Medical Conditions

Holoprosencephaly in Babies

Medically reviewed by Dr. Michael Okonkwo, MD, FAAP · Board-Certified Neonatologist

Content reviewed against published NIH, AAP, Carter Centers guidelines

Editorial policy

Last reviewed:

If your baby has been diagnosed with or you suspect holoprosencephaly in babies, here is what the evidence says.

The short answer

Holoprosencephaly (HPE) is a brain malformation that occurs when the developing forebrain (prosencephalon) fails to divide into two hemispheres during early pregnancy (weeks 3-6). It is the most common structural malformation of the human brain, occurring in about 1 in 250 pregnancies, though most end in miscarriage, with approximately 1 in 8,000 to 16,000 live births affected. HPE exists on a spectrum from severe (alobar, with no separation) to mild (lobar or middle interhemispheric variant). Facial features often correlate with brain severity, ranging from cyclopia in the most severe forms to closely spaced eyes or a single central incisor in milder forms. Outcomes depend heavily on the type and severity.

Key takeaways

  • Holoprosencephaly (HPE) is a brain malformation that occurs when the developing forebrain (prosencephalon) fails to divide into two hemispheres during early pregnancy (weeks 3-6). It is the most common structural malformation of the human brain, occurring in about 1 in 250 pregnancies, though most end in miscarriage, with approximately 1 in 8,000 to 16,000 live births affected. HPE exists on a spectrum from severe (alobar, with no separation) to mild (lobar or middle interhemispheric variant). Facial features often correlate with brain severity, ranging from cyclopia in the most severe forms to closely spaced eyes or a single central incisor in milder forms. Outcomes depend heavily on the type and severity.
  • Usually normal when: Your baby has closely spaced eyes but brain imaging is completely normal — mild hypotelorism can be a normal variant
  • Call your doctor if: Your baby with HPE develops signs of cortisol deficiency during illness — lethargy, low blood sugar, poor feeding, or shock — this is life-threatening and requires emergency stress-dose steroids and immediate medical care
  • Varies by age — see the age-by-age breakdown below
“Fever itself is not an illness — rather, it is a sign or symptom that the body is fighting an infection. Fever stimulates certain defenses, such as the white blood cells, which attack and destroy invading bacteria.”
— Fever and Your Child, American Academy of Pediatrics (AAP)

This is one of the most common questions parents ask. Searching for answers means you care.

What Parents Should Know

According to NIH, AAP, Carter Centers guidelines, holoprosencephaly (HPE) is a brain malformation that occurs when the developing forebrain (prosencephalon) fails to divide into two hemispheres during early pregnancy (weeks 3-6). It is the most common structural malformation of the human brain, occurring in about 1 in 250 pregnancies, though most end in miscarriage, with approximately 1 in 8,000 to 16,000 live births affected. HPE exists on a spectrum from severe (alobar, with no separation) to mild (lobar or middle interhemispheric variant). Facial features often correlate with brain severity, ranging from cyclopia in the most severe forms to closely spaced eyes or a single central incisor in milder forms. Outcomes depend heavily on the type and severity. At Prenatal, hPE is often detected on prenatal ultrasound, particularly the more severe forms, by the presence of a single ventricle, fused brain structures, or facial abnormalities. Fetal MRI provides more detailed assessment of the brain. Genetic testing is recommended, as HPE can be caused by chromosomal abnormalities (such as trisomy 13 or trisomy 18), gene mutations (SHH, ZIC2, SIX3, TGIF1), or environmental factors (maternal diabetes). The diagnosis often leads to extensive prenatal counseling regarding prognosis, which varies based on the type and underlying cause. It is generally considered normal when your baby has closely spaced eyes but brain imaging is completely normal — mild hypotelorism can be a normal variant. However, you should contact your pediatrician promptly if your baby with HPE develops signs of cortisol deficiency during illness — lethargy, low blood sugar, poor feeding, or shock — this is life-threatening and requires emergency stress-dose steroids and immediate medical care.

