Mount Sinai Medical Center
New York, New York
What Is It?
First described by Michail et al in 19571 as broad thumb–hallux disorder, the syndrome was named for Drs. Rubenstein and Taybi who published a case series of seven cases in 1963.2 The condition is characterized by growth retardation, intellectual disability, distinctive facial features (micrognathia, hypertelorism, arched eyebrows, asymmetry and macrocephaly), and broad thumbs and first toes.2 Additional features include eye abnormalities, heart and kidney defects, dental problems, a high arched or cleft palate, and obesity.3 The risk for developing noncancerous and cancerous tumors, including certain kinds of brain tumors and leukemia, is increased.
In most cases, Rubinstein-Taybi syndrome (RTS) is due to a de novo genetic mutation that is not present in or carried by the parents. The risk for having a second affected child therefore is less than 1%. RTS also may be inherited in an autosomal dominant pattern. Etiology generally involves a microdeletion syndrome of chromosomal segment 16p13.3 and is characterized by mutations in the CREB-binding protein (cyclic AMP response element-binding protein) gene. The CREB-binding protein helps regulate cell growth and division and is essential for normal fetal development. Normal growth requires two copies. With destruction or mutilation of one copy of the CREB-binding protein gene, cells make only half of the normal amount of CREB-binding protein, thus disrupting normal development both before and after birth. Mutations in the EP300gene are responsible for 3% to 8% of RTS cases.
Incidence and Prognosis
The incidence is about 1:100,000 to 125,000. Males and females are equally affected. Most patients are born at term, apparently healthy and without complications, although polyhydramnios has been found in around 40% of pregnancies. About 20% of newborns have perinatal problems, such as apnea, poor feeding and severe constipation—all requiring intensive care. The long-term prognosis is generally good, depending on the systems involved, and some live to adulthood. Developmental delay and intellectual disability are common, but most patients older than 6 years of age can learn to read. Complex cardiac defects, cancer and respiratory infections are the most common causes of death.
The Genetic Testing Registry provides information about genetic tests for RTS, which provide definitive diagnosis. Diagnosis is also based on the many clinical presentations of broad thumbs and toes, as well as poor feeding and other facial characteristics.
There is no known cure. Treatment is based on management of the major symptoms and may require feeding tube placement and care of frequent respiratory infections. Support and information are available from the Rubinstein-Taybi Parent Group (www.rubinstein-taybi.org), the Rubinstein-Taybi Syndrome Children’s Foundation (www.facebook.com/ RTSCF), the American Association for Pediatric Ophthalmology and Strabismus (www.aapos.org), Genetics Home Reference (https://ghr.nlm.nih.gov/ ), MedlinePlus (https://medlineplus.gov), and the National Organization for Rare Disorders (https://rarediseases.org/ ).
Many of the associated conditions in patients with RTS may affect anesthetic care and should be identified during preanesthetic assessment. Children with RTS undergo about 10 times more surgeries and hospitalizations than the average child.4 Most common interventions are strabismus repair, nasolacrimal probing and orchiopexy (in males). Although underdevelopment is common in younger children, older patients tend to be obese. Visual (80%) and behavioral problems (90%) are frequent. Difficult airway management is to be expected.5,6 Patients are at high risk for aspiration on induction and emergence. Although somewhat controversial, supraglottic airways have been used successfully. Hypotonia, hyperreflexia, lax ligaments and hyperextensibility occur, and use of neuromuscular blocking agents should be minimized. A case of prolonged paralysis after atracurium administration has been described.7 Myelomeningocele—either apparent or hidden—may exist. Cardiac anomalies are seen in about one-third of patients, and range from benign to life-threatening. Urinary and respiratory tract infections must be treated preoperatively. Keloid formation may develop after minimal skin invasion. No single anesthetic technique has been shown to be superior.