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A rare, genetic malformation syndrome characterized by congenital anomalies (microcephaly, specific facial characteristics, and broad thumbs and halluces), short stature, intellectual disability and behavioral characteristics.
ORPHA:783Classification level: Disorder
Birth prevalence is estimated at around 1/100,000 to 125,000.
Facial features, which become more prominent with age, include highly arched eyebrows, long eyelashes, downslanting palpebral fissures, convex nasal ridge, low hanging columella, highly arched palate and micrognathia. Talon cusps are very frequent on the permanent incisors. An unusual smile with almost complete closure of the eyes is present in most individuals. Other physical findings may include eye anomalies (nasolacrimal duct obstruction, congenital glaucoma, refractive errors), a variety of congenital heart defects (e.g. ventricular and atrial septal defect, patent ductus arteriosus), joint hypermobility, and skin anomalies (in particular keloid formation). Feeding difficulties are frequently observed in the first year, and respiratory tract infections are very common in infancy and childhood. Constipation is generally a life-long problem, and patients may become overweight during late childhood or early puberty. The children have a marked ability to establish excellent social contacts. In adulthood, sudden mood changes and obsessive-compulsive behavior may gradually become more frequent. Other than previously thought, persons with Rubinstein-Taybi syndrome under the age of 40 have no increased risk of getting malignant tumors. It is unclear whether this risk is increased in the elderly with Rubinstein-Taybi syndrome.
Causes of Rubinstein-Taybi syndrome include: a microdeletion of chromosome 16p13.3 or chromosome 22q13.2, a variant in CREB-binding protein (CREBBP, 16p13.3) or a variant in E1A-binding protein p300 (EP300, 22q13.2). CREBBP and EP300 show a very high degree of homology and both play important roles as transcriptional coactivators; however, the exact pathogenesis of the syndrome remains uncertain. There is no significant genotype-phenotype correlation, except in the case of individuals with a EP300 mutation who on average have a higher level of functioning, less marked distal limb malformations, and a more pronounced microcephaly.
The diagnosis is in essence based on clinical examination. A cytogenetic or molecular abnormality can be detected in about 65% of individuals.
The syndrome can sometimes be difficult to differentiate from Saethre-Chotzen syndrome, Floating Harbor syndrome and Cornelia de Lange syndrome.
If a cytogenetic or molecular abnormality is found in the affected child, reliable prenatal diagnosis is possible in future pregnancies through chorionic villus biopsy. Prenatal ultrasound only rarely allows a reliable diagnosis.
The syndrome is almost always sporadic, most cases resulting from de novo mutations. For a couple with an affected child, accumulating data suggest a recurrence risk of approximately 0.5%. If a person with Rubinstein-Taybi syndrome is able to reproduce, the recurrence risk is 50% as the transmission is autosomal dominant.
Management and treatment
All individuals should have a cardiac assessment at the time of diagnosis and should be checked for hearing loss or diminished vision (every 3 years in children and every 5 years in adults). Specialized educational programs are required, with early emphasis on psychomotor development and speech therapy. Children should be tested at regular intervals with a systematic developmental assessment starting at age 3-4 years, to ensure adequate educational support compatible with each child's potential. If surgery is required, individuals undergoing general anesthesia should be under the care of an anesthesiologist comfortable with complex airway problems and aware of the increased risk of aspiration and cardiac arrhythmia upon the use of cardioactive drugs.
Life expectancy does not seem to be explicitly altered.
A summary on this disease is available in Français (2014) Português (2004) Deutsch (2019) Español (2019) Italiano (2019) Nederlands (2019) Suomi (2014, pdf) Hebrew (2020, pdf) Slovak (2007, pdf) Polski (2014, pdf)
- Article for general public
- Français (2010, pdf) - Orphanet
- Svenska (2016) - Socialstyrelsen
- Clinical practice guidelines
- Français (2017) - PNDS
- Anesthesia guidelines
- Czech (2018) - Orphananesthesia
- English (2018) - Orphananesthesia
- Português (2018) - Orphananesthesia
Disease review articles
- Review article
- English (2015) - Ital J Pediatr
- Clinical genetics review
- English (2019) - GeneReviews
- Disability factsheet
- Dansk (2018) - Sjaeldne Diagnoser
- Français (2018, pdf) - Orphanet
- Guidance for genetic testing
- English (2010) - Eur J Hum Genet
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