ConditionChildren's health
Holoprosencephaly (HPE)
Holoprosencephaly (HPE) is a birth defect in which the front part of the embryo's brain (the forebrain) does not fully divide into left and right halves during the first weeks of pregnancy. It ranges from severe forms, often with major facial differences and not survivable, to mild forms with near-normal brain structure. It is linked to chromosome conditions such as trisomy 13, single-gene changes and maternal diabetes. Care focuses on feeding, seizures, hormone problems and developmental support.
Also called: HPE, arhinencephaly (older term), alobar, semilobar and lobar holoprosencephaly
At a glance
- What it is
- Incomplete separation of the forebrain into two hemispheres in early pregnancy.
- How common
- About 1 in 10,000 live births, but far more common in early pregnancies, many of which miscarry.
- Types
- Alobar (most severe), semilobar, lobar, and middle interhemispheric variant.
- Causes
- Trisomy 13 and other chromosome changes, gene variants such as SHH, maternal diabetes.
- Care
- Supportive: feeding, seizure control, hormone replacement, managing fluid on the brain, therapies.
When to get help
Call 911 or go to the ER
- A baby or child with HPE who has a prolonged seizure, breathing pauses, or is very hard to wake
- Very high fever or very low body temperature, or extreme sleepiness with heavy urination and thirst (possible sodium imbalance from diabetes insipidus)
See a doctor within a day or two
- Poor feeding, vomiting, fewer wet diapers or weight loss
- A rapidly enlarging head, bulging soft spot or vomiting (possible hydrocephalus)
- Signs of aspiration: coughing or choking with feeds, or repeated chest infections
Book a routine appointment
- New or more frequent seizures, or changes in tone or movement
- A prenatal ultrasound finding of HPE: ask for referral to fetal medicine and genetics
- Planning another pregnancy after an affected pregnancy, or diabetes before pregnancy
What happens in holoprosencephaly
Around the fifth to sixth week after conception, the forebrain normally splits into two cerebral hemispheres, and the face develops in coordination with it. In HPE, this division is incomplete. Because brain and face develop together, more severe HPE is often accompanied by facial differences along the midline: the saying "the face predicts the brain" holds in many cases.
Types of holoprosencephaly
| Type | Brain | Typical facial features |
|---|---|---|
| Alobar | No separation, a single ventricle, absent midline structures | Often severe: closely set or single eye (cyclopia), absent or tube-like nose (proboscis) |
| Semilobar | Partial separation at the back of the brain | Closely set eyes, flat nose, cleft lip or palate |
| Lobar | Mostly separated, with fusion at the front | Face may be normal or mildly affected |
| Middle interhemispheric variant (syntelencephaly) | Fusion in the middle of the brain | Often normal face |
| Microform | Normal brain | Subtle midline signs such as a single central upper incisor or closely set eyes |
Causes and risk factors
- Chromosome abnormalities: especially trisomy 13 (Patau syndrome), and also trisomy 18 and triploidy.
- Single-gene changes: SHH, ZIC2, SIX3 and TGIF1 are among the best known. These can be inherited, sometimes from a mildly affected parent, or arise new.
- Syndromes such as Smith-Lemli-Opitz syndrome.
- Maternal diabetes, especially poorly controlled diabetes in early pregnancy.
- Other factors that have been suggested include alcohol and some medicines in early pregnancy.
Symptoms and associated problems
Severity varies widely. Problems may include:
- Developmental delay and intellectual disability, from mild to profound
- Seizures
- Abnormal muscle tone, stiffness or floppiness, similar to cerebral palsy
- Feeding and swallowing difficulties, reflux and aspiration
- Hormone problems from an underdeveloped hypothalamus and pituitary: diabetes insipidus (very common), and deficiencies of growth hormone, thyroid hormone or cortisol
- Problems controlling body temperature, sleep and heart rate
- Hydrocephalus or a small head (microcephaly)
- Cleft lip and palate, and vision and hearing problems
Diagnosis
- Prenatal ultrasound: severe forms are often seen at the first trimester scan (11 to 14 weeks) or the anatomy scan (18 to 22 weeks). Milder forms may be missed.
- Fetal MRI gives more detail of brain structure.
- Genetic testing: chromosome analysis or microarray of the pregnancy or baby, then gene panels if chromosomes are normal. Parents may also be tested.
- After birth: brain MRI, hormone testing, eye and hearing exams, and feeding assessment.
Treatment and care
There is no cure. Care is supportive and tailored to the child:
- Feeding: specialized bottles, thickened feeds and often a gastrostomy (feeding tube) to ensure nutrition and reduce aspiration.
- Seizures: anti-seizure medicines.
- Hormone replacement: desmopressin for diabetes insipidus, and cortisol, thyroid or growth hormone if needed.
- Hydrocephalus: a shunt in some children.
- Cleft repair and dental care.
- Therapies: physical, occupational and speech therapy, and early intervention.
- Palliative care for babies with severe forms, focusing on comfort and family support.
- Genetic counseling: to explain the cause and recurrence risk in future pregnancies.
Outlook
Outlook depends on the type and associated conditions. Many pregnancies with alobar HPE or trisomy 13 end in miscarriage, and babies born with severe forms often live days to months. Children with semilobar and lobar HPE often live into childhood and beyond, with varying degrees of disability. Children with microforms or milder lobar forms may have mild or no disability.
Frequently asked questions
What is holoprosencephaly?
Holoprosencephaly is a birth defect in which the forebrain does not fully divide into two halves early in pregnancy. It ranges from severe forms that are not survivable to mild forms with few symptoms. It is often associated with differences along the middle of the face.
What are the types of holoprosencephaly?
The main types, from most to least severe, are alobar (no division), semilobar (partial division), lobar (mostly divided) and the middle interhemispheric variant. A microform has a normal brain with subtle midline facial features.
What causes holoprosencephaly?
Common causes include trisomy 13 and other chromosome changes, variants in genes such as SHH, ZIC2 and SIX3, some genetic syndromes and maternal diabetes. In many cases the cause is not found. Genetic testing helps families understand the cause and recurrence risk.
What is the life expectancy with holoprosencephaly?
It depends on the type. Babies with alobar HPE, especially with trisomy 13, usually survive only days to months. Children with semilobar and lobar forms often live into childhood or adulthood with varying disabilities. Mild forms may not affect life expectancy.
Sources
This guide was written from current patient and clinical guidance, including:
- National Institute of Neurological Disorders and Stroke (NINDS): Holoprosencephaly
- MedlinePlus Genetics: Holoprosencephaly
- National Organization for Rare Disorders (NORD): Holoprosencephaly
- GeneReviews (NCBI): Holoprosencephaly overview
- Carter Centers for Brain Research in Holoprosencephaly: Information for families