Sources: [1], [2], [3]

Normal vs. Concerning

Usually Normal
Worth Discussing
Your baby has closely spaced eyes but brain imaging is completely normal — mild hypotelorism can be a normal variant
Your baby with HPE develops signs of cortisol deficiency during illness — lethargy, low blood sugar, poor feeding, or shock — this is life-threatening and requires emergency stress-dose steroids and immediate medical care
Your baby has a single central incisor but no other features of HPE and normal brain MRI
Your baby with HPE develops signs of increased intracranial pressure: rapid head growth, bulging fontanelle, persistent vomiting, or decreasing alertness — possible hydrocephalus requiring urgent neurosurgical evaluation
Your child has mild lobar HPE, is making developmental progress, and has stable medical status
Your baby with HPE has a prolonged seizure lasting more than 5 minutes or has difficulty breathing

When to Seek Immediate Care

  • Your baby with HPE develops signs of cortisol deficiency during illness — lethargy, low blood sugar, poor feeding, or shock — this is life-threatening and requires emergency stress-dose steroids and immediate medical care
  • Your baby with HPE develops signs of increased intracranial pressure: rapid head growth, bulging fontanelle, persistent vomiting, or decreasing alertness — possible hydrocephalus requiring urgent neurosurgical evaluation
  • Your baby with HPE has a prolonged seizure lasting more than 5 minutes or has difficulty breathing

By Age

What to expect by age

Prenatal

HPE is often detected on prenatal ultrasound, particularly the more severe forms, by the presence of a single ventricle, fused brain structures, or facial abnormalities. Fetal MRI provides more detailed assessment of the brain. Genetic testing is recommended, as HPE can be caused by chromosomal abnormalities (such as trisomy 13 or trisomy 18), gene mutations (SHH, ZIC2, SIX3, TGIF1), or environmental factors (maternal diabetes). The diagnosis often leads to extensive prenatal counseling regarding prognosis, which varies based on the type and underlying cause.

0-3 months

Severe forms (alobar and semilobar) present at birth with significant neurological impairment, including poor feeding requiring tube feeding, seizures, abnormal muscle tone, temperature instability, and endocrine problems (particularly diabetes insipidus and growth hormone deficiency due to hypothalamic involvement). Hydrocephalus may develop. Facial features vary: severe cases may have absent nasal structures, cleft lip/palate, or closely spaced eyes (hypotelorism). Milder forms (lobar HPE) may have subtler facial and neurological findings.

3-12 months

Babies with severe HPE have profound developmental delays and often require comprehensive medical support including gastrostomy feeding, seizure management, and hormone replacement therapy. Some develop hydrocephalus requiring shunting. Babies with lobar HPE may achieve some motor milestones and show social responsiveness. Endocrine evaluation is important, as pituitary dysfunction is common and can cause cortisol deficiency (which can be life-threatening if untreated), thyroid problems, and growth issues.

1-3 years

Children with milder forms of HPE may make slow but meaningful developmental progress with early intervention services. Communication development, even if nonverbal, is an important focus. Movement and positioning therapy helps prevent contractures. Some children with lobar HPE may walk, use gestures, and engage socially. Children with more severe forms require full supportive care. Palliative care consultation can be helpful for families navigating complex medical decisions. Despite challenges, children with HPE are often described by their families as socially engaged and responsive.

3+ years

Long-term outcomes span a very wide spectrum. Some individuals with the mildest forms of HPE (microform, including single central maxillary incisor) may have near-normal intelligence. Those with lobar HPE may have moderate to severe disability but can have meaningful quality of life with appropriate support. Severe forms carry a more guarded prognosis. Ongoing care involves neurology, endocrinology, developmental medicine, and family support. The Carter Centers for Brain Research and genetic counseling provide specialized resources for families.

