Holoprosencephaly (HPE) is a rare congenital anomaly in which an embryo’s brain does not properly divide into two halves, known as the left and right hemispheres.

HPE affects brain development and can cause facial irregularities that may affect the nose, upper lip, and eyes.

This article discusses the causes, signs and symptoms, types, and management of HPE. It also looks at prevention and the outlook for the condition and answers some frequently asked questions.

A couple getting an ultrasound scan for an unborn baby. -1Share on Pinterest
Maskot/Getty Images

In HPE, the forebrain, or prosencephalon, does not develop as usual.

The forebrain is the region of the brain in a fetus that later develops into areas of the adult brain, including the hippocampus, cerebral cortex, and the hypothalamus.

During typical development, a fetus’ forebrain separates into two distinct halves, called cerebral hemispheres, during the first few weeks of gestation. In HPE, the brain does not divide into the left and right halves.

Depending on the type of HPE, the brain may partially divide or may not divide at all.

The condition affects brain development, which can lead to cognitive difficulties, health complications, and disabilities.

It may also cause irregularities of the skull and face, such as a cleft palate and cleft lip. In severe cases, the anomalies may lead to the death of the fetus before birth or cause death shortly after birth.

HPE is rare, although it is the most common anomaly that affects the development of the forebrain.

The condition occurs in around 1 in 250 conceptions and has a live birth prevalence of 1 in 8,000–16,000.

Experts do not know the exact causes of HPE. However, genetics likely play a role, as around one-third of children born with HPE have an abnormality of the chromosomes.

Although various chromosomal abnormalities may result in HPE, the most common is trisomy 13. This is when a person has three copies of chromosome 13 instead of two.

HPE may also occur with certain genetic conditions or may be due to a change in a gene that causes the genes to function unusually.

Some factors may increase the risk of having a fetus with HPE. These include pregestational diabetes and exposure to certain substances in the environment.

Substances that may increase the risk of HPE include:

  • ethanol, or alcohol
  • retinoic acid, present in animal-sourced foods and as a laboratory-made ingredient in certain skin medications, such as Accutane
  • salicylate, present in certain foods, medications, and cosmetics
  • cyclopamine, a naturally occurring steroidal alkaloid present in certain plants
  • cigarette smoke
  • THC, a cannabinoid in cannabis
  • piperonyl butoxide from indoor dust

HPE varies in severity and may cause varying degrees of face and brain irregularities.

The signs and symptoms of the condition in a baby include:

To diagnose HPE, a doctor will look for signs of congenital anomalies in the fetus or baby and ask questions about a person’s family history and environmental exposures.

A doctor can evaluate a fetus for HPE before birth using an MRI scan or an ultrasound. The imaging scans may reveal specific anomalies that doctors associate with HPE and can help determine the type of HPE.

A doctor may also perform genetic testing to determine if a person has chromosomal abnormalities.

There are four main subtypes of HPE:

  • Alobar holoprosencephaly: In this type of HPE, the brain does not divide into separate hemispheres at all and remains a single structure. Alobar HPE typically results in severe health complications and severe facial irregularities, such as cyclopia.
  • Semilobar holoprosencephaly: In semilobar HPE, there is some separation between the two halves of the brain. The degree of severity of health complications and facial irregularities is highly variable in this type and can range from minor to severe. Children with this type of HPE typically have profound intellectual disabilities.
  • Lobar holoprosencephaly: In this type, most of the brain has separated into two distinct hemispheres, but the division is incomplete. Children with this type of HPE may have typical or relatively typical facial features. Health complications, such as seizures and developmental delays later in life, may prompt diagnosis.
  • Middle interhemispheric holoprosencephaly: This type is generally less severe and involves irregular fusion in the middle of the brain. Children with this type of HPE may not have facial irregularities and typically have less severe symptoms.

The management of HPE can vary between individuals based on the type and severity of the condition and related complications.

Management and treatment can include:

  • Medications: A child with HPE may require medication for complications such as:
  • Physical and occupational therapy: A physical or occupational therapist may be able to help manage and improve low muscle tone and muscle rigidity.
  • Surgery: Some children may require surgery to help treat hydrocephalus, a cleft palate and lip, and other structural irregularities. If gastroesophageal problems are present, a doctor may place a gastronomy tube.
  • Psychological interventions: Some children with HPE may develop neurological or psychological problems, such as depression, anxiety, learning disorders, or attention deficit hyperactivity disorder. These disorders may require psychotherapy, medication, or both.

A person cannot typically prevent HPE from occurring in a fetus, as experts do not know its precise cause.

Genetic testing may be able to help a person understand their risk of genetic changes that may lead to a condition such as HPE.

A person may also be able to avoid certain potential risk factors of HPE, such as environmental exposure to harmful substances.

The outlook for HPE can vary depending on the type, severity, and complications of the condition.

The outlook for moderate to severe HPE is typically unfavorable. According to the National Library of Medicine:

  • 33% of newborns die within 24 hours of birth
  • 58% die within 1 month of birth
  • 50% die within 4–5 months of birth
  • 70–80% die within 1 year of birth

Children with mild to moderate HPE often survive into adulthood and typically experience various health complications.

Around 50% of people with lobar HPE can walk and communicate verbally.

Below are the answers to some common questions about holoprosencephaly (HPE).

What is the life expectancy of a child with holoprosencephaly?

The life expectancy of a child with HPE depends on the type and severity of the condition.

Newborns with moderate to severe HPE do not typically survive past 1 year.

Children with mild to moderate HPE can often survive into adulthood.

How does a baby get holoprosencephaly?

Experts do not know the exact causes of HPE, although they believe the condition has probable links to genetic anomalies.

Holoprosencephaly (HPE) is a congenital anomaly that develops within the first few weeks of gestation.

It prevents the brain of the fetus from dividing into two distinct hemispheres. This can affect brain development and lead to various health complications and structural facial irregularities.

Experts do not know the exact causes of HPE but believe it may have links to changes in specific genes. Exposure to certain substances in the environment may also increase the risk of the condition.

Management of HPE can include medication, surgery, physical and occupational therapy, and psychotherapy.