Atypical focal cortical dysplasia in a patient with Cowden syndrome

Cheung, Ka-Ming; Lam, Christina; Chan, Yiu Kay; Siu, Wai-Kwan; Liao, Yong

doi:10.12809/hkmj133863

Cited by 18 publications

(9 citation statements)

References 10 publications

(13 reference statements)

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“…The underlying etiology of these brain hamartomas is currently unknown. Several cases of Cowden syndrome with cortical dysplasia in childhood have been reported ( 8 , 9 ); however, only one case of adult-onset Cowden syndrome with cortical dysplasia has been published ( 10 ).…”

Section: Discussionmentioning

confidence: 99%

Cowden Syndrome with a Novel <i>PTEN</i> Mutation Presenting with Partial Epilepsy Related to Focal Cortical Dysplasia

et al. 2018

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Abstract:Cowden syndrome is a rare autosomal dominant disorder characterized by multiple hamartomas of the ectoderm and brain. A 36-year-old Japanese man presented with right facial seizure during sleep and was admitted to our hospital. He showed cobblestoning over the tongue and palmar pitting but no neurological abnormalities while he was not having a seizure. Brain magnetic resonance imaging showed focal cortical dysplasia in the left frontal lobe. Electroencephalography showed sharp waves over the left frontal lesion. A genetic analysis revealed a novel mutation of PTEN. The administration of carbamazepine ended the seizures. This is the first Japanese case of Cowden syndrome with a novel PTEN gene mutation and cortical dysplasia.

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Section: Discussionmentioning

confidence: 99%

Cowden Syndrome with a Novel <i>PTEN</i> Mutation Presenting with Partial Epilepsy Related to Focal Cortical Dysplasia

et al. 2018

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“…This could suggest a positive role for mitochondrial PTEN in mediating TLE-related neuronal excitoxicity. On the other hand, total or partial loss-of-function mutations at the PTEN gene are frequent in the germline of patients with Cowden disease, one of the major manifestations of PHTS, and several cases of patients with Cowden disease associated to epilepsy have been reported [ 172 , 173 , 174 , 175 , 176 ]. This suggests that impaired PTEN function may favor epilepsy episodes, in agreement with the notion of using inhibitors of the mTOR PTEN downstream effector as antiepileptic drugs [ 177 ].…”

Section: Pten Inhibition By Small Molecules In Human Disease Theramentioning

confidence: 99%

PTEN Inhibition in Human Disease Therapy

Pulido

2018

Molecules

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The tumor suppressor PTEN is a major homeostatic regulator, by virtue of its lipid phosphatase activity against phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3], which downregulates the PI3K/AKT/mTOR prosurvival signaling, as well as by its protein phosphatase activity towards specific protein targets. PTEN catalytic activity is crucial to control cell growth under physiologic and pathologic situations, and it impacts not only in preventing tumor cell survival and proliferation, but also in restraining several cellular regeneration processes, such as those associated with nerve injury recovery, cardiac ischemia, or wound healing. In these conditions, inhibition of PTEN catalysis is being explored as a potentially beneficial therapeutic intervention. Here, an overview of human diseases and conditions in which PTEN inhibition could be beneficial is presented, together with an update on the current status of specific small molecule inhibitors of PTEN enzymatic activity, their use in experimental models, and their limitations as research or therapeutic drugs.

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“…Recently, a series of case reports demonstrated epileptic seizures in PTEN mutation-positive patients, often linked to cortical dysplasia [30][31][32][33][34]. In 2011, Conti et al [34] presented the first case of a 14-year-old boy with a deletion of PTEN exon 2, whose seizures began when he was 8 years old and could be controlled with valproic acid.…”

Section: Connecting Phenotype and Genotype Across The Lifespanmentioning

confidence: 99%

Balancing Proliferation and Connectivity in PTEN-associated Autism Spectrum Disorder

2015

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Germline mutations in PTEN, which encodes a widely expressed phosphatase, was mapped to 10q23 and identified as the susceptibility gene for Cowden syndrome, characterized by macrocephaly and high risks of breast, thyroid, and other cancers. The phenotypic spectrum of PTEN mutations expanded to include autism with macrocephaly only 10 years ago. Neurological studies of patients with PTENassociated autism spectrum disorder (ASD) show increases in cortical white matter and a distinctive cognitive profile, including delayed language development with poor working memory and processing speed. Once a germline PTEN mutation is found, and a diagnosis of phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome made, the clinical outlook broadens to include higher lifetime risks for multiple cancers, beginning in childhood with thyroid cancer. First described as a tumor suppressor, PTEN is a major negative regulator of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (mTOR) signaling pathway-controlling growth, protein synthesis, and proliferation. This canonical function combines with less well-understood mechanisms to influence synaptic plasticity and neuronal cytoarchitecture. Several excellent mouse models of Pten loss or dysfunction link these neural functions to autism-like behavioral abnormalities, such as altered sociability, repetitive behaviors, and phenotypes like anxiety that are often associated with ASD in humans. These models also show the promise of mTOR inhibitors as therapeutic agents capable of reversing phenotypes ranging from overgrowth to low social behavior. Based on these findings, therapeutic options for patients with PTEN hamartoma tumor syndrome and ASD are coming into view, even as new discoveries in PTEN biology add complexity to our understanding of this master regulator.

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Atypical focal cortical dysplasia in a patient with Cowden syndrome

Cited by 18 publications

References 10 publications

Cowden Syndrome with a Novel <i>PTEN</i> Mutation Presenting with Partial Epilepsy Related to Focal Cortical Dysplasia

Cowden Syndrome with a Novel <i>PTEN</i> Mutation Presenting with Partial Epilepsy Related to Focal Cortical Dysplasia

PTEN Inhibition in Human Disease Therapy

Balancing Proliferation and Connectivity in PTEN-associated Autism Spectrum Disorder

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