Last updated 2mo ago
A newborn male has 2-3 toe syndactyly, ambiguous genitalia (undervirilization), microcephaly, and cleft palate. 7-dehydrocholesterol is markedly elevated.
AR; DHCR7 (7-dehydrocholesterol reductase)
- Final step of cholesterol biosynthesis
- 2-3 toe syndactyly (highly characteristic)
- Microcephaly, intellectual disability
- Genital anomalies (males - hypospadias to female external genitalia)
- Cleft palate, micrognathia
- Ptosis, anteverted nares
- Congenital heart defects
- Behavioral problems (autism, self-injury)
- Elevated 7-dehydrocholesterol (7-DHC); low cholesterol
- Cholesterol supplementation (limited efficacy)
"SLOppy Joes are full of Cholesterol": SLOS is a cholesterol synthesis defect. DHCR7 catalyzes the last step: 7-dehydrocholesterol to cholesterol.
Patients are "SLLOW.": Short stature, Limb defects (polydactyly/syndactyly, proximal thumb), Learning disability + microcephaly, Openings issues (hypospadias, cleft palate), W looks like 2 digits (extra or fused toes, i.e. 2-3 syndactyly).
Sonic hedgehog is fast, the opposite of "SLO": cholesterol is essential for hedgehog signaling (sonic hedgehog mediates midline development, explaining holoprosencephaly and midline defects in severe cases).