Cowden sendromu - Vikipedi

Cowden sendromu (Bannayan-Zozana sendromu, Lhermitte-Duclos sendromu, Riley-Smith sendromu, Ruvalcaba-Myhre-Smith sendromu), otosomal dominant yolla aktarılan kalıtsal bir sendromdur. PTEN hamartoma tümör sendromları kümesi üyelerindendir. Bazı kaynakların listelerinde, PTEN kümesi sendromlarının tümü Cowden sendromu başlığı altında toplanmaktadır.^[1]^[2]^[3]^[4]^[5]

Yenidoğandaki belli belirsiz makrosefali, aylar geçtikçe belirginleşir (progresif makrosefali).^[5]^[6]^[7] Yüz derisinde papüller oluşturan minik tümörcükler vardır (fasiyal trikolemmoma).^[7]^[8]

Ağız açıklığı küçüktür (mikrostomi). Ağız mukozasınsada çok sayıda beyaz renkli siğilsi tümörcükler görülür (hiperkeratotik papillomatozis). Dişeti büyümeleri (gingival hiperplazi), dişeti, dil ve yanak mukozasında minik kabarıklıklar vardır (fibromatöz papüller). Dil yüzeyinde derin oluklar saptanır (skrotal dil). Her iki çene hipoplaziktir (mikrognati). Sert damak kubbesi yüksektir. Yumuşak damak ve uvula hipoplazisi izlenir.^[7]^[9]

Yüzdeki tümörcüklere (trikolemmoma) derinin her yerinde rastlanabilir; ayrıca, papillomatöz oluşumlar, deride damar tümörleri (hemangiomalar) vardır. Avuç ve taban derileri kalındır (hiperkeratoz).^[8]

Çeşitli dokularda ve organlarda malformasyonlar ve yüksek tümör riski vardır:^[7]^[10]^[11]^[12]^[13]^[14]

Deri ve ağız mukozası: Skuamöz hücreli karsinom riski
Meme patolojileri: Fibroadenomlar, fibrokistik lezyonlar, duktal hiperplazi/papilloma, hyalin nodülleri, karsinom riski
Tiroid patolojileri: Multinodular guatr, Hashimoto tiroiditi, adenom, karsinom riski
Genital sistem patolojileri: Malformasyonlar, serviks ve ovaryum ca, ovaryum kistleri, uterus myomları, endometrium tümörleri; erkeklerde testis yağlanması (lipomatozis) ve jinekomasti
Böbrekler: Karsinom riski
Sindirim sistemi patolojileri: Hamartomatöz polipler, kolorektal kanserler
Sinir sistemi: Beyinde damarsal malformasyonlar, gangliyositoma ve meningioma riski
Kemikler: Kemiklerde erime alanları (litik alanlar), kifoz, kifoskolyoz

Başkaca bulgular: İmmun yetmezlik bulguları, otizm, zeka geriliği.^[11]^[14]

