Introduction: Rubinstein-Taybi syndrome (RSTS) is an extremely rare autosomal dominant genetic disease, with an estimated prevalence of one case per 125,000 live births. RSTS is characterized by slow development of height and weight, microcephaly, dysmorphic facial features, broad thumbs, and big toes, intellectual disability and postnatal growth retardation. Mutations in the genes encoding the cyclic-AMP-regulated enhancer binding protein (CREBBP) and the E1A-binding protein p300 (EP300) contributed to the development of RSTS, but many cases have only been clinically diagnosed. Case: The infant was delivered by vaginal delivery at the 40 weeks gestational age with a birth weight of 3.93kg (＞90th centile), a body length of 50cm (50th–75th centile), occipito-frontal circumference of 35.5cm (75th–90th centile). The child had a big thumb, broad great toe, narrow forehead, down slanting palpebral fissure, prominent nose, short columella, low anterior hair line, hirsutism, small chin, high arched and narrow palate, and highly arched eyebrows. After birth he was admitted to neonatal intensive care unit because of tachypnea. The echocardiogram showed a large patent ductus arteriosus ( PDA) and flow was bidirectional. About 2 months of age, echocardiogram showed PDA and pulmonary hypertension. He experienced recurrent infections and treated with antibiotics for 31days. Lymphocyte compartment showed abnormal CD3, CD4, CD8+, T, and CD19+ B cells. Serum immunoglobulin (Ig) M is decreased 98mg/dL. The patient was started on intravenous IgG at a dose of 0.4g/kg monthly. After PDA ligation and intravenous IgG therapy, he responded favorably to therapy with fewer and less severe infection. He patient left the hospital after 4 months of life with oxygen therapy. The chromosomal analysis showed normal karyotype and molecular analysis of the major causative gene revealed a previously unreported heterozygous truncating mutation of CREBBP (c.4395-1G＞T). Conclusion: We present a case of unique presentation of RSTS with PDA, pulmonary hypertension and immunodeficiency. Despite this syndrome’s strong association with recurrent infection, there has been few reports describing immunological deficiencies. Early diagnosis of this immunological deficit and institution of intravenous IgG may improve the quality of life of these patients.