What to Tell Your Pediatrician

  • Describe when you first noticed holoprosencephaly in babies and how it has changed over time.
  • Note your baby's current age and which age-specific patterns you are seeing.
  • Mention if your baby was diagnosed with HPE prenatally and you need postnatal evaluation and care planning.
  • Mention if your baby has closely spaced eyes, facial midline defects, or a single central incisor along with developmental concerns.
  • Let your doctor know if you have noticed any related concerns, such as changes in feeding, sleep, or movement patterns.
  • Bring a list of any questions or observations you want to discuss at the appointment.

What Should You Do?

When to take action

Probably normal when...
  • Your baby has closely spaced eyes but brain imaging is completely normal — mild hypotelorism can be a normal variant
  • Your baby has a single central incisor but no other features of HPE and normal brain MRI
  • Your child has mild lobar HPE, is making developmental progress, and has stable medical status
Mention at your next visit when...
  • Your baby was diagnosed with HPE prenatally and you need postnatal evaluation and care planning
  • Your baby has closely spaced eyes, facial midline defects, or a single central incisor along with developmental concerns
  • Your child with HPE is having increased seizures, changes in feeding tolerance, or new endocrine symptoms (excessive thirst/urination, poor growth)
Act now when...
  • Your baby with HPE develops signs of cortisol deficiency during illness — lethargy, low blood sugar, poor feeding, or shock — this is life-threatening and requires emergency stress-dose steroids and immediate medical care
  • Your baby with HPE develops signs of increased intracranial pressure: rapid head growth, bulging fontanelle, persistent vomiting, or decreasing alertness — possible hydrocephalus requiring urgent neurosurgical evaluation
  • Your baby with HPE has a prolonged seizure lasting more than 5 minutes or has difficulty breathing

What You Can Do at Home

  • Keep track of when you notice holoprosencephaly in babies — noting the time of day, duration, and any triggers can help your pediatrician.
  • Remember that your baby has closely spaced eyes but brain imaging is completely normal — mild hypotelorism can be a normal variant — this is generally within the range of normal.
  • At Prenatal, focus on observation rather than intervention unless your pediatrician advises otherwise.
  • Follow any care instructions from your pediatrician. Keep a written log of symptoms to bring to appointments.
  • While monitoring at home, seek immediate care if your baby with HPE develops signs of cortisol deficiency during illness — lethargy, low blood sugar, poor feeding, or shock — this is life-threatening and requires emergency stress-dose steroids and immediate medical care.

Signs of Hydrocephalus in Babies

Hydrocephalus occurs when cerebrospinal fluid accumulates in the brain ventricles, causing increased pressure. In babies, the most noticeable sign is rapidly increasing head circumference (head growing faster than expected). Other signs include a bulging or tense fontanelle, prominent scalp veins, downward gaze of the eyes ("sunsetting"), irritability, vomiting, and developmental delays. Treatment typically involves surgical placement of a shunt or endoscopic third ventriculostomy to drain excess fluid.

Early Signs of Epilepsy in Babies

Seizures in babies can look very different from seizures in older children or adults. Subtle signs may include repeated eye blinking or deviation, lip smacking, cycling leg movements, brief stiffening episodes, or clusters of head drops (infantile spasms). Infantile spasms are a neurological emergency that requires urgent evaluation. Not all unusual movements are seizures - babies commonly have benign tremors and startle reflexes - but any movement pattern that seems involuntary, repetitive, and cannot be interrupted deserves medical evaluation.

Lissencephaly (Smooth Brain) in Babies

Lissencephaly (meaning "smooth brain") is a rare brain malformation in which the brain surface lacks the normal folds (gyri) and grooves (sulci). It occurs when neurons fail to migrate to their proper positions during brain development between weeks 12-24 of pregnancy. Lissencephaly is classified as complete (agyria) or partial (pachygyria, with simplified, broad folds). It affects approximately 1 in 100,000 births and is typically caused by genetic mutations (most commonly in the LIS1 or DCX genes). Children with lissencephaly usually have severe developmental delays, epilepsy, and feeding difficulties, though the severity depends on the extent of brain involvement.

