About Holoprosencephaly

Learn more about holoprosencephaly.

What is Holoprosencephaly (HPE)?

Holoprosencephaly (HPE) is a birth defect that occurs very early in pregnancy, when the developing brain grows and divides into two halves, or hemispheres. In HPE, a part of the brain called the prosencephalon does not grow forward and divide as it should.

Holo = whole or entire (not separated into two halves)
Prosen =  prosencephalon refers to the front part of the developing brain
Cephaly =  disorder or condition affecting the head

What are the types of HPE?

The four main types of HPE range from very mild to severe:

Middle Interhemispheric Variant (MIHV) (very mild)

Where the middle of the brain (posterior frontal and parietal lobes) are not well separated.

  • Least common type of HPE
  • The middle section of the brain is not well separated

Lobar (mild)

  • Occurs in less than 12% of children with HPE
  • The brain is almost completely divided
  • Problems (or abnormalities) of the brain are mild/less severe
  • Some children have a version called Septopreoptic HPE
    • This type is very mild/less severe
    • Only a small area of the brain is not divided
    • The problems (or abnormalities) are very mild
    • Children with this subtype usually have good motor function

Semilobar (moderate)

  • This is the second most common type
  • The brain is divided in the back but not in the front
  • Problems (or abnormalities) are moderate or less severe

Alobar (severe)

  • This is the most common type of HPE
  • The brain is not divided at all
  • Severe problems  are present because:
    • some parts of the brain may not completely develop or may be missing entirely.
    • some parts of the brain may be “stuck” together.

How common is HPE?

HPE affects between 1 in 5,000 to 10,000 live births. Since many of these pregnancies end in miscarriage, the true rate of HPE may be higher: one in 200-250.  Current studies show that only 3% of fetuses with HPE survive to delivery. The majority do not survive past the first six months of life.

What are the common problems?

Children diagnosed with HPE may have:

  • A small head (microcephaly)
  • Too much fluid in the brain (hydrocephalus)
  • Developmental delays (speech, sitting, crawling, standing, walking and running and hand control)
  • Epilepsy (seizures)
  • Hormone (endocrine) issues including low thyroid, cortisol and growth hormone levels
  • Almost 75% of children with HPE have diabetes insipidus (high sodium/salt levels)
  • Muscle or motor control and movement problems including tight muscles, unpredictable movements, balance issues and/or weakness
  • Problems with sleep
  • Problems with body temperature regulation
  • Feeding issues
  • Facial deformities such as a flat, single-nostril nose, close-set eyes, cleft lip and/or palate or other severe facial abnormalities
  • Self-abusive behavior such as biting, hitting, hair pulling or scratching

What causes Holoprosencephaly?

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

  • Maternal diabetes
  • Certain infections during pregnancy
  • Various drugs taken during pregnancy, such as alcohol, aspirin, lithium, Thorazine, anticonvulsants, hormones and retinoic acid
  • A previous miscarriage
  • First trimester bleeding
  • Specific chromosomal abnormalities have been identified in some patients
  • Several different types of gene mutations (some inherited and some not inherited) may cause HPE.

What to expect?

The outlook depends on the severity of HPE and other existing problems.

  • Severely affected children may live several months or years, and the least affected may live a normal life span
  • HPE is not a fatal disorder and does not get worse over time
  • Some common problems such as seizures or breathing issues may get worse over time

Because HPE affects the development and function of many body systems, a child may have some of these tests throughout life:

  • Brain scans (MRI or CAT scans) to diagnose the condition. Scans may be repeated annually if your child has hydrocephalus
  • Genetic testing for chromosome abnormalities or gene mutations during the initial work-up for HPE and may be repeated as genetic testing advances
  • Cognitive testing (I.Q., problem solving, memory skills, etc.) to assist the schools with creating an educational plan
  • Speech and language evaluation (spoken words, use of words and their meanings)
  • Social skills assessment (family relationships, peer-to-peer interactions)
  • Motor evaluation (writing, eating, dressing, sitting, crawling, standing, walking, running, etc.) repeated annually as your child grows

What is the treatment?

There is no cure for HPE. Treatment depends on the severity of HPE and other factors.
These may include:

  • Medications to treat certain signs or symptoms
  • Surgery for facial deformities, tight muscles, dislocated hips, or scoliosis
  • Physical and occupational therapy to help with motor skills and function
  • Speech therapy to help with feeding, cognitive and language skills
  • Wheelchairs, walkers and other mobility equipment to help the child to maintain good posture and to help with function
  • Special feeding equipment and special diets to help with growth and managing certain related conditions
  • Communication aids tools to help the child express his or her needs and develop relationships
  • Individual and family counseling
  • Accommodations for school