Ultra-Rare Syndromes: The Example of Rubinstein-Taybi Syndrome

Abstract

Rubinstein-Taybi syndrome (RSTS) is a rare, congenital, plurimalformative, and neurodevelopmental disorder. Clinical diagnosis can be complicated by the heterogeneous clinical presentation and the lack of a consensus list of diagnostic criteria, and it is confirmed by molecular tests in approximately 55 to 78% of cases. The etiology is partially known with mutations in two functionally related genes: CREBBP and EP300. Notwithstanding the knowledge on clinical, genetic, and allelic heterogeneity, no clear genotype-phenotype correlation has yet been established. Standardized guidelines for the management of pediatric patients are available and therapy for RSTS patients is currently only symptomatic. In this article, several clinic and genetic aspects of RSTS are critically reviewed.

Keywords: Rubinstein–Taybi syndrome; clinical and molecular diagnosis; genotype–phenotype correlation; management; therapy.

Fig. 1

Schematic representation of clinical features shared by Rubinstein–Taybi, genitopatellar, floating harbor, and Cornelia de Lange syndromes. The main clinical characteristics of RSTS, GTPTS, FLHS, and CdLS are grouped by continuous, dashed, dotted, and double lines, respectively. CdLS, Cornelia de Lange syndrome; FLHS, Floating–Harbor syndrome ; GTPTS, genitopatellar syndrome; RSTS, Rubinstein–Taybi syndrome;

Fig. 2

Mutational spectra of RSTS. (A) Genetic and allelic heterogeneity of RSTS. The relative frequency of CREBBP and EP300 mutations found in RSTS patients is reported in the pie chart. (B) Frequency of mutations found in CREBBP (upper panel) and EP300 (lower panel). Proportion of point mutations versus rearrangements is on the left. Details of specific type of point mutations versus rearrangements are on the right.