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PubMed This is a summary of 21 peer-reviewed journal articles Updated
Neonatology

Physical Features and Associated Conditions

At a Glance

Babies with alobar holoprosencephaly (HPE) often have distinct facial and physical differences because the brain fails to divide properly during early development. Common features include closely set eyes, cleft lip or palate, and sometimes issues with the heart, kidneys, or abdomen.

When a baby is diagnosed with alobar holoprosencephaly (HPE), the physical appearance of their face and body can be one of the most difficult aspects for parents to process.

There is a deep biological connection between the brain and the face. The same biological signals (like the Sonic Hedgehog (SHH) pathway) that tell the brain to divide into two halves also tell the facial bones and features where to grow [1][2]. When those signals are disrupted, the midline of the face reflects the same lack of division seen in the brain [3].

Understanding Facial Midline Differences

Because alobar HPE is the most severe form of the spectrum, the facial differences can be significant. Learning about these physical differences can be deeply shocking and emotionally overwhelming. Knowing these terms before seeing medical reports or imaging can help you prepare and protect you from being caught off guard.

  • Hypotelorism: This is the most common feature, where the eyes are set unusually close together [4][5].
  • Cyclopia: In this very severe and rare form, the eyes fail to separate at all, resulting in a single eye located in the middle of the face [6][7].
  • Proboscis: This is a small, tube-like structure (resembling a small trunk) that may appear on the face, often located above the eyes [7][6].
  • Ethmocephaly: A combination of eyes being extremely close together (hypotelorism) and the presence of a proboscis located between the eyes [8].
  • Cebocephaly: This features eyes that are very close together and a nose with a single, often “blind-ended” (not fully open) nostril [8][9].
  • Cleft Lip or Palate: Many babies with HPE will have a cleft (an opening) in the upper lip or the roof of the mouth, often right in the middle (a median cleft) [10][11].

Associated Body Anomalies

While the brain and face are the primary areas affected by HPE, other organs can also develop differently, especially if the cause is a chromosomal condition like Trisomy 13 [12][13].

Common Internal Findings

  • Heart Defects: Many babies have “holes” in the heart, such as ventricular septal defects (VSD) or atrioventricular canal defects [14][6].
  • Abdominal Issues: An omphalocele—where some of the abdominal organs (like the liver or intestines) stay outside the body in a sac at the base of the belly button—is sometimes seen [15][16].
  • Kidney Issues: This may include hydronephrosis (fluid buildup in the kidneys) or kidneys that are smaller than normal (renal hypoplasia) [14][17].

Other Physical Markers

  • Polydactyly: Having extra fingers or toes, which is a very strong indicator that the cause might be Trisomy 13 [16][18].
  • Clubfoot: A condition where the foot is turned inward or downward [10].
  • Aplasia Cutis Congenita: Small areas on the scalp where the skin did not fully form [18][19].

Focus on Compassion

Seeing these features for the first time can be a shock, and it is okay to feel a wide range of emotions—from grief to fear. These physical differences are simply the outward map of an early developmental event [3]. Your medical team’s role is to ensure your baby is comfortable and that you are supported in seeing your child for who they are, beyond their physical malformations [20][21].

Common questions in this guide

What facial differences are common in babies with alobar holoprosencephaly?
Because the brain and face are connected during development, babies with alobar HPE often have facial midline differences. These can include eyes set very close together, a median cleft lip, or more rarely, a single central eye or a small tube-like structure called a proboscis.
Will my baby with alobar HPE have issues with other organs?
Yes, it is possible for other organs to develop differently, especially if the condition is caused by a chromosomal difference like Trisomy 13. Common findings include heart defects, kidney issues, or an omphalocele, which affects the abdomen.
What does it mean if my baby has extra fingers or toes?
The presence of extra fingers or toes, known as polydactyly, is a physical marker often associated with certain genetic conditions. In babies with alobar HPE, polydactyly is a strong indicator that the underlying cause might be Trisomy 13.
How will a proboscis affect my baby's ability to breathe?
A proboscis is a tube-like structure that sometimes appears on the face above the eyes in severe cases of HPE. Your medical team will assess how this structure impacts your baby's airway and breathing, and will guide you on how to safely hold and care for your child to ensure their comfort.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.What do the facial features of my child tell us about the specific internal brain structure?
  2. 2.If a 'proboscis' is present, how will it affect my child's ability to breathe or be held?
  3. 3.Are there any heart, kidney, or abdominal issues (like omphalocele) that we need to be aware of?
  4. 4.Do my child's physical features, like polydactyly (extra fingers/toes), point specifically toward Trisomy 13?
  5. 5.How do these physical differences affect my child's comfort or our ability to care for them after birth?

Questions For You

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References

References (21)
  1. 1

    SHH signaling mediated by a prechordal and brain enhancer controls forebrain organization.

