How cleft lip and cleft palate can arise

Cleft lip and cleft palate are among the most common birth defects.

These defects, which appear when the tissues that form the lip or the roof of the mouth do not join completely, are thought to be caused by a mix of genetic and environmental factors.

In a new study,  biologists have discovered how a genetic variant often found in people with these facial malformations leads to the development of cleft lip and cleft palate.

Their findings suggest that the variant diminishes cells' supply of transfer RNA, a molecule that is critical for assembling proteins. When this happens, embryonic face cells are unable to fuse to form the lip and roof of the mouth.

A non-syndromic orofacial cleft risk locus links tRNA splicing defects to neural crest cell pathologies, The American Journal of Human Genetics (2025). DOI: 10.1016/j.ajhg.2025.03.017. www.cell.com/ajhg/fulltext/S0002-9297(25)00138-7

Nontraditional risk factors shed light on unexplained strokes in adults younger than 50

Adults younger than 50 years of age had more than double the risk of having a stroke from migraine or other nontraditional stroke risk factors rather than traditional risks such as high blood pressure, according to research published in Stroke.

Previous research indicates the rate of ischemic (clot-caused) stroke among adults 18–49 years old is increasing and propelled by a corresponding rise in cryptogenic strokes (strokes of unknown cause) in adults without traditional risk factors, including high blood pressure, smoking, obesity, high cholesterol and type 2 diabetes.

Up to half of all ischemic strokes in younger adults are of unknown causes, and they are more common in women. For effective prevention, careful and routine assessment of both traditional and nontraditional risk factors in younger people is critical. 

Researchers analyzed data for more than 1,000 adults aged 18–49 in Europe, with a median age of 41 years. Half of the participants had experienced a cryptogenic ischemic stroke, while half had no history of stroke.

The study examined the associations of 12 traditional risk factors, 10 nontraditional risk factors and five risk factors specific to women (such as gestational diabetes or pregnancy complications). Researchers also closely reviewed participants with a heart defect called patent foramen ovale (PFO), a hole between the heart's upper chambers.

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A PFO is usually harmless yet is known to increase the odds of stroke. The study aimed to determine which risk factors contribute the most to unexplained strokes.

The analysis found:

Traditional risk factors were more strongly associated with stroke in men and women without a PFO.
In contrast, nontraditional risk factors, such as blood clots in the veins, migraine with aura, chronic kidney disease, chronic liver disease or cancer, were more strongly associated with stroke among study participants with a PFO.
In those without a PFO, each additional traditional risk factor increased stroke risk by 41%, while each nontraditional risk factor increased stroke risk by 70%.
Risk factors related to women also increased stroke risk by 70% independent of traditional and nontraditional risk factors.
Among participants with a PFO, each traditional risk factor increased the risk of stroke by 18%. However, after considering individual demographic factors, such as age, sex and level of education, nontraditional risk factors more than doubled the odds of having an ischemic stroke.
Researchers also analyzed the study population's attributable risk (determining how a disease would be impacted if a certain risk factor were eliminated). To calculate population-attributable risk, researchers analyzed each risk factor and their contribution to the increased risk separately and found:

For strokes that occur without a PFO, traditional risk factors accounted for about 65% of the cases, nontraditional risk factors contributed 27% and risk factors specific to women made up nearly 19% of the cases.
In contrast, for strokes associated with a PFO, traditional risk factors contributed about 34%, nontraditional risk factors accounted for 49% and female-specific risk factors represented about 22%.
Notably, migraine with aura was the leading nontraditional risk factor associated with strokes of unknown origin, with a population-attributable risk of about 46% for strokes among people with a PFO and about 23% for those without a PFO, indicating a higher risk for people with PFO.
The role of non-traditional risk factors, especially migraine headaches, which seems to be one of the leading risk factors in the development of strokes in younger adults, is a new revelation.

Burden of Modifiable Risk Factors in YoungOnset Cryptogenic Ischemic Stroke by High-Risk Patent Foramen Ovale, Stroke (2025). DOI: 10.1161/STROKEAHA.124.049855

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