Lhermitte-Duclos disease is a rare hamartomatous tumor of the cerebellum resulting from a mutation in the phosphatase and tensin homolog (PTEN) gene: it has been reported in fewer than 10 infants.
This case of Lhermitte-Duclos disease associated with paraspinal AVF and mutation of the PTEN gene suggests a relationship between Lhermitte-Duclos disease and Cowden disease.
In vivo functional analysis of the counterbalance of hyperactive phosphatidylinositol 3-kinase p110 catalytic oncoproteins by the tumor suppressor PTEN.
At 6 months before his death, the patient complained of hoarseness and dysphagia, and clinical whole-body examinations revealed advanced lung adenocarcinoma (T4N2M1b, Stage IV), multiple skin verrucas, gastrointestinal polyposis, goiters, and cerebellar dysplastic gangliocytoma (Lhermitte-Duclos disease), while PTEN gene mutation was detected in his serum.
It remains unclear whether all cases of LDD, even without features of CS, are caused by germline PTEN mutation and whether somatic PTEN mutation occurs in sporadic LDD.
A heterozygous frameshift mutation of the PTEN/MMAC1 gene in a patient with Lhermitte-Duclos disease - only the mutated allele was expressed in the cerebellar tumor.
The diagnosis of Cowden syndrome with PTEN gene mutation, linked to higher risk of neoplasia and occurrence of hamartomatous lesions characteristic of the Lhermitte-Duclos disease (LDD), was confirmed by genetic investigation.
A PTEN mutation, c.1003C>T p.(Arg335Ter), was subsequently identified as the cause of Cowden syndrome in another family member (a nephew) with dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos disease), and genetic testing in the proband's daughter indicated that he was an obligate carrier of the mutation.
In addition, the differential PTEN mutation status with corresponding LDD phenotypes suggests a potential correlation between germline or somatic mutation and coexisting LDD/CS or isolated LDD, respectively.
A candidate tumour suppressor gene, PTEN, has recently been identified within chromosome 10q23, the locus of the Cowden syndrome/Lhermitte Duclos disease susceptibility gene.
Mutations in the PTEN gene are associated with a broad spectrum of disorders, including Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome, and Lhermitte-Duclos disease.
The VDR AA homozygous genotype was seen in 30(16.7%) patients with LDD and 20(8.7%) controls (codominant model: OR = 2.48; 95% CI 1.30-4.73, P = .005) with an estimated approximately 2.5-fold risk of developing LDD in individuals with this genotype.