Pericentric Inversions

 

inv(X)

inv(Y)

Inv(9)

 

 

 

Epidemiology and Etiology:

·          

 

Common sites:

·          

 

Gross features:

·          

 

Histologic features:

·          

 

Immunophenotype:

Marker:

Sensitivity:

Specificity:

 

 

 

 

Molecular features:

·          

 

Other features:

·         Harmless common inversions:

·         Those involving centromeric and paracentromeric heterochromatin

·         Inv(2)(p11.2q13)

·         Only 2 recorded cases in the world with a possibly related pathogenic recombination

·         Inv(3)(p11~13q11~12)

·         Inv(5)(p13q13)

·         Inv(10)(p11.2q21.2)

·         Parent with a pericentric inversion:

·         Risk of chromosomally unbalanced liveborn child due to a recombinant chromosome

·         The viability of the recombinant conceptus is determined by the functional content of the noninverted segments

·         Only those inversions with genetically small distal segments will ever have a chromosomally imbalanced abnormal liveborn child

·         Excepting chromosomes 13, 18, 21

·         See fig. 8-8 (p. 150) and table 8-1 (p. 151) in Gardner for specific inversion that have been reported as viable

·         Ascertainment via recombinant child:

·         Consensus risk is 5-10%

·         10-15% at amniocentesis

·         Inv(8)(p23q22) – 6.2% (all have del(p)/dup(q) form)

·         Inv(18)(p11q11 or q12 or q21) – 8%

·         The shorter the distal segments (longer the inversion segment) the greater the risk

·         Sex of carrier parent is a factor in the minority of cases:

·         Female heterozygote greater genetic risk in some families

·         Ex. inv(21)(p12q21.1) with recombinant dup(21)(q) has only been seen when mother is carrier

·         No history of recombinant child:

·         Overall risk ~1%

·         Individual risk depends on the actual inversion

·         Significant risk for those previously observed in liveborns (table 8-1 in Gardner) or longer inverted segment

·         Chromosomes 13,18,21 are well-recognized as potentially viable

·         One breakpoint very close to telomere – consider viability of duplication on its own

·         Close to 0% for inversions much shorter in length than any in table 8-1

·          

·         Risk of miscarriage

·         Risk of complete infertility:

·         Uncommon

·         Abnormal synapsis of the chromosome pair can affect cellular mechanics at meiosis, arresting spermatogenesis

·         More likely if the inversion involves a larger chromosome

·         Risk of passing on balanced inversion to child:

·         50%

·          

 

References:

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