Agenesis of the Corpus Callosum (ACC)

Agenesis of the corpus callosum (ACC) is a condition in which the corpus callosum — the bundle of nerve fibers connecting the left and right hemispheres of the brain — fails to develop partially or completely. It occurs in approximately 1 in 4,000 births and is one of the most common brain malformations. ACC can be detected on prenatal ultrasound or postnatal MRI. Outcomes vary enormously: some individuals with isolated ACC have normal intelligence and minimal difficulties, while others (especially when ACC occurs alongside other brain abnormalities or genetic syndromes) may have significant developmental delays. The variability means that prenatal counseling and postnatal monitoring are both essential.

Milestone

Month-by-Month Development

Detailed monthly development guides from birth through 24 months.

Guide

When to Call the Doctor

General guide on when to call the pediatrician, visit urgent care, or go to the ER.

Frequently asked questions

Is holoprosencephaly in babies normal?
Holoprosencephaly (HPE) is a brain malformation that occurs when the developing forebrain (prosencephalon) fails to divide into two hemispheres during early pregnancy (weeks 3-6). It is the most common structural malformation of the human brain, occurring in about 1 in 250 pregnancies, though most end in miscarriage, with approximately 1 in 8,000 to 16,000 live births affected. HPE exists on a spectrum from severe (alobar, with no separation) to mild (lobar or middle interhemispheric variant). Facial features often correlate with brain severity, ranging from cyclopia in the most severe forms to closely spaced eyes or a single central incisor in milder forms. Outcomes depend heavily on the type and severity.
When should I call the doctor about holoprosencephaly in babies?
Your baby with HPE develops signs of cortisol deficiency during illness — lethargy, low blood sugar, poor feeding, or shock — this is life-threatening and requires emergency stress-dose steroids and immediate medical care Your baby with HPE develops signs of increased intracranial pressure: rapid head growth, bulging fontanelle, persistent vomiting, or decreasing alertness — possible hydrocephalus requiring urgent neurosurgical evaluation Your baby with HPE has a prolonged seizure lasting more than 5 minutes or has difficulty breathing
When is holoprosencephaly in babies normal?
Your baby has closely spaced eyes but brain imaging is completely normal — mild hypotelorism can be a normal variant Your baby has a single central incisor but no other features of HPE and normal brain MRI Your child has mild lobar HPE, is making developmental progress, and has stable medical status
What causes holoprosencephaly in babies?
Holoprosencephaly (HPE) is a brain malformation that occurs when the developing forebrain (prosencephalon) fails to divide into two hemispheres during early pregnancy (weeks 3-6). It is the most common structural malformation of the human brain, occurring in about 1 in 250 pregnancies, though most end in miscarriage, with approximately 1 in 8,000 to 16,000 live births affected. HPE exists on a spectrum from severe (alobar, with no separation) to mild (lobar or middle interhemispheric variant). Facial features often correlate with brain severity, ranging from cyclopia in the most severe forms to closely spaced eyes or a single central incisor in milder forms. Outcomes depend heavily on the type and severity. Common explanations include: Your baby has closely spaced eyes but brain imaging is completely normal — mild hypotelorism can be a normal variant. Your baby has a single central incisor but no other features of HPE and normal brain MRI.
What should I mention to my pediatrician about holoprosencephaly in babies?
You should mention holoprosencephaly in babies at your next visit if: Your baby was diagnosed with HPE prenatally and you need postnatal evaluation and care planning. Your baby has closely spaced eyes, facial midline defects, or a single central incisor along with developmental concerns. Your child with HPE is having increased seizures, changes in feeding tolerance, or new endocrine symptoms (excessive thirst/urination, poor growth).
Is holoprosencephaly in babies normal at Prenatal?
HPE is often detected on prenatal ultrasound, particularly the more severe forms, by the presence of a single ventricle, fused brain structures, or facial abnormalities. Fetal MRI provides more detailed assessment of the brain. Genetic testing is recommended, as HPE can be caused by chromosomal abnormalities (such as trisomy 13 or trisomy 18), gene mutations (SHH, ZIC2, SIX3, TGIF1), or environmental factors (maternal diabetes). The diagnosis often leads to extensive prenatal counseling regarding prognosis, which varies based on the type and underlying cause.
Is holoprosencephaly in babies normal at 0-3 months?
Severe forms (alobar and semilobar) present at birth with significant neurological impairment, including poor feeding requiring tube feeding, seizures, abnormal muscle tone, temperature instability, and endocrine problems (particularly diabetes insipidus and growth hormone deficiency due to hypothalamic involvement). Hydrocephalus may develop. Facial features vary: severe cases may have absent nasal structures, cleft lip/palate, or closely spaced eyes (hypotelorism). Milder forms (lobar HPE) may have subtler facial and neurological findings.
Should I go to the ER for holoprosencephaly in babies?
Seek emergency care if your baby with HPE develops signs of cortisol deficiency during illness — lethargy, low blood sugar, poor feeding, or shock — this is life-threatening and requires emergency stress-dose steroids and immediate medical care, or if your baby with HPE develops signs of increased intracranial pressure: rapid head growth, bulging fontanelle, persistent vomiting, or decreasing alertness — possible hydrocephalus requiring urgent neurosurgical evaluation. When in doubt, call your pediatrician's after-hours line for guidance.
Does holoprosencephaly in babies go away on its own?
In many cases, holoprosencephaly in babies resolves on its own, especially when your baby has closely spaced eyes but brain imaging is completely normal — mild hypotelorism can be a normal variant. By 3+ years, long-term outcomes span a very wide spectrum. Some individuals with the mildest forms of HPE (microform, including single central maxillary incisor) may have near-normal intelligence. Those with lobar HPE may have moderate to severe disability but can have meaningful quality of life with appropriate support. Severe forms carry a more guarded prognosis. Ongoing care involves neurology, endocrinology, developmental medicine, and family support. The Carter Centers for Brain Research and genetic counseling provide specialized resources for families.
NIHAAPCARTER CENTERS

