LDD可单发，也可是Cowden综合征的一种颅内表现，在一项211例Cowden综合征患者的研究中，有32%的患者发展为小脑发育不良神经节细胞瘤[12]。Cowden综合征是一种常染色体显性疾病，患病率为1/百万每年[13]。其特征是多发性错构瘤，可累及内、中、外三个胚层的组织[14]。约85%的Cowden综合征患者具有位于10q22-23的编码同源性磷酸酶-张力蛋白（phosphatase and tensin homolog，PTEN）的抑癌基因PTEN的胚系突变（也称为PTEN错构瘤综合征），包括基因内突变、启动子突变、和大片段缺失或基因重排[15-17]。未发生PTEN胚系突变的患者可能与SDHB或SDHD的胚系突变有关，这两种突变体均可影响与PTEN相同的下游信号通路[18]。其他非PTEN突变阳性的Cowden综合征和Cowden样综合征的改变，与包括SEC23B、USF3、KLLN和WWP1基因改变有关[19]。WWP1是一种E3泛素连接酶，功能获得性胚系突变，可增加PTEN的泛素化和降解，模拟PTEN胚系突变[20]。几乎在所有成人发病的LDD病例中都发现了PTEN突变，但在儿童发病的病例中没有发现，这表明两者在生物学上有所不同。因此，成人在确诊LDD后，应尽早行PTEN及相关基因检测。
[1] Eng C, Murday V, Seal S, et al. Cowden syndrome and Lhermitte-Duclos disease in a family: a single genetic syndrome with pleiotropy? J Med Genet, 1994, 31(6): 458-461.[2] Longy M, Lacombe D. Cowden disease. Report of a family and review. Ann Genet, 1996, 39(1): 35-42.[3] Borni M, Kammoun B, Kolsi F, et al. The Lhermitte-Duclos disease: a rare bilateral cerebellar location of a rare pathology. Pan Afr Med J, 2019, 33(118.[4] Khandpur U, Huntoon K, Smith-Cohn M, et al. Bilateral Recurrent Dysplastic Cerebellar Gangliocytoma (Lhermitte-Duclos Disease) in Cowden Syndrome: A Case Report and Literature Review. World Neurosurg, 2019, 127(319-325.[5] Vinchon M, Blond S, Lejeune J P, et al. Association of Lhermitte-Duclos and Cowden disease: report of a new case and review of the literature. J Neurol Neurosurg Psychiatry, 1994, 57(6): 699-704.[6] Giorgianni A, Pellegrino C, De Benedictis A, et al. Lhermitte-Duclos disease. A case report. Neuroradiol J, 2013, 26(6): 655-660.[7] Milbouw G, Born J D, Martin D, et al. Clinical and radiological aspects of dysplastic gangliocytoma (Lhermitte-Duclos disease): a report of two cases with review of the literature. Neurosurgery, 1988, 22(1 Pt 1): 124-128.[8] Douglas-Akinwande A C, Payner T D, Hattab E M. Medulloblastoma mimicking Lhermitte-Duclos disease on MRI and CT. Clin Neurol Neurosurg, 2009, 111(6): 536-539.[9] Mittal P, Gupta K, Saggar K, et al. Adult medulloblastoma mimicking Lhermitte-Duclos disease: can diffusion weighted imaging help? Neurol India, 2009, 57(2): 203-205.[10] Hair L S, Symmans F, Powers J M, et al. Immunohistochemistry and proliferative activity in Lhermitte-Duclos disease. Acta Neuropathol, 1992, 84(5): 570-573.[11] Abel T W, Baker S J, Fraser M M, et al. Lhermitte-Duclos disease: a report of 31 cases with immunohistochemical analysis of the PTEN/AKT/mTOR pathway. J Neuropathol Exp Neurol, 2005, 64(4): 341-349.[12] Riegert-Johnson D L, Gleeson F C, Roberts M, et al. Cancer and Lhermitte-Duclos disease are common in Cowden syndrome patients. Hered Cancer Clin Pract, 2010, 8(1): 6.[13] Starink T M, van der Veen J P, Arwert F, et al. The Cowden syndrome: a clinical and genetic study in 21 patients. Clin Genet, 1986, 29(3): 222-233.[14] Tan M H, Mester J L, Ngeow J, et al. Lifetime cancer risks in individuals with germline PTEN mutations. Clin Cancer Res, 2012, 18(2): 400-407.[15] Liaw D, Marsh D J, Li J, et al. Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nat Genet, 1997, 16(1): 64-67.[16] Marsh D J, Coulon V, Lunetta K L, et al. Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation. Hum Mol Genet, 1998, 7(3): 507-515.[17] Zhou X P, Waite K A, Pilarski R, et al. Germline PTEN promoter mutations and deletions in Cowden/Bannayan-Riley-Ruvalcaba syndrome result in aberrant PTEN protein and dysregulation of the phosphoinositol-3-kinase/Akt pathway. Am J Hum Genet, 2003, 73(2): 404-411.[18] Ni Y, Zbuk K M, Sadler T, et al. Germline mutations and variants in the succinate dehydrogenase genes in Cowden and Cowden-like syndromes. Am J Hum Genet, 2008, 83(2): 261-268.[19] Yehia L, Eng C. PTEN hamartoma tumour syndrome: what happens when there is no PTEN germline mutation? Hum Mol Genet, 2020, 29(R2): R150-R157.[20] Lee Y R, Yehia L, Kishikawa T, et al. WWP1 Gain-of-Function Inactivation of PTEN in Cancer Predisposition. N Engl J Med, 2020, 382(22): 2103-2116.
