what does holoprosencephaly mean

What is holoprosencephaly and what causes it?

Holoprosencephaly is a disorder caused by the failure of the prosencephalon (the embryonic forebrain) to sufficiently divide into the double lobes of the cerebral hemispheres. The result is a single-lobed brain structure and severe skull and facial defects.

What is the lobar form of holoprosencephaly?

In the lobar form, most of the brain has separated into right and left sides, though there is incomplete division into the two halves. Holoprosencephaly is a malformation sequence with a very variable degree of severity for both the brain and facial abnormalities.

What is the prognosis of holoprosencephaly?

There is no standard course of treatment for holoprosencephaly. Treatment is symptomatic and supportive. The prognosis for individuals with the disorder depends on the severity of the brain and facial deformities. Was this page helpful?

Is there a test for holoprosencephaly?

The best diagnostic procedure is a brain scan (CT or MRI). Molecular testing for several HPE genes are available. Is there a test for holoprosencephaly? The best diagnostic procedure is a brain scan (CT or MRI). Molecular testing for several HPE genes are available.

Can holoprosencephaly be cured?

There isn't a cure or main treatment for holoprosencephaly (HPE). Instead, healthcare providers target treatment toward the specific symptoms that each child with HPE has. Treatment may require the coordinated efforts of a team of specialists, including: Pediatricians.

What does holoprosencephaly cause?

Signs & Symptoms Holoprosencephaly is a malformation sequence with a very variable degree of severity for both the brain and facial abnormalities. Intellectual disability is associated with HPE and seizures are often present.

Is holoprosencephaly compatible with life?

Holoprosencephaly is estimated to occur in approximately 1 in every 250 conceptions and most cases are not compatible with life and result in fetal death in utero due to deformities to the skull and brain.

How is holoprosencephaly inherited?

Holoprosencephaly can be caused by genetic changes 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.

How long do babies with holoprosencephaly live?

Severely affected children typically do not survive beyond early infancy, while a significant proportion of more mildly affected children survive past 12 months and many live into adulthood.

What treatment is there for holoprosencephaly?

There is no standard course of treatment for holoprosencephaly. Treatment is symptomatic and supportive. The prognosis for individuals with the disorder depends on the severity of the brain and facial deformities.

What is the survival rate of holoprosencephaly?

The prognosis of HPE is very poor and depends on the degree and type of HPE and the extent of facial dysmorphic features. Only 50% of patients with alobar HPE will survive by 4-5 months of age. Only 20% of these cases will survive by 12 months of age.

How early can holoprosencephaly be detected?

Ultrasound done at 18-20 weeks gestation is the ideal modality for screening for holoprosencephaly [6, 7], though the earliest detection of the alobar variety of holoprosencephaly has been reported at 10-12 weeks using the transvaginal ultrasonography (TVS).

Do babies with HPE survive?

HPE affects about one in 5,000 live births. Most children with HPE have the severe form of the disorder. Therefore, the majority do not survive past the first six months of life.

What does it mean if eyes are close together?

It's important to understand that the distance between the eyes varies from patient to patient. Although your eyes are close together, they're still within the normal range. This condition is called hypotelorism and is related to the shape of the underlying boney orbits.

What causes small eyes?

Causes of Small Eye Syndrome Exposure to harmful chemicals and toxins during pregnancy. Exposure to harmful radiations like X-rays. Infections during pregnancy like rubella. Deficiency of vitamins during pregnancy especially vitamin A.

What gene is mutated in holoprosencephaly?

SHH is the major gene implicated in holoprosencephaly (12.7% of HPE cases: 50% of overall point mutations and 38% of overall large deletions) [50, 51].

Do babies with HPE survive?

HPE affects about one in 5,000 live births. Most children with HPE have the severe form of the disorder. Therefore, the majority do not survive past the first six months of life.

Whats it called when a baby is born without a brain?

Anencephaly (pronounced an-en-sef-uh-lee) is a serious birth defect in which a baby is born without parts of the brain and skull.

What is the most serious form of holoprosencephaly?

There are four classifications of holoprosencephaly. Gross pathology specimen from a case of alobar holoprosencephaly. Alobar holoprosencephaly, the most serious form, in which the brain fails to separate, is usually associated with severe facial anomalies, including lack of a nose and the eyes merged to a single median structure (see cyclopia ).

