Conditions · Metabolism: cholesterol and lipoproteins
Smith–Lemli–Opitz syndrome !
An inherited disorder in which the last step of cholesterol synthesis fails; it causes malformations, intellectual disability and behaviour problems.
Updated 2026-11-01
Structures involved
Tap one to see what it is and open it in 3D.
In biochemistry
What it is
An autosomal recessive disorder caused by 7-dehydrocholesterol reductase (DHCR7) deficiency: the body makes little cholesterol and accumulates 7-dehydrocholesterol.
Who gets it
It is estimated at 1 in 20,000 to 60,000 newborns and is more common in people of European ancestry. No figures are published for Colombia.
Causes
- Two DHCR7 gene variants
- Autosomal recessive inheritance
Risk factors
- Carrier parents
- An affected sibling (25% risk in each pregnancy)
Pathophysiology
The embryo needs cholesterol to build membranes and myelin and to activate Sonic hedgehog signalling, which shapes the face, brain and limbs. With little cholesterol and excess 7-dehydrocholesterol (and its toxic oxysterols) these processes go wrong. The placenta supplies little maternal cholesterol, so malformations occur even when the mother is healthy.
Classification
- Mild: subtle features and learning or behaviour problems
- Classic
- Severe: multiple malformations, sometimes lethal
Symptoms and signs
- Microcephaly and intellectual disability
- Syndactyly of the 2nd and 3rd toes (a very typical sign)
- Cleft palate and distinctive facial features (ptosis, small upturned nose)
- Ambiguous genitalia or hypospadias in boys
- Feeding difficulty, hypotonia and poor growth
- Autistic features, self-injury and photosensitivity
Diagnosis
- Clinical
- A combination of microcephaly, 2–3 toe syndactyly, cleft palate, genital anomalies and developmental delay.
- Tests
- High plasma 7-dehydrocholesterol with low or normal cholesterol (gas chromatography–mass spectrometry) and DHCR7 genetic testing; before birth, low maternal oestriol and 7-dehydrocholesterol in amniotic fluid.
- Imaging
- Prenatal ultrasound (malformations, growth restriction); brain MRI and echocardiography for brain and heart malformations.
Treatment
- Medical
- Dietary cholesterol and, in some cases and under study, statins to lower 7-dehydrocholesterol
- Rehabilitation
- Developmental, speech and feeding therapy
- Surgical
- Repair of cleft palate and genital or heart malformations
- Follow-up
- Monitoring of adrenal function, growth and behaviour; sun protection
Complications
- Intellectual disability
- Congenital heart disease
- Adrenal insufficiency
- Early death in severe forms
Prognosis
Highly variable: mild forms reach adulthood; severe forms can be fatal in the first months.
Test yourself
Think of the answer, then tap the question to see it.
Which enzyme is missing in Smith–Lemli–Opitz syndrome?
7-Dehydrocholesterol reductase (DHCR7), the last step of cholesterol synthesis.
Which molecule is high in blood and confirms the diagnosis?
7-Dehydrocholesterol, with low or normal cholesterol.
Which foot finding is very typical?
Syndactyly of the second and third toes.
Why does a healthy mother not make up for the fetus's lack of cholesterol?
The placenta passes little maternal cholesterol; the embryo depends mainly on its own synthesis.
Related conditions
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Smith-Lemli-Opitz syndrome: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); DHCR7 gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026).
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.
