Phenotype of the 22q11.2 deletion in individuals identified through an affected relative: cast a wide FISHing net!

Genet Med. 2001 Jan-Feb;3(1):23-9. doi: 10.1097/00125817-200101000-00006.


Purpose: The chromosome 22q11.2 deletion has been identified in the majority of patients with DiGeorge syndrome, velocardiofacial syndrome, and conotruncal anomaly face syndrome and in some patients with the autosomal dominant Opitz G/BBB syndrome and Cayler cardiofacial syndrome. In addition, 22q11.2 deletion studies are becoming part of a standardized diagnostic workup for some isolated defects such as conotruncal cardiac anomalies and velopharyngeal incompetence. However, there is little information available on the clinical findings of unselected patients. For example, those individuals identified during prenatal diagnosis, as part of a generalized screening protocol, or following the diagnosis in a relative. This information will be invaluable in defining the variability of the disorder and in observing long-term outcome in the absence of targeted remediations. This study allows one to examine the first unselected cohort of patients and serves to highlight the importance of deletion testing in parents of affected probands.

Methods: Thirty individuals with a 22q11.2 deletion were identified following the diagnosis in a relative. Nineteen were adults ascertained only following the diagnosis in their child, 10 were children identified following the diagnosis in their sibling, and one was a child diagnosed prenatally following the diagnosis in her parent.

Results: Sixty percent of patients had no visceral anomalies. In fact, only 6 of the 19 adults (32%) and 6 of the 11 children (55%) had major findings which would have brought them to medical attention. Deletion sizing demonstrated the same large 3-4 MB deletion in most families despite wide inter and intrafamilial variability and there was no difference in clinical findings based on the parent of origin. Thus, no genotype-phenotype correlations could be made.

Conclusion: We report the first unselected cohort of patients with the 22q11.2 deletion identified through an affected relative. Analysis of this series of 30 patients, many with very mild manifestations of the deletion, allows one to examine the outcome in individuals who lacked specific remediations for this disorder. It emphasizes the importance of broadening the index of suspicion in order to provide appropriate recurrence risk counseling, cognitive remediation, and medical management. Further, it underscores the lack of familial concordance and the current lack of genotype-phenotype correlations in this disorder, and it raises the possibility that the deletion is more common than previously reported.

MeSH terms

  • Abnormalities, Multiple / diagnosis*
  • Abnormalities, Multiple / genetics
  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 22*
  • Cohort Studies
  • DiGeorge Syndrome / diagnosis
  • DiGeorge Syndrome / genetics
  • Facies
  • Family Health
  • Female
  • Genotype
  • Humans
  • In Situ Hybridization, Fluorescence / methods*
  • Infant
  • Male
  • Middle Aged
  • Pedigree
  • Phenotype