Record Review: Alobar Holoprosencephaly
- Jamie Thomsen
- Jan 14
- 4 min read
In today's Record Review video we are going to cover Alobar Holoprosencephaly, a complex malformation of cortical development. The blog information below reflects the information on this condition discussed in the video with resources cited below. We will discuss:
What is holoprosencephaly?
Classification of types
What is alobar holoprosencephaly?
Clinical features of alobar holoprosencephaly after birth
What causes holoprosencephaly (HPE)?
How is holoprosencephaly (HPE) diagnosed?
EEG findings in HPE
Prognosis in HPE
What is holoprosencephaly?
Holoprosencephaly (HPE) is a birth defect (congenital condition) that causes the fetal brain to not properly separate into two halves or hemispheres. If the brain does not fully separate during development the baby is diagnosed with HPE. HPE can affect the development of a fetus’s head and face. HPE ranges in severity causing several types of issues.
Classification holoprosencephaly types
There are three main types of holoprosencephaly (HPE). Ordered from most to least severe, they include:
Alobar -The brain’s halves are completely connected or fused together.
Semilobar - The halves are mostly connected but separated slightly at the back of the brain.
Lobar - The brain’s halves are mostly separated, only connected in the frontal lobe. In lobar HPE, the corpus callosum, which allows the two halves of the brain to communicate, is mostly formed.
What is alobar holoprosencephaly?
Alobar holoprosencephaly: This type means the fetal brain hasn’t divided into two hemispheres at all. This results in the loss of midline structures of it’s brain and face, as well as fusion of the cavities of their brain. It’s usually associated with severe facial deformities. Babies with this type of HPE are often stillborn or die shortly after birth.
A. MRI of alobar holoprosencephaly (HPE), the most severe form of HPE, characterized by an enlarged midline monoventricle (holoventricle, red/thin arrow) with fusion of the frontal lobes and the midline gray matter structures (thalami and basal ganglia, blue/thick arrow). Typically, the corpus callosum and the third ventricle are absent.
B. Facial features seen in the alobar HPE spectrum, characterized by a single eye-like structure (cyclopia, red/thin arrow) and an overriding nose-like structure (proboscis, blue/thick arrow)
Clinical features of alobar holoprosencephaly after birth
Severe developmental delay
Epilepsy
Movement disorders
Hypotonia
Hypothalamic/pituitary dysfunction
Feeding difficulties
Abnormal vision and hearing
What causes holoprosencephaly (HPE)?
The cause is largely not well understood, but thought to be multifactorial, a combination of genetic and environmental factors
Less than half have a detectable chromosomal abnormality. In this case, there are missing or copied sections of chromosomes. It could also man syndromes of duplicated chromosomes like Trisomy 13 (patau syndrome), which is commonly linked to alobar holoprosencephaly.
Less the a quarter might have a single gene mutation, especially in genes that are important for embryonic development. Some of those genes include SHH or TGIF-1. These mutations have variable expressivity, meaning that it does not don’t cause symptoms in everyone who has them
In many cases, healthcare providers can’t determine the exact cause.
Other single gene mutations that are associated with HPE:
SHH.
SIX3.
TGIF1.
ZIC2.
PTCH1.
FOXH1.
NODAL.
CDON.
FGF8.
GLI2.
How is holoprosencephaly (HPE) diagnosed?
Healthcare providers can often identify holoprosencephaly, especially more severe cases, before birth through a prenatal ultrasound. They can also diagnose the condition pre-birth with fetal magnetic resonance imaging (MRI).
If there is no prenatal imaging, or if the case is more subtle, HPE may be diagnosed after delivery when facial abnormalities or neurologic issues are present. A head ultrasound and if needed, subsequent MRI can be done at that point.
Infants with mild forms of HPE may not be diagnosed until around a year old when developmental delays may signal a possible neurological issues. Brain imaging will confirm diagnosis.
24 week gestation ultrasound suggestive of alobar HPE
Brain MRI performed at 32 days old
EEG findings in HPE
Depends on severity
Slowing of background
Chaotic, some areas of fast
Generalized or focal spike/spike and slow
Seizures
Helps to know in these alobar cases what their imaging is like
Prognosis in HPE
Milder forms, depends on what their issues are and complications
Alobar HPE is the most severe
Many die at the time or within a short time of birth. About half by the time they are 4-5 months of age. About 20% make it past 1 year of life.
Difficult to tell just by imaging and their clinical status
Special thank you to Dr. Rachna Patel for sharing her time and expertise!
Resources:
Bain Vesicle image from Wikipedia -
Holoprosencephaly classification chart from Cleveland clinic - https://my.clevelandclinic.org/health/diseases/22919-holoprosencephaly-hpe
Holoprosencephaly classification chart with MRI imaging from halkhatib_radiology Instagram page.
Patient MRI and image of alobar holoprosencephaly and description provided by Holoprosencephaly Overview in GeneReviews
Tekendo-Ngongang C, Muenke M, Kruszka P. Holoprosencephaly Overview. 2000 Dec 27 [Updated 2020 Mar 5]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Figure 1. [Alobar HPE]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1530/figure/hpe-overview.F1/
Prenatal ultrasound and post natal MRI with descriptions provided from article "Alobar Holoprosencephaly in a Newborn: A Case Report of Prenatal Diagnosis and a Review of the Literature"
Chafiq K, Toumi K, Khayi F, et al. (November 25, 2024) Alobar Holoprosencephaly in a Newborn: A Case Report of Prenatal Diagnosis and a Review of the Literature. Cureus 16(11): e74462. doi:10.7759/cureus.74462
Additional resources include:
Children's Hospital Colorado Holoprosencephaly information -
Children with holoprosencephaly brain imaging and EEG examples.
Yang MT, Lee WT, Peng SS, Lin HC, Tseng CL, Liang JS, Wang PJ, Shen YZ. The roles of electroencephalography and neuroimaging in children with holoprosencephaly. Epileptic Disord. 2004 Sep;6(3):173-80. PMID: 15504716.
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