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Understanding Your Child's Diagnosis of Holoprosencephaly (HPE)

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At a Glance

Holoprosencephaly (HPE) is a congenital condition where a baby's brain fails to divide into two separate halves during early pregnancy. It is diagnosed via ultrasound or MRI, exists on a wide spectrum of severity, and is caused by early genetic factors, not by anything a parent did.

Key Takeaways

  • • Holoprosencephaly occurs when the forebrain fails to divide into left and right hemispheres during the first weeks of pregnancy.
  • • The condition is caused by a complex combination of genetic changes and environmental factors, not by parental actions or lifestyle choices.
  • • HPE is typically diagnosed using high-resolution imaging such as prenatal ultrasounds, fetal MRIs, or postnatal CT scans.
  • • The severity of HPE exists on a wide spectrum, ranging from alobar (severe) to lobar (milder), meaning outcomes vary greatly.

Receiving a diagnosis of Holoprosencephaly (HPE) is a profound and often overwhelming moment for any parent. It is natural to feel a sense of shock, grief, or confusion as you begin to process what this means for your child and your family. While the medical details are complex, understanding the foundation of this condition can help you find your footing as you move forward.

This guide will walk you through the Biology and Causes, the different Subtypes and Features, how to Build Your Care Team, and what to expect regarding Prognosis and Quality of Life.

What is Holoprosencephaly?

At its simplest, Holoprosencephaly is a condition where the brain does not divide into two separate halves as it should [1]. In a typical pregnancy, the forebrain (the front part of the brain) undergoes a process called cleavage, where it splits down the middle to create the left and right hemispheres [2].

In cases of HPE, this cleavage is incomplete or entirely absent [1]. Because the brain and face share the same early developmental pathways, this lack of division can also affect facial features, such as the eyes, nose, and upper lip [3].

Why and When Does This Happen?

HPE is a developmental event that occurs very early in pregnancy, typically during the first few weeks after conception [1][2].

  • Timing: The failure of the brain to divide happens during the first trimester, a period of rapid and complex embryonic growth. It happens long before the condition can actually be seen on a 12- or 20-week ultrasound [1].
  • The Cause: Science shows that HPE is caused by a complex mix of genetics and environmental factors [4][5]. It is often the result of changes in specific genes that guide brain development, such as the SHH pathway [6]. In many cases, these genetic changes are “de novo,” meaning they happened randomly and were not passed down from the parents [7].

How HPE is Diagnosed

Most families learn of an HPE diagnosis through high-resolution imaging:

  1. Prenatal Ultrasound: Many cases, especially more severe forms, are detected during routine ultrasounds in the first or second trimester [8][9]. Doctors look for the fusion of brain cavities or the absence of the midline structures that normally separate the two sides of the brain [10].
  2. Fetal MRI: If an ultrasound shows a potential concern, a Fetal MRI may be used to get a more detailed look at the brain’s anatomy and help confirm the diagnosis [11][12].
  3. Postnatal Evaluation: If the diagnosis is made after birth, doctors use a brain MRI or CT scan to evaluate the extent of the malformation and guide the baby’s care plan [13][14].

Three Stabilizing Facts for the Initial Shock

As you navigate these first days and weeks, keep these three truths close:

  • This is not your fault. HPE is a biological event that occurs extremely early in development [1]. It is not caused by anything you did or did not do, such as your diet, exercise, or routine activities during pregnancy [7][15].
  • HPE is a wide spectrum. No two children with HPE are exactly alike. The condition ranges from very severe (alobar) to much milder forms (lobar) [16]. While the diagnosis is serious, the impact on a child’s development varies significantly across this spectrum [17][14].
  • You are not alone. Although HPE is rare, there is a dedicated community of medical specialists, researchers, and other families who understand this journey [16][18]. Your medical team is there to provide the specific information and support your family needs to care for your child.

Frequently Asked Questions

What is holoprosencephaly (HPE)?
Holoprosencephaly is a condition where a baby's forebrain does not fully divide into two separate left and right halves during early pregnancy. Because the brain and face share early developmental pathways, this lack of division can also affect how facial features form.
When does holoprosencephaly happen during pregnancy?
The failure of the brain to divide happens very early in development, typically during the first few weeks after conception in the first trimester. This occurs long before the condition is visible on standard ultrasound scans.
Did I do something during pregnancy to cause my baby's HPE?
No. Holoprosencephaly is a biological event that occurs extremely early in development and is not your fault. It is caused by a complex mix of genetics and environmental factors, not by your diet, exercise, or routine activities during pregnancy.
How is holoprosencephaly diagnosed?
HPE is most often diagnosed before birth using high-resolution prenatal ultrasounds or a fetal MRI, which look for the fusion of brain cavities. If detected after birth, doctors will use a brain MRI or CT scan to evaluate the brain's anatomy.
Will my child's holoprosencephaly be severe?
HPE exists on a wide spectrum, and no two children are exactly alike. It ranges from very severe forms, known as alobar HPE, to much milder forms, known as lobar HPE. Because of this, the impact on development and quality of life varies significantly from child to child.