Which form of holoprosencephaly is the least severe?

Semilobar holoprosencephaly, in which the brain's hemispheres have somewhat divided, is an intermediate form of the disease. Lobar holoprosencephaly, in which there is considerable evidence of separate brain hemispheres, is the least severe form. In some cases of lobar holoprosencephaly, the patient's brain may be nearly normal.

What is HPE in biology?

Holoprosencephaly ( HPE) is a cephalic disorder in which the prosencephalon (the forebrain of the embryo) fails to develop into two hemispheres. Normally, the forebrain is formed and the face begins to develop in ...

What is the medical term for the failure of the prosencephalon to develop into two hemispheres?

Medical condition. Holoprosencephaly. Diagram depicting the main subdivisions of the embryonic vertebrate brain. Specialty. Medical genetics. Holoprosencephaly ( HPE) is a cephalic disorder in which the prosencephalon (the forebrain of the embryo) fails to develop into two hemispheres. Normally, the forebrain is formed and ...

What causes HPE?

Causes. The exact cause (s) of HPE are yet to be determined. Mutations in the gene encoding the Sonic Hedgehog protein, which is involved in the development of the central nervous system (CNS), can cause holoprosencephaly. In other cases, it often seems that there is no specific cause at all.

Is HPE inherited?

There is evidence that in some families, HPE is inherited ( autosomal dominant as well as autosomal or X-linked recessive inheritance ). Features consistent with familial transmission of the disease (e.g., a single central maxillary incisor) should be carefully assessed in parents and family members.

Is syntelencephaly a variant of HPE?

Syntelencephaly, or middle interhemispheric variant of holoprosencephaly (MIHV), in which the posterior frontal lobe and the parietal lobe are not properly separated, but the rostro basal forebrain properly separates; it is possible that this is not a variant of HPE at all, but it is currently classified as such.

What is the cause of holoprosencephaly?

Holoprosencephaly is a disorder caused by the failure of the prosencephalon (the embryonic forebrain) to sufficiently divide into the double lobes of the cerebral hemispheres. The result is a single-lobed brain structure and severe skull and facial defects.

What are the different types of holoprosencephaly?

There are three classifications of holoprosencephaly: 1 Alobar, in which the brain has not divided at all, is usually associated with severe facial features. 2 Semilobar, in which the brain's hemispheres have somewhat divided, causes an intermediate form of the disorder. 3 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.

What is the cause of HPE?

The cause of HPE in any individual family is often unknown. What do we know about holoprosencephaly? Holoprosencephaly (HPE) is a relatively common birth defect of the brain, which often can also affect facial features, including closely spaced eyes, small head size, and sometimes clefts of the lip and roof of the mouth, ...

What is the least severe facial anomaly in HPE?

Approximately 80 percent of severe HPE have characteristic facial features. The least severe of the facial anomalies in holoprosencephaly is the median cleft lip ( premaxillary agenesis ). The most severe is cyclopia, an abnormality characterized by a single eye located in the area normally occupied by the root of the nose, ...

What causes HPE in families?

The risk of reoccurrence is small in most families. There are a number of causes of HPE, including genetic alterations and environmental effects. The cause of HPE in any individual family is often unknown.

How many prevelances does holoprosencephaly have?

This birth defect occurs soon after conception. It has a prevelance of 1 in 250 during early embryo development, and 1 in 10,000 to 1 in 20,000 at term. There are three classifications of holoprosencephaly: Alobar, in which the brain has not divided at all, is usually associated with severe facial features.

What is a flat nose with a single nostril?

Cebocephaly, another facial anomaly, is characterized by a small, flattened nose with a single nostril situated below incomplete or underdeveloped closely-set eyes. Not all individuals with HPE are affected to the same degree, even in families where more than one individual has this predisposition.

What causes holoprosencephaly in the fetus?

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.

How many live births are there in holoprosencephaly?

The incidence of holoprosencephaly has been estimated at 1 in 250 during early embryonic development, and approximately 1 in 16,000 live births.

What is the failure of the prosencephalon?

