Hypothalamic Hamartoma
Overview
- Tumor-like malformations that are present at birth and grow with the rest of the brain.
- Two key clinical manifestations (phenotypes):
- Central precocious puberty
- Epilepsy (gelastic (laughing) seizures) with related neurobehavioral symptoms
- 95% are sporadic, the remaining are most often part of Pallister-Hall syndrome, which is associated with a GLI3 gene mutation and which causes select other body malformations.
Central Precocious Puberty
- Premature release of GnRH (gonadotropin-releasing hormone)
- Onset < 8 y.o., GnRH release stimulates production of sex hormones: estrogen/progesterone (females) or testosterone (males).
- Clinical manifestations in girls:
- Premature onset of breast development and menses.
- Clinical manifestations in boys:
- Premature penile enlargement, scrotum maturation, voice deepening, and acne.
- Treatment: Gonadotropin-releasing hormone (GnRH) agonists (eg, leuprolide acetate (Lupron)), which inhibits pulsatile release of GnRH.
- Lupron suppresses GnRH release, thus suppressing puberty.
Epilepsy with Related Neurobehavioral Symptoms
- Gelastic (laughing) seizures are the characteristic finding in this disorder.
- They often begin in infancy and although they are called "laughing" seizures, they are usually distinguishable from true laughter: laughter-like vocalization with a forced smile.
- These seizures do NOT respond to anti-epileptic therapy.
- Additional seizure types develop later in childhood, which are typically refractory to anti-epileptic drug therapy and are often intractable.
- Surgical resection is typically required.
Pallister-Hall Syndrome
- Hypothalamic hamartomas
- Body malformations:
- Polydactyly and syndactyly
- Laryngeal malformations (eg, bifid epiglottis)
- Pulmonary segmentation anomalies
- Imperforate anus
- Panhypopituitarism
References
- Adesina, Adekunle M., Tarik Tihan, Christine E. Fuller, and Tina Young Poussaint. Atlas of Pediatric Brain Tumors. Springer, 2016.
- Gray, Frangoise, Charles Duyckaerts, and Umberto De Girolami. Escourolle and Poirier’s Manual of Basic Neuropathology. OUP USA, 2013.
- “Hypothalamic Hamartoma.” NORD (National Organization for Rare Disorders) (blog). Accessed July 25, 2018. https://rarediseases.org/rare-diseases/hypothalamic-hamartoma/.
- Téllez-Zenteno, José F, Cesar Serrano-Almeida, and Farzad Moien-Afshari. “Gelastic Seizures Associated with Hypothalamic Hamartomas. An Update in the Clinical Presentation, Diagnosis and Treatment.” Neuropsychiatric Disease and Treatment 4, no. 6 (December 2008): 1021–31.
- Yachnis, Anthony T., and Marie L. Rivera-Zengotita. Neuropathology E-Book: A Volume in the High Yield Pathology Series. Elsevier Health Sciences, 2012.