Authors:

Michelle R. Christie, MD; Nancy J. Clegg, BSN, MSN, PhD, CCRP, Scottish Rite for Children – Dallas, Texas 

Reviewed: April 2021 

SUMMARY

Holoprosencephaly (HPE) is a rare birth defect. Early in pregnancy, a baby’s brain ordinarily separates into two sections. This does not happen completely in children with HPE.   

The cause of HPE is unknown but may include genetic disorders. Children with HPE can experience developmental delays, seizures, respiratory problems, and difficulty maintaining a normal temperature. The abilities of, and challenges for, a child diagnosed with HPE depends on the type of HPE. Symptoms can be affected by how other parts of the brain developed. They also depend on whether there are other problems present.   

Disorder Overview

DESCRIPTION

Holoprosencephaly is a birth defect that occurs during the first few weeks of pregnancy. During this time, the brain should grow and split into two halves. In babies with HPE, the brain does not grow as it should. In mild HPE, part of the brain is separated but some areas are not. In severe HPE, the brain does not divide at all.   

Only 3% of fetuses with HPE survive to delivery. 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. 

The four main types of HPE: 

The outlook for children with HPE depends on the severity of the disorder and on other coexisting problems. Severely affected children may live several months or several years. The least affected may live a normal lifespan but are unable to live independently.   

SIGNS AND SYMPTOMS

HPE is often diagnosed with an ultrasound during pregnancy. However, milder forms may not be noticed until a baby is born. If the baby shows developmental delays, an MRI, or magnetic resonance imaging, of the brain can be used. An MRI can show HPE.  

Children diagnosed with HPE may have: 

• Microcephaly. This means having a small head. 
• Hydrocephalus. This means having too much fluid in the brain. 
• Developmental delays. Examples include being late to sit, craw, stand, or walk. 
• Epilepsy. This means the child may experience seizures. 
• Endocrine issues. Hormone problems may include low levels of thyroid, cortisol, or growth hormones. 
• Diabetes insipidus. This form of diabetes results in high sodium levels in the blood and excessive urination.  High sodium can cause seizures.  Diabetes insipidus affects 3 in 4 children with HPE. 
• Problems with muscle control, motor control, or movement. This can include tight muscles, unpredictable movements, balance issues, or muscle weakness. 
• Difficulty falling asleep or staying asleep. Child may sleep during the day instead of at night. In addition, obstructive sleep apnea and/or sleep apnea may be present and interrupt sleep. 
• Trouble with body temperature regulation. Child may become too hot or too cold even if the room temperature is normal.  
• Feeding issues. Many children with HPE will need a feeding tube. 
• Facial deformities. These may include a flat, single-nostril nose, close-set eyes, a cleft lip or palate, or other severe facial abnormalities. 
• Self-abusive behavior. This can look like biting, hitting, hair pulling, or scratching. 

CAUSES

The exact cause of HPE is unknown. However, risk factors include:  

• Maternal diabetes. Some cases of HPE have been associated with gestational diabetes, however this is rare.  
• Certain infections during pregnancy. Some infections are associated with HPE. These include syphilis, toxoplasmosis, rubella, herpes, and cytomegalovirus. 
• Use of certain drugs and medicines during pregnancy. Drugs associated with HPE include alcohol, aspirin, lithium, antipsychotics, anticonvulsants, hormones, and retinoic acid. 
• Chromosomal abnormalities. Many children with HPE have normal chromosomes. However, specific chromosomal abnormalities have been identified in some patients.  
• Gene mutations. Several types of both inherited and non-inherited gene mutations may cause HPE. 

LABORATORY INVESTIGATIONS  

Various testing and imaging procedures can useful in diagnosing and understanding HPE. 

• Brain imaging scans. MRI and CT scans (computerized tomography scans) can help diagnose HPE.  
• Genetic tests. Genetic tests are often ordered during an initial examination for HPE. They may be repeated as genetic testing advances. 
• Lab tests. Blood and urine tests can look for problems associated with HPE. They can help detect diabetes insipidus, as well as thyroid, cortisol, and growth hormone deficiencies. 

TREATMENTS

The treatments used will depend on the severity of the HPE and associated issues.  

OUTLOOK 

There is no cure for HPE. Developmental delay is universal. Still, the severity of HPE varies considerably.  

Children with moderate or severe HPE may never be able to sit independently, crawl, or walk. They may have difficulty with motor functions. Weak and stiff muscles may require intensive therapy, bracing, and special equipment.  

Almost 3 in 4 children with HPE will require a feeding tube for nutrition, fluids, and medication. Most will be unable to talk. Communication will be limited. All children with HPE are at risk for feeding, breathing, and hormone issues. Almost half have seizures.  

Because the brain malformation cannot be treated, all care is based on symptoms.  

Research 

ClincalTrials.gov for holoprosencephaly (birth to 17 years) are clinical trials that are recruiting or will be recruiting. Updates are made daily, so you are encouraged to check back frequently.  

ClinicalTrials.gov is a database of privately and publicly funded clinical studies conducted around the world. This is a resource provided by the U.S. National Library of Medicine (NLM), which is an institute within the National Institutes of Health (NIH). Listing a study does not mean it has been evaluated by the U.S. Federal Government. Please read the NLM disclaimer for details.   

Before participating in a study, you are encouraged to talk to your health care provider and learn about the risks and potential benefits.  

The information in the CNF Child Neurology Disorder Directory is not intended to provide diagnosis, treatment, or medical advice and should not be considered a substitute for advice from a healthcare professional. Content provided is for informational purposes only.  CNF is not responsible for actions taken based on the information included on this webpage. Please consult with a physician or other healthcare professional regarding any medical or health related diagnosis or treatment options. 

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