biology

Smith–Lemli–Opitz syndrome

Smith–Lemli–Opitz syndrome is a biology topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Smith–Lemli–Opitz syndrome rather than just read about it. In short: Smith–Lemli–Opitz syndrome is an inborn error of cholesterol synthesis. It is an autosomal recessive, multiple malformation syndrome caused by a mutation in the enzyme 7-Dehydrocholesterol reductase encoded by the DHCR7 gene.

Key takeaways

Smith–Lemli–Opitz syndrome belongs to biology; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Smith–Lemli–Opitz syndrome to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Smith–Lemli–Opitz syndrome from memory before moving on to harder problems.

Reference excerpt

Smith–Lemli–Opitz syndrome is an inborn error of cholesterol synthesis. It is an autosomal recessive, multiple malformation syndrome caused by a mutation in the enzyme 7-Dehydrocholesterol reductase encoded by the DHCR7 gene. It causes a broad spectrum of effects, ranging from mild intellectual disability and behavioural problems to lethal malformations.

Signs and symptoms SLOS can present itself differently in different cases, depending on the severity of the mutation and other factors. Originally, SLOS patients were classified into two categories (classic and severe) based on physical and mental characteristics, alongside other clinical features. Since the discovery of the specific biochemical defect responsible for SLOS, patients are given a severity score based on their levels of cerebral, ocular, oral, and genital defects. It is then used to classify patients as having mild, classical, or severe SLOS.

Physical characteristics

The most common facial features of SLOS include microcephaly, bitemporal narrowing (reduced distance between temples), ptosis, a short and upturned nose, micrognathia, epicanthal folds, and capillary hemangioma of the nose. Other physical characteristics include:

low-set and posteriorly rotated ears high-arched, narrow, hard palate cleft lip/palate agenesis or hypoplasia of the corpus callosum cerebellar hypoplasia increased ventricular size decreased frontal lobe size polydactyly of hands or feet short, proximally placed thumb other finger malformations syndactyly of second and third toes ambiguous or female-like male genitalia congenital heart defects renal, pulmonary, liver and eye abnormalities

Behavioural characteristics Certain behaviours and attributes are commonly seen among patients with SLOS. They may have low normal intelligence, and react negatively or with hypersensitivity to different sensory stimuli. This is particularly true for certain auditory and visual stimuli. Many patients show aggressiveness and self-injurious behaviours, and sleep disturbances are common. Specific behaviours resembling those of people with autism are often present as well as hyperactivity, which provides genetic and biological insights into autism spectrum disorders. The autistic behaviours most characteristic of SLOS patients are opisthokinesis (an upper body movement), stretching of the upper body, and hand flicking. Autism is typically diagnosed separately from SLOS using the DSM-V, and approximately 50–75% of SLOS patients meet the criteria for autism. Other behaviours associated with SLOS can be linked directly to physical abnormalities. For example, infants often show feeding problems or feeding intolerance, and patients may require increased caloric intake due to accelerated metabolism. Recurrent infections, including ear infections and pneumonia, are also common.

Biochemical phenotype Given that SLOS is caused by a mutation in an enzyme involved in cholesterol synthesis, the resulting biochemical characteristics may be predictable. Most patients have lowered plasma cholesterol levels (hypocholesterolemia). However, approximately 10% may show normal cholesterol levels, and decreased concentrations of cholesterol are not solely indicative of SLOS. Increased levels of cholesterol precursors are also common in SLOS. In particular, elevated levels of 7-dehydrocholesterol are fairly specific to SLOS.

Genetics

DHCR7

The gene encoding DHCR7 (labeled as DHCR7) was cloned in 1998, and has been mapped to chromosome 11q12–13. It is 14100 base pairs of DNA in length, and contains nine exons, the corresponding mRNA is 2786 base pairs in length (the remaining DNA sequence is intronic). The structure of the DHCR7 rat gene is very similar to the structure of the human gene. The highest levels of DHCR7 expression have been detected in the adrenal gland, the testis, the liver and in brain tissue. Its expression is induced by decreased sterol concentrations via sterol regulatory binding proteins (SREBP). There is also evidence that its activity may be regulated by tissue specific transcription, and alternative splicing. As outlined above, the enzyme DHCR7 catalyzes the reduction of 7DHC to cholesterol, as well as the reduction of 7-dehydrodesmosterol to desmosterol. It requires NADPH as a cofactor for this reduction, and may involve the activity of cytochrome-P450 oxidoreductase. It is also thought to contain iron. DHCR7 is an integral membrane protein of the endoplasmic reticulum, and computer models have predicted up to nine transmembrane domains. DHCR7 is most efficient at reducing 7DHC, but it is known to reduce the carbon 7 double bond of other sterols, indicating a range of substrate specificity. The human version of this enzyme is predicted to have a molecular weight of 54,489 kDa, and an isoelectric point of 9.05. The amino acid sequence that encodes DHCR7 is predicted to contain 475 amino acids, as well as several protein motifs. It contains multiple sterol reductase motifs, as would be expected given its function. It contains a potential sterol-sensing domain (SSD), whose function is unknown but thought to be necessary for binding sterol substrates. It also includes multiple sites of phosphorylation, including potential protein kinase C and tyrosine kinase sites (regulatory enzymes responsible for phosphorylation). The exact function of phosphorylating DHCR7 is yet unknown, but it is thought to be involved in the regulation of its activity.

Mutations and incidence

… excerpt ends here. Continue reading the full article.

Illustrations

Smith–Lemli–Opitz syndrome: Missense mutations account for 87.6% of the SLOS spectrum. — Missense mutations account for 87.6% of the SLOS spectrum.

Worked examples

Example 1 — a first encounter with Smith–Lemli–Opitz syndrome

Start with the simplest possible case. Write down what Smith–Lemli–Opitz syndrome claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In biology, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Smith–Lemli–Opitz syndrome before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Smith–Lemli–Opitz syndrome ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Smith–Lemli–Opitz syndrome

In research: Smith–Lemli–Opitz syndrome appears in biology research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Smith–Lemli–Opitz syndrome in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Smith–Lemli–Opitz syndrome is common in secondary-school and first-year university syllabi. It links to neighbouring topics Autosomal recessive disorders, Cholesterol and steroid metabolism disorders, Genodermatoses, so understanding it makes those chapters shorter.
In everyday life: Look for Smith–Lemli–Opitz syndrome outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

Ask Teacher Smith questions about this articleOpens your AI tutor with a question about “Smith–Lemli–Opitz syndrome” →

Affiliate

Preply — study more efficiently by working with a personal tutor. 50% off.

How to study Smith–Lemli–Opitz syndrome in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Smith–Lemli–Opitz syndrome means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Smith–Lemli–Opitz syndrome out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Smith–Lemli–Opitz syndrome in simple terms?

Why does Smith–Lemli–Opitz syndrome matter?

Because it connects several biology ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Smith–Lemli–Opitz syndrome?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Smith–Lemli–Opitz syndrome.