Pericentric Inversion X

Epidemiology and Etiology:

· Rare

· Transmitted by males and females

Common sites:

·

Gross features:

·

Histologic features:

·

Immunophenotype:

Marker:

Sensitivity:

Specificity:

Molecular features:

·

Other features:

· Parent with inv(X):

· Risk of having an unbalanced child:

· Near zero for having an unbalanced male child due to nullisomy

· If breakpoint very near telomere, there is a risk of major physical abnormalities and severe mental retardation

· Female inv(X) heterozygote

· Risk of gonadal dysfunction (primary amenorrhea, premature ovarian failure)

· Breakpoint within Xq13-q22 or Xq22-q26

· Particularly with family history of POF

· Male inv(X) hemizygote:

· Normal fertility and phenotype

· Daughters are all heterozygotes

· Many will have normal gonadal function

· Family history of POF might predict the same problem

· Child with inherited inv(X) (not recombinant)

· Normal if parent of same sex with inversion is normal

· If parent carrier is opposite sex, phenotype less certain

· Males are typically of normal fertility or phenotype

· Child with recombinant X:

· Female:

· Del(X)(q)/dup(X)(p)

· Normal or tall stature

· Ovarian dysgenesis

· Del(X)(p)/dup(X)(q)

· Short stature

· Loss of SHOX (and other genes)

· Intact ovarian function

· Male:

· Not viable unless the nullisomy segment is the “tiniest” segment

· The disomic portion also has a major deleterious effect, as it is not inactivated

· Major dysmorphogenesis

· Severe neurodevelopmental compromise

References:

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