Lhermitte–Duclos disease caused by a novel germline PTEN mutation R173P in a patient presenting with psychosis

Due to the common replacement of the inner granular layer or its most superficial region by hypertrophic ganglion cells, it has been hypothesized that aberrant granule cell migration and hypertrophy may play a role in Lhermitte–Duclos disease (LDD), while cell proliferation apparently does not. The abnormal neuronal cells send their hypertrophic and hypermyelinated axons into an enlarged molecular layer and may thus represent hypertrophic granule cells[1,2]. Mitoses have not been found in these cells. Despite the benign nature of LDD, surgical excision appears to be the only effective treatment to relieve the symptoms[2], such as headache, dizziness, vomiting, tremor, ataxia, unstable gait and seizures. Sometimes LDD occurs in the context of Cowden syndrome (CS), an autosomal dominant hamartoma tumour syndrome, with a high risk of malignant tumours[3]. Therefore, patients have to be monitored for additional lesions, indicating the development of CS. Germline mutations in PTEN (Phosphatase and TENsin homologue deleted on chromosome TEN), on 10q23.3, are found in 80–85% of individuals with CS[4,5]. PTEN is a tumour suppressor dual-specificity phosphatase. Its lipid phosphatase activity antagonizes the action of PI3-kinase (phosphoinositide-3 kinase), which activates the kinase Akt. Akt promotes proliferative, anti-apoptotic and prosurvival pathways[6]. In an unselected series of 18 patients presenting with LDD, 15, all adults, were found to carry PTEN mutations[5]. At least four with PTEN mutations only had LDD, without other clinical features of CS. All 18 presented with cerebellar signs and/or signs consistent with space occupying lesions. In the present study, we describe a patient with LDD and a novel germline PTEN mutation presenting with psychosis. The 42-year-old woman had a 12-year history of several admissions to the department of psychiatry of Magdeburg University. She suffered from mild mental retardation, alcohol addiction and frequent suicidal ideation and attempts. In 2005, paranoid schizophrenia was diagnosed because of acoustic hallucinations, that is, imperative voices telling her to perform suicide. In 2008, she was readmitted to the department after a suicide note was found. She complained about episodic headache, nausea, drowsiness and dizziness with a tendency to fall, and still suffered from alcohol addiction. She was obese, macrocephalic and had a neglected appearance. Hirsutism, multiple cutaneous facial papules and a papillomatous growth on the tongue were observed during examination of skin and mucosa. Palmoplantar keratosis and verrucoid papules were present on dorsal hands and feet. A scar from thyroid goitre resection was visible. No abnormal distortions, swelling or nodules were found in the breasts (mammography was refused). Apart from hypertension, no cardiovascular abnormalities were detected. Examination of the respiratory, gastrointestinal and genitourinary system showed no pathological findings. Apart from suspected swelling of the optic papillae, neurological examination showed signs of cerebellar ataxia, such as a dysmetric finger-nose/heel-shin test, dysdiadochokinesia and a negative Romberg’s test. Psychiatric assessment found mild to moderate death thoughts, suicide ideation, affective lability and dysphoria. Acoustic hallucinations with imperative voices were present