Lhermitte‐duclos disease and cowden disease: A single phakomatosis

Padberg, George W.; Schot, J. D. L.; Vielvoye, G. J.; Bots, G. Th. A. M.; Beer, F

doi:10.1002/ana.410290511

Cited by 182 publications

(89 citation statements)

References 14 publications

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“…However, the systematic ascertainment and characterisation of head circumference has not been performed in CS or BRRS nor in the molecularly defined PHTS. Furthermore, while it is presumed that the aetiology of the macrocephaly is megencephaly from single case-report imaging, 11 we do not know if this is the case. Therefore, we sought to systematically measure and characterise the OFC from our adult and paediatric research participants found to have germline pathogenic PTEN mutations.…”

Section: Introductionmentioning

confidence: 90%

Analysis of prevalence and degree of macrocephaly in patients with germline PTEN mutations and of brain weight in Pten knock-in murine model

et al. 2011

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PTEN Hamartoma Tumour Syndrome (PHTS) includes Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS), and other conditions resulting from germline mutation of the PTEN tumour suppressor gene. Although macrocephaly, presumably due to megencephaly, is found in both CS and BRRS, the prevalence and degree have not been formally assessed in PHTS. We evaluated head size in a prospective nested series of 181 patients found to have pathogenic germline PTEN mutations. Clinical data including occipital-frontal circumference (OFC) measurement were requested for all participants. Macrocephaly was present in 94% of 161 evaluable PHTS individuals. In patients r18 years, mean OFC was +4.89 standard deviations (SD) above the population mean with no difference between genders (P¼0.7). Among patients 418 years, average OFC was 60.0 cm in females and 62.8 cm in males (Po0.0001). To systematically determine whether macrocephaly was due to megencephaly, we examined Pten M3M4 missense mutant mice generated and maintained on mixed backgrounds. Mice were killed at various ages, brains were dissected out and weighed. Average brain weight for Pten M3M4 homozygous mice (N¼15) was 1.02 g compared with 0.57 g for heterozygous mice (N¼29) and 0.49 g for wild-type littermates (N¼24) (Po0.0001). Macrocephaly, secondary to megencephaly, is an important component of PHTS and more prevalent than previously appreciated. Patients with PHTS have increased risks for breast and thyroid cancers, and early diagnosis is key to initiating timely screening to reduce patient morbidity and mortality. Clinicians should consider germline PTEN testing at an early point in the diagnostic work-up for patients with extreme macrocephaly.

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Section: Introductionmentioning

confidence: 90%

Analysis of prevalence and degree of macrocephaly in patients with germline PTEN mutations and of brain weight in Pten knock-in murine model

et al. 2011

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“…8,9 Megalencephaly and LDD are the most important neurological features of CD and the cause of symptoms like tremor, ataxia, and mental retardation. [8][9][10] In addition to these benign symptoms, CD patients have an increased risk of developing malignancies. They include follicular cell carcinoma of the thyroid, carcinomas of the breast and malignant cancers of the urogenital and digestive tract.…”

Section: Introductionmentioning

confidence: 99%

Novel PTEN mutations in patients with Cowden disease: absence of clear genotype–phenotype correlations

Nelen¹,

et al. 1999

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Cowden disease (CD) is characterised by multiple hamartomas in a variety of tissues. The pathological hallmark is the presence of a number of trichilemmomas. Several neurological symptoms are also part of CD with megalencephaly and Lhermitte-Duclos disease (LDD) as the most important features. Early recognition of CD patients is important because of the increased risk of developing malignancies. Breast cancer is the most frequent malignancy, but also urogenital, digestive tract, and thyroid cancers are found with higher frequencies. CD was localised to chromosome 10q23 and the PTEN gene (also known as MMAC1 or TEP1) was shown to be involved. Germline mutations were identified in both familial and sporadic CD patients. We identified eight PTEN mutations, of which seven were novel, in 13 CD patients. Combined with previous data we have identified 17 independent CD mutations. Gross DNA alterations in CD patients were not detected. Genotype-phenotype relations are discussed. The only correlation suggested to exist is that missense mutations are not detected in LDD patients. However, larger numbers are needed to confirm this. Association of PTEN mutations and the occurrence of malignant breast disease found in an earlier study cannot be confirmed. Clinical features of five CD patients without a PTEN mutation in the coding sequence do not differ from CD patients with a PTEN mutation. Furthermore, it is likely that we have identified the majority of CD patients in the Netherlands. From this we estimate that CD has a prevalence of about 1 in 250 000 in the Dutch population with a low mutation frequency.

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“…The most characteristic lesions are multiple facial trichilemnomas, acral keratosis and multiple oral papillomas, occurring in 99% of CD patients (1 -4). Lhermitte-Duclos disease (LDD), characterized by a dysplastic gangliocytoma of the cerebellum, leading to progressive cerebellar syndrome and frequent hydrocephaly, is now established as a component of CD (5)(6)(7)(8).…”

Section: Letter To the Editormentioning

confidence: 99%

“…Megencephaly/macrocephaly is present in 38% of CD patients and 80% of LDD patients (4,6,7). CNS tumors, both malignant and benign, may also be components of CD.…”

Section: Letter To the Editormentioning

confidence: 99%

A Novel Germline Mutation of the PTEN/MMAC1 Gene in a Patient with Cowden Disease

Sanson

Zhou²,

Jl³

et al. 1999

Acta Oncologica

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Lhermitte‐duclos disease and cowden disease: A single phakomatosis

Cited by 182 publications

References 14 publications

Analysis of prevalence and degree of macrocephaly in patients with germline PTEN mutations and of brain weight in Pten knock-in murine model

Analysis of prevalence and degree of macrocephaly in patients with germline PTEN mutations and of brain weight in Pten knock-in murine model

Novel PTEN mutations in patients with Cowden disease: absence of clear genotype–phenotype correlations

A Novel Germline Mutation of the PTEN/MMAC1 Gene in a Patient with Cowden Disease

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