Monozygotic twins incompletely concordant for narcolepsy

Area of Science:

• Neuroscience
• Genetics

Background:

• Narcolepsy is a complex sleep disorder with a known genetic predisposition, particularly involving HLA-DRB1*1501/DQB1*0602.
• Monozygotic twins, genetically identical, often exhibit discordance for narcolepsy, suggesting environmental or epigenetic factors play a crucial role.

Observation:

• A pair of monozygotic twins, both positive for HLA-DRB1*1501/DQB1*0602, were clinically evaluated for narcolepsy.
• The second-born twin presented with a typical narcolepsy course.
• The first-born twin exhibited a significantly delayed onset of narcolepsy symptoms, including recurrent daytime sleepiness and cataplexy, appearing at ages 45 and 50, respectively.

Findings:

• The first-born twin's late-onset narcolepsy was apparently triggered by chronic emotional stress and sleep insufficiency.
• Cataplexy in the first-born twin was preceded by sustained polyphasic sleep patterns.
• This case presents a marked difference in the age of onset between genetically identical twins.

Implications:

• The findings support a multifactorial model for narcolepsy development, integrating genetic susceptibility with environmental triggers.
• This case suggests that even in genetically predisposed individuals, narcolepsy might manifest later in life under significant stress.
• Unaffected co-twins in discordant narcolepsy twin pairs may still be at risk of developing the disorder later in life, especially during stressful periods.