Prader-Willi Syndrome and hypothalamic injury-induced obesity
Prader-Willi Syndrome (PWS) has a birth incidence rate of about 1:15,000. The syndrome mainly results from the loss of paternally-inherited chromosome region 15q11-q13 (the Prader-Willi Syndrome critical region). This defect results in damage to the hypothalamus - the homeostasis center in the brain that controls important functions such as hunger, sleep and body temperature. In PWS, there is an initial extreme hypotonia and failure to thrive, followed in early childhood by a marked preoccupation with food, leading to the hallmark symptom of hyperphagia (excessive appetite and inability to feel ‘full’) as well as disabling neuropsychiatric behaviors and disorders including temper outbursts, repetitive and ritualistic behaviors, rigid thinking, skin picking, depression, and psychosis in some cases.
Video credit: Foundation for Prader-Willi Research, (
To learn about Prader-Willi Syndrome, please visit the websites of Foundation for Prader-Willi Research,
While PWS is caused by a genetic defect, the most common cause of hypothalamic injury-induced obesity is related to a rare non-cancerous tumor called a craniopharyngioma. When this tumor is removed, the hypothalamus can get damaged, leading to the symptoms of hypothalamic obesity. Other causes for hypothalamic obesity include other rare tumors, head trauma, and swelling in the brain. Patients share many symptoms with the PWS patients, including hyperphagia, rapid weight gain, low metabolic rate, and decreased physical activity. Similar to PWS, hypothalamic injury-induced obesity patients often suffer from neuropsychiatric disorders, including anxiety, depression, apathy, and OCD. An excellent recent review of hypothalamic injury-induced obesity is here. The Raymond A. Wood Foundation provides quality of life support for childhood brain tumor survivors and their families.
Please refer to the NIH GARD website for more information on PWS and of hypothalamic injury-induced obesity.
There is no effective or approved treatment for PWS or hypothalamic injury-induced obesity. Patients
and their loved ones are devastated by the lack of safe and effective therapeutic interventions.
Narcolepsy Type 1 (Narcolepsy with cataplexy)
Narcolepsy Type 1 (NT1) is a rare and acquired chronic neurological disorder that affects the brain’s ability to regulate the normal sleep-wake cycle. NT1 is estimated to affect about 1 in 2,000 people in the USA. However, although awareness of the disorder is increasing it is likely still underdiagnosed. NT1 can begin at any age and is caused by an auto-immune attack on orexin-producing neurons in the hypothalamus region of the brain. These orexin-producing neurons usually function to regulate sleep-wake states. Therefore, as orexin levels reduce NT1 symptoms such as excessive daytime sleepiness (EDS) and cataplexy appear. EDS is usually the first symptom of NT1 to appear and it is described as an irresistible urge to sleep during the day. Cataplexy is defined by sudden muscular weakness triggered by strong emotions, with severity ranging from subtle loss of tone in facial muscles through to a total body collapse.
Narcolepsy can profoundly impact upon all aspects of daily life. Treatment is currently targeted towards the specific symptoms displayed by each individual and can involve both medication and lifestyle interventions. However, treatment approaches are currently only partially effective.
For more information on NT1 please refer to the National Organization of Rare Disorders (NORD) website: https://rarediseases.org/rare-diseases/narcolepsy/