Rubinstein-Taybi syndrome

Rubinstein-Taybi syndrome — Summary Information

1) Disease Description (Causes and Symptoms)

• Causes and pathophysiology
  • It is primarily associated with mutations in the CREBBP (CREB-binding protein, CBP) gene (approximately 60% or more) and, rarely, mutations in the EP300 gene. These two proteins are transcriptional coactivators involved in basic cellular functions, including DNA repair and the regulation of cell differentiation, growth, and death. Most cases occur spontaneously (de novo) and show an autosomal dominant inheritance pattern.
• Main symptoms (clinical features)
  • Developmental delay and intellectual disability (mean IQ approximately 51, IQ range 30–79)
  • Characteristic facial features: broad forehead, prominent brow, beak-shaped nose (nasal bridge), small mouth, short upper lip, etc.
  • Limb abnormalities: broad thumbs and first toes (in almost all patients), hand and foot deformities (including syndactyly and polydactyly)
  • Hypotonia, feeding difficulties during infancy, and growth delay (tendency toward short stature)
  • Ophthalmic abnormalities (strabismus, eyelid abnormalities, possible cataracts and glaucoma) and hearing abnormalities (including external ear deformities)
  • Congenital heart defects (approximately 30%: patent ductus arteriosus, ventricular/atrial septal defects, etc.)
  • Genitourinary abnormalities (high frequency of undescended testes in boys), skin findings (hypertrichosis and a tendency to develop keloids)
  • Other features: frequent respiratory infections, abnormal electroencephalogram and risk of seizures, and possible problems during anesthesia
• Diagnostic principles
  • The condition is suspected based on clinical features, and confirmation is performed through molecular genetic testing, particularly testing of the CREBBP and EP300 genes.

2) Treatment Methods and Precautions

• Treatment principles

  • There is no definitive cure, and symptom-specific, multidisciplinary management is needed, involving pediatrics, medical genetics, cardiology, orthopedics, neurology, ophthalmology, otolaryngology, rehabilitation therapy, and other specialties.

• Main treatment and management areas

  • Developmental therapy: physical therapy, occupational therapy, speech therapy, and special education programs
  • Feeding and nutrition: feeding assistance during infancy (special nipples, supplementary feeding, etc.), growth monitoring, and nutritional counseling
  • Heart disease: evaluation with echocardiography followed by medical or surgical treatment if necessary
  • Ophthalmic and hearing care: regular vision and hearing tests and, when necessary, surgery (for strabismus, cataracts, etc.) and hearing aids
  • Orthopedic management: corrective surgery or assistive devices for thumb and toe deformities, scoliosis, and other conditions
  • Nervous system: anticonvulsant treatment if seizures occur, with continued developmental assessments and rehabilitation
  • Skin, oral, and dental care: dental and oral-maxillofacial treatment for dental and cleft lip/palate problems
  • Genetic counseling: family testing and preconception counseling are recommended after confirmation of the diagnosis

• Precautions (especially regarding hospitals and surgery)

  • Problems with breathing and airway management during anesthesia and sleep have been reported, so a detailed pre-anesthesia assessment is necessary, including evaluation of airway anatomy and cardiac and respiratory status.
  • Because there may be a tendency to develop keloids during wound healing, careful postoperative management is important.
  • Prevention and early treatment of frequent respiratory infections are recommended.

• Recommended follow-up tests (initial and regular)

  • Echocardiography, hearing and vision tests, growth and developmental assessments, neurological observation, and, when necessary, endocrine (growth) and genitourinary evaluations

• Prognosis

  • There is considerable individual variation. Intellectual and developmental disabilities persist, but functioning can improve with early rehabilitation and special education. The presence or absence of cardiac and respiratory complications has a major impact on prognosis.

3) Checkpoints Before an Outpatient Visit (Including Items to Bring and Example Questions)

• Items to bring (recommended)
  • A list of currently used medications, including directions and dosages
  • Copies or summaries of previous test results (genetic test results, echocardiography, hearing and vision tests, electroencephalography, etc.)
  • Growth charts (weight, height, and head circumference records) and vaccination records
  • Developmental history (when the child sat up, began walking, started speaking, etc.) and records of recent changes
  • Surgery and hospitalization records, and photographs (showing characteristic appearance and deformities)—useful for diagnosis and counseling
  • Family history (similar symptoms and history of genetic diseases) and whether the parents have undergone genetic testing
• Symptom changes that are useful for the doctor to know during the visit (notes)
  • Feeding and intake amount, weight changes, sleep patterns, whether seizures have occurred, and the frequency of recurrent respiratory infections
  • Breathing difficulty, cyanosis, high fever, and risk factors before surgery, etc.
• Example questions before the appointment (questions for patients and caregivers to prepare themselves)
  • Which of the current symptoms should be evaluated as a priority?
  • What additional tests or specialist consultations are needed?

4) Examples of General Questions to Ask the Doctor

• What are the side effects, advantages, and disadvantages of this medication (or treatment)?
• What is the expected short-term and long-term prognosis? How should daily-life and educational support be planned?
• If surgery or anesthesia is needed, are any preoperative tests or special preparations required?

5) Examples of Disease-Specific Questions (1–2)

• A variant in CREBBP (or EP300) was identified in the genetic test. What does this result mean for family members (siblings and future children), and what are the recommendations regarding family testing or preconception testing?
• When planning future surgery (such as cardiac surgery or orthopedic correction), what special precautions related to anesthesia or additional tests are needed?

Note: Diagnosis and treatment vary depending on the individual patient's condition, so multidisciplinary evaluation based on confirmatory test results and current symptoms is recommended.