What is the management plan for Rubenstein-Taybi syndrome?

Management of Rubinstein-Taybi Syndrome

Rubinstein-Taybi syndrome requires comprehensive multidisciplinary management addressing neurological, developmental, behavioral, orthopedic, and cancer surveillance needs, with early intervention services being critical for optimizing developmental outcomes. 1

Diagnostic Confirmation and Initial Evaluation

• Genetic testing should confirm the diagnosis through identification of pathogenic variants in CREBBP (RTS type 1, ~95% of cases) or EP300 (RTS type 2, ~5% of cases). 1, 2
• At diagnosis, obtain baseline brain MRI to evaluate for structural anomalies including Chiari malformation (present in 19% of cases), hydrocephalus, and spinal cord abnormalities. 2
• Perform baseline spinal MRI to assess for low-lying conus medullaris (present in 48% of cases) and tethered cord syndrome. 2

Neurological and Neurosurgical Management

• Refer to neurology at diagnosis for baseline evaluation, as patients are at risk for seizures (including infantile spasms), Chiari I malformation, and tethered cord syndrome. 3, 2
• Monitor for symptoms of Chiari malformation including headaches, neck pain, difficulty swallowing, and upper extremity weakness; 75% of patients with Chiari I malformation require decompression surgery. 2
• Evaluate for tethered cord syndrome with clinical examination for lower extremity weakness, bladder/bowel dysfunction, or back pain; 30% of patients with low-lying conus require surgical detethering. 2
• Obtain EEG if seizure activity is suspected, with accurate seizure classification to guide medical management. 3
• Families should receive anticipatory guidance about the risk of infantile spasms and other seizure types at diagnosis. 3

Developmental and Behavioral Management

• Immediate referral to early childhood intervention services at diagnosis is essential, as all patients have intellectual disability with severe delays in expressive language, vocal imitation, and symbolic play skills. 1, 4
• Initiate speech and language therapy focusing on oral-motor functioning, articulation, and expressive/receptive language; consider augmentative and alternative communication systems for severe delays. 3, 4
• Provide physical therapy targeting hypotonia and gross motor delays, which are universal features. 3, 4
• Implement occupational therapy addressing hypotonia, sensory integration, and fine motor skills. 3
• Screen for neuropsychiatric and behavioral challenges early in childhood (before school age), as these are primary factors impacting quality of life and include anxiety, hyperactivity/inattention, self-injury, repetitive behaviors, and aggression. 5
• School-age children (ages 5-12) demonstrate peak challenging behaviors including increased hyperactivity (particularly in females with RTS1), stereotypic behaviors, and OCD-like symptoms; anticipate these challenges and implement behavioral interventions proactively. 5
• Upon school entry, obtain comprehensive neuropsychological evaluation and develop an Individualized Education Plan (IEP) with specific accommodations for intellectual disability and behavioral concerns. 3
• Consider behavioral therapy, mental health services, and functional behavior assessments addressing sensory concerns, communication deficits, and attentional difficulties. 3

Growth and Endocrine Surveillance

• Refer to endocrinology between ages 2-3 years for growth monitoring, as postnatal growth retardation and short stature are characteristic features. 3, 6
• Obtain baseline thyroid function tests (TSH, free T4) and growth hormone studies (IGF-1, IGF-BP3) at initial endocrine evaluation. 3
• Monitor growth parameters (height, weight, head circumference) at every visit, with microcephaly being a consistent finding. 3, 6
• Assess nutritional status regularly, as feeding difficulties and failure to thrive occur frequently. 3

Gastrointestinal Management

• Refer to gastroenterology in early infancy for feeding difficulties, gastroesophageal reflux, and poor growth. 3
• Evaluate for swallowing dysfunction with modified barium swallow studies and pH probe studies as recommended by gastroenterology. 3
• Consider proton pump inhibitors for documented gastroesophageal reflux. 3
• Assisted feeding via nasogastric or gastrostomy tube is necessary in 40-50% of patients with failure to thrive; surgical recommendations should be guided by gastroenterology. 3
• Initiate feeding therapy evaluation and ongoing treatment for persistent feeding difficulties. 3
• Treat constipation proactively as it is a common comorbidity. 3

Cancer Surveillance

• Cancer surveillance is NOT routinely indicated for Rubinstein-Taybi syndrome, as the tumor risk for meningiomas (5%) and pilomatricomas (10%) does not warrant systematic screening. 3
• Educate families about the increased risk of benign skin tumors (pilomatricomas) and meningiomas, advising them to seek medical evaluation for new masses, persistent headaches, or neurological symptoms. 3
• Do not perform routine brain imaging solely for cancer surveillance in asymptomatic patients. 3

Orthopedic Considerations

• Monitor for limb deformities, scoliosis, and joint mobility limitations related to broad thumbs and halluces. 6
• Involve orthopedic surgery for evaluation and management of skeletal abnormalities as they arise. 6

Adaptive Functioning and Long-Term Outcomes

• Recognize that the gap between adaptive behavior/living skills and typically developing peers widens with age, requiring ongoing support and realistic expectations for independence. 5
• RTS2 (EP300 variants) patients demonstrate better adaptive behavior and living skills with less stereotypic behaviors but higher social phobia compared to RTS1 (CREBBP variants). 5
• Over 90% of individuals with RTS survive to adulthood, necessitating transition planning for adult healthcare services. 6

Critical Pitfalls to Avoid

• Do not delay genetic testing; molecular confirmation guides prognosis and genetic counseling. 1
• Do not overlook spinal cord abnormalities; failure to diagnose tethered cord can result in irreversible neurological deficits. 2
• Do not attribute all behavioral challenges to intellectual disability alone; specific neuropsychiatric conditions (anxiety, OCD-like symptoms) require targeted treatment. 5
• Do not wait for behavioral crises to implement interventions; proactive screening and early behavioral therapy improve outcomes. 5
• Do not underestimate the complexity and cost of healthcare for these patients; coordinate care through a medical home model with multidisciplinary team involvement. 6