Rubinstein Taybi Syndrome in an Indian Child due to EP300 Gene Mutation.

Abstract

To the Editor : A 10-y-old girl was diagnosed with Rubinstein Taybi Syndrome (RTS) based on distinctive facial features (low hanging columella, high palate, grimacing smile, talon cusps), broad, angulated thumbs and great toes, short stature and moderate intellectual disability (Fig. 1). Her younger sister, who died at 11 mo of age due to acute myeloid leukemia, did not have clinical features of RTS. Complete sequencing of CREBBP and EP300 genes was done for the proband as previously described [1, 2]. No pathogenic mutation was noted in CREBBP gene. She was found to be heterozygous for c.1282C > T or p.P428S mutation in exon five of EP300 gene (Fig. 1). The mutation is predicted to affect the donor splicing [3]. The patient’s mother was heterozygous for the same mutation. Prenatal diagnosis was offered to the couple and the fetus did not carry this mutation, and was confirmed to be unaffected postnatally. This mutation was not identified in 100 normal unrelated individuals. Deletion/duplication analysis of CREBBP and EP300 gene was not available. Our patient had horizontal palpebral fissures as described with EP300 related RTS, compared with CREBBP related RTS, who have anti-mongoloid slant [4]. Although patients with EP300 mutation have broad thumbs or toes, radial deviation has not been reported [2] (Fig. 1). This mutation was inherited from her mother who had mild hypertelorism, broad nasal bridge, normal intelligence and hands/feet. Negri et al. reported a patient with mutation in EP300 gene (p.N1511T) that was inherited from a healthy mother. Low penetrance in EP300 related RTS may present a challenge during genetic counseling and prenatal diagnosis [2]. EP300 gene somatic mutations are reported in acute leukemia and RTS patients have an increased incidence of cancer [2, 5]. Thus, we report an Indian child with Rubinstein Taybi Syndrome with familial EP300 gene mutation.