Frontonasal dysplasia

What causes frontonasal dysplasia?

Frontonasal dysplasia is caused by changes (mutations) in different genes. Frontonasal dysplasia type 1 is caused by changes in the ALX3 gene. Type 2 is caused by changes in the ALX4 gene. And type 3 is caused by changes in the ALX1 gene. These three genes all provide instructions to the body to make a type of protein called transcription factors, which are responsible for controlling other genes. Specifically, these three genes code proteins that control other genes that affect how the eyes, nose, and mouth develop. When there are changes in one of these three genes, they are not able to properly control the way the face forms. This causes the features associated with frontonasal dysplasia.

Last updated on 05-01-20

How is frontonasal dysplasia diagnosed?

Frontonasal dysplasia is often first suspected when a doctor sees the features of the disorder in a newborn or baby. To be diagnosed with frontonasal dysplasia, a person must be born with at least two of the following physical features:

  • Widely spaced eyes (hypertelorism)
  • A flat, broad nose
  • A groove (cleft) in one or both sides of the nose, which can cause it to separate into two parts
  • Missing tip of the nose
  • Cleft involving the nose, upper lip, or roof of the mouth (cleft lip and/or palate)
  • A skin-covered gap in the front of the skull where bone should be (anterior cranium bifidum occultum)
  • Widow’s peak hairline

A doctor may also order other tests such as an X-ray of all of the bones in the body (skeletal survey) in order to determine exactly how the disease is affecting the person and to rule out other possible diseases. Genetic testing may be used to confirm the diagnosis and type.

Last updated on 05-01-20

How is frontonasal dysplasia inherited?

Frontal dysplasia can run in a person’s family, but the way it can be passed down depends on the type. Types 1 and 3 are inherited in an autosomal recessive manner. This means that both copies of the ALX3 or ALX1 __gene must be changed in order to have symptoms of the disorder. We inherit one copy of each gene from our mother and one from our father. Men and women with a mutation in only one copy of the genes are known as carriers of frontonasal dysplasia, meaning they do not have signs or symptoms of the disease, but they can pass the changed gene down to their children. When two carriers of a ALX3 or ALX1 mutation have children together, for each child there is a:

  • 25% chance that the child will have frontonasal dysplasia
  • 50% chance that the child will be a carrier of frontonasal dysplasia like the parents
  • 25% chance that the child will have two working copies of the genes, so the child will not have frontonasal dysplasia and will not be a carrier

If a person has type 1 or 3 frontal dysplasia and they have a child with a person who does not have frontonasal dysplasia and is not a carrier of the same type of the disease (in other words, both copies of the gene work normally), all of the person’s children will be carriers of frontonasal dysplasia, but none will have the disease.

If a person has type 1 or 3 frontal dysplasia and they have a child with a person who is a carrier of the same type, each of their children has a:

  • 50% chance of being a carrier
  • 50% chance of having the same type of frontonasal dysplasia

Type 2 frontonasal dysplasia is inherited in an autosomal dominant manner. This means that only one copy of the ALX4 gene needs to be changed for a person to have signs and symptoms of the disorder.

In some cases, people with type 2 frontonasal dysplasia are the first people in their family who are diagnosed with the disorder. This may occur when the genetic change that causes the disorder is new in the affected person (de novo), and it is not inherited from either parent. In other cases, people with the autosomal dominant form of frontonasal dysplasia have inherited the disorder from an affected parent.

If a person with type 2 frontonasal dysplasia has children with a person who does not have type 2 frontonasal dysplasia, each of their children will have a:

  • 50% chance of not having type 2
  • 50% chance of having type 2

Many people find talking to a genetic counselor before they decided to get pregnant helpful, so they can better understand the chance they may pass their type of frontonasal dysplasia onto their children.

Last updated on 05-01-20

What is the long-term outlook for people affected with frontonasal dysplasia?

The long-term outlook for people who have frontonasal dysplasia depends on the the type of the disease, as well as the severity of any associated birth defects. People who are born with facial clefts that do not affect breathing or swallowing and either have no heart defect or a surgically correctable heart defect are reported to have a normal lifespan

In some cases, people who are born with facial differences struggle to make friends or to fit in at school. Counseling with a psychologist or social worker may be helpful in these situations.

Last updated on 05-01-20

How might frontonasal dysplasia be treated?

The treatment for frontonasal dysplasia depends on the changes the disease caused in the person. Surgical procedures to correct facial clefts or other physical differences may be an option. In general, these surgeries are multi- stage procedures that take place when the child is around 6-8 years old. If the facial clefts are impacting the ability to breathe or swallow food, the procedures may occur at a younger age.

If a person with frontonasal dysplasia has intellectual disability or developmental delay, early intervention may be offered. When the child gets older, special education may be helpful. A team of specialists may be required for proper treatment and evaluation of possible associated birth defects, for example, a pediatric cardiologist may check for a heart defect, a pediatric ophthalmologist may check for eye problems, and a pediatric audiologist may screen for hearing loss.

Last updated on 05-01-20

Name: FACES: The National Craniofacial Association PO Box 11082
Chattanooga, TN, 37401, United States
Phone: 423-266-1632 Toll Free: 800-332-2373 Email: Url:
Name: Children's Craniofacial Association 13140 Coit Road Suite 517
Dallas, TX, 75240 , United States
Phone: +1-214-570-9099 Toll Free: 1-800-535-3643 Fax : +1-214-570-8811 Email: Url:
Name: Ameriface PO Box 751112
Las Vegas, NV, 89136, United States
Phone: 702-769-9264 Toll Free: 888-486-1209 Email: Url:

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The RareGuru disease database is regularly updated using data generously provided by GARD, the United States Genetic and Rare Disease Information Center.

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