Genetics · MU Sofia

44. Syndromes caused by imprinting disorders: Prader-Willi syndrome and Angelman syndrome.

Explains genomic imprinting, the parent-of-origin silencing of one allele, and how the same 15q11–q13 region gives two different syndromes. Prader–Willi syndrome is covered first, with its paternal-loss mechanisms, pathophysiology, clinical stages, diagnosis and management, followed by Angelman syndrome, with maternal loss of UBE3A. Mechanism frequency tables for each syndrome are included.

Inside: 16 sections · 5 labelled pictures · 3 tables · 16 flashcards · 3 min

Topic 44 of 65 in the MU Sofia syllabus for Genetics (Medicine, Year 3). The free AceMed note covers it in 11 sections, about 386 words (3 min of reading), with 16 flashcards.

In this note

  1. Syndromes caused by imprinting disorders: Prader-Willi syndrome and Angelman syndrome.
  2. Key Concepts in Imprinting Disorders
  3. I. PRADER–WILLI SYNDROME (PWS)
  4. Genetic and Molecular Basis
  5. Mechanisms Causing PWS
  6. Pathophysiology
  7. Clinical Features
  8. Diagnosis
  9. Management
  10. II. ANGELMAN SYNDROME (AS)
  11. Mechanisms Causing AS

Syndromes caused by imprinting disorders: Prader-Willi syndrome and Angelman syndrome.

Genomic imprinting is an epigenetic mechanism in which only one parental copy of a gene is expressed, while the other is silenced by DNA methylation. This parent-of-origin–specific expression is established during gametogenesis and maintained throughout life.

As a result:

  • loss of the active allele causes disease,
  • loss of the imprinted (silenced) allele has no effect.

Imprinting disorders typically involve:

  • microdeletions,
  • uniparental disomy (UPD),
  • imprinting center defects.

Key Concepts in Imprinting Disorders

Parental Origin Matters

  • The same chromosomal region, if lost from mother vs father, can cause different syndromes.
  • Best example: chromosome 15q11–q13.

I. PRADER–WILLI SYNDROME (PWS)

Prader–Willi syndrome is a genomic imprinting disorder caused by loss of paternally expressed genes in the 15q11–q13 region, leading to hypotonia, hyperphagia, obesity, hypogonadism, and intellectual disability.

Genetic and Molecular Basis

Critical Region

  • Chromosome: 15q11–q13
  • Normal situation:
  • Paternal allele → active
  • Maternal allele → imprinted (silenced)

Pathophysiology

  1. 1. Loss of paternally expressed genes in 15q11–q13.
  2. 2. Dysfunction of hypothalamic regulation.
  3. 3. Impaired satiety control → hyperphagia.
  4. 4. Reduced growth hormone and gonadotropin secretion.
  5. 5. Developmental delay and cognitive impairment.

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