Rubinstein–Taybi syndrome

Overview

Rubinstein–Taybi syndrome (RTS) is a rare genetic disorder characterized by distinctive facial features, broad thumbs and toes, short stature, intellectual disability, and various congenital anomalies. First described by Drs. Jack Rubinstein and Hooshang Taybi in 1963, the syndrome affects multiple organ systems and can range in severity. Individuals with RTS often exhibit developmental delays, behavioral issues, and an increased risk of certain cancers and other medical complications.

While RTS is present from birth, it may not be diagnosed immediately due to variability in features. With early intervention and a multidisciplinary approach, individuals with Rubinstein–Taybi syndrome can achieve improved developmental outcomes and quality of life.

Causes

Rubinstein–Taybi syndrome is primarily caused by mutations or deletions in genes that regulate chromatin remodeling and gene transcription. The most commonly implicated genes include:

Genetic Causes:

• CREBBP gene: Mutations or deletions in the CREBBP gene (chromosome 16p13.3) are found in about 50–60% of cases. This gene is involved in regulating gene expression during development.

• EP300 gene: Mutations in this gene (chromosome 22q13) account for a smaller proportion of cases (~3–8%) and often result in milder phenotypes.

Inheritance Pattern:

• Most cases occur sporadically due to de novo mutations (new mutations not inherited from parents).

• In rare cases, RTS can be inherited in an autosomal dominant pattern if a parent is affected.

Symptoms

The clinical presentation of Rubinstein–Taybi syndrome varies but typically includes a recognizable combination of physical, developmental, and behavioral features.

Facial and Craniofacial Features:

• Down-slanting palpebral fissures (eye openings)

• Prominent or beaked nose

• Highly arched eyebrows and long eyelashes

• Microcephaly (small head circumference)

• High-arched or cleft palate

Limbs and Skeletal Features:

• Broad thumbs and great toes (hallux), often deviated or angled

• Short stature with delayed bone age

• Joint laxity or stiffness

• Scoliosis (spinal curvature) in some cases

Neurological and Developmental Features:

• Moderate to severe intellectual disability

• Delayed speech and motor development

• Learning difficulties and poor fine motor coordination

• Seizures in a small percentage of individuals

Behavioral Features:

• Friendly and sociable personality

• Repetitive behaviors or obsessive interests

• Attention deficit and hyperactivity symptoms

Other Medical Concerns:

• Congenital heart defects (e.g., atrial septal defect, ventricular septal defect)

• Kidney or urinary tract anomalies

• Feeding difficulties and gastroesophageal reflux

• Vision and hearing problems

• Increased risk of certain tumors, such as meningioma and leukemia

Diagnosis

Diagnosis of Rubinstein–Taybi syndrome is based on clinical features, physical examination, and confirmed through genetic testing.

Clinical Assessment:

• Characteristic facial appearance and broad thumbs/toes

• Developmental history and growth measurements

Genetic Testing:

• Molecular testing for CREBBP and EP300 mutations: Confirms the diagnosis in many cases

• Chromosomal microarray: Detects deletions involving CREBBP or other chromosomal abnormalities

Imaging and Additional Tests:

• Brain MRI (if seizures or neurological symptoms are present)

• Cardiac echocardiogram to assess for heart defects

• Hearing and vision assessments

• Renal ultrasound to detect kidney anomalies

Treatment

There is no cure for Rubinstein–Taybi syndrome. Treatment is supportive and tailored to the individual’s specific symptoms and needs. A coordinated, multidisciplinary approach is essential for optimal outcomes.

1. Developmental and Educational Support:

• Early intervention programs with physical, occupational, and speech therapy

• Special education services tailored to cognitive level

• Behavioral therapy to address attention or repetitive behaviors

2. Medical Management:

• Treatment of heart defects (medication or surgery as needed)

• Management of gastroesophageal reflux and feeding issues

• Regular monitoring for tumor development

• Hearing aids or corrective lenses for sensory impairments

3. Surgical Interventions:

• Thumb or toe correction in severe cases affecting function

• Palate repair if cleft is present

4. Family and Genetic Counseling:

• Support for families to manage long-term care needs

• Genetic counseling for recurrence risk in future pregnancies

Prognosis

The prognosis for individuals with Rubinstein–Taybi syndrome varies depending on the severity of symptoms and associated medical conditions. With early diagnosis and supportive care, many individuals can achieve basic functional skills and lead fulfilling lives, although they often require lifelong assistance and supervision.

While physical and cognitive impairments persist, most individuals show a happy and engaging disposition. Life expectancy may be near normal if major complications (such as heart defects or malignancy) are properly managed. Regular follow-up with a multidisciplinary team helps optimize quality of life and detect complications early.