Genotype-phenotype analysis of ocular findings in Rubinstein-Taybi syndrome - A case report and review of literature.

Background: Rubinstein-Taybi syndrome (RSTS) is a rare genetic syndrome with a wide range of phenotypic presentations, including characteristic facial features. A variety of ocular abnormalities have been described in patients with RSTS. The genetic etiology of RSTS is heterogeneous but often involves two major genes, CREBBP (cAMP-response element binding protein-binding protein) and EP300 (E1A binding protein p300), with CREBBP variants responsible for the majority of the cases.

Materials and methods: We report a new case of female patient with a novel variant in CREBBP (c.4495C>G), with clinical features consistent with RSTS. We performed a literature review to search for possible genotype-phenotype relationships between the type of variant in CREBBP and frequency of ocular presentations. A PubMed search generated 12 articles that met our inclusion criteria. With the addition of our patient, there were a total of 163 patients included for mutation analysis (164 variants given one patient had two different variants).

Results: Our review revealed that the most common variant types were frameshift (25%), gross deletion (23%), nonsense (18%), and intragenic deletions (13%). There does not appear to be an obvious hot spot location. A total of 127 patients were included for genotype-phenotype analysis of ocular features (36 patients were excluded as unable to discern variant type). The most frequent ocular features in patients with RSTS were down-slanting palpebral fissure (74%), arched eyebrows (56%), long eyelashes (52%), and strabismus (23%).

Conclusions: Our results suggest that currently there is no clear genotype-phenotype relationship between the type of variant and frequency of associated ocular features in RSTS patients.