Chromosomal Abnormalities and Prenatal Screening

Chromosomal Abnormalities

• Chromosomal abnormalities result from breakage and incorrect rejoining of chromosomal segments, leading to disease.
• Environmental factors responsible for structural abnormalities include: • Ionizing radiation • Ultraviolet light • Chemical agents • Viral infections

Indications for Chromosome Investigation

• Prenatal screening: • Down's syndrome, especially in cases of advanced maternal age (>35 years) or 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

Types of Structural Chromosomal Abnormalities

• Balanced rearrangements: • Exchange or rearrangement of genetic material without loss or gain of genetic material • Generally harmless, but carriers are at risk of producing children with unbalanced chromosomal complement
• Unbalanced rearrangements: • Incorrect amount of chromosomal material, resulting in severe clinical effects

Deletions

• Loss of genetic material, resulting in monosomy for the segment of the chromosome
• Types of deletions: • Terminal deletion: involves a single break of the terminal part of the chromosome • Interstitial deletion: involves two breaks and loss of the intervening portion of the chromosome
• Example: Cri-du-Chat syndrome (46,XX,5p- or 46,XY,5p-)

Duplications

• Extra copies of a chromosome part

Inversions

• Involves two breaks along the chromosome, resulting in a reversal of a segment
• Types of inversions: • Pericentric inversion: involves both p and q arms with centromere • Paracentric inversion: involves only one arm

Ring Chromosomes

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

Isochromosomes

• Creation of two non-identical chromosomes, one with a combination of short arms, the other with a combination of long arms

Insertions

• Rearrangement of genetic material to a non-homologous chromosome, without loss of genetic material

Translocations

• Exchange of genetic material between two chromosomes
• Types of translocations: • Reciprocal translocation: no loss of genetic material, but an exchange of genetic material between two non-homologous chromosomes • Robertsonian translocation (centric fusion): involves break at or near the centromere in two acrocentric chromosomes and subsequent fusion of their long arms

Karyotype Nomenclature

• Normal female or male: 46,XX or 46,XY
• Extra or missing entire chromosome: e.g., 47,XX,+21 or 45,XX,-15
• Missing piece of a chromosome: e.g., 5p-
• Other notations include: • del (deletion) • dup (duplication) • inv (inversion) • ins (insertion) • rob (Robertsonian translocation) • t (translocation)