Holoprosencephaly

From WikiGenetics

1 Name of Condition
2 Definition
3 Description, Signs and Symptoms
4 Inheritance
5 Demographics
6 Diagnosis
7 Treatment and Management
8 Prognosis
9 Resources
10 References

[edit] Name of Condition

Holoprosencephaly, or HPE.

[edit] Definition

During pregnancy, the fetal brain grows and develops along with the rest of the body. A normal part of this growth is for the brain to move forward in the skull and divide in half, creating the two lobes of the brain. If the brain does not divide, it causes the disorder known as HPE. Depending on the severity of the condition, HPE symptoms vary, from severe retardation and malformation to mild cases where almost no symptoms are present.

[edit] Description, Signs and Symptoms

Holoprosencephaly is classified into four different types ranging from mild to severe:

Alobar (severe)--where the brain is not divided at all and severe abnormalities occur Semi-Lobar (moderate)--where the brain is partially divided and there are some moderate abnormalities Lobar (mild)--where the brain is divided and there are some mild abnormalities Middle Interhemispheric Variant (MIHV) -- where the middle of the brain (posterior frontal and parietal lobes) are not well separated.

Some symptoms in more severe cases that may lead to a diagnosis include microcephaly, or a small head, hydrocephalus, or excessive fluid surrounding the brain, mental retardation, epilepsy, and abnormalities of the organ systems or endocrine system. Some children, however, experience no symptoms.

Frequently, facial deformities are present in children diagnosed with HPE. Mild forms of facial abnormalities may include a flat single-nostril nose (cebocephaly), close set eyes (hypotelorism), cleft lip and/or palate, or just one upper middle tooth (single maxillary central incisor). More severe facial deformities may include a single central eye (cyclopia), a nose located on the forehead (proboscis), or missing facial features.

[edit] Inheritance

Approximately 25-50% of individuals with HPE have it due to a chromosomal abnormality. This can include trisomy 13, trisomy 18, and triploidy. These multiplications of chromosomes cause other defects besides HPE, but HPE is associated with these disorders.

18-25% of individuals with HPE have it due to a single-gene mutation. Currently more then 25 different mutations are known, and some of these mutations are inherited in an autosomal dominant pattern, while others have an autosomal recessive pattern.

Some cases of HPE are due strictly or in part to environmental factors, not necessarily genetic factors. Environmental causes include a mother with diabetes mellitus, low cholesterol, or if the mother is exposed to drugs, certain medications, or infections during pregnancy. The most severe cases of HPE are often due to a mixture of genetic and environmental factors.

[edit] Demographics

HPE affects between 1 in 5000-10,000 live births. However, severe cases often result in a miscarriage, so the actual frequency of HPE in all pregnancies may be much higher, possibly as common as 1 in 200.

[edit] Diagnosis

HPE can be diagnosed by doing a CT scan or MRI of the brain after finding abnormal facial symptoms. If the case is mild and craniofacial symptoms are not present, this brain imaging scan may not take place until the child is old enough that the parents notice developmental delays and/or failure to thrive. By doing an MRI, which is the recommended route, the HPE diagnosis can be confirmed, and the severity of the malformations can be determined.

[edit] Treatment and Management

Presently there is no course of treatment for individuals with HPE. Symptoms may be treated by surgery or medication, and families may find help with support groups and the assistance of medical professionals.

[edit] Prognosis

Current studies indicate that only 3% of fetuses that develop HPE survive to birth, while most are lost by miscarriage. Of the surivors, most do not survive longer than six months. The prognosis for a child diagnosed with HPE depends on the type of HPE and the severity and range of symptoms. The most severely affected children may live several months or years and the least affected may live a normal life span.