Holoprosencephaly (HPE) is the failure of the prosencephalon, or forebrain, to develop normally. The forebrain is a region of the brain in the fetus that develops into parts of the adult brain, including the cerebral cortex. Instead of the normal complete separation of the left and right halves of the forebrain, there is an abnormal continuity between the two sides. There are several different types of holoprosencephaly. In the alobar form, there is no separation between the right and left halves at all. In semilobar HPE, at least some separation of the two halves is present. In the lobar form, most of the brain has separated into right and left sides, though there is incomplete division into the two halves.

What is the most common chromosomal abnormality associated with HPE?

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.

Who should assess holoprosencephaly?

Relatives of a child with holoprosencephaly may have an increased risk of having a child with holoprosencephaly, and this should be assessed and discussed by the child’s physicians, especially the neurologist and/or clinical geneticist.

Is the National Organization for Rare Disorders copyrighted?

The content of the website and databases of the National Organization for Rare Disorders (NORD) is copyrighted and may not be reproduced, copied, downloaded or disseminated, in any way, for any commercial or public purpose, without prior written authorization and approval from NORD.

Is there separation between the right and left halves of the brain?

In the alobar form, there is no separation between the right and left halves at all. In semilobar HPE, at least some separation of the two halves is present. In the lobar form, most of the brain has separated into right and left sides, though there is incomplete division into the two halves.

What is holoprosencephaly?

Listen. 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, ...

How long can a child live with holoprosencephaly?

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. [1] The life expectancy for individuals with semi-lobar holoprosencephaly depends on the underlying cause of the condition and the presence of associated anomalies. [2] [4]

What is the term for a complete failure of the brain to divide into the right and left hemispheres

Alobar holoprosencephaly is when there is a complete failure of the brain to divide into right and left hemispheres which results in the loss of midline structures of the brain and face as well as fusion of the cavities of the brain, known as lateral ventricles and the third ventricle (which are normally separated).

How long do people with semilobar holoprosencephaly live?

More than 50 percent of children with semi-lobar or lobar holoprosencephaly without significant malformations of other organs are alive at age 12 months. [1] . The life expectancy for individuals with semi-lobar holoprosencephaly depends on the underlying cause of the condition and the presence of associated anomalies.

What is the name of the condition where the brain is fused in the middle?

Lobar holoprosencephaly, is when there are two ventricles (right and left) but the cerebral hemispheres are fused in the frontal cortex. Features may include bilateral cleft lip , closely spaced eyes, depressed nose or an almost normal looking face. Middle interhemispheric variant results when the brain is fused in the middle.

What are the features of semilobar holoprosencephaly?

Other features may include a flattened bridge and tip of the nose, one nostril, a median cleft lip or bilateral cleft lip, and a cleft palate . Lobar holoprosencephaly, is when there are two ventricles ...

How many types of holoprosencephaly are there?

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). [1] . In general, the severity of any facial defects corresponds to the severity of the brain defect.

What is holoprosencephaly?

holoprosencephaly. a developmental anomaly consisting of failure of cleavage of the prechordal mesoderm with a deficit in the for ebrain and midline facial development ; in the severe form there may be cyclopia. It is sometimes associated with trisomy 13 syndrome. The facial features in holoprosencephaly. The eyes are close together and there is ...

Which gene is responsible for holoprosencephaly?

Gripp (33) identified the fourth gene, TGIF gene, responsible for the holoprosencephaly phenotype located on 18p at a distance of 3.5 Mb from the telomere.

What is cyclopia in biology?

hol·o·pros·en·ceph·a·ly. Failure of the forebrain or prosencephalon to divide into hemispheres or lobes; cyclopia occurs in the severest form. It is often accompanied by a deficit in midline facial development.

What is the disorder in which the developing forebrain fails to correctly separate into right and left hemisphere

holoprosencephaly. A disorder in which the developing forebrain fails to correctly separate into right and left hemispheres, which is accompanied by facial deformities. Molecular pathology. Holoprosencephaly is attributed to mutations of the SHH gene. Segen's Medical Dictionary. © 2012 Farlex, Inc. All rights reserved.

Is holoprosencephaly noted on ultrasound?

A single case of holoprosencephaly, not noted on the prenatal ultrasound report, was identified during pathology examination; however, this case was unusual in that cervical dilation allowed the extraction of an intact specimen.

