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Don’t fight Frontonasal dysplasia alone.
Find your community on the free RareGuru App.Frontonasal dysplasia is a rare disease that results from abnormal development of the head and face before birth. Symptoms often vary, however more common symptoms include wide spaced eyes, a widow's peak, and a broad nose. Less common features include eye abnormalities, missing the connection between the two halves of the brain (agenesis of the corpus callosum), hearing loss, and undescended testicles in males (cryptorchidism). Most people with the dysplasia have normal intelligence. There are three main types of frontonasal dysplasia that are distinguished by their genetic causes and symptoms. Other frontonasal dysplasia syndromes have also been described. Frontonasal dysplasia is very rare, with around 100 cases reported in the literature.
Type 1 frontonasal dysplasia is caused by mutations (changes) in the ALX3 gene, type 2 is caused by mutations in the ALX4 gene, and type 3 is caused by mutations in the ALX1 gene. Type 1 and type 3 frontonasal dysplasia are inherited in an autosomal recessive manner, whereas frontonasal dysplasia type 2 is inherited in an autosomal dominant manner. Diagnosis is often first suspected when a baby has features consistent with frontonasal dysplasia. X-rays and genetic testing may be used to confirm the diagnosis. Treatment of the disease may include one or more surgeries to correct certain birth defects, as well as early intervention and special education services, if needed.
Source: GARD Last updated on 05-01-20
The different types of frontonasal dysplasia can have different signs and symptoms. However, all types of frontonasal dysplasia involve the abnormal development of the head and face, which changes the physical features of the face. People with frontonasal dysplasia are usually born with wide spaced eyes (hypertelorism), a flat broad nose, and a vertical groove (cleft) affecting the middle of the face. Some may be born with a skin-covered gap in the front of the skull where bone should be (anterior cranium bifidum occultum). Other features of the disease include hearing loss and eye defects such as missing tissue in the eye (coloboma).
Other features of type 1 frontonasal dysplasia include a widow’s peak, small nostrils, cleft lip and/or palate, and having a short and small head (brachycephaly). People born with type 2 frontonasal dysplasia may have large differences in the way the skull is formed such as the premature closure of bones that form the skull (craniosynostosis). Other features of type 2 include rapid hair loss, absence of hair (alopecia), or having more facial hair than expected (facial hypertrichosis).
People with type 3 frontonasal dysplasia may be born without eyes (anophthalmia) or have very small eyes (microphthalmia). Other differences may include having low-set, posteriorly rotated ears, a heart defect known as tetralogy of Fallot, and abnormalities of the brain such as having too much liquid in the brain (hydrocephalus). People with type 3 frontonasal dysplasia also may have skeletal abnormalities such as absent tibia, having an extra toe (polydactyly), or clubfeet (talipes).
Some people with frontonasal dysplasia types 2 and 3 may have intellectual disability. Males with frontonasal dysplasia types 2 and 3 may have undescended testes (cryptorchidism).
Last updated on 05-01-20
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
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:
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
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:
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:
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:
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
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
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
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