Rubinstein-Taybi Syndrome

Rubinstein-Taybi Syndrome (RSTS)

Definition

Rubinstein-Taybi syndrome is a rare genetic condition characterized by distinctive facial features, broad thumbs and great toes, short stature, and intellectual disability. First described by Rubinstein and Taybi in 1963.

Key Points

Incidence: 1 in 100,000 to 125,000 births
Primary features include:
- Characteristic facial appearance
- Broad thumbs and halluces
- Growth retardation
- Intellectual disability
- Microcephaly
Most cases are sporadic
Autosomal dominant inheritance pattern

Epidemiology

No gender predilection
Present at birth
Occurs in all ethnic groups
Life expectancy into adulthood

Clinical Manifestations

Craniofacial Features

Facial Characteristics:
- High arched eyebrows
- Long eyelashes
- Downslanting palpebral fissures
- Broad nasal bridge
- Beaked nose
- High-arched palate
- Grimacing smile
- Micrognathia
- Low-set ears
Dental Anomalies:
- Talon cusps (>90% of cases)
- Crowded teeth
- High-arched palate
- Malocclusion

Skeletal Features

Upper Limbs:
- Broad thumbs
- Radially deviated thumbs
- Broad terminal phalanges
- Persistent fetal pads
Lower Limbs:
- Broad halluces (great toes)
- Angulation of halluces
- Overlapping toes
General Features:
- Short stature
- Delayed bone age
- Pectus excavatum
- Scoliosis
- Joint hypermobility
- Cervical vertebral abnormalities

Organ Systems

Cardiac (24-38%):
- Patent ductus arteriosus
- Atrial septal defect
- Ventricular septal defect
- Coarctation of aorta
Ophthalmologic:
- Strabismus
- Refractive errors
- Ptosis
- Nasolacrimal duct obstruction
- Glaucoma (>30%)
Respiratory:
- Upper airway obstruction
- Sleep apnea
- Recurrent infections
Genitourinary:
- Cryptorchidism
- Renal anomalies
- Vesicoureteral reflux

Genetic Basis

Molecular Genetics

Primary Genetic Causes:
- CREBBP mutations (50-60%):
  - Located on chromosome 16p13.3
  - Codes for CREB-binding protein
  - Histone acetyltransferase activity
- EP300 mutations (8%):
  - Located on chromosome 22q13
  - Similar function to CREBBP
Types of Mutations:
- Deletions
- Point mutations
- Splice site mutations
- Complex rearrangements

Genotype-Phenotype Correlations

CREBBP mutations:
- More severe cognitive impairment
- Distinctive facial features
- Higher frequency of angulated thumbs
EP300 mutations:
- Milder phenotype
- Less distinctive facial features
- Variable thumb anomalies

Diagnostic Approach

Clinical Diagnosis

Major Diagnostic Criteria:
- Characteristic facial features
- Broad thumbs/halluces
- Growth deficiency
- Developmental delay
Supporting Features:
- Feeding difficulties in infancy
- Cardiac anomalies
- Joint hypermobility
- Dental anomalies

Molecular Diagnosis

Testing Strategy:
- Chromosome microarray
- CREBBP sequencing
- EP300 sequencing
- Deletion/duplication analysis
Diagnostic Yield:
- CREBBP testing: ~55%
- EP300 testing: ~8%
- Combined yield: ~60-65%

Management Approach

Multidisciplinary Care

Core Team Members:
- Clinical geneticist
- Developmental pediatrician
- Physical therapist
- Occupational therapist
- Speech therapist
- Special educator
Specialty Care:
- Orthopedic surgeon
- Cardiologist
- Ophthalmologist
- Dentist
- Sleep specialist
- Gastroenterologist

Specific Interventions

Physical Therapy:
- Gross motor development
- Joint mobility
- Balance training
- Coordination exercises
Occupational Therapy:
- Fine motor skills
- Self-care activities
- Adaptive devices
Speech Therapy:
- Language development
- Feeding therapy
- Alternative communication

Development and Growth

Growth Parameters

Birth measurements typically normal
Postnatal growth:
- Height: -2 to -5 SD
- Weight: -2 to -4 SD
- Head circumference: -2 to -3 SD

Developmental Progress

Cognitive:
- IQ typically 35-50
- Range: mild to severe ID
- Better verbal than performance skills
Motor:
- Walking age: 2-4 years
- Persistent motor planning difficulties
- Coordination problems
Speech:
- First words: 2-3 years
- Limited vocabulary
- Better receptive than expressive language

Health Surveillance

Regular Monitoring

Growth:
- Height/weight every 3-6 months
- Head circumference
- Puberty progression
Development:
- Regular developmental assessments
- School performance evaluation
- Behavioral assessment
Medical:
- Annual cardiac evaluation
- Eye examination every 6-12 months
- Dental review every 6 months
- Sleep study if indicated
- Orthopedic assessment as needed

Special Considerations

Anesthesia Risks

Airway Challenges:
- Difficult intubation
- Small mouth opening
- Micrognathia
Cardiac Considerations
Aspiration risk

Behavioral Issues

Common Behaviors:
- Mood swings
- Attention problems
- Obsessive traits
- Anxiety
Management:
- Behavioral therapy
- Routine importance
- Environmental modifications

Further Reading