Questions for Your Doctor

  • • Based on the imaging, where does our child's diagnosis fall on the HPE spectrum?
  • • Was this diagnosis caused by a chromosomal issue (like Trisomy 13) or is it considered an isolated genetic event?
  • • What specific brain structures are involved or missing in this case?
  • • How does this diagnosis affect our birth plan and the immediate care our baby will receive after delivery?
  • • Can you refer us to a genetic counselor to help us understand the specific causes and future risks?

Questions for You

  • • What are the most pressing questions or fears I need to share with the medical team today?
  • • Who is in my 'inner circle' that I can rely on for emotional and practical support right now?
  • • Are there specific terms or explanations I've heard that I don't fully understand and need more clarity on?

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The Biology and Causes of HPE

References

  1. 1

    Disorders of Ventral Induction/Spectrum of Holoprosencephaly.

    Calloni SF, Caschera L, Triulzi FM

    Neuroimaging clinics of North America 2019; (29(3)):411-421 doi:10.1016/j.nic.2019.03.003.

    PMID: 31256862
  2. 2

    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
  3. 3

    Antenatal Ultrasonographic Diagnosis of a Constellation of Alobar Holoprosencephaly, Ethmocephaly, and Hydronephrosis in a Case of Early-Onset Intrauterine Growth Retardation: A Case Report.

    Ghanta PR, Phatak S, Bhansali PJ, et al.

    Cureus 2022; (14(7)):e27375 doi:10.7759/cureus.27375.

    PMID: 36046320
  4. 4

    Concepts in Multifactorial Etiology of Developmental Disorders: Gene-Gene and Gene-Environment Interactions in Holoprosencephaly.

    Lo HF, Hong M, Krauss RS

    Frontiers in cell and developmental biology 2021; (9()):795194 doi:10.3389/fcell.2021.795194.

    PMID: 35004690
  5. 5

    Are the prevalence of Trisomy 13 and the incidence of severe holoprosencephaly increasing in Africa?

    Okoye JO, Ngokere AA

    Prenatal diagnosis 2020; (40(12)):1616-1617 doi:10.1002/pd.5777.

    PMID: 32715507
  6. 6

    Prenatal exposure to pesticides and risk for holoprosencephaly: a case-control study.

    Addissie YA, Kruszka P, Troia A, et al.

    Environmental health : a global access science source 2020; (19(1)):65 doi:10.1186/s12940-020-00611-z.

    PMID: 32513280
  7. 7

    Semilobar Holoprosencephaly Caused by a Novel and De Novo ZIC2 Pathogenic Variant.

    Nonkulovski D, Sofijanova A, Spasovska T, et al.

    Balkan journal of medical genetics : BJMG 2023; (25(2)):71-76 doi:10.2478/bjmg-2022-0017.

    PMID: 37265970
  8. 8

    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
  9. 9

    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
  10. 10

    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
  11. 11

    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
  12. 12

    A rare case of bilateral proboscis lateralis: Prenatal US and MRI findings.

    Sarsmaz K, Lafci O, Cayonu Kahraman N, et al.

    Journal of clinical ultrasound : JCU 2021; (49(6)):632-635 doi:10.1002/jcu.22982.

    PMID: 33547639
  13. 13

    Antenatal and Postnatal Diagnosis of Semilobar Holoprosencephaly: Two Case Reports.

    Meryem B, Amine N, Houssein O, et al.

    Global pediatric health 2023; (10()):2333794X231156037 doi:10.1177/2333794X231156037.

    PMID: 36814536
  14. 14

    Congenital external hydrocephalus: A rare presentation of lobar holoprosencephaly in a neonate.

    Agrawal R, Raj N, Dhawan V, et al.

    Radiology case reports 2025; (20(5)):2323-2327 doi:10.1016/j.radcr.2025.01.080.

    PMID: 40129779
  15. 15

    Reply: Another case of holoprosencephaly associated with RAD21 loss-of-function variant.

    Kruszka P

    Brain : a journal of neurology 2020; (143(8)):e65 doi:10.1093/brain/awaa177.

    PMID: 32712652
  16. 16

    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
  17. 17

    Holoprosencephaly: Review of Embryology, Clinical Phenotypes, Etiology and Management.

    Malta M, AlMutiri R, Martin CS, Srour M

    Children (Basel, Switzerland) 2023; (10(4)) doi:10.3390/children10040647.

    PMID: 37189898
  18. 18

    Challenging issues arising in counseling families experiencing holoprosencephaly.

    Hadley DW, Kruszka P, Muenke M

    American journal of medical genetics. Part C, Seminars in medical genetics 2018; (178(2)):238-245 doi:10.1002/ajmg.c.31627.

    PMID: 30182441

This page provides general educational information about holoprosencephaly (HPE) for parents and caregivers. It does not replace professional medical advice; always consult your maternal-fetal medicine specialist, pediatric neurologist, or genetic counselor regarding your baby's specific diagnosis.

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