[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Conditions](https://durgical.com/en/conditions/) › Smith–Lemli–Opitz syndrome

[Conditions](https://durgical.com/en/conditions/) · [Metabolism: cholesterol and lipoproteins](https://durgical.com/en/conditions/)

# 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.

- [Frontal lobe](https://durgical.com/en/anatomy/superior-frontal-gyrus/)
- [Second toe](https://durgical.com/en/anatomy/second-toe/)
- [Third toe](https://durgical.com/en/anatomy/third-toe/)
- [Corpus callosum](https://durgical.com/en/anatomy/corpus-callosum/)
- [Soft palate](https://durgical.com/en/anatomy/soft-palate/)
- [Spongy urethra](https://durgical.com/en/anatomy/spongy-urethra/)

## In biochemistry

- [Cholesterol synthesis: Step 12 · 7-Dehydrocholesterol reductase (DHCR7)](https://durgical.com/en/biochemistry/pathways/cholesterol-synthesis/#paso-12)

## 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

## Red flags

- Newborn with multiple malformations and poor feeding
- Signs of adrenal insufficiency
- Low maternal oestriol on prenatal screening

## 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.

[Add to my cards (4)](https://durgical.app/estudiar/?add=/en/conditions/smith-lemli-opitz-syndrome/)

## Related conditions

- [Hypospadias](https://durgical.com/en/conditions/hypospadias/)
- [Adrenal insufficiency](https://durgical.com/en/conditions/adrenal-insufficiency/)

Educational information, not medical advice. For any symptom, see a health professional.

Sources: [Smith-Lemli-Opitz syndrome: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/smith-lemli-opitz-syndrome/) (MedlinePlus, US National Library of Medicine, 2026); [DHCR7 gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/dhcr7/) (MedlinePlus, US National Library of Medicine, 2026).

[← All conditions](https://durgical.com/en/conditions/)

## **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/conditions/smith-lemli-opitz-syndrome/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/conditions/smith-lemli-opitz-syndrome/