Holoprosencephaly
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| Brain | Face | Clinical Findings |
| Alobar HP | Cyclopia | Median single or fused eyes; may have no eye; proboscis present or absent |
| Alobar HP | Ethmocephaly | Rarest facial type; severe ocular hypotelorism with proboscis |
| Generallyalobar HP | Cebocephaly | Ocular hypotelorism and blind-ended, single nostril nose |
| Generallyalobar HP | Median cleft lip | Ocular hypotelorism, flat nose, median cleft lip |
| Semilobar or lobar HP | Mild dysmorphism | Spectrum of milder abnormalities, including ocular hypotelorism, flattened midface and nose, unilateral or bilateral cleft lip, iris coloboma, single central incisor. Could also appear normal. |
Alobar HP - Cyclopia
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Drugs and Substances Implicated in Holoprosencephaly:
1. Alcohol
- Fetal
Alcohol Syndrome (FAS) is a known risk factor.
- Ethanol
disrupts the Sonic Hedgehog (SHH) signaling pathway, crucial for
forebrain and midline development.
2. Retinoic Acid (Vitamin A Derivatives)
- Example:
Isotretinoin (Accutane), used for severe acne.
- Strong
teratogen; interferes with neural tube development and SHH pathway.
- High
risk of midline defects, including HPE, micrognathia, and cardiac
anomalies.
3. Anticonvulsants
- Especially
valproic acid (valproate):
- Increases
risk of neural tube defects and possibly HPE.
- Teratogenic
effects are dose-dependent.
- Mechanism:
Histone deacetylase (HDAC) inhibition and interference with folate
metabolism.
4. Cholesterol-lowering drugs
- Statins:
Disrupt cholesterol synthesis, which is essential for SHH protein
activation.
- SHH
must be modified by cholesterol for proper signaling.
- Experimental
data suggest potential for HPE, though human evidence is limited.
5. Maternal Diabetes (not a drug, but relevant)
- Hyperglycemia
in early gestation increases oxidative stress and apoptosis in the neural
plate.
- Strongly
associated with HPE and other neural tube defects.
Snapshot
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