When Is Holoprosencephaly Diagnosed in Pregnancy?
At a Glance
Holoprosencephaly (HPE) is typically diagnosed during pregnancy ultrasounds. Severe cases are often detected as early as 11 to 14 weeks, while milder forms are usually found during the 18 to 22-week anatomy scan. A fetal MRI is highly recommended to confirm the diagnosis and severity.
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Receiving unexpected news about your baby’s development is overwhelming and frightening. If you are facing a potential diagnosis of holoprosencephaly (HPE), you likely have questions about when and how this was caught. Holoprosencephaly is typically diagnosed during routine pregnancy ultrasounds, but the exact timing depends on how severe the condition is. The most severe form (alobar HPE) can often be seen as early as 11 to 14 weeks into the pregnancy [1][2]. However, milder forms (semilobar and lobar HPE) are usually not visible until the detailed anatomy scan around 18 to 22 weeks [3][4]. Because ultrasound images can sometimes be unclear or mistaken for other conditions, doctors frequently use a fetal MRI (magnetic resonance imaging) to get a more detailed look at the baby’s brain and confirm the diagnosis [5].
The Diagnostic Timeline
- 11 to 14 Weeks: During the first-trimester ultrasound, doctors look for major developmental milestones. Severe cases, known as alobar HPE (where the brain has not divided at all), are often detected at this stage [1]. The ultrasound may show a single, fused brain structure instead of two distinct halves [2].
- 18 to 22 Weeks: Milder variations, such as semilobar (partial division) or lobar (mostly divided but incomplete) HPE, are typically caught during the mid-pregnancy anatomy scan [3][4]. The mildest form, lobar HPE, is rarely detected in the first trimester because the brain structures are still too small and developing [6].
Can the Ultrasound Be Wrong?
It is natural to wonder if a prenatal diagnosis could be a mistake, and to hold onto hope. While ultrasound is highly accurate for severe cases, it does have limitations:
- Milder forms can be subtle: Diagnosing semilobar or lobar HPE requires seeing very specific, small brain structures, such as the absence of the cavum septum pellucidum (a small fluid-filled space in the brain) [7]. If the baby is in a difficult position, these details can be missed or mischaracterized [8].
- Mimicking conditions: Certain other brain issues, like large fluid cysts or severe hydrocephalus (fluid buildup in the brain), can sometimes look very similar to HPE on an ultrasound [9][10].
The Role of Fetal MRI
Because an ultrasound alone may not provide the complete picture, a fetal MRI is considered a crucial next step when HPE is suspected [5][11]. An MRI is safe during pregnancy—typically performed without contrast dye—and uses magnetic fields to create highly detailed images of the baby’s brain.
A fetal MRI helps by:
- Confirming or refuting the diagnosis: The MRI can definitively show whether the condition is truly HPE or a different issue that just looked similar on the ultrasound [5][12].
- Determining the exact severity: By providing a clearer picture of which parts of the brain are fused, doctors can accurately classify the type of HPE [11][13]. This is vital for understanding what to expect, as severe forms like alobar HPE are often life-limiting, while milder forms have different prognoses.
- Finding other anomalies: An MRI can detect additional brain, structural, or facial differences (which are common in HPE) that the ultrasound might have missed [14].
Recommended Next Steps
If your ultrasound suggests holoprosencephaly, your medical team will likely recommend a few important follow-up steps to give you the most accurate information possible:
- Fetal MRI: To confirm the diagnosis and understand the brain’s exact structure [15].
- Fetal Echocardiogram: A specialized ultrasound of the baby’s heart, as HPE can sometimes be accompanied by heart differences [15].
- Genetic Counseling and Testing: HPE is frequently associated with chromosomal conditions, most commonly Trisomy 13 [16][17]. To check for this, your doctor may recommend tests like a chromosomal microarray. It is important to know that diagnostic genetic testing requires obtaining fetal cells, typically through an invasive procedure like an amniocentesis or chorionic villus sampling (CVS).
- Consultation with Specialists: Meeting with a Maternal-Fetal Medicine (MFM) specialist (a high-risk pregnancy doctor) and a pediatric neurologist or neurosurgeon to discuss the findings and what they mean for your family [8]. In cases of severe HPE, you may also want to connect with palliative care or perinatal hospice specialists to discuss all your options and ensure your family feels supported.
Common questions in this guide
When is holoprosencephaly usually detected on an ultrasound?
Can an ultrasound diagnosis of holoprosencephaly be wrong?
Why do I need a fetal MRI if my ultrasound already shows holoprosencephaly?
What genetic testing is recommended if my baby has holoprosencephaly?
Questions to Ask Your Doctor
Curated prompts to bring to your next appointment.
- 1.Based on the imaging we have so far, which specific type of holoprosencephaly (alobar, semilobar, or lobar) is suspected?
