HYPOTHALAMIC HAMARTOMA

OVERVIEW

Hypothalamic hamartomas are rare malformations of fetal brain development, affecting development of the hypothalamus, and are placed within the spectrum of grey matter heterotopia. Pathologically, lesions show mature neuronal and glial cells and some myelinated fibres.

Clinical context

Hypothalamic hamartomas are associated with different clinical presentations, depending upon the site of attachment of the hamartoma. Hamartomas that are attached posteriorly in the region of the mammillary bodies cause seizures. Hamartomas attached anteriorly in the region of the tuber cinereum cause central precocious puberty. Larger lesions with anterior and posterior attachment cause both seizures and central precocious puberty. Hypothalamic hamartoma occurs in both sexes, with a male predominance (1.3M:F). Seizure onset is typically under the age of 1 year, typically with focal emotional seizures with laughter (gelastic seizures) present from birth, but often recognized in retrospect after emergence of other seizure types. Developmental and learning impairments (of variable severity) and psychiatric disorders are seen in 80%.

CAUTION developmental and cognitive outcome may be worse in children with uncontrolled seizures in early life, especially if epileptic spasms or generalized seizure types appear, therefore proactive seizure control is important, this may include epilepsy surgery, if seizures are not controlled with medication.

Causes

• Sporadic (95%)
• Pallister-Hall syndrome (5%)

PALLISTER HALL SYNDROME

This syndrome includes polydactyly, a bifid epiglottis, dysplastic nails, imperforate anus, kidney abnormalities and hypothalamic hamartoma. It is associated with a pathogenic variant in GLI3 (on chromosome 7p13).