Rubinstein-Taybi Syndrome: A Female Patient with a De Novo Reciprocal Translocation T(2; 16)(Q36.3; P13.3) and Dysgranulopoiesis

Rubinste in-Taybi syndrome (RTS) is a rare developmental disorder characterized by craniofacial dysmorphisms, broad thumbs and toes as well as mental and statural deficiencies. RTS has a prevalence of 1 in 330,000 births and usually occurs sporadically, although it can be inherited as an autosomal dominant disorder. The diagnosis is based on characteristic features. The main clinical symptoms are failure to thrive, cardiac defects and recurrent respiratory infections. Other variable findings are colobomas, cataracts, renal anormalities and orodental anomalies. RTS patients also have an increased risk of developing neoplasias. Several tumors have been reported in RTS patients, including meningiomas, rhabdomyosarcomas, neuroblastomas, oligodendromas, seminomas, choristomas and leukemias. CREBBP and EP300 are the only genes associated with RTS. Microdeletions at band 16p13.3 occur in 10%–25% of RTS patients. Sequence analyses have detected CREBBP mutations in another 56% of affected individuals. Schorry et al. (2008) evaluated genotype-phenotype correlations in 93 RTS patients and performed complete sequencing of all 31 coding regions of the CREBBP gene. The authors concluded that there were no statistically significant differences in the classic dysmorphic findings of RTS patients (e.g., typical facial aspects and broad thumbs and toes) with and without CREBBP mutations. Mutations in EP300 have been identified in 3% of RTS patients. RTS typically occurs as a de novo mutation in a family. Most individuals represent simplex cases (i.e., the only affected member in a family); in most instances, the parents of an individual with RTS are not affected. In this case, the empiric recurrence risk for siblings is approximately 0.1%. Although individuals with RTS rarely reproduce, the theoretical risk for the offspring is 50%. Prenatal testing for at-risk pregnancies is possible if the disease-causing CREBBP mutation or deletion in the family is known.