Bülent HACIHAMDİOĞLU, A. Avni ATAY, M. Emre TAŞCILAR, A. Emin KÜREKCİ

Rubinstein-Taybi Sendromlu Bir Kız Hastada Prematüre Telarş ve Prematüre Vajinal Kanama

Rubinstein-Taybi sendromu (RTS), mikrosefali, dismorfik yüz, boy kısalığı, mental retardasyon, geniş el ve ayak başparmağı ile karakterizedir. Rubinstein-Taybi sendromlu çocuklarda prematüre telarş bildirilmekle birlikte prematüre vajinal kanama sadece bir olguda bildirilmiştir. Rubinstein-Taybi sendromunun hücre içi bir çok sinyal iletim yolaklarının bozulmasına yol açan mutasyonlar (CREB-bağlayıcı protein-CBP veya EP300) ile ilişkili olabileceği gösterilmiştir. Rubinstein-Taybi sendromlu olgularda gelişebilen prematüre telarşın, hücre içi sinyalizasyon defektine bağlı oluşabilecek olası bir hormonal bozukluğa ikincil olarak gelişebileceği ileri sürülmüştür. Burada ilk kez 7.2 yaşında takibimize giren, prematüre telarş ve prematüre vajinal kanama nedeni ile değerlendirilen, 2 yaşında akut lenfoblastik lösemi (ALL) tanısı almış RTS’li bir olgu sunulmuştur.

Anahtar Kelimeler:

Rubinstein-Taybi Sendromu, prematüre telarş, prematüre vajinal kanama

A GIRL WITH RUBINSTEIN-TAYBI SYNDROME AND PREMATURE THELARCHE AND PREMATURE VAGINAL BLEEDING

The Rubinstein–Taybi syndrome (RTS) is characterized by microcephaly, dysmorphic face, short stature, mental retardation, broad thumbs and big toes. Although premature thelarche had been described in children with Rubinstein–Taybi syndrome, premature vaginal bleeding had been described only in one case.It is shown that RTS can be caused by mutations in intracellular multiple signal transduction pathways (CREBbinding protein-CBP or EP300). It is speculated that premature thelarche in RTS is caused by hormonal deficiency secondary to intracellular signal transduction defects. Here we report a 7.2-year-old girl with RTS, premature thelarche and premature vaginal bleeding who was diagnosed as ALL when she was 2 years old

Keywords:

Rubinstein-Taybi Syndrome, Premature thelarche, premature vaginal bleeding,

PDF

___

Hennekam RC. Rubinstein-Taybi syndrome. Eur J Hum Genet 2006; 14: 981-985.
Roelfsema JH, Peters DJ. Rubinstein-Taybi syndrome: clinical and molecular overview. Expert Rev Mol Med 2007; 9: 1-16.
Miller RW, Rubinstein JH. Tumors in Rubinstein-Taybi syn drome. Am J Med Genet 1995; 56: 112-115.
Kurosawa K, Masuno M, Imaizumi K, Matsuo M, Kuroki Y, Tachibana K. Premature thelarche in Rubinstein-Taybi syndrome. Am J Med Genet 2002; 109: 72-73.
Gonzalez G A, Montminy M R. Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133. Cell 1989; 59: 675- 680.
Chrivia JC, Kwok RP, Lamb N, Hagiwara M, Montminy MR, Goodman RH. Phosphorylated CREB binds specifically to the nuclear protein CBP. Nature 1993; 365: 855-859.
Turnell A , Stewart G, Grand, R J, Rookes S, Martin A, Yamano H, Elledge SJ, Gallimore PH. The APC/C and CBP/p300 cooperate to regulate transcription and cell-cycle progression. Nature 2005; 438: 690-695.
Chen XN, Korenberg JR. Localization of human CREBBP (CREB binding protein) to 16p13.3 by fluorescence in situ hybridization. Cytogenet Cell Genet 1995; 71: 56-57.
Gayther SA, Batley S J, Linger L, Bannister A, Thorpe K, Chin SF, Daigo Y, Russell P, Wilson A, Sowter HM, Delhanty JD, Ponder BA, Kouzarides T, Caldas C. Mutations truncating the EP300 acetylase in human cancers. Nature Genet 2000; 24: 300-303.
Roelfsema JH, White SJ, Ariyürek Y, Bartholdi D, Niedrist D, Papadia F, Bacino CA, den Dunnen JT, van Ommen GJ, Breuning MH, Hennekam RC, Peters DJ. Genetic heterogeneity in Rubinstein-Taybi syndrome: mutations in both the CBP and EP300 genes cause disease. Am J Hum Genet 2005; 76: 572-580.
Guasconi V, Ait-Si-Ali S. Chromatin dynamics and cancer. Cancer Biol Ther 2004;3: 825-830.
Stevens CA, Carey JC, Blackburn BL. Rubinstein-Taybi syndrome: a natural history study. Am J Med Genet Suppl 1990; 6: 30-37.
Izumikawa Y, Chinen Y, Tohma T, Naritomi K. Three cases of Rubinstein-Taybi syndrome. J Hum Genet 1990; 43: 46.
Ihara K, Kuromaru R, Takemoto M, Hara T. Rubinstein-Taybi syndrome: a girl with a history of neuroblastoma and premature thelarche. Am J Med Genet 1999; 83: 365-366.