What is the prognosis of holoprosencephaly?

Prognosis. Holoprosencephaly (H PE) is a birth defect of the brain that occurs shortly after conception. During embryo development, its incidence is approximately one in 250. In full-term babies, it occurs in roughly one in 10,000 to 20,000 infants. HPE occurs when the prosencephalon, or the embryonic forebrain, ...

Which type of HPE has a single eye?

Alobar. In this type, the brain is not divided into two hemispheres at all and facial deformities are typically severe, including a single eye or tubular-shaped nose. Semilobar . With this type of HPE, the brain has somewhat divided into two hemispheres. Lobar.

How long does it take for an alobar HPE to die?

For alobar HPE, the most severe type, a fetus with this condition may be stillborn or die within six months of being born.

What are the symptoms of HPE?

Other signs of HPE can include seizures, neural tube defects, short stature, difficulties with feeding, hydrocephalus, and unstable vital signs like temperature or heart rate.

Is there a treatment for HPE?

Treatment. There is no one set of treatments for HPE since each child with the condition has a specific set of symptoms and malformations, as well as a specific degree of severity. Treatment is personalized to the child and is largely supportive and focused on relieving symptoms.

Is HPE inherited?

Sometimes HPE is inherited, but not always. When there are hereditary causes of HPE, it could be due to a chromosome abnormality—this is the case for about one-third of those with HPE. This is caused by a single gene mutation that causes syndromic disorders, or a mutation of a gene that causes non-syndromic HPE.

What is holoprosencephaly?

Definition: Holoprosencephaly is a neural developmental disorder where the forebrain does not successfully divide into two hemispheres.

Causes of holoprosencephaly

In development, the neural precursor cells respond to a variety of molecular signals that cause the cells to act in certain ways. One such signal molecule is called Sonic hedgehog (Shh).

What is holoprosencephaly?

Holoprosencephaly. Holoprosencephaly (HPE) is a rare congenital brain malformation resulting from incomplete separation of the two hemispheres. Classically three subtypes have been recognized, however additional entities are now included in the spectrum of the disease.

How many births are there with holoprosencephaly?

Epidemiology. Although rare in absolute terms, holoprosencephaly is the most common brain malformation and is seen in 1 per 10,000-16,000 live births 3,9. The early embryonic occurrence may be even higher but may not be detected due to most fetuses aborting in early gestation.

What is the least affected subtype of holoprosencephaly?

Lobar holoprosencephaly. This is the least affected subtype. Patients demonstrate more subtle areas of midline abnormalities such as fusion of the cingulate gyrus and thalami. The olfactory tracts are absent or hypoplastic. There may be hypoplasia or absence of the corpus callosum.

Is semilobar holoprosencephaly fused?

Semilobar holoprosencephaly. The basic structure of the cerebral lobes are present but are fused most commonly anteriorly and at the thalami. The olfactory tracts and bulbs are usually not present, and there is agenesis or hypoplasia of the corpus callosum. For more details see the article on semilobar holoprosencephaly.

Can holoprosencephaly be seen on MRI?

As with most cerebral structural congenital abnormalities, holoprosencephaly is visible on all modalities, but in general is identified on antenatal ultrasound, and best characterized by MRI. On antenatal ultrasound, there may be also evidence of polyhydramnios , a secondary feature due to impaired fetal swallowing.

How is holoprosencephaly classified?

Lobar (mild) – The least frequent form of HPE. The brain is divided but there is some fusion of structures and mild abnormalities.

What causes HPE?

Although the cause of holoprosencephaly is not known, it has been linked to both genetic alterations and environmental exposures.

How common is HPE?

Between 1 in 5,000-10,000 babies are born with HPE each year. Since only about 3% of fetuses with HPE survive till birth, the actual frequency may be as high as 1 in 200-250.

What are the risks of reoccurrence?

The risk of reoccurrence is small in most families, but genetic counseling is recommended.

What is the prognosis for a child with HPE?

Babies with the most severe forms of holoprosencephaly often die before they are born or shortly after birth. However some children even with the most severe forms of HPE may live several months or years after birth. Children with the mildest forms of HPE may have a normal life span.

Overview

Signs and symptoms

Diagnosis

Causes

Prognosis

See also

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