[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Embryology](https://durgical.com/en/embryology/) › [Nervous system and senses](https://durgical.com/en/embryology/#a-nervous) › Holoprosencephaly [Embryology](https://durgical.com/en/embryology/) · [Nervous system and senses](https://durgical.com/en/embryology/#a-nervous) # Holoprosencephaly - Malformation The forebrain does not divide properly into two halves; the midline of the face is affected too, from a single eye to a single central incisor. Updated 2026-11-01 **See it in 3D:** [Lateral ventricles](https://durgical.com/en/anatomy/lateral-ventricle/) · [Thalamus](https://durgical.com/en/anatomy/thalamus/) · [Corpus callosum](https://durgical.com/en/anatomy/corpus-callosum/) · [Frontal lobe](https://durgical.com/en/anatomy/superior-frontal-gyrus/) ## Key points - Failure of forebrain division, linked to SHH. - Trisomy 13 is the classic associated chromosomal disorder. - Smith–Lemli–Opitz: not enough cholesterol for SHH signalling. - Cyclopia in the severe form; single central incisor in the microform. - Maternal diabetes and alcohol are risk factors. ## What it is Holoprosencephaly is failure of the prosencephalon to divide into two cerebral hemispheres. It is a spectrum: the alobar form has a single ventricle and severe facial defects; mild forms show only subtle facial features. It is the classic example of failed midline SHH signalling and of 'the face predicting the brain'. ## Key facts - Types, from most to least severe: alobar, semilobar, lobar and middle interhemispheric variant. - Frequency: about 1 in 10,000 newborns; far more common in early miscarriages. - Genes: SHH, ZIC2, SIX3 and TGIF1 account for about a quarter of nonsyndromic cases. - Syndromic causes: trisomy 13 and Smith–Lemli–Opitz syndrome (a cholesterol defect). - Associated teratogens: maternal diabetes and alcohol. - Face: cyclopia with a proboscis, hypotelorism, median cleft lip, single central incisor. ## Embryological cause - Weeks 4–5: the prosencephalon must divide into telencephalon and diencephalon, and the telencephalon into two hemispheres. - The prechordal plate secretes SHH, which sets up the ventral midline of the forebrain and splits the single eye field in two. - If SHH fails (mutation, low cholesterol that blocks its action, alcohol), the midline does not form: fused hemispheres and a single ventricle. - The same midline deficit affects the frontonasal prominence: close-set or fused eyes, defective nose and median lip. ## Markers - SHH - ZIC2 - SIX3 - TGIF1 - PTCH1 - GLI2 ## How it presents - Alobar: single ventricle, fused thalami, cyclopia or ethmocephaly; usually lethal. - Less severe forms: microcephaly, hypotelorism, median cleft lip and palate, flat nose. - Developmental delay and intellectual disability in most. - Pituitary dysfunction, especially diabetes insipidus; seizures, feeding and temperature-control problems. - Microform: single upper central incisor, sometimes with no visible brain findings. ## Diagnosis - Prenatal ultrasound: single ventricle, absent midline, facial findings. - Brain MRI to classify the type. - Karyotype or microarray (trisomy 13) and genetic testing; sterols if Smith–Lemli–Opitz is suspected. ## Memory aid 'Holo' means all in one piece: without SHH nobody draws the midline, so brain, eyes and lip stay fused. ## Test yourself Think of the answer, then tap the question to see it. ## Which prechordal plate signal typically fails in holoprosencephaly? Sonic hedgehog (SHH), which sets up the forebrain midline. ## Which trisomy is classically associated with holoprosencephaly? Trisomy 13 (Patau syndrome). ## Why can Smith–Lemli–Opitz syndrome cause holoprosencephaly? Because of a lack of cholesterol, which SHH signalling needs to work. ## What minimal finding may be the only clue to a mild form? A single upper central incisor. [Add to my cards (4)](https://durgical.app/estudiar/?add=/en/embryology/holoprosencephaly/) ## See it in 3D The structures of Durgical's 3D anatomy where it is found. - [Lateral ventricles](https://durgical.com/en/anatomy/lateral-ventricle/) - [Thalamus](https://durgical.com/en/anatomy/thalamus/) - [Corpus callosum](https://durgical.com/en/anatomy/corpus-callosum/) - [Frontal lobe](https://durgical.com/en/anatomy/superior-frontal-gyrus/) ## Related - [Brain vesicles: from three to five and what each becomes](https://durgical.com/en/embryology/brain-vesicles-from-three-to-five-and-what-each-becomes/) - [Molecular regulation: Shh, Wnt, FGF, BMP, Hox genes and retinoic acid](https://durgical.com/en/embryology/molecular-regulation-shh-wnt-fgf-bmp-hox-genes-and-retinoic-acid/) - [The face: five prominences](https://durgical.com/en/embryology/the-face-five-prominences/) - [Eye: optic vesicle, optic cup and lens](https://durgical.com/en/embryology/eye-optic-vesicle-optic-cup-and-lens/) - [Pituitary gland: Rathke pouch and the neurohypophysis](https://durgical.com/en/embryology/pituitary-gland-rathke-pouch-and-the-neurohypophysis/) - [Alcohol: fetal alcohol spectrum disorder](https://durgical.com/en/embryology/alcohol-fetal-alcohol-spectrum-disorder/) - [Maternal diabetes and obesity as teratogens](https://durgical.com/en/embryology/maternal-diabetes-and-obesity-as-teratogens/) - [Meiosis and nondisjunction: where trisomies come from](https://durgical.com/en/embryology/meiosis-and-nondisjunction-where-trisomies-come-from/) ## Related conditions - [Diabetes insipidus (central and nephrogenic)](https://durgical.com/en/conditions/diabetes-insipidus/) - [Cleft lip and palate](https://durgical.com/en/conditions/cleft-lip-and-palate/) [← All of embryology](https://durgical.com/en/embryology/) Educational content on embryonic development; not a guide to prenatal diagnosis or to medicines in pregnancy and no substitute for a health professional's advice. No doses are given. Sources: [Nonsyndromic holoprosencephaly: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/nonsyndromic-holoprosencephaly/) (U.S. National Library of Medicine, 2024); Langman's Medical Embryology, 13th ed., ch. 18: Central Nervous System (Wolters Kluwer, 2015). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/embryology/holoprosencephaly/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/embryology/holoprosencephaly/