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PubMed This is a summary of 17 peer-reviewed journal articles Updated
Radiology

The Diagnostic Journey: Imaging and Testing

At a Glance

Alobar holoprosencephaly (HPE) is primarily diagnosed through specialized prenatal imaging, such as a Level 2 ultrasound and fetal MRI, which reveal the brain's failure to divide into two hemispheres. Following imaging, genetic testing like microarrays helps identify the underlying cause.

Confirming a diagnosis of alobar holoprosencephaly (HPE) involves a detailed look at the brain’s physical structure through imaging and an analysis of the “genetic blueprint” through specialized testing. Because this condition is rare and severe, doctors use several layers of technology to ensure the diagnosis is correct and to distinguish it from other conditions that might look similar on a standard ultrasound.

Imaging: Seeing the Structure

The diagnosis usually begins with a Level 2 Ultrasound (an anatomy scan). In a healthy developing brain, the first-trimester ultrasound shows a “butterfly sign,” which is created by the normal appearance of the choroid plexus (the tissue that makes brain fluid) in two separate halves [1][2]. In alobar HPE, this “butterfly” is absent [1].

Key Imaging Markers

Radiologists look for three specific findings to confirm the alobar form:

  • Monoventricle: Instead of two separate fluid-filled chambers (lateral ventricles), there is one large, single central cavity [1][3].
  • Fused Thalami: The thalami (the brain’s relay centers) are joined together in the middle rather than being two distinct structures [1][4].
  • Absent Midline Structures: Several key structures that normally separate the two halves of the brain are missing, including the falx cerebri (the membrane between hemispheres), the corpus callosum (the bridge between hemispheres), and the septum pellucidum [1][5].

A Fetal MRI is often ordered after an ultrasound to provide a much clearer, high-resolution picture. This helps doctors confirm the grade of severity and ensure they aren’t seeing hydranencephaly (where the brain is mostly missing but the thalami are usually not fused) or severe hydrocephalus (where the brain has divided but is being compressed by excess fluid) [6][7].

Genetic Testing: Finding the “Why”

Once the physical structure is identified, genetic testing is used to see if there is an underlying chromosomal or gene-level cause. This can be done prenatally via amniocentesis (testing the fluid around the baby) or after birth via a blood sample.

  1. Chromosomal Microarray (CMA): This is often the first step. It looks for “extra” or “missing” pieces of genetic material [8]. It is excellent at finding conditions like Trisomy 13 [9].
  2. Targeted Gene Panels: Often used as an intermediate step, these panels look specifically at a known list of genes associated with HPE (like SHH and ZIC2) [10].
  3. Whole Exome Sequencing (WES): If the microarray and panels are normal, doctors may suggest this more detailed test. It “reads” the individual letters of the DNA to find tiny mutations [11][12].
  4. Trio Analysis: Sometimes, doctors test both parents along with the baby. This helps determine if a genetic change was inherited or if it happened for the first time in the baby (a de novo mutation) [11].

Your Radiology Report Checklist

When you receive a radiology or pathology report, you can look for these specific terms to ensure a thorough evaluation was performed [13][14]:

Essential Report Item What It Means
Fusion of Thalami Confirms the central relay centers are joined.
Monoventricle Confirms a single fluid cavity instead of two.
Presence/Absence of Falx Confirms if the dividing membrane is missing.
Cavum Septum Pellucidum Its absence is a hallmark of the HPE spectrum.
Facial Midline Assessment Notes on the eyes, nose, and upper lip, which often correlate with brain severity [15].

Empowering yourself with these terms helps you engage with your medical team. If a report is vague, you have the right to ask for a “second opinion” review by a specialized neuro-radiologist who has expertise in fetal brain malformations [16][17].

Common questions in this guide

How is alobar holoprosencephaly diagnosed on an ultrasound?
Doctors use a Level 2 ultrasound to look for the absence of the normal 'butterfly sign' in the fetal brain. They specifically check for a single fluid cavity, known as a monoventricle, and joined relay centers called fused thalami to confirm the diagnosis.
Why might a fetal MRI be ordered if I already had an ultrasound?
A fetal MRI provides a clearer, high-resolution picture of the baby's developing brain. This helps doctors confirm the exact severity of the holoprosencephaly and rule out similar-looking conditions like severe hydrocephalus or hydranencephaly.
What genetic tests are used for alobar holoprosencephaly?
Genetic testing usually starts with a Chromosomal Microarray to check for missing or extra genetic material, such as Trisomy 13. If that is clear, doctors may use targeted gene panels or Whole Exome Sequencing to look for specific mutations in genes related to brain development.
What does 'fused thalami' mean on my radiology report?
The thalami are the brain's central relay centers, which are normally two distinct structures. 'Fused thalami' means these centers are joined together in the middle, which is a key diagnostic marker for alobar holoprosencephaly.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Does the imaging report specifically mention whether the thalami are fused or separate?
  2. 2.Was the 'butterfly sign' seen on the first-trimester scan, or was it noted as absent?
  3. 3.How did you distinguish this from severe hydrocephalus or hydranencephaly in my child's specific case?
  4. 4.Which genetic test is most appropriate for us right now: a targeted gene panel, a chromosomal microarray, or whole exome sequencing?
  5. 5.If we choose an amniocentesis for genetic testing, what are the specific risks and what exact answers will it provide?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (17)
  1. 1

    Alobar holoprosencephaly with cebocephaly in a neonate: A rare case report from Northern Tanzania.

