Cleft palate happens when the tissue forming the roof of a baby’s mouth doesn’t fully fuse during early pregnancy. There’s rarely a single cause. Instead, it results from a combination of genetic factors, certain medications, maternal health conditions, and lifestyle exposures during a narrow window of fetal development. In the United States, about 1 in 1,563 babies is born with cleft palate alone, and about 1 in 1,031 is born with cleft lip with or without cleft palate.
How the Palate Forms (and What Goes Wrong)
The palate develops in two stages. First, the primary palate forms near the front of the mouth as tissue from either side of the developing face grows toward the midline and merges. Then two shelves of tissue, one from each side, grow inward to form the secondary palate, which makes up most of the roof of the mouth. This fusion process begins around the eighth week of pregnancy and is typically completed during or after the ninth week.
For the two palatal shelves to fuse successfully, a thin layer of cells along their edges has to break down through a process of programmed cell death. Specific signaling proteins drive this breakdown. If those signals are disrupted for any reason, the cell layer persists, the shelves can’t join, and a gap remains. The result is a cleft palate, which can range from a small opening in the soft palate at the back of the mouth to a gap that extends through the hard palate toward the front.
Sometimes the tissue covering the palate closes normally while the muscles underneath don’t fuse. This is called a submucous cleft palate, and it can be harder to detect at birth. A split in the small flap of tissue hanging at the back of the throat (a bifid uvula) is one visible clue.
Genetic Causes
Genetics play the largest role in cleft palate. Variations in a gene called IRF6, which helps regulate how facial tissue develops, are one of the best-studied contributors. Changes in this gene can interfere with normal palate formation even when no other birth defects are present. But IRF6 is far from the only gene involved. Researchers have identified dozens of genes that influence palate development, and in many cases, it’s the combined effect of small variations across several genes that raises risk rather than a single mutation.
A family history of cleft lip or palate increases the likelihood, though most babies born with a cleft have no affected relatives. When cleft palate does run in families, the pattern of inheritance is usually complex, meaning multiple genes and environmental triggers interact rather than following a simple dominant or recessive pattern.
Cleft Palate as Part of a Genetic Syndrome
In roughly 30% of cases, cleft palate appears alongside other health issues as part of a recognized genetic syndrome. One of the more common is 22q11.2 deletion syndrome, which results from a missing piece of chromosome 22. The loss of a gene called TBX1 on that chromosome is thought to be responsible for many of the syndrome’s features, including heart defects, cleft palate, distinctive facial features, hearing loss, and low calcium levels. Children with this deletion often have a highly arched palate or a submucous cleft.
Pierre Robin sequence is another well-known association. Babies with this condition are born with a very small lower jaw, which causes the tongue to sit farther back in the mouth and physically block the palatal shelves from closing. Van der Woude syndrome, caused by mutations in the IRF6 gene itself, is the most common single-gene cause of cleft lip and palate, accounting for roughly 2% of all cases.
Medications Taken During Pregnancy
Certain anti-seizure medications taken during the first trimester significantly raise the risk. The baseline rate of oral clefts in the general population is about 1 per 1,000 births. For babies exposed in the womb to valproate, phenobarbital, or topiramate, that rate jumps above 10 per 1,000, a tenfold increase. Carbamazepine and phenytoin carry a smaller but still elevated risk. Lamotrigine, another common anti-seizure drug, has shown a more modest and debated association, with reported cleft rates ranging from 1.0 to 4.5 per 1,000.
High-dose vitamin A derivatives (retinoids), used to treat severe acne and some skin conditions, are also well-established causes of facial birth defects including cleft palate. The critical takeaway is that the first trimester, particularly the first two months, is the danger zone, because that’s when the palate is actively forming. Women who take these medications and are considering pregnancy should talk with their doctor well in advance about alternatives or timing.
Smoking and Alcohol
Smoking during pregnancy raises the risk of cleft lip (with or without cleft palate) by about 79%, based on large studies that adjusted for other factors. Alcohol consumption during pregnancy is more specifically linked to isolated cleft palate, roughly doubling the odds. These risks apply primarily to use during the first trimester, when palate formation is underway, though many women may not yet realize they’re pregnant during this window.
Maternal Health and Body Weight
Pre-pregnancy weight matters. Obese women have about a 26% higher risk of having a baby with an orofacial cleft compared to women at a normal BMI. For cleft lip specifically, the risk climbs roughly 23% for every 10-point increase in BMI. The biological mechanism isn’t fully understood, but it may relate to how excess body fat affects inflammation, nutrient metabolism, or blood sugar regulation during early fetal development.
Pre-existing diabetes (type 1 or type 2 diagnosed before pregnancy) carries a notably higher risk, nearly doubling the odds of an orofacial cleft. Gestational diabetes, which develops later in pregnancy, does not appear to increase the risk, likely because it typically arises after the palate has already formed.
Environmental Exposures
The evidence linking air pollution or specific environmental chemicals to cleft palate is weaker and less consistent than the evidence for genetics, medications, or lifestyle factors. Studies examining common air pollutants like carbon monoxide, nitrogen dioxide, ozone, sulfur dioxide, and particulate matter have not found a reliable, consistent link to oral cleft defects. Some older studies suggested a possible connection to living near chemical waste incineration sites or lead-emitting facilities, but the evidence remains limited. Occupational exposures to certain solvents and pesticides have been flagged in a handful of studies, though no specific chemical has been firmly established as a cause.
Folic Acid and Prevention
Folic acid supplementation is well known for preventing neural tube defects like spina bifida, but its role in cleft prevention is more nuanced. Standard prenatal doses (400 to 800 micrograms per day) have not been shown to reduce cleft risk on their own. Research from a large study published in Pediatrics found that only high pharmacological doses, around 6 milligrams per day, taken during the first two months of pregnancy appeared to reduce the occurrence of cleft lip and cleft palate. For isolated cleft palate specifically, the protective window extended through the first four months.
These high doses are far above what’s in a typical prenatal vitamin and are generally only recommended under medical supervision for women who have already had a child with an orofacial cleft. For most women, standard folic acid supplementation remains important for overall fetal development, even if it doesn’t specifically lower cleft risk at typical doses.
Prenatal Detection
Cleft lip can sometimes be spotted on ultrasound as early as 13 weeks into pregnancy, and 3D ultrasound techniques may detect it even sooner. Cleft palate alone, however, is much harder to see on imaging because the palate sits inside the mouth and isn’t easily visible from outside the face. Many isolated cleft palates aren’t diagnosed until after birth, either during a newborn exam or when feeding difficulties arise. If a cleft lip is detected prenatally, doctors will typically look more carefully for an accompanying cleft palate, but even then, a definitive diagnosis often waits until delivery.