS affects multiple body systems, the management approach is multidisciplinary and focuses on addressing the individual’s specific needs throughout their lifetime. Early intervention services are highly recommended to support developmental progress in young children:
- Physical therapy to improve strength and motor skills.
- Occupational therapy to assist with daily living activities.
- Speech and language therapy, as communication delays are common due to cognitive differences and structural issues like a high-arched palate.
- Educational support through specialized programs tailored to the level of intellectual difference to foster learning and social skills.
Behavioral issues, such as short attention spans and hyperactivity, may also require specialized support strategies.
Routine and comprehensive medical screenings are an important part of ongoing care due to the associated health risks. This involves regular monitoring of the heart for structural defects and the kidneys for any anatomical abnormalities. Ophthalmological examinations are also needed to detect and manage common eye issues, such as strabismus, refractive errors, or congenital cataracts. Furthermore, individuals with RTS should be evaluated for obstructive sleep apnea, which may require intervention to ensure adequate rest and oxygenation. The medical team must coordinate specialists across cardiology, nephrology, ophthalmology, and developmental pediatrics to provide holistic care. Anesthesia complications, such as a difficult airway or irregular heart rhythms, are a known concern, necessitating careful planning for any surgical procedures.