References

  1. [1]National Institute of Neurological Disorders and Stroke. Holoprosencephaly Information Page. NINDS, 2023. NIH
  2. [2]Levey EB, Stashinko E, Clegg NJ, Delgado MR. Management of Children With Holoprosencephaly. American Journal of Medical Genetics Part C. 2010;154C(1):183-190. AAP
  3. [3]Carter Centers for Brain Research in Holoprosencephaly and Related Malformations. Texas Scottish Rite Hospital for Children, 2024. Carter Centers

Doctor Visit Checklist

Bring this checklist to your next pediatrician visit to discuss Holoprosencephaly in Babies.

Things to mention

  • Describe when you first noticed holoprosencephaly in babies and how it has changed over time.
  • Note your baby's current age and which age-specific patterns you are seeing.
  • Mention if your baby was diagnosed with HPE prenatally and you need postnatal evaluation and care planning.
  • Mention if your baby has closely spaced eyes, facial midline defects, or a single central incisor along with developmental concerns.
  • Let your doctor know if you have noticed any related concerns, such as changes in feeding, sleep, or movement patterns.
  • Bring a list of any questions or observations you want to discuss at the appointment.

Observations to share

  • Your baby was diagnosed with HPE prenatally and you need postnatal evaluation and care planning
  • Your baby has closely spaced eyes, facial midline defects, or a single central incisor along with developmental concerns
  • Your child with HPE is having increased seizures, changes in feeding tolerance, or new endocrine symptoms (excessive thirst/urination, poor growth)

Urgent signs to report immediately

  • Your baby with HPE develops signs of cortisol deficiency during illness — lethargy, low blood sugar, poor feeding, or shock — this is life-threatening and requires emergency stress-dose steroids and immediate medical care
  • Your baby with HPE develops signs of increased intracranial pressure: rapid head growth, bulging fontanelle, persistent vomiting, or decreasing alertness — possible hydrocephalus requiring urgent neurosurgical evaluation
  • Your baby with HPE has a prolonged seizure lasting more than 5 minutes or has difficulty breathing

My notes

From ismybabyalright.com — free, evidence-based baby health guides

All content follows our editorial policy and is reviewed against published clinical guidelines.