    Sagai T, Amano T, Maeno A, et al.

    Proceedings of the National Academy of Sciences of the United States of America 2019; (116(47)):23636-23642 doi:10.1073/pnas.1901732116.

    PMID: 31685615
  2. 2

    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
  3. 3

    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
  4. 4

    Ophthalmologic Findings in an Induced Model of Holoprosencephaly in Zebrafish.

    Bulk J, Kyrychenko V, Heermann S

    The Journal of comparative neurology 2025; (533(11)):e70113 doi:10.1002/cne.70113.

    PMID: 41207878
  5. 5

    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
  6. 6

    Fetal Cyclopia, Proboscis, Holoprosencephaly, and Polydactyly: A Case Report With Review of Literature.

    Kollu R, Kotamraju S, Uligada S, Varunya M

    Cureus 2023; (15(2)):e34576 doi:10.7759/cureus.34576.

    PMID: 36883090
  7. 7

    Cyclopia in a newborn rhesus macaque born to a dam infected with SIV and receiving antiretroviral therapy during pregnancy.

    Doyle-Meyers L, Dong C, Xu EQ, et al.

    Current trends in immunology 2023; (24()):91-103.

    PMID: 39640529
  8. 8

    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
  9. 9

    Rare manifestations of alobar holoprosencephaly and the potential causes: a report of two cases.

    Nakawa W, Alkhalil S, Martini N, Alawad I

    Annals of medicine and surgery (2012) 2023; (85(2)):252-256 doi:10.1097/MS9.0000000000000176.

    PMID: 36845789
  10. 10

    Alobar Holoprosencephaly Associated with Meningomyelocoele and Omphalocoele: An Unusual Coexistence.

    Waghmare TP, Sathe PA, Goel NA, Kandalkar BM

    Journal of clinical and diagnostic research : JCDR 2016; (10(11)):ED23-ED24 doi:10.7860/JCDR/2016/22453.8932.

    PMID: 28050387
  11. 11

    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
  12. 12

    Sonography of fetal holoprosencephaly: a guide to recognize the lesser varieties.

    Montaguti E, Cariello L, Brunelli E, 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 2022; (35(25)):9717-9723 doi:10.1080/14767058.2022.2050900.

    PMID: 35272544
  13. 13

    Impact of holoprosencephaly, exomphalos, megacystis and increased nuchal translucency on first-trimester screening for chromosomal abnormalities.

    Syngelaki A, Guerra L, Ceccacci I, et al.

    Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology 2017; (50(1)):45-48 doi:10.1002/uog.17286.

    PMID: 27558969
  14. 14

    The Role of Antenatal Ultrasound Scans in the Early Detection of Alobar Holoprosencephaly: A Case Report.

    Mohamed ME, Ahmed SR, Elsayed Ahmed EM, Ibrahim EH

    Cureus 2024; (16(10)):e70843 doi:10.7759/cureus.70843.

    PMID: 39493208
  15. 15

    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
  16. 16

    Application of quantitative fluorescent polymerase chain reaction analysis for the rapid confirmation of trisomy 13 of maternal origin in a pregnancy with fetal holoprosencephaly, cyclopia, polydactyly, omphalocele and cell culture failure.

    Chen CP, Wang LK, Chern SR, et al.

    Taiwanese journal of obstetrics & gynecology 2022; (61(1)):135-137 doi:10.1016/j.tjog.2021.11.022.

    PMID: 35181024
  17. 17

    13q Deletion Syndrome Presenting with Lymphopenia Detected Through Newborn Screening for Primary Immunodeficiencies.

    Efimova I, Mukhina A, Markova Z, et al.

    International journal of molecular sciences 2025; (26(19)) doi:10.3390/ijms26199302.

    PMID: 41096571
  18. 18

    Trisomy 13 With Bilateral Congenital Anophthalmia: A Case Report.

    Bahari H, Hajaj H, Ayyad A, et al.

    Cureus 2024; (16(5)):e60264 doi:10.7759/cureus.60264.

    PMID: 38872687
  19. 19

    Multiple Aplasia Cutis Congenita Lesions of the Scalp: A Case Study.

    Whalen M

    Neonatal network : NN 2020; (39(2)):83-91 doi:10.1891/0730-0832.39.2.83.

    PMID: 32317338
  20. 20

    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
  21. 21

    Surgical outcomes in children with Trisomy 13: An ACS NSQIP - Pediatric review.

    Cook BH, Choi PM, Lucas DJ

    Journal of pediatric surgery 2023; (58(3)):384-388 doi:10.1016/j.jpedsurg.2022.08.010.

    PMID: 36008197

This page provides educational information about the physical features associated with alobar holoprosencephaly. It is not a substitute for professional medical advice, diagnosis, or counseling from your maternal-fetal medicine specialist or neonatologist.

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