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[General pathology](https://durgical.com/en/general-pathology/) · [Genetic disease](https://durgical.com/en/general-pathology/#a-genetic)

# Genomic imprinting: Prader–Willi and Angelman

- Mechanism

Some genes work only when they come from the father and others only from the mother; losing the active copy causes disease even if the other is intact.

Updated 2026-11-01

## Key points

- Prader-Willi: the paternal 15q11-q13 contribution is missing; paternal deletion in about 70%, maternal uniparental disomy in about 25%.
- Angelman: the maternal UBE3A gene, the only active copy in neurons, is missing; maternal deletion in about 70% and, less often, paternal disomy or a UBE3A mutation.
- Uniparental disomy means inheriting both chromosomes of a pair from the same parent.
- Methylation testing of 15q11-q13 detects all three Prader-Willi mechanisms; FISH detects only the deletion.
- Beckwith-Wiedemann (11p15): IGF2 overexpression, macrosomia, macroglossia, omphalocele, neonatal hypoglycaemia and a risk of Wilms tumour and hepatoblastoma.

## What it is

Imprinting is an epigenetic mark, mainly DNA methylation, laid down in the gametes according to the parent's sex, which silences one allele in the child. At 15q11-q13, losing the paternal contribution causes Prader-Willi syndrome and losing the maternal one causes Angelman syndrome: the same deletion, opposite pictures.

## Step by step

- During gamete formation old marks are erased and new ones set according to the parent's sex.
- At 15q11-q13 the maternal chromosome silences the Prader-Willi genes (such as SNRPN) by methylation.
- In neurons, the paternal chromosome silences UBE3A; only the maternal copy works.
- If the paternal region is lost (deletion, maternal disomy or imprinting defect), no Prader-Willi genes are active.
- If the maternal region or maternal UBE3A is lost, neurons have no UBE3A: Angelman syndrome.
- The marks persist in the child and are reset again in the child's own germ line.

## Prader-Willi versus Angelman

| Feature | Prader-Willi | Angelman |
| --- | --- | --- |
| Missing contribution | Paternal 15q11-q13 | Maternal (UBE3A gene) |
| Mechanisms | Paternal deletion, maternal disomy, imprinting defect | Maternal deletion, paternal disomy, UBE3A mutation, imprinting defect |
| Newborn | Marked hypotonia and weak suck | Usually looks normal at birth |
| Childhood and adulthood | Hyperphagia and obesity, short stature, small hands and feet, hypogonadism, mild to moderate intellectual disability | Severe intellectual disability, absent speech, ataxic gait, seizures, frequent laughter, microcephaly |

## Clinical notes

- In Prader-Willi, obesity from hyperphagia is the main source of complications; controlling access to food is central.
- In Beckwith-Wiedemann, regular abdominal ultrasound is used to watch for embryonal tumours in childhood.

## Memory aid

Prader-Willi: Pa's piece is gone; Angelman: Ma's piece is gone, and the little angel laughs without words.

## Test yourself

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

## What happens if a child inherits both chromosomes 15 from the mother?

Maternal uniparental disomy: no active paternal Prader-Willi genes, so the child develops Prader-Willi syndrome.

## Which gene explains most of the neurological picture of Angelman syndrome?

UBE3A, which in neurons is expressed only from the maternal chromosome.

## Which test detects deletion, disomy and imprinting defect in Prader-Willi?

DNA methylation analysis of the 15q11-q13 region.

## Which tumours are screened for in Beckwith-Wiedemann syndrome?

Wilms tumour and hepatoblastoma, especially in the first years of life.

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## Related

- [Nonclassic inheritance: repeat expansions, mitochondrial genes, imprinting, mosaicism](https://durgical.com/en/general-pathology/nonclassic-inheritance-repeat-expansions-mitochondrial-genes-imprinting-mosaicis/)
- [Chromosome abnormalities: number and structure](https://durgical.com/en/general-pathology/chromosome-abnormalities-number-and-structure/)
- [Tumours of infancy and childhood](https://durgical.com/en/general-pathology/tumours-of-infancy-and-childhood/)

## Related conditions

- [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/)
- [Wilms tumour (nephroblastoma)](https://durgical.com/en/conditions/wilms-tumour/)
- [Obesity](https://durgical.com/en/conditions/obesity/)
- [Neonatal hypoglycaemia (including infant of a diabetic mother)](https://durgical.com/en/conditions/neonatal-hypoglycaemia/)
- [Male hypogonadism](https://durgical.com/en/conditions/male-hypogonadism/)

## Elsewhere in DurgiPedia

- [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/)
- [FISH (fluorescence in situ hybridization)](https://durgical.com/en/biochemistry/topics/fish/)

[← All of general pathology](https://durgical.com/en/general-pathology/)

Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.

Sources: [What are genomic imprinting and uniparental disomy?: MedlinePlus Genetics](https://medlineplus.gov/genetics/understanding/inheritance/updimprinting/) (MedlinePlus, US National Library of Medicine, 2026); [Prader-Willi syndrome: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/prader-willi-syndrome/) (MedlinePlus, US National Library of Medicine, 2026); [Angelman syndrome: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/angelman-syndrome/) (MedlinePlus, US National Library of Medicine, 2026); [Beckwith-Wiedemann syndrome: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/beckwith-wiedemann-syndrome/) (MedlinePlus, US National Library of Medicine, 2026).

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Representative model, for educational purposes only.

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/genomic-imprinting-prader-willi-and-angelman/