title: A unique phenotype in a patient with a rare triplication of the 22q11.2 region and new clinical insights of the 22q11.2 microduplication syndrome: a report of two cases.
abstract: BACKGROUND
  The rearrangements of the 22q11.2 chromosomal region, most frequently deletions and duplications, have been known to be responsible for multiple congenital anomaly disorders. These rearrangements are implicated in syndromes that have some phenotypic resemblances. While the 22q11.2 deletion, also known as DiGeorge/Velocardiofacial syndrome, has common features that include cardiac abnormalities, thymic hypoplasia, characteristic face, hypocalcemia, cognitive delay, palatal defects, velopharyngeal insufficiency, and other malformations, the microduplication syndrome is largely undetected. This is mainly because phenotypic appearance is variable, milder, less characteristic and unpredictable. In this paper, we report the clinical evaluation and follow-up of two patients affected by 22q11.2 rearrangements, emphasizing new phenotypic features associated with duplication and triplication of this genomic region.
  
  
  METHODS
  Patient 1 is a 24 year-old female with 22q11.2 duplication who has a heart defect (ostium secundum atrial septal defect) and supernumerary teeth (hyperdontia), a feature previously not reported in patients with 22q11.2 microduplication syndrome. Her monozygotic twin sister, who died at the age of one month, had a different heart defect (truncus arteriousus). Patient 2 is a 20 year-old female with a 22q11.2 triplication who had a father with 22q11.2 duplication. In comparison to the first case reported in the literature, she has an aggravated phenotype characterized by heart defects (restrictive VSD and membranous subaortic stenosis), and presented other facial dysmorphisms and urogenital malformations (ovarian cyst). Additionally, she has a hemangioma planum on the right side of her face, a feature of Sturge-Weber syndrome.
  
  
  CONCLUSIONS
  In this report, we described hyperdontia as a new feature of 22q11.2 microdeletion syndrome. Moreover, this syndrome was diagnosed in a patient who had a deceased monozygotic twin affected with a different heart defect, which corresponds to a phenotypic discordance never reported in the literature. Case 2 is the second clinical report of 22q11.2 triplication and presents an aggravated phenotype in contrast to the patient previously reported.
authors: Department of Pediatrics of Hospital of Divino Espírito Santo of Ponta Delgada, EPE, Av. D. Manuel I, 9500-370, Ponta Delgada, São Miguel Island, Azores, Portugal. saravaz87@gmail.com.
authors: Sara O
authors: SO
authors: Vaz
authors: Molecular Genetics and Pathology Unit, Hospital of Divino Espírito Santo of Ponta Delgada, EPE, Av. D. Manuel I, 9500-370, Ponta Delgada, São Miguel Island, Azores, Portugal. Renato.HM.Pires@azores.gov.pt.|Biosystems & Integrative Sciences Institute (BioISI), Faculty of Sciences, University of Lisboa, 1749-016, Lisboa, Portugal. Renato.HM.Pires@azores.gov.pt.
authors: Renato
authors: R
authors: Pires
authors: Cytogenetics and Genomics Laboratory, Faculty of Medicine, University of Coimbra, 3000-354, Coimbra, Portugal. lmpires@yahoo.com.
authors: Luís M
authors: LM
authors: Pires
authors: Cytogenetics and Genomics Laboratory, Faculty of Medicine, University of Coimbra, 3000-354, Coimbra, Portugal. i_marques@hotmail.com.|Centro de Investigação em Meio Ambiente, Genética e Oncobiologia (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-354, Coimbra, Portugal. i_marques@hotmail.com.|Centre of Neurosciences (CNC), University of Coimbra, 3000-354, Coimbra, Portugal. i_marques@hotmail.com.
authors: Isabel M
authors: IM
authors: Carreira
authors: Department of Pediatric Cardiology, Hospital of Santa Cruz, Av. Prof. Dr. Reinaldo dos Santos, 2790-134, Carnaxide, Portugal. ranjos@netcabo.pt.
authors: Rui
authors: R
authors: Anjos
authors: Department of Pediatrics of Hospital of Divino Espírito Santo of Ponta Delgada, EPE, Av. D. Manuel I, 9500-370, Ponta Delgada, São Miguel Island, Azores, Portugal. belomaciel@sapo.pt.
authors: Paula
authors: P
authors: Maciel
authors: Molecular Genetics and Pathology Unit, Hospital of Divino Espírito Santo of Ponta Delgada, EPE, Av. D. Manuel I, 9500-370, Ponta Delgada, São Miguel Island, Azores, Portugal. Luisa.MQ.Vieira@azores.gov.pt.|Biosystems & Integrative Sciences Institute (BioISI), Faculty of Sciences, University of Lisboa, 1749-016, Lisboa, Portugal. Luisa.MQ.Vieira@azores.gov.pt.|Instituto Gulbenkian de Ciência, Rua da Quinta Grande, 6, 2780-156, Oeiras, Portugal. Luisa.MQ.Vieira@azores.gov.pt.
authors: Luisa
authors: L
authors: Mota-Vieira
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics*; D002869:Chromosome Aberrations; D058674:Chromosome Duplication / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D004062:DiGeorge Syndrome / Q000175:diagnosis* / Q000235:genetics*; D019066:Facies; D005260:Female; D006330:Heart Defects, Congenital / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D010048:Ovarian Cysts / Q000175:diagnosis / Q000235:genetics; D010641:Phenotype; D014096:Tooth, Supernumerary / Q000175:diagnosis* / Q000235:genetics*; D014430:Twins, Monozygotic; D055815:Young Adult