2,705 evidence-based guides6 authoritative medical sources5 medical advisory board members

Related Resources

Well-Baby Visit PrepBaby Sign Language GuideEmergency ContactsBaby Tracker

Bottom line

Most cases of holoprosencephaly in babies are normal. Talk to your pediatrician if your baby with hpe develops signs of cortisol deficiency during illness — lethargy, low blood sugar, poor feeding, or shock — this is life-threatening and requires emergency stress-dose steroids and immediate medical care.

Trust your instincts. If something feels wrong, reach out to your pediatrician. Worrying about your baby means you care — that is a good thing.

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Related Medical Concerns

Signs of Hydrocephalus in Babies

Hydrocephalus occurs when cerebrospinal fluid accumulates in the brain ventricles, causing increased pressure. In babies, the most noticeable sign is rapidly increasing head circumference (head growing faster than expected). Other signs include a bulging or tense fontanelle, prominent scalp veins, downward gaze of the eyes ("sunsetting"), irritability, vomiting, and developmental delays. Treatment typically involves surgical placement of a shunt or endoscopic third ventriculostomy to drain excess fluid.

Early Signs of Epilepsy in Babies

Seizures in babies can look very different from seizures in older children or adults. Subtle signs may include repeated eye blinking or deviation, lip smacking, cycling leg movements, brief stiffening episodes, or clusters of head drops (infantile spasms). Infantile spasms are a neurological emergency that requires urgent evaluation. Not all unusual movements are seizures - babies commonly have benign tremors and startle reflexes - but any movement pattern that seems involuntary, repetitive, and cannot be interrupted deserves medical evaluation.

Lissencephaly (Smooth Brain) in Babies

Lissencephaly (meaning "smooth brain") is a rare brain malformation in which the brain surface lacks the normal folds (gyri) and grooves (sulci). It occurs when neurons fail to migrate to their proper positions during brain development between weeks 12-24 of pregnancy. Lissencephaly is classified as complete (agyria) or partial (pachygyria, with simplified, broad folds). It affects approximately 1 in 100,000 births and is typically caused by genetic mutations (most commonly in the LIS1 or DCX genes). Children with lissencephaly usually have severe developmental delays, epilepsy, and feeding difficulties, though the severity depends on the extent of brain involvement.

Agenesis of the Corpus Callosum (ACC)

Agenesis of the corpus callosum (ACC) is a condition in which the corpus callosum — the bundle of nerve fibers connecting the left and right hemispheres of the brain — fails to develop partially or completely. It occurs in approximately 1 in 4,000 births and is one of the most common brain malformations. ACC can be detected on prenatal ultrasound or postnatal MRI. Outcomes vary enormously: some individuals with isolated ACC have normal intelligence and minimal difficulties, while others (especially when ACC occurs alongside other brain abnormalities or genetic syndromes) may have significant developmental delays. The variability means that prenatal counseling and postnatal monitoring are both essential.

My Baby's Head Shape Looks Abnormal

Many babies develop temporary head shape irregularities that are completely normal. A cone-shaped head from vaginal delivery reshapes within days. Mild positional flattening (plagiocephaly) from sleeping on the back is very common and usually improves with repositioning and tummy time. However, head shape changes involving ridges, a persistently bulging fontanelle, or rapid head growth changes should be evaluated to rule out craniosynostosis.

Achondroplasia (Dwarfism) in Babies

Achondroplasia is the most common form of short-limbed dwarfism, affecting about 1 in 15,000 to 40,000 births. It is caused by a mutation in the FGFR3 gene and is usually apparent at birth with characteristic features including short limbs, a larger head, and a prominent forehead. Intelligence is normal. With monitoring for specific complications and supportive care, children with achondroplasia lead full, active, and independent lives.