Investigators at the Institute for Research on Mental Retardation and Brain Aging, Troina, and University of Naples, Italy report a case of Cowden syndrome presenting with unilateral perisylvian dysplasia and with drug resistant focal seizures. A 14-year-old girl was born with hemiparesis and at 4 months she presented with seizures. Birth weight, height, and head circumference were above the 90th centile. MRI showed a dysplastic cleft and polymicrogyria in the right Sylvian region. The left cerebellar hemisphere was enlarged with dysplastic and hamartomatous appearance characteristic of Lhermitte-Duclos disease, part of the Cowden syndrome. At 7 years of age she developed obstructive hydrocephalus with herniation of cerebellar tonsils, relieved by a VP shunt and removal of the cerebellar hamartoma, histologically a cerebellar gangliocytoma. Seizures involving left side were refractory to medications. Intestinal examination showed small duodenal polyps. PTEN sequence analysis showed a de novo missense mutation. [1]

COMMENT. Cowden (or multiple hamartoma) syndrome, named after the first patient reported [2], is characterized by macrocephaly, intestinal hamartomatous polyps, benign skin tumors, and dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos disease). The occurrence of drug resistant epilepsy with Cowden syndrome is explained by an associated cortical dysplasia.