Holoprosencephaly: Causes, Symptoms, and Treatment
Medically reviewed by Harsha Moole, MD, Internal Medicine. Last reviewed: October 23, 2026.
What kind of doctor treats Holoprosencephaly?
A pediatric neurologist, a doctor who treats brain conditions in children, often helps lead care. A geneticist, a doctor who works with inherited conditions, and an endocrinologist, a hormone doctor, are often part of the team. A direct primary care or concierge doctor can be a first stop for an evaluation and can refer you to a specialist when needed.
What is holoprosencephaly?
Holoprosencephaly (HPE) is a birth defect in which the front part of the brain, called the forebrain, does not develop normally. Normally the forebrain separates into left and right halves. In HPE, the two sides do not fully separate. It arises during the first few weeks of pregnancy.
There are several types. In the alobar form, there is no separation between the right and left halves at all. In the semilobar form, at least some separation is present. In the lobar form, most of the brain has separated, though the division is incomplete.
HPE is rare, at about 1 in 16,000 live births. It affects males and females in equal numbers before birth.
Symptoms
HPE ranges from very mild to very severe for both the brain and the face. Intellectual disability is linked to HPE, and seizures are often present. A child may have:
- A small head (microcephaly).
- Extra fluid in the brain (hydrocephalus).
- A single central upper front tooth.
- Cleft lip, cleft palate, or both.
- Hormone problems, called endocrine problems.
- Differences in how the nose forms.
The most severely affected children may have cyclopia, a single central eye, but this is very rare. Problems with the pituitary gland can cause low blood sugar, low blood sodium, or genital differences.
Causes and who gets it
For most children, no outside cause that led to HPE is found. Diabetes in the mother during pregnancy can raise the risk. About one-third of children with HPE have a chromosome change. The most common is trisomy 13, which means three copies of chromosome 13. In other children, a change in a single gene is the cause. Genes linked to HPE include SHH, SIX3, TGIF1, and ZIC2. HPE can also occur as part of genetic syndromes that affect other organs, such as Smith-Lemli-Opitz syndrome. For many people, the exact cause is not found.
How doctors diagnose it
HPE is usually diagnosed with an MRI or CT scan of the brain. It can sometimes be seen before birth on an ultrasound or MRI, but mild forms may not be found this way. Chromosome and gene testing is often done. Families should also get a genetics evaluation and genetic counseling once the diagnosis is made.
Treatment
Care for HPE is supportive and based on the medical problems each child has. A hormone doctor should check for pituitary problems. A neurologist can guide treatment for seizures if they are present. Plastic surgery may be needed for cleft lip and palate or other facial features. A developmental pediatrician can help direct therapies for development. Many professionals plan care together, including pediatricians, neurologists, dentists, special education teachers, surgeons, therapists, and psychologists.
When to see a doctor
Doctors can sometimes find HPE before birth on an ultrasound or MRI. After birth, a child with signs such as a small head or a cleft lip or palate should be seen by a doctor. Call 911 or go to the emergency room if your child has trouble or abnormal breathing, bluish or grey skin, a seizure that lasts more than 5 minutes, or cannot be woken up.
How a direct primary care or concierge doctor fits in
A direct primary care doctor charges a flat monthly fee instead of billing insurance, while a concierge doctor usually charges more and often works alongside insurance. Either can help track your child's overall health and keep the many specialists in touch with each other.
Common questions
Is holoprosencephaly always severe?
Not always. It ranges from very mild to very severe. In most cases the brain malformations are so severe that babies die before birth. In less severe cases, babies are born with normal or near-normal brain development but may have facial differences.
Can holoprosencephaly run in families?
Sometimes, because relatives of a child with HPE may have a higher chance of having a child with it. Doctors may look for signs in parents, such as a single central upper front tooth. Genetic counseling is advised for families.
Can holoprosencephaly be found before birth?
Sometimes, through ultrasound or MRI. Mild forms may not be reliably found before birth.
How common is holoprosencephaly?
It is rare, with about 1 in 16,000 live births. It is estimated to be far more common early in development, at about 1 in 250.
How is holoprosencephaly treated?
Holoprosencephaly is treated with supportive care that depends on each child's specific medical problems. A team may include a neurologist for seizures, an endocrinologist for pituitary problems, and surgeons for cleft lip and palate.
Sources
- NORD (National Organization for Rare Disorders) - Holoprosencephaly
- National Institute of Neurological Disorders and Stroke - Birth Disorders of the Brain and Spinal Cord
Medical Disclaimer
This content is for general educational and informational purposes only and is not medical advice. It is not a substitute for professional medical advice, diagnosis, or treatment, and reading it does not create a doctor-patient relationship. Always seek the advice of your physician or another qualified health provider with any questions about a medical condition, and never disregard or delay seeking professional advice because of something you read here. If you think you may have a medical emergency, call 911 (or your local emergency number) immediately.
