Interstitial lung disease in two patients with Rubinstein-Taybi syndrome. R. Kosaki1, S. Kikuchi2, G. Koinuma2, M. Higuchi2, K. Kawasaki2, K. Kosaki3 1) Div.Clin Genet & Mol Med, Natl Ctr Child Health & Dev, Tokyo, Japan; 2) Div. Pul , Natl Ctr Child Health & Dev, Tokyo, Japan; 3) Dept Ped, Keio Univ Sch Med, Tokyo, Japan.
Rubinstein-Taybi syndrome (RTS) is characterized by broad thumbs and great toes, short stature, mental retardation, and distinctive facial features including downslanting palpebral fissures, columella extending below the nares. CREBBP and EP300 are the causative genes for RTS. Here we report on two patients with RTS who developed interstitial lung disease. [Case 1] The patient was born after 38 weeks of gestation with a birth weight of 2840g. At age 6 weeks, he started to develop tachypnea and cyanosis. Based on a hazy ground glass appearance on the chest X-ray and elevated serum marker KL-6, he was diagnosed as having interstitial lung disease. After treatment with corticosteroids, his respiratory status improved. He had typical RTS phenotype and a complex CREBBP mutation involving a 6-base deletion and an 11-base insertion that truncates protein [Case 2] The patient was born after 37 weeks of gestation with a birth weight of 1943g. At birth he had PDA, congestive heart failure, and pulmonary hypertension. PDA was ligated at age 1 month. After age 4 months, he experienced several episodes of pneumonia that required occasional ventilatory support. At age 12 months, X-ray revealed a hazy ground glass appearance. Based on elevated serum KL-6, he was diagnosed as having interstitial lung disease. He died because of irespiratory failure. Dysmorphic features of the patient were compatible with RTS. To the best of our knowledge, development of interstitial lung disease has never been reported previously in relation to RTS. Nevertheless, the similarity of the clinical course of two patients herein reported suggests that patients with RTS may be susceptible to interstitial lung disease. Recurrent pulmonary infection, a relatively common complication of RTS, may have contributed to fibrotic process of the lung. Alternatively, mutations in CREBBP, a transcoactivator of various transcriptional factors, may have direct impact on the structural integrity of the alveolar wall.