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GENATLAS PHENOTYPE
last update : 19-05-2015
Symbol DEL22Q11
Location 22q11.2
Name chromosome 22q11.2 microdeletion syndrome
Other name(s)
  • DiGeorge syndrome (DGS)
  • velocardiofacial syndrome (VCFS)
  • Shprintzen syndrome, conotruncal anomaly face syndrome
  • Caylor cardiofacial syndrome, monosomy 22q11.2
    • Corresponding gene TBX1 , UFD1L , DGCR8
    Other symbol(s) CATCH22, DGS, VCFS, 22Q11DS
    Main clinical features
  • great phenotypic variability, inter and intra-familial
  • characteristic facial features, congenital heart defects particularly conotruncal malformations, palatal anomalies including velopharyngeal incompetence (VPI), immune deficiency and learning difficulties
  • additional findings : hypocalcemia, significant feeding problems, renal anomalies, hearing loss, growth retardation, psychiatric illness, autoimmune disease, skeletal abnormalities of extremities, Mullerian agenesis with amenorrhea, absent uterus
  • schizophrenia, hypothyroidism, non-neonatal hypocalcemia and cholelithiasis are observed in adult patients
    • Genetic determination chromosomal
    genomic disorder
    Prevalence could be as frequent as 1/4000 livebirths
    Related entries LCR22, HPI, VCF, DEL22Q11D
    Function/system disorder defense and immunity
    cardiovascular
    multisystem/generalized
    mental retardation
    Type MCA/MR
    Gene product
    Name contiguous gene syndrome with haploinsufficiency for an undetermined number of genes
    Mechanism(s)
    Gene mutationChromosome rearrangementEffectComments
      deletion haploinsufficiency commonly deleted region of 3 Mb, or less frequently 1.5Mb
    various types   haploinsufficiency missense and frameshift mutations in TBX1 gene recently identified in non-deleted DGS patients
    missense   abnormal protein/gain of function some missence mutations of TBX1 resulting in gain of function associate with the same phenotypic spectrum as haploinsufficiency
    Remark(s)
  • common DNA variations in TBX1 do not explain variable cardiovascular expression in 22q11DS patients PMID: 21796729;;
  • the MOZ/MYST3 gene (8q11.21) that modifies chromatin may contribute to the wide variability in severity of velocardio-facial(VCF)/DiGeorge syndrome, PMID: 22921202
  • abnormal processing of miRNAs resulting from DGCR8 haploinsufficiency could explain the neurological and behavioural phenotype;
  • craniofacial and cardiac outflow tract defects observed in patients with a distal 22q11.2 micro-deletion are explained by deficiencies in neural crest autonomous MAPK1 signaling
  • unique model for learning about the deleterious effects of decreased dosage of the COMT gene on brain function (Gothelf 2007)
  • alterations in the corpus callosum volume in children with del22q11 are associated with cognition and specific genotypes in the 22q11.2 interval(PMID: 22763378))
  • SLC2A3 duplication might serve as a genetic modifier of CHDs and/or aortic arch anomalies in individuals with del22q11 (PMID: 25892112))
    • Genotype/Phenotype correlations
  • phenotypic variability due to SNAP29 mutations on the non-deleted chromosome PMID: 23231787
  • deletion of 3Mb in size in 75p.100 of patients and 1,5 Mb in 8p.100 ; atypical deletions in some patients ; 7p100 of cases are inherited from a parent with 1,5 Mb deletions more often linked to familial inheritance than 3 Mb ones;
  • atypical deletions comprising distal part of the commonly deleted region not including TBX1 show phenotypic variability and had fewer CHD (28 vs75 percent) suggesting a position effect on TBX1, PMID: 22893440
  • among adult or adolescent VCFS subjects, a subset of patients with severe hyperprolinemia has a phenotype distinguishable from that of other VCFS patients and reminiscent of HPI; an inverse correlation between plasma proline level and IQ was found