[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Biochemistry](https://durgical.com/en/biochemistry/) › Epigenetic disorders, environment and methylation testing

# Epigenetic disorders, environment and methylation testing

Diseases can come from faulty epigenetic marks or from genes that write and read them; methylation tests now diagnose many of them.

Updated Nov 13, 2026

## Key facts

- Imprinting disorders arise from deletions, uniparental disomy or imprinting-centre defects: Prader–Willi, Angelman, Beckwith–Wiedemann and Silver–Russell syndromes.
- Disorders of the epigenetic machinery («chromatinopathies») come from variants in genes that methylate DNA or modify histones: Rett (MECP2), Kabuki (KMT2D), Sotos (NSD1), CHARGE (CHD7).
- Repeat expansions can silence a gene by methylation: in fragile X syndrome the expanded FMR1 promoter is methylated and the gene switched off.
- Methylation tests at an imprinted locus detect deletion, uniparental disomy and imprinting defects together; for Prader–Willi syndrome they find almost all cases.
- Episignatures are genome-wide methylation patterns typical of many chromatinopathies; they confirm a diagnosis and help reclassify uncertain variants.

## In detail

- Environment and epigenome: famine, maternal diabetes and smoking in pregnancy leave methylation changes associated with later metabolic and cardiovascular risk, the idea behind the developmental origins of health and disease.
- Skewed X inactivation can make a carrier woman show an X-linked disease.
- In cancer, promoter methylation silences tumour suppressors: MLH1 methylation explains most sporadic colorectal cancers with mismatch-repair loss (and argues against Lynch syndrome), and MGMT methylation predicts response to temozolomide in glioblastoma.
- Drugs that change epigenetic marks are used in cancer (DNA methyltransferase and histone deacetylase inhibitors); trofinetide is approved for Rett syndrome, and gene therapies are in trials.

**Also called**
Chromatinopathies and imprinting disorders, Episignatures

## Clinical notes

- A child with hypotonia, feeding difficulty in infancy and later hyperphagia should have a methylation test of 15q11–q13.
- In a colorectal tumour with loss of MLH1, testing MLH1 promoter methylation (or BRAF) helps decide whether germline testing for Lynch syndrome is needed.

## Test yourself

Think of the answer, then tap the question to see it.

## Why is a methylation test the first test for suspected Prader–Willi syndrome?

It detects all three main causes, deletion, maternal uniparental disomy and imprinting defects, in one test.

## What is an episignature?

A genome-wide DNA methylation pattern typical of a specific disorder of the epigenetic machinery, used to confirm a diagnosis or classify a variant.

## What does MLH1 promoter methylation in a colorectal cancer suggest?

A sporadic tumour with silenced MLH1, rather than Lynch syndrome.

[Add to my cards (3)](https://durgical.app/estudiar/?add=/en/biochemistry/topics/epigenetic-disorders-environment-and-methylation-testing/)

## Connections

## Related conditions 5

- [Rett syndrome](https://durgical.com/en/conditions/rett-syndrome/)
- [Prader–Willi and Angelman syndromes (imprinting)](https://durgical.com/en/conditions/prader-willi-and-angelman-syndromes/)
- [Beckwith–Wiedemann syndrome](https://durgical.com/en/conditions/beckwith-wiedemann-syndrome/)
- [Fragile X syndrome](https://durgical.com/en/conditions/fragile-x-syndrome/)
- [Lynch syndrome (hereditary non-polyposis colorectal cancer)](https://durgical.com/en/conditions/lynch-syndrome/)

## Related 4

- [Epigenetics: DNA and histone methylation](https://durgical.com/en/biochemistry/topics/epigenetics-dna-and-histone-methylation/)
- [5-Methylcytosine](https://durgical.com/en/biochemistry/molecules/5-methylcytosine/)
- [Control of gene expression in human cells](https://durgical.com/en/biochemistry/topics/control-of-gene-expression-in-human-cells/)
- [Genetic tests: what each one finds](https://durgical.com/en/biochemistry/topics/genetic-tests-what-each-one-finds/)

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

Sources: [What is epigenetics?: MedlinePlus Genetics](https://medlineplus.gov/genetics/understanding/howgeneswork/epigenome/) (MedlinePlus, US National Library of Medicine, 2026); [What are genomic imprinting and uniparental disomy?: MedlinePlus Genetics](https://medlineplus.gov/genetics/understanding/inheritance/updimprinting/) (MedlinePlus, US National Library of Medicine, 2026); [Epigenetics](https://www.genome.gov/genetics-glossary/Epigenetics) (National Human Genome Research Institute (NHGRI), 2026); [Methylation](https://www.genome.gov/genetics-glossary/Methylation) (National Human Genome Research Institute (NHGRI), 2026).

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

## **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/biochemistry/topics/epigenetic-disorders-environment-and-methylation-testing/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/biochemistry/topics/epigenetic-disorders-environment-and-methylation-testing/