Independent de novo 22q11.2 deletions in first cousins with DiGeorge/velocardiofacial syndrome

Am J Med Genet A. 2004 Jan 30;124A(3):313-7. doi: 10.1002/ajmg.a.20421.


Deletions of chromosome 22q11.2 are found in the vast majority of patients with DiGeorge/velocardiofacial syndrome (DGS/VCFS). This most frequent microdeletion syndrome is estimated to occur in 1 in 4,000 live births. The majority of deletions are de novo, with 10% or less inherited from an affected parent. Here, we report two separate families with recurrence of a 22q11.2 deletion in first cousins. In each family, unaffected siblings (brother and sister) had an affected child. Fluorescence in situ hybridization (FISH) studies of the parents of each affected child were normal and hence, relatives were not considered at an increased risk for recurrence in another pregnancy. We used highly polymorphic microsatellite repeat markers from within 22q11.2 to determine the parental origin of each cousin's deletion and to assess whether parental germline mosaicism for the 22q11.2 deletion might be a factor in these cases. This analysis confirmed that in each case, the deletion occurred on a chromosome 22 derived from unrelated parents, consistent with independent de novo deletion events. Thus, we concluded that germline mosaicism as the underlying mechanism for affected cousins in these families was unlikely. Our findings underscore the high frequency with which the 22q11.2 deletion occurs in the general population and demonstrate the important role that PCR-based parental origin determination can have in recurrence risk counselling. Furthermore, relatives of affected individuals may benefit from genetic counselling and consider prenatal testing for the 22q11.2 deletion in future pregnancies, despite a low recurrence risk.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Abnormalities, Multiple / pathology
  • Child, Preschool
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 22 / genetics*
  • Craniofacial Abnormalities / pathology
  • DiGeorge Syndrome / genetics*
  • DiGeorge Syndrome / pathology
  • Family Health
  • Female
  • Genotype
  • Haplotypes
  • Heart Defects, Congenital / pathology*
  • Humans
  • Male
  • Microsatellite Repeats
  • Pedigree
  • Syndrome