Is holoprosencephaly inherited?

Holoprosencephaly (HPE) can be inherited, but it is not always inherited.

Inherited causes of holoprosencephaly may include:

The risk for family members to have HPE depends on the specific cause of HPE in the family, if known. For example, nonsyndromic HPE is usually inherited in an autosomal dominant manner. This means that having a variation (mutation) in only one copy of the responsible gene in each cell is enough to cause the condition. When a person with a mutation that causes an autosomal dominant condition has children, each child has a 50% (1 in 2) chance to inherit that mutation. However, not all people with a gene mutation that causes HPE will have HPE. This is called reduced penetrance.

For people with HPE without a known cause, recurrence risk for family members is likely to be low, but may be as high as 50%.

People with personal questions about recurrence risks for themselves or family members are encouraged to speak with agenetic counselor or other genetics professional.

Last updated on 05-01-20

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. There are 4 types of holoprosencephaly, distinguished by severity. From most to least severe, the 4 types are alobar, semi-lobar, lobar, and middle interhemispheric variant (MIHV). 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 disability 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 (teratogens). 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.

Last updated on 05-01-20

Can an unaffected sibling of a person with holoprosencephaly carry a mutation?

The genetic risk to siblings of a person with HPE depends on the genetic status of their parents.

Some people with autosomal dominant nonsyndromic HPE have an affected parent. If a parent is affected, or has a mutation that causes autosomal dominant HPE (even with no features), the risk for each sibling to inherit the mutation is 50% (1 in 2). If a person does not inherit a mutation from a parent with a mutation, that person cannot pass the mutation on to his/her children (i.e. the mutation has been eliminated from that lineage).

Others with HPE are affected due to having a new mutation in the responsible gene (not inherited from a parent). If the parents are unaffected and the family history is negative, the risk for siblings of an affected person to carry a mutation appears to be low.

It is possible for someone to have a mutation associated with HPE and be unaffected. Not everyone with a mutation that causes HPE will have HPE; this phenomenon is called reduced penetrance. Furthermore, the features of people with mutations in genes associated with nonsyndromic HPE can vary greatly, even within the same family. For example, a mutation may cause the severest form of HPE in one family member, while appearing not to cause any abnormalities in another.

A careful family history by a clinical geneticist familiar with HPE is important for affected families in order to establish who might be at risk to carry or inherit a mutation associated with HPE.

Last updated on 05-01-20

What is the prognosis for holoprosencephaly?

The prognosis depends on the sub-type. The alobar holoprosencephaly is the most severe type of the defect and the affected fetus are usually stillbirth, or die soon after birth, or during the first 6 months of life. However, a significant proportion of more mildly affected children (as well as some severely affected children) survive past age 12 months. More than 50 percent of children with semi-lobar or lobar holoprosencephaly without significant malformations of other organs are alive at age 12 months. The life expectancy for individuals with semi-lobar holoprosencephaly depends on the underlying cause of the condition and the presence of associated anomalies.

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: faces@faces-cranio.org Url: http://www.faces-cranio.org/
Name: The Carter Centers for Brain Research in Holoprosencephaly and Related Malformations Texas Scottish Rite Hospital for Children, Department of Neurology 2222 Welborn Street
Dallas, TX, 75219-3993,
Phone: (214) 559-8411 Toll Free: (800) 421-1121 Email: hpe@tsrh.org Url: http://www.hperesearch.org/index.html
Name: myFace 333 East 30th Street, Lobby Unit
New York, NY, 10016,
Phone: (212) 263-6656 Email: info@myface.org Url: http://www.myface.org

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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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