Structural Chromosomal Aberrations Overview

Structural Chromosomal Aberrations

• Structural chromosomal aberrations are abnormalities in the structure of chromosomes, specifically structural rearrangements or mutations of chromosomes.
• Causes include radiation, viruses, drugs, and insecticides.

Types of Structural Aberrations

• Intrachromosomal aberrations: These aberrations occur within a single chromosome.

  • Breaks: Relatively common, involving simple breakage followed by rapid healing of the broken ends.

  • Deletion: Partial monosomy, caused by loss of a segment of a chromosome due to breaks. Can be terminal (one break) or interstitial (two breaks).

    • Examples: Wolf syndrome, Cri du chat syndrome.
    • A terminal deletion involves the loss of a chromosome tip, usually containing telomeres.
    • An interstitial deletion results from a break within a chromosome arm, leading to the loss of a segment between the breakpoints.

  • Ring chromosome: Two terminal breaks on the same chromosome, resulting in a circular arrangement, usually with deletion of the telomeres.

    • Loss of part of the chromosome, potentially affecting genes.

  • Inversion: A segment of a chromosome reverses its orientation and reattaches to the same chromosome. Classified as paracentric (segment inversion excludes the centromere) or pericentric (segment inversion includes the centromere).

  • Duplication: Partial trisomy, which is the presence of extra copies of a particular chromosome segment or the entire chromosome. Caused by replication errors or unequal crossing over between homologous chromosomes.

• Interchromosomal aberrations: These aberrations occur between different chromosomes.

  • Translocation: A part of one chromosome breaks off and attaches to a different, non-homologous chromosome. Can be reciprocal (no gain or loss of genetic information) or Robertsonian (fusion of two whole arms ending in a single chromosome, often involving acrocentric chromosomes).

    • Examples: Philadelphia chromosome (Ch 22 & 9 translocation), Down syndrome (translocation variant).

  • Insertion: Structural chromosomal rearrangement involving 3 breaks in two different (heterologous) chromosomes. One segment is deleted from one chromosome and added to another.

  • Isochromosome: An unbalanced structural abnormality. Formed by the misdivision of a chromosome's centromere, resulting in two identical arms.

Karyotype Symbols

• p: Short arm of a chromosome.
• q: Long arm of a chromosome.
• cen: Centromere.
• del: Deletion.
• dup: Duplication.
• fra: Fragile site.
• i: Isochromosome.
• inv: Inversion.
• ish: In-situ hybridization.
• r: Ring.
• t: Translocation.
• ter: Terminal or end.
• + or -: Indicate gain or loss of part of that chromosome, in relation to the normal karyotype.

Clinical Features of Cri du Chat Syndrome

• High-pitched cry (like a cat), common in newborn babies.
• Ear malformations.
• Broad and depressed (flat) nose.
• Widely set, slanting eyes.
• Small receding mandible.
• Small head.
• Heart defects
• Mental Retardation
• Facial defects
• Small head and low birth weight.

Specific Diseases related to chromosomal anomalies

• Down Syndrome: Caused by an extra copy of chromosome 21 (trisomy). Causes a variety of developmental issues.

Case Study Summaries

• Case 1: A 10-year-old girl with short stature, low-set ears, low posterior hairline, and streak ovaries suggests Turner syndrome. XO is the diagnosis.

• Case 2: A 28-year-old man with infertility, tall stature, and feminine hair distribution, and enlarged breasts suggests a possible sex chromosome abnormality, like Klinefelter syndrome (47, XXY).

• Case 3: A 40-year-old pregnant woman with a newborn having umbilical cord knots and a weak mewing cat-like cry suggests Cri du chat syndrome.

• Mechanism of chromosomal anomalies: Different mechanisms (including X-ray exposure) can cause structural chromosomal alterations such as inversion, deletion, duplication, translocation, etc. This can lead to abnormalities.