The main symptom of Kleine-Levin syndrome – excessive sleepiness (hypersomnolence) – is also a key characteristic of many other sleep disorders, such as narcolepsy. Additionally, there are currently no observed biomarkers related to this condition. For these reasons, Kleine-Levin syndrome can often be hard to diagnose. However, shares the American Journal of Managed Care (AJMC), a case report evaluating a woman and her family with excessive daytime sleepiness suggests that LMOD3 gene mutations could be a potential diagnostic biomarker for Kleine-Levin syndrome – particularly for cases that do not present with typical manifestations.
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Studying the Family
In 2001, the woman featured in the case report had been battling a viral infection. After this caused muscle weakness, the woman fell. Following this, she began experiencing excessive sleepiness and unintended weight loss. Even after her overall sleepiness got better, she still found herself excessively fatigued during the day. Over the next three years, the woman had to leave school due to her fatigue. Her condition did not improve with medicine.
From 2004-2018, the woman still experienced symptoms, but on a much lower basis. Her worst symptom continued to be excessive daytime sleepiness. Later, researchers determined that her family members also experienced sleep interruptions, ranging from excessive daytime sleepiness and extreme fatigue to insomnia. The woman’s grandfather also had schizophrenia. Her symptoms got worse from 2018-2020, then improved again.
After testing, researchers were able to rule out idiopathic hypersomnia and narcolepsy as potential causes. Researchers continued to test, using electroencephalographies and other measures. Eventually, researchers determined that the patient had both familial periodic hypersomnia and atypical Kleine-Levin syndrome.
Past research has suggested LMOD3 gene mutations were associated with Kleine-Levin syndrome. Therefore, prior to official diagnosis, the researchers also sequenced the genes for the patient and her family. Those who had not shown sleep-related symptoms – such as her father and brother – had no LMOD3 mutations. Alternately, the woman and her symptomatic family members all showed a specific LMOD3 variant.
Researchers suggest that additional testing is needed in the future to confirm these findings. If these findings can be confirmed or replicated in a larger study, LMOD3 could be used as a Kleine-Levin syndrome biomarker in the future.
About Kleine-Levin Syndrome (KLS)
Also known as “Sleeping Beauty Syndrome,” Kleine-Levin syndrome (KLS) is a rare sleep disorder characterized by recurrent episodes or periods or excessive sleepiness (sleeping for up to 20 hours daily), cognitive changes, and behavioral changes. These episodes, which often manifest abruptly, may last for a few days or a few weeks at a time. Doctors are not exactly sure what causes Kleine-Levin syndrome. It is hypothesized that genetic factors, autoimmune issues, or hypothalamic malfunctions could play a role. Around 70% of those with KLS are male, and it often affects adolescent males. Symptoms during episodes, which are normally preceded by respiratory or flu-like symptoms, include:
- Excessive sleepiness
- Hallucinations or disorientation
- Childish behavior
- Heightened appetite
- Increased sex drive
- Memory loss
- Depression or other mood-related issues