Rare Disease Day

What is holoprosencephaly?

Holoprosencephaly is an abnormality of brain development in which the brain doesn’t properly divide into the right and left hemispheres. The condition can also affect development of the head and face. In general, the severity of any facial defects corresponds to the severity of the brain defect. The most severely affected people have one central eye (cyclopia) and a tubular nasal structure (proboscis) located above the eye. In the less severe forms, the brain is only partially divided, and the eyes usually are set close together. Other signs and symptoms often include intellectual disabilities and pituitary gland problems. Holoprosencephaly can be caused by mutations in any of at least 14 different genes; chromosome abnormalities; or agents that can cause birth defects. It may also be a feature of several unique genetic syndromes. In many cases, the exact cause is unknown. Life expectancy for people with this condition varies, and treatment depends on the symptoms and severity in each person. (https://rarediseases.info.nih.gov/diseases/6665/holoprosencephaly/cases/27877)

Subdivisions of Holoprosencephaly

*Alobar, in which the brain has not divided at all, is usually associated with severe facial deformities. 

*Semilobar, in which the brain’s hemispheres have somewhat divided, causes an intermediate form of the disorder. 

*Lobar, in which there is considerable evidence of separate brain hemispheres, is the least severe form. In some cases of lobar holoprosencephaly the baby’s brain may be nearly normal.

Causes

Holoprosencephaly is a birth defect that arises during the first few weeks of the pregnancy. Diabetes in the mother during the pregnancy can increase the risk of holoprosencephaly in the fetus. However, for most children, no known intrauterine exposure is identified that is causally related to holoprosencephaly in that child.

Some children will have an identifiable genetic cause of holoprosencephaly. Approximately one-third of children born with holoprosencephaly have an abnormality of the chromosomes, which contain the genetic material (DNA). The most common chromosomal abnormality associated with HPE is when there are 3 copies of chromosome 13 (trisomy 13), although a number of other chromosomal changes can also cause holoprosencephaly.

In other children, holoprosencephaly is due to a change in a specific gene. These changes cause the genes and their proteins to function abnormally, and this affects the development of the brain, resulting in holoprosencephaly. Some of these genes are SHH, SIX3, TGIF1, ZIC2, PTCH1, FOXH1, NODAL, CDON, FGF8, and GLI2. Holoprosencephaly can also occur in certain genetic syndromes in which there are other medical issues besides those mentioned in this report that affect organs in addition to the brain and face (e.g., Smith-Lemli-Opitz syndrome).

Despite the above understanding of the causes of holoprosencephaly, the exact cause of the condition is not identified for many individuals. There are likely to be additional genetic causes other than those already known and mentioned above. (https://rarediseases.org/rare-diseases/holoprosencephaly/)

One Comment on “Rare Disease Day

  1. This is a very good and succinct description and explanation of what holoprosencephaly is, maybe the best I’ve seen. Kudos for its dissemination. (Kind of odd that the spellchecker here doesn’t recognize the disorder, though.)

    My only quibble is that it doesn’t include my daughter’s diagnosis, a subclassification of lobar HPE named septopreoptic holoprosencephaly, which usually results in mild cognitive problems but also some craniofacial involvement.

    Thanks for all you do here.

    Susan, mom of Beth, 30, septopreoptic HPE

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