    Ariyo IJ, Mchaile DN, Magwizi M, et al.

    International journal of surgery case reports 2022; (93()):106960 doi:10.1016/j.ijscr.2022.106960.

    PMID: 35364389
  2. 2

    Detection of non-cardiac fetal abnormalities on ultrasound at 11-14 weeks: systematic review and meta-analysis.

    Karim JN, Di Mascio D, Roberts N, et al.

    Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology 2024; (64(1)):15-27 doi:10.1002/uog.27649.

    PMID: 38547384
  3. 3

    Alobar Holoprosencephaly in an Aborted American Quarter Horse Fetus.

    Henker LC, Lorenzett MP, Piva MM, et al.

    Journal of equine veterinary science 2022; (112()):103898 doi:10.1016/j.jevs.2022.103898.

    PMID: 35150851
  4. 4

    Phenotypic Spectrum and Chromosomal Discordance in Alobar Holoprosencephaly: A Comparative Case Series from a Tertiary Referral Center.

    Caropeboka MFA, Nisa AS, Pramatirta AY, et al.

    International medical case reports journal 2026; (19()):569641 doi:10.2147/IMCRJ.S569641.

    PMID: 41710465
  5. 5

    Prenatal diagnosis of holoprosencephaly.

    Kousa YA, du Plessis AJ, Vezina G

    American journal of medical genetics. Part C, Seminars in medical genetics 2018; (178(2)):206-213 doi:10.1002/ajmg.c.31618.

    PMID: 29770996
  6. 6

    Hydranencephaly in a Newborn: A Case Report and a Review of the Literature.

    Toumi K, Chafiq K, Khayi FE, Daoudi A

    Cureus 2024; (16(12)):e75435 doi:10.7759/cureus.75435.

    PMID: 39791062
  7. 7

    Alobar holoprosencephaly: Exploring mothers' perspectives on prenatal decision-making and prognostication.

    Elfarawi H, Tolusso L, McGowan ML, et al.

    Prenatal diagnosis 2022; (42(5)):617-627 doi:10.1002/pd.6130.

    PMID: 35253927
  8. 8

    Cytogenetics and holoprosencephaly: A chromosomal microarray study of 222 individuals with holoprosencephaly.

    Hu T, Kruszka P, Martinez AF, et al.

    American journal of medical genetics. Part C, Seminars in medical genetics 2018; (178(2)):175-186 doi:10.1002/ajmg.c.31622.

    PMID: 30182442
  9. 9

    Prenatal ultrasound findings of holoprosencephaly spectrum: Unusual associations.

    El-Dessouky SH, Aboulghar MM, Gaafar HM, et al.

    Prenatal diagnosis 2020; (40(5)):565-576 doi:10.1002/pd.5649.

    PMID: 31955448
  10. 10

    Recent advances in the diagnosis and molecular pathogenesis of holoprosencephaly: a review.

    Glista F, Nienartowicz J, Bukowska-Olech E

    Journal of applied genetics 2025; doi:10.1007/s13353-025-01017-8.

    PMID: 41102431
  11. 11

    Holoprosencephaly: A clinical genomics perspective.

    Solomon BD, Retterer K, Juusola J

    American journal of medical genetics. Part C, Seminars in medical genetics 2018; (178(2)):194-197 doi:10.1002/ajmg.c.31613.

    PMID: 29749690
  12. 12

    Holoprosencephaly in Kabuki syndrome.

    Daly T, Roberts A, Yang E, et al.

    American journal of medical genetics. Part A 2020; (182(3)):441-445 doi:10.1002/ajmg.a.61454.

    PMID: 31846209
  13. 13

    The wide spectrum of ultrasound diagnosis of holoprosencephaly.

    Ionescu CA, Vladareanu S, Tudorache S, et al.

    Medical ultrasonography 2019; (21(2)):163-169 doi:10.11152/mu-1614.

    PMID: 31063520
  14. 14

    Neuropathology of holoprosencephaly.

    Fallet-Bianco C

    American journal of medical genetics. Part C, Seminars in medical genetics 2018; (178(2)):214-228 doi:10.1002/ajmg.c.31623.

    PMID: 30182440
  15. 15

    Cyclopia: Facial deformity indicating severe holoprosencephaly with imaging findings of brain: A case report.

    Aryal S, Rimal B, Paudel S, Marasini K

    Radiology case reports 2026; (21(4)):1706-1711 doi:10.1016/j.radcr.2025.12.059.

    PMID: 41727820
  16. 16

    Holoprosencephaly spectrum: an up-to-date overview of classification, genetics and neuroimaging.

    Gomez GD, Corrêa DG, Trapp B, et al.

    Japanese journal of radiology 2025; (43(1)):13-31 doi:10.1007/s11604-024-01655-8.

    PMID: 39259418
  17. 17

    Radiogenomics of congenital brain malformations: Linking embryology, genetics, and imaging.

    AlRayahi J, AlDasuqi K, AlSubhi M, et al.

    Neuroradiology 2026; (68(5)):1213-1233 doi:10.1007/s00234-026-03916-x.

    PMID: 41670708

This page provides educational information about diagnosing alobar holoprosencephaly. Always consult your maternal-fetal medicine specialist or genetic counselor for the interpretation of your specific ultrasound and genetic test results.

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