Rubinstein-Taybi syndrome

Rubinstein-Taybi syndrome (RTS), also known as broad thumb-hallux syndrome, is a rare congenital disorder characterized by distinctive facial features, broad thumbs and first toes, short stature, and intellectual disability. The condition was first described by Jack Rubinstein and Hooshang Taybi in 1963. RTS is caused by mutations or deletions in the CREBBP gene (located on chromosome 16p13.3) in approximately 50-60% of cases, or in the EP300 gene (on chromosome 22q13.2) in about 8-10% of cases. Both genes encode histone acetyltransferases that function as transcriptional coactivators, playing critical roles in cell growth and differentiation during embryonic development. The syndrome affects multiple body systems. Characteristic craniofacial features include a beaked nose with the nasal septum extending below the alae nasi, downslanting palpebral fissures, heavy or highly arched eyebrows, a grimacing smile, and micrognathia. Broad and often angulated thumbs and great toes are hallmark features. Individuals typically have moderate to severe intellectual disability, with IQ scores commonly ranging from 25 to 79. Growth retardation is evident from birth, with short stature persisting into adulthood. Affected individuals may also experience feeding difficulties in infancy, recurrent respiratory infections, congenital heart defects (in approximately 33% of patients), eye abnormalities including coloboma and glaucoma, renal anomalies, cryptorchidism in males, and skeletal abnormalities. There is an increased risk of developing certain tumors, particularly in childhood, including brain tumors and leukemia. There is currently no cure for Rubinstein-Taybi syndrome, and management is supportive and symptom-based. Treatment involves a multidisciplinary approach including early intervention programs, speech therapy, occupational therapy, and physical therapy to optimize developmental outcomes. Cardiac, ophthalmologic, and renal anomalies are managed according to standard clinical protocols. Regular monitoring for potential tumor development is recommended. Orthopedic interventions may be needed for skeletal complications. Genetic counseling is important for affected families, as most cases arise de novo, though the condition follows an autosomal dominant inheritance pattern.

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