Rubinstein-Taybi syndrome (RTS) has an estimated prevalence of 1 in 100,000 to 125,000. It is considered to have autosomal dominant patterns of inheritance but most cases result from de novo mutations.
Mutation in the CREBBP gene on chromosome 16 which acts as a regulator of other genes in cell growth and division is the commonest mutation. A small percentage have mutations of a similar gene (EP300) and tend to have milder skeletal abnormalities. A deletion of the genetic material on the short arm of chromosome 16 which includes the CREBBP (16p13.3) is associated with severe forms. However, in 50 % of cases no genetic basis is found. Major causes of deaths, particularly during the first year, are aspiration pneumonia and heart disease. There are no definite diagnostic features in RTS. However, the following are usually
• Short stature
• Moderate to severe intellectual disability
• Distinctive facial features (which become more prominent with age, include highly arched eyebrows, long eyelashes, down-slanting palpebral fissures, convex nasal ridge, highly arched narrow palate, abnormally large or "beak-shaped" nose, retrognathia and micrognathia). An unusual smile with almost complete closure of the eyes is present in most cases. These lead to an increase risk of dental problems and obstructive sleep apnoea (OSA). There is also an association with choanal atresia.
• Broad thumbs and 1st toes (often angulated in the varus/valgus position). RTS is also frequently associated with the following:
• Eye abnormalities: Over 80 % of children with RTS have some form of eye abnormality, e.g. lacrimal duct obstruction (43 % are bilateral), ptosis and strabismus (55 %). Congenital glaucoma or glaucoma which develops in early life has been described.
Renal and urinary tract: Renal anomalies are present in 50 % and for this reason all children should have renal ultrasound on diagnosis. Almost all boys will have incomplete or delayed descent of testes with hypospadias being present in 11 %. As a result of these anomalies, there is an increased risk of chronic kidney disease and urinary infections.
• Musculoskeletal: There is an increased risk of scoliosis, hyperkyphosis and spina bifida with general hypermobility.
• An increased risk of tumours (mainly leukaemia in childhood and meningioma in adulthood) has been observed. There is also an association with neuroendocrine tumours.
• An increased risk of keloid scarring.