- 2.When can we schedule a fetal MRI to get a clearer picture of the baby's brain development?
- 3.Are there any other physical or structural differences visible on the ultrasound, such as facial or heart anomalies?
- 4.What are the risks and benefits of pursuing an amniocentesis for genetic testing in our specific situation?
- 5.Can you refer us to a maternal-fetal medicine specialist and, if appropriate, a perinatal palliative care team?
Questions For You
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References
References (17)
- 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
Further evidence for complex inheritance of holoprosencephaly: Lessons learned from pre- and postnatal diagnostic testing in Germany.
Hinreiner S, Wieczorek D, Mueller D, et al.
American journal of medical genetics. Part C, Seminars in medical genetics 2018; (178(2)):198-205 doi:10.1002/ajmg.c.31625.
PMID: 30182445 - 3
Prenatal diagnosis of syndromic alobar holoprosencephaly associated with digynic triploidy fetus.
Albu CC, Albu DF, Pătraşcu A, et al.
Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie 2020; (61(4)):1309-1316 doi:10.47162/RJME.61.4.32.
PMID: 34171079 - 4
Alobar holoprosencephaly associated with a rare chromosomal abnormality: Case report and literature review.
Ionescu CA, Calin D, Navolan D, et al.
Medicine 2018; (97(29)):e11521 doi:10.1097/MD.0000000000011521.
PMID: 30024536 - 5
In Utero MR Imaging of Fetal Holoprosencephaly: A Structured Approach to Diagnosis and Classification.
Griffiths PD, Jarvis D
AJNR. American journal of neuroradiology 2016; (37(3)):536-43 doi:10.3174/ajnr.A4572.
PMID: 26564444 - 6
The role of routine first-trimester ultrasound screening for central nervous system abnormalities: a longitudinal single-center study using an unselected cohort with 3-year experience.
Hu Y, Sun L, Feng L, et al.
BMC pregnancy and childbirth 2023; (23(1)):312 doi:10.1186/s12884-023-05644-z.
PMID: 37138220 - 7
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 - 8
A rare case of trisomy 13 mosaicism with only findings on first-trimester ultrasound single umbilical artery and increased nuchal translucency.
Gerede A, Zafrakas M, Papasozomenou P, et al.
Hippokratia 2024; (28(1)):38-40.
PMID: 39399405 - 9
Middle Interhemispheric Variant of Holoprosencephaly - Presenting as Non-Visualized Cavum Septum Pellucidum and An Interhemispheric Cyst in A 19-Weeks Fetus.
Vasudeva A, Nayak SS, Kadavigere R, et al.
Journal of clinical and diagnostic research : JCDR 2015; (9(9)):QD11-3 doi:10.7860/JCDR/2015/14076.6525.
PMID: 26500966 - 10
Prenatal diagnosis of middle interhemispheric variant of holoprosencephaly: Report of two cases.
Zantow E, Bryant S, Pierce SL, et al.
Journal of clinical ultrasound : JCU 2021; (49(7)):765-769 doi:10.1002/jcu.22984.
PMID: 33559178 - 11
Holoprosencephaly: antenatal and postnatal diagnosis and outcome.
Kaliaperumal C, Ndoro S, Mandiwanza T, et al.
Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery 2016; (32(5)):801-9 doi:10.1007/s00381-016-3015-4.
PMID: 26767839 - 12
The additional value of fetal MRI to ultrasonography in prenatal diagnosis: an evaluation based on postnatal confirmation.
Yasar E, Kahramanoglu O, Kunt Isguder C, et al.
Journal of perinatal medicine 2026; (54(2)):381-390 doi:10.1515/jpm-2025-0398.
PMID: 41502307 - 13
Fetal Congenital Anomalies: Multi-Regional Magnetic Resonance Imaging Evaluation with Prenatal Ultrasound Correlation.
Akyel NG, Ozgul H, Omac Birinci A, Arslanoglu T
Turkish archives of pediatrics 2025; (60(6)):599-607 doi:10.5152/TurkArchPediatr.2025.25170.
PMID: 41257425 - 14
Accuracy of prenatal ultrasound in the diagnosis of corpus callosum anomalies.
Santirocco M, Rodó C, Illescas T, et al.
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 2021; (34(3)):439-444 doi:10.1080/14767058.2019.1609931.
PMID: 31035852 - 15
Fetal Magnetic Resonance Imaging (MRI) in Holoprosencephaly and Associations With Clinical Outcome: Implications for Fetal Counseling.
Riddle A, Nagaraj U, Hopkin RJ, et al.
Journal of child neurology 2021; (36(5)):357-364 doi:10.1177/0883073820972290.
PMID: 33226281 - 16
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 - 17
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
This page provides educational information about the prenatal diagnosis of holoprosencephaly. It does not replace professional medical advice, and you should always discuss your specific ultrasound findings and next steps with your maternal-fetal medicine specialist.
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