Journal Article

Mosaic CREBBP mutation causes overlapping clinical features of Rubinstein–Taybi and Filippi syndromes

R Monroe, Glen, de Vries, Tamar I, van der Lans, Christian A, van Haaften, Gijs, van Belzen, Martine J, Savelberg, Sanne MC, Nievelstein, Rutger A, van Haelst, Mieke M, Newman, William G

2016

Overview

Rubinstein-Taybi syndrome (RTS, OMIM 180849) and Filippi syndrome (FLPIS, OMIM 272440) are both rare syndromes, with multiple congenital anomalies and intellectual deficit (MCA/ID). We present a patient with intellectual deficit, short stature, bilateral syndactyly of hands and feet, broad thumbs, ocular abnormalities, and dysmorphic facial features. These clinical features suggest both RTS and FLPIS. Initial DNA analysis of DNA isolated from blood did not identify variants to confirm either of these syndrome diagnoses. Whole-exome sequencing identified a homozygous variant in C9orf173, which was novel at the time of analysis. Further Sanger sequencing analysis of FLPIS cases tested negative for CKAP2L variants did not, however, reveal any further variants. Subsequent analysis using DNA isolated from buccal mucosa revealed a mosaic variant in CREBBP. This report highlights the importance of excluding mosaic variants in patients with a strong but atypical clinical presentation of a MCA/ID syndrome if no disease-causing variants can be detected in DNA isolated from blood samples. As the striking syndactyly observed in the present case is typical for FLPIS, we suggest CREBBP analysis in saliva samples for FLPIS syndrome cases in which no causal CKAP2L variant is detected.

• Publisher: Nature Publishing Group
• Subject: Child / CREB-Binding Protein - genetics / Cytoskeletal Proteins - genetics / Diagnosis, Differential / Facies / Genetic Testing - methods / Growth Disorders - diagnosis / Growth Disorders - genetics / Homozygote / Humans / Intellectual Disability - diagnosis / Intellectual Disability - genetics / Male / Microcephaly - diagnosis / Microcephaly - genetics / Mosaicism / Mutation / Phenotype / Rubinstein-Taybi Syndrome - diagnosis / Rubinstein-Taybi Syndrome - genetics / Short Report / Syndactyly - diagnosis / Syndactyly - genetics