3-way exchange

3-way complex chromosomal rearrangement (CCR)

Epidemiology and Etiology:

· Most are familial

· Usually transmitted through the mother

· CCRs typically originate in male gametogenesis

Common sites:

·

Gross features:

·

Histologic features:

·

Immunophenotype:

Marker:

Sensitivity:

Specificity:

Molecular features:

·

Other features:

· Parent with a 3-way CCR:

· Infertility risk

· Overall 50% SA risk (for CCRs in general)

· Risk of abnormal conception

· Overall 20% (for CCRs in general)

· Mode of ascertainment modifies this risk

· Family history of unbalanced liveborns or multiple miscarriages modifies the risk

· Malsegregation of hexavalent

· Possible segregation combinations of hexavalent:

· 3:3

· 2 arising from alternate segregation are balanced

· 18 others are unbalanced

· Most common abnormal live birth is due to adjacent-1 segregation (but it depends on the translocation)

· 4:2

· Many severely unbalanced

· Characterizes CCRs with an acrocentric chromosome (ex. addition of a chromosome 21 to the balanced complement)

· 5:1 (theoretically)

· 6:0 (theoretically)

· In some rearrangements the tendency may be for alternate segregation and / or there may be very early lethality of severely unbalanced conceptuses

· Therefore a fair chance of having a normal pregnancy

· Generation of a recombinant chromosome (rare)

· Fetus / Child with a 3-way CCR:

· De novo:

· High risk of abnormal phenotype

· ~50% in one small study (numbers are very small)

· Risk of cryptic imbalance

References:

· Gardner RJM, Sutherland GR. Chromosome abnormalities and genetic counseling. Oxford University Press; 2004.