22q11.2 Deletion Syndrome / Di George / VCF

22q11.2 deletion syndrome is an "underdiagnosed" syndrome that occurs in 1:4000 births and 1:1000 fetuses, which major features includes: distinctive facial features, congenital heart disease (frequently conotruncal), velopharyngeal insufficiency or cleft palate, hypocalcemia, immune deficiency, learning delays or Intellectual disabilities and other less frequent features as renal defects, ophthalmological anomalies, skeletal defects, autoimmune disorders, hearing loss, psychiatric disturbances, among others. The phenotype is highly variable, even within families. Males and females are equally affected. The prevalence of psychiatric disorders is 25-35% in young adults with an increase during adolescence. Certain adults may develop Parkinson's disease. The most common deletion, which is a 3Mb/2.54Mb (LCR22A-D) is seen in approximately 85% of patients. A smaller 1.5 Mb deletion (LCR22A-B) is less frequent, and even less frequently a 2 Mb deletion (LCR22A-C) is present. The deletion mechanism may involve unstable blocks of the 11.2 region of the long arm of chromosome, named low copy repeats (LCR). LCRs coincide with the breakpoints of the deletion, and promote improper meiotic recombination in gametogenesis, resulting in aberrant chromosome rearrangements. In our country, this deletion can be detected by different methods: Fluorescent in situ hybridization (FISH) with probes that hybridize in the LCR22A-B region, which detects typical deletions (80-90% of cases) but not the atypical ones. Multiplex Ligation-dependent Probe Amplification (MLPA) detects typical and some atypical deletions. Microarray (array-CGH) when MLPA cannot be performed or when an additional associated pathology can mask the symptoms of the syndrome. Less than 1% of patients may present chromosomal rearrangements that can be identified by standard cytogenetic diagnostic testing. In this commonly deleted region maps around 45 known genes. This region is not imprinted. We evaluated 395 patients, males (51%)/females (49%), the median age at diagnosis was 14 months. The main reasons for diagnostic suspicion were facial abnormalities, congenital heart disease and developmental delay. These patients present: facial abnormalities (98,5%); congenital heart disease (78,7%); immune disturbance (64,2%); intellectual disabilities/learning delays (88%); palate defects (76,41%); hearing loss (34,5%); hypocalcemia (37%); renal abnormalities (12,38%). To improve patient management, a multidisciplinary