Supernumerary bisatellited dicentric marker derived from chr 22

 

Epidemiology and Etiology:

    • Inv dup(22)(pter->q11.2)
      • Two copies of 22p
      • Small segment of proximal 22q (22q11.2)
        • Tetrasomy for 22q11.2
        • Breakpoint is usually one of the Digeorge breakpoints
        • Critical region is proximal to the Digeorge region (we don’t have a probe for this region in our lab)
      • Not necessarily symmetrical
    • Interstitial duplication of 22q11
      • Most of CES region and the DGS/VCFS region, varying degrees of more distal regions
      • 3 copies of these regions are sufficient to cause the syndrome
    • de novo mostly
    • phenotype ranges from mild to severe
      • can vary considerably within and between families
    • mosaicism may be seen

 

Common sites:

    •  

 

Gross features:

    • Cat eye syndrome (if critical region on proximal 22q is present)
      • Craniofacial anomalies
        • Vertical coloboma of the iris (cat-eye) (55-60%)
        • Coloboma of the choroid or optic nerve
        • Preauricular skin tags/pits
        • Down-slanting palpebral fissures
        • Hypertelorism
        • Low-set or dysplastic ears
        • Epicanthal folds
        • Strabismus
        • micrognathia
      • Anal atresia
        • Rectovestibular fistula
      • Cardiac defects (>1/3)
        • TAPVR typically
        • Septal defects
      • Renal malformations
        • Unilateral agenesis
        • Unilateral or bilateral hypoplasia / dysplasia
      • Less frequent:
        • Microphthalmia
        • Microtia
        • Atresia of external auditory canal
        • Biliary atresia
        • Malrotation of the gut
        • Male genital anomalies
        • Skeletal defects

 

Histologic features:

    •  

 

Immunophenotype:

Marker:

Sensitivity:

Specificity:

 

 

 

 

Molecular features:

    • Breakpoint is usually one of the Digeorge breakpoints
      • Type I CES: both breakpoints at proximal LCR
      • Type II CES: one or both breakpoints at distal LCR
      • No obvious difference between the phenotypes of type I and type II markers
    • Critical region is proximal to the Digeorge region (we don’t have a probe for this region in our lab)
    •  

 

Other features:

    • Phenotype:
      • Normal if no euchromatin present
      • Cat-eye syndrome (see gross features)
        • Variable severity
      • Intelligence usually low normal to mildly deficient
      • Phenotype doesn’t correlate well with the size of the chromosome

 

References:

    • Gersen SL, Keagle MB, eds.  Principles of Clinical Cytogenetics (2005)
    • Gardner RJM, Sutherland GR. Chromosome Abnormalities and Genetic Counseling. 2nd ed. Oxford University Press, USA; 1996.
    • DECIPHER v4.4 (accessed 2010)