Kaynakça

^ Eng C. PTEN: one gene, many syndromes. Human Mutation, 22(3):183-198, 2003
^ Blumenthal GM, Dennis PA. PTEN hamartoma tumor syndromes. European Journal of Human Genetics, 16: 1289-1300, 2008
^ Pilarski R, Eng C. Will the real Cowden syndrome please stand up (again)? Expanding mutational and clinical spectra of the PTEN hamartoma tumour syndrome (Commentary). Journal of Medical Genetics, 41: 323-326, 2004
^ Tan M-H, Mester J, Peterson C, et al. A clinical scoring system for selection of patients for PTEN mutation testing is proposed on the basis of a prospective study of 3042 probands. American Journal of Human Genetics, 88: 42-56, 2011
^ ^a ^b Pezzolesi MG, Platzer P, Waite KA, Eng C. Differential expression of PTEN-targeting microRNAs miR-19a and miR-21 in Cowden syndrome. American Journal of Human Genetics, 82: 1141-1149, 2008
^ Pilarski R, Stephens JA, Noss R, et al. Predicting PTEN mutations: an evaluation of Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome clinical features. Journal of Medical Genetics, 48: 505-512, 2011
^ ^a ^b ^c ^d Eng C. Will the real Cowden syndrome please stand up: revised diagnostic criteria. Journal of Medical Genetics, 37(11):828-830, 2000
^ ^a ^b Mester J, Eng C. When overgrowth bumps into cancer: the PTENopathies. American Journal of Medical Genetics Part C: Seminars in Medical Genetics, 163C(2): 114–121, 2013
^ Haritha A, Jayakumar A. Syndromes as they relate to periodontal disease. Periodontology 2000, 56:65–86, 2011
^ Yehia L, Niazi F, Ni Y, et al. Germline heterozygous variants in SEC23B are associated with Cowden syndrome and enriched in apparently sporadic thyroid cancer. American Journal of Human Genetics, 97: 661-676, 2015
^ ^a ^b Driessen GJ, IJspeert H, Wentink M, et al. Increased PI3K/Akt activity and deregulated humoral immune response in human PTEN deficiency. Journal of Allergy & Clinical Immunology, 138: 1744-1747, 2016
^ Yu W, Ni Y, Saji M, et al. Cowden syndrome-associated germline succinate dehydrogenase complex subunit D (SDHD) variants cause PTEN-mediated down-regulation of autophagy in thyroid cancer cells. Human Molecular Genetics, 26(7):1365-1375, 2017
^ Tan MH, Mester JL, Ngeow J, Rybicki LA, Orloff MS, Eng C. Lifetime cancer risks in individuals with germline PTEN mutations. Clinical Cancer Research, 18(2):400–407, 2012
^ ^a ^b Browning MJ, Chandra A, Carbonaro V, et al. Cowden's syndrome with immunodeficiency. Journal of Medical Genetics, 52: 856-859, 2015

[1] Eng C. PTEN: one gene, many syndromes. Human Mutation, 22(3):183-198, 2003

[2] Blumenthal GM, Dennis PA. PTEN hamartoma tumor syndromes. European Journal of Human Genetics, 16: 1289-1300, 2008

[3] Pilarski R, Eng C. Will the real Cowden syndrome please stand up (again)? Expanding mutational and clinical spectra of the PTEN hamartoma tumour syndrome (Commentary). Journal of Medical Genetics, 41: 323-326, 2004

[4] Tan M-H, Mester J, Peterson C, et al. A clinical scoring system for selection of patients for PTEN mutation testing is proposed on the basis of a prospective study of 3042 probands. American Journal of Human Genetics, 88: 42-56, 2011

[:0-5] Pezzolesi MG, Platzer P, Waite KA, Eng C. Differential expression of PTEN-targeting microRNAs miR-19a and miR-21 in Cowden syndrome. American Journal of Human Genetics, 82: 1141-1149, 2008

[6] Pilarski R, Stephens JA, Noss R, et al. Predicting PTEN mutations: an evaluation of Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome clinical features. Journal of Medical Genetics, 48: 505-512, 2011

[:1-7] Eng C. Will the real Cowden syndrome please stand up: revised diagnostic criteria. Journal of Medical Genetics, 37(11):828-830, 2000

[:2-8] Mester J, Eng C. When overgrowth bumps into cancer: the PTENopathies. American Journal of Medical Genetics Part C: Seminars in Medical Genetics, 163C(2): 114–121, 2013

[9] Haritha A, Jayakumar A. Syndromes as they relate to periodontal disease. Periodontology 2000, 56:65–86, 2011

[10] Yehia L, Niazi F, Ni Y, et al. Germline heterozygous variants in SEC23B are associated with Cowden syndrome and enriched in apparently sporadic thyroid cancer. American Journal of Human Genetics, 97: 661-676, 2015

[:3-11] Driessen GJ, IJspeert H, Wentink M, et al. Increased PI3K/Akt activity and deregulated humoral immune response in human PTEN deficiency. Journal of Allergy & Clinical Immunology, 138: 1744-1747, 2016

[12] Yu W, Ni Y, Saji M, et al. Cowden syndrome-associated germline succinate dehydrogenase complex subunit D (SDHD) variants cause PTEN-mediated down-regulation of autophagy in thyroid cancer cells. Human Molecular Genetics, 26(7):1365-1375, 2017

[13] Tan MH, Mester JL, Ngeow J, Rybicki LA, Orloff MS, Eng C. Lifetime cancer risks in individuals with germline PTEN mutations. Clinical Cancer Research, 18(2):400–407, 2012

[:4-14] Browning MJ, Chandra A, Carbonaro V, et al. Cowden's syndrome with immunodeficiency. Journal of Medical Genetics, 52: 856-859, 2015

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