The Application of Clinical Genetics Dovepress 22q11 Deletion Syndrome: Current Perspective

Chromosome 22q11 is characterized by the presence of chromosome-specific low-copy repeats or segmental duplications. This region of the chromosome is very unstable and susceptible to mutations. The misalignment of low-copy repeats during nonallelic homologous recombination leads to the deletion of the 22q11.2 region, which results in 22q11 deletion syndrome (22q11DS). The 22q11.2 deletion is associated with a wide variety of phenotypes. The term 22q11DS is an umbrella term that is used to encompass all 22q11.2 deletion-associated phenotypes. The haploinsufficiency of genes located at 22q11.2 affