An international team of scientists has unraveled the biological mechanisms that cause severe sleep disorders in patients with FOXP1 syndrome. The research, co-led by the Girona Biomedical Research Institute (IDIBGI) and the Radboud University Medical Center in Nijmegen, places these problems as a central symptom of the disorder.
Insomnia fragments the night
Children affected by this genetic condition suffer very frequently from difficulties resting. The study defines a clear pattern of insomnia characterized by the inability to maintain sleep during the night. Patients experience frequent awakenings and get up much earlier than usual.
For years, medicine considered these alterations as minor side effects.
"For years they have been considered a secondary or irrelevant symptom, but our results indicate that they are part of the core of the disorder." - Anna Castells, IDIBGI researcher
The genetic analysis carried out in the general population confirms this link. Common variants of the FOXP1, FOXP2, and FOXP4 genes show a direct association with insomnia symptoms and a shorter total duration of nighttime rest.
The fruit fly reveals the cause
The researchers used the fruit fly as an experimental model to validate their hypotheses. The loss of function of the FOXP gene in this organism reproduces almost identical phenotypes to those observed in humans. These include severe sleep fragmentation and profound alterations of the circadian rhythm.
The alteration affects specific neurons in the brain responsible for regulating rest. These cells release signaling molecules called neuropeptides that are essential for sleep architecture. Their dysfunction explains the severity of symptoms in patients.
Improving rest could alleviate other global affections of the syndrome.
"We must pay more attention to sleep problems in these patients, as they can contribute to worsening the overall condition. If we manage to improve sleep, perhaps we can also improve other aspects of the disorder." - Anna Castells, IDIBGI researcher
The work opens the door to new clinical strategies by identifying specific brain communication mechanisms. These findings may serve as potential therapeutic targets in the future. The scientific teams now plan to study whether other pathologies linked to the FOXPs genes share this same sleep pathophysiology.