Genetics: Structural Abnormalities

Structural Abnormalities

• Unbalanced rearrangement: results in incorrect amount of chromosomal material, associated with severe clinical effects

Types of Structural Abnormalities

• Deletion: loss of genetic material, resulting in monosomy for the segment
  • Terminal deletion: involves a single break of the terminal part of the chromosome, broken part is lost
  • Interstitial deletion: involves two breaks, intervening portion of the chromosome is lost
  • Cri-du Chat syndrome: deletion of short arm of chromosome 5, incidence 1:20,000 to 1:50,000 births, characterized by underdevelopment of larynx, mental retardation, microcephaly, and facial anomalies

Duplication

• Extra copies of a chromosome part

Inversion

• Involves two breaks along the chromosome, resulting in a reversed segment
  • Pericentric inversion: inverted segment involved both p and q arms with centromere
  • Paracentric inversion: inverted segment involved only one arm

Ring Chromosome

• Loss of telomeres or ends of both arms of the chromosome, forming a ring structure

Isochromosome

• Creation of two non-identical chromosomes, one a combination of two short arms, the other a combination of two long arms
  • Turner syndrome: example of an isochromosome

Insertion

• Rearrangement of genetic material to a non-homologous chromosome, no loss of genetic material

Translocation

• Exchange of genetic material between two chromosomes
  • Reciprocal translocation: exchange of genetic material between two non-homologous chromosomes, no loss of genetic material
  • Robertsonian translocation (centric fusion): break at or near the centromere in two acrocentric chromosomes, subsequent fusion of long arms, and loss of fragment formed by fusion of short arms

Causes of Structural Abnormalities

• Environmental factors: ionizing radiation, ultraviolet light, chemical agents, viral infections

Patient Ascertainment

• Indications for routine chromosome investigation:
  • Constitutional (congenital) abnormalities
  • Prenatal screening (Down's syndrome, especially raised maternal age, family history of chromosome abnormality, abnormal ultrasound scan of fetus)
  • Birth defects (malformations, mental retardation)
  • Abnormal sexual development (e.g., Klinefelter's syndrome)
  • Infertility
  • Recurrent fetal loss
  • Acquired abnormalities (leukemia and related disorders)

Test your knowledge of structural abnormalities, including deletion, and their effects on chromosomal material. Learn about the different types of deletions and their clinical implications.