Medical Genetics · MU Plovdiv

8. Chromosomal pathology. Chromosomal diseases associated with structural aberrations of autosomes. Partial monosomies and trisomies. Microdeletion syndromes. Subtelomeric aberrations. Molecular cytogenetics.

Inside: 10 sections · 16 labelled pictures · 1 table · 27 flashcards · 7 min

Topic 8 of 33 in the MU Plovdiv syllabus for Medical Genetics (Medicine, Year 4). The free AceMed note covers it in 10 sections, about 989 words (7 min of reading), with 27 flashcards.

In this note

  1. Introduction
  2. General mechanisms and pathogenesis
  3. Classification of structural autosomal aberrations
  4. I. Chromosomal deletions
  5. II. Microdeletion syndromes (contiguous gene syndromes)
  6. III. Chromosomal duplications
  7. IV. Inversions
  8. V. Translocations
  9. VI. Ring autosomes
  10. VII. Isochromosomes (autosomal)

Introduction

Structural autosomal aberrations are chromosomal disorders caused by breakage and abnormal rearrangement of chromosome segments. The total chromosome number is usually normal (46), but the structure of one or more autosomes is altered, leading to loss, gain, or misplacement of genetic material. This topic covers deletions (partial monosomies), duplications (partial trisomies), inversions, translocations, ring chromosomes, isochromosomes and the microdeletion (contiguous gene) syndromes.

These abnormalities cause disease mainly through:

  • gene loss (haploinsufficiency),
  • gene dosage excess,
  • disruption of gene structure or regulation.

General mechanisms and pathogenesis

Structural aberrations arise due to:

  • errors in meiotic recombination,
  • faulty DNA repair after double-strand breaks,
  • abnormal chromosomal segregation.
  • Chromosome breakage occurs at specific sites.
  • Incorrect rejoining of fragments alters chromosome structure.
  • Essential genes may be deleted, duplicated, or disrupted.
  • Gene dosage imbalance interferes with normal development.
  • Balanced carriers are often phenotypically normal but produce abnormal gametes.

I. Chromosomal deletions

A chromosomal deletion is the loss of a segment of an autosome, leading to partial monosomy. Deletions are always pathogenic because genetic material is lost.

Types of deletions

  • Terminal deletion – loss of the end of a chromosome
  • Interstitial deletion – loss of an internal segment

Pathogenesis of deletions

  • Loss of one copy of multiple genes.
  • Reduced gene dosage → haploinsufficiency.
  • Disruption of developmental pathways.
  • Severity depends on size and gene content of deleted region.

Cri-du-chat syndrome (5p deletion)

  • Chromosome: 5p15
  • Main mechanism: deletion of genes involved in brain and laryngeal development

Clinical features:

  • High-pitched, cat-like cry
  • Microcephaly
  • Severe intellectual disability
  • Hypotonia
  • Facial dysmorphism (round face, hypertelorism)

Wolf–Hirschhorn syndrome (4p deletion)

  • Chromosome: 4p16.3
  • Main mechanism: loss of genes critical for craniofacial and brain development

Clinical features:

  • “Greek warrior helmet” face
  • Severe growth retardation
  • Seizures
  • Congenital heart defects
  • Profound intellectual disability

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