Background: Rubinstein-Taybi syndrome (RSTS) is a rare genetic syndrome characterized by postnatal growth retardation, intellectual disability, microcephaly, peculiar facial features, broad thumbs and big toes and other organs malformations. There are two forms: RSTS type 1 characterized by CREBBP gene mutations (16p13.3); RSTS type 2 dues to mutations/ deletions in EP300 gene (22q13.2). The type 2 is associated with mild phenotype with possible absence of the typical diagnostic signs as broad thumbs and big toes.
Clinical case: V.B.G has come to our attention at the age of 4 years for diagnostic study. He was born at 36 weeks of gestational age by caesarean section for IUGR. At birth he presented congenital heart disease, hypospadias, post-axial appendix of left hand, choroidal cysts, dysmorphia of corpus callosum, rostrum hypoplasia, agenesis of right olfactory bulb, enlargement of cerebral ventricles and CSF spaces. The array-CGH showed 22q13.2 deletion of 1.69 Mb with diagnosis of RSTS type 2. At the age of 3 years he presented psychomotor regression with onset of focal seizures. At our observation the child had growth retardation, dysphagia for liquids, constipation, characteristic face, broad toes, limbs dystonia, absent language.
Conclusion: In literature there are known 34 cases of RSTS associated with EP300 alteration. Of these, only one has complete gene deletion (del22q13.2) of 376 Kb. This patient has a complex phenotype in contrast with mild phenotype of the other patients. Because of the larger size of our childs deletion his clinical complexity could also be related to the involvement of adjacent genes. In addition it would be useful scanning EP300 gene also on other tissues to identify a possible mosaicism. Our case represents the second known patient suffering from type 2 RSTS with complete EP300 deletion and clinical features in contrast with a mild phenotype. A genotype-phenotype correlation for EP300 disruptive mutations is needed.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology