Cleft Lip (Yun, 2019) – Is cleft lip genetic?

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Nebula Genomics DNA Report for Cleft Lip

Is cleft lip genetic? We created a DNA report based on a study that attempted to answer this question. Below you can see a SAMPLE DNA report. To get your personalized DNA report, purchase our Whole Genome Sequencing!

Sample report on cleft lip from Nebula Genomics
Sample variant on cleft lip from Nebula Genomics
To learn more about how Nebula Genomics reports genetic variants in the table above, check out the Nebula Research Library Tutorial.

What is Cleft Lip? (Part 1 of Is cleft lip genetic?)

Cleft lip is part of a larger condition called orofacial cleft that includes both the lip and palate. The former occurs when there is an opening in the upper lip that may extend into the nose. It can occur on one or both sides of the nose or in the middle. Cleft palate is when the opening is on the roof of the mouth, or soft palate, and continues into the nose. 

A child with cleft lip
A child with cleft lip. Wikipedia. CC-Attribution-Share Alike 3.0 Unported.

Children with these conditions often have feeding problems, speech problems, hearing problems, and frequent ear infections. It also leads to psychological and social problems if left untreated. 

This condition is a birth defect that occurs when tissues in the baby’s face do not join properly during development in the womb. In most cases of cleft lip, the cause is often unknown but certain risk factors involving the mother appear to be associated with its development, including smoking and diabetes during pregnancy. 

The condition can be diagnosed before birth and early surgery within the first few months of life is often enough to correct the unjoined tissue. If treated, the prognosis for the children tends to be very good.

Is Cleft lip Genetic?

Several genetic variants have been associated with cleft lip and palate syndromes. Since the condition tends to run in families, it is suspected that there is some heredable component. However, it is also possible that a mother’s environmental exposures that increase the risk are common among family members.

These conditions often cause dental issues. Colgate notes some of the most common genes also affect tooth health including Transforming growth factor-alpha (TGF-α), BCL3, DLX2, MSX1, TGFB3, and IRF6. 

Result of surgical treatment
Surgical treatment usually results in good outcomes. ReSurge International. Flickr.

There are also several other genetic variants identified that are specific to certain conditions that involve cleft lip. Some of these candidate genes are:

  • TP63
  • RIPK4
  • TFAP2A
  • PVRL1
  • CDH1
  • PTCH1
  • GLI2
  • SHH
  • SIX3
  • TGIF
  • FGFR1
  • MID1
  • GLI3
  • OFD1
  • IRF6
  • WNT3
  • PHF8
  • MLL2, KDM6A

Even more genes are observed in patients with cleft palate alone.

Epidemiology (Part 3 of Is cleft lip genetic?)

Cleft lip and mouth palate are some of the most common birth defects in the world. 

Overall, the condition is thought to affect 1 in 1000 births. However, that incidence is largely based on ethnicity, geography, and socioeconomic background. The chances of developing cleft lip are highest in Asia and the Americas and least common in Africa. Additionally, men tend to be born with a cleft lip more often while women have a higher incidence of the palate version. 

A study in 2016 noted that the incidence of cleft palate varied significantly from 1.3 to 25.3 cases per 10,000 live births, with the highest rates in British Columbia, Canada and the lowest rates in Nigeria, Africa. No matter the rate, girls were more at risk of developing a cleft palate than boys. This number agrees with the World Health Organization’s estimates, which also include the prevalence ranging 3.4 to 22.9 cases per 10,000 live births for cleft lip alone.

In the United States, 1 in 2,800 babies are born with cleft lip, 1 in 1,700 babies are born with cleft palate, and about 1 in 1,600 babies are born with both both conditions.

Symptoms (Part 4 of Is cleft lip genetic?)

The most obvious symptom of cleft lip or cleft palate is a split identified immediately after birth. It can often be observed early in pregnancy through ultrasound. A cleft lip is a split in the upper lip that can range from a small notch to a large gap in the gum and jaw. A cleft palate is an opening in the roof of the mouth. Many babies are born with both conditions. The split in either type can be unilateral (restricted to one side) or bilateral (encompassing both sides). 

Unilateral and bilateral cleft lip and palate
Unilateral and bilateral cleft lip and palate. Wikipedia. CC-Attribution-Share Alike 4.0 International.

In addition to the physical signs, infants and children with cleft lip may also experience:

  • Feeding issues (inability to latch or maintain consistent suck)
  • Dental problems (crooked, poorly shaped or missing teeth)
  • Speech and language difficulties
  • Hearing impairment
  • Social and self-esteem challenges

Causes (Part 5 of Is cleft lip genetic?)

The definite cause of a baby with these conditions is usually unknown. It is believed to be a combination of genetic and environmental factors that affect the mother during pregnancy.

Around the fifth to sixth week of pregnancy, the two sides of the upper lip fuse together and around the eighth to ninth week, the roof of the mouth forms. The conditions occur when something interrupts the natural fusion and a baby develops a split in this location.  

Some environmental factors include:

  • Maternal smoking or drinking alcohol during pregnancy
  • The mother having diabetes
  • Use of certain medications, such as those for epilepsy, during pregnancy 
  • Not enough folic acid during pregnancy 
  • Family history

Diagnosis (Part 6 of Is cleft lip genetic?)

Both cleft lip and palate are diagnosed through visual observation shortly after birth. Sometimes, they can even be diagnosed before birth through prenatal ultrasound.

An ultrasound will use soundwaves to take pictures of a fetus before birth. Through these pictures, doctors may be able to visualize facial structures. The condition will begin to be visible around the 13th week of pregnancy and will become more obvious as the pregnancy progresses. Cleft palate alone is more difficult, but not impossible, to diagnose before birth since it occurs inside the mouth and is harder to see on an ultrasound.

If the condition is observed, a mother may be able to allow a sample of amniotic fluid to be taken from the uterus to test for genetic conditions that may have caused the condition. However, in most cases, the direct cause will remain unknown. 

Treatment (Part 7 of Is cleft lip genetic?)

Treatment for the condition is designed to improve a child’s ability to eat, speak and hear normally and to achieve a normal facial appearance. Ultimately, the only cure for the condition is surgery to repair the defect. A cleft team of medical professionals will usually include surgeons, pediatricians, pediatric dentists, auditory or hearing specialists, speech therapists, and psychologists.

Surgery

Surgery options will be provided based on the specific condition of the infant. In most cases, the first surgery will involve closing the cleft, or split. Additional treatment to help speech and to further improve facial features may be necessary. Typical surgeries that are performed include:

  • Cleft lip repair — within the first 3 to 6 months of age
  • Cleft palate repair — by the age of 12 months, or earlier if possible
  • Follow-up surgeries — between age 2 and late teen years
Results of cleft lip repair
Results of cleft lip repair. Wikipedia. CC-Attribution-Share Alike 4.0 International.

For these surgeries, children are placed under general anesthetic. Some procedures that may be used are:

  • Lip repair: A surgeon makes incisions on both sides of the lip to create a flap that can be stitched together to give it a more normal appearance and allow it to function normally. Initial nasal repair, if needed, is usually done at the same time.
  • Palate repair: A surgeon will make incisions on both sides of the cleft and reposition the tissue and muscles so that the gap can be closed. Various procedures may be used based on the specific condition.
  • Ear tube surgery: For children with cleft palate, ear tubes may be placed to reduce the risk of chronic ear fluid, which can lead to hearing loss. 

Additional surgeries may be needed to improve the appearance of the mouth, lip and nose. Risk factors associated with these surgeries include bleeding, infection, poor healing, widening or elevation of scars, and temporary or permanent damage to nerves, blood vessels or other structures.

Other treatments

The complications that accompany this condition may be treated through non-surgical means. Depending on the child’s case, your doctor may recommend:

  • Feeding strategies
  • Speech therapy
  • Orthodontic adjustments (such as braces)
  • Monitoring and treatment for ear infections
  • Hearing aids
  • Psychology sessions 

You can visit the National Institutes of Health National Institute of Dental and Craniofacial Research website or the Cleft Lip and Palate Association where you can get involved in the research council. 

If you liked this article, you should check out our other posts in the Nebula Research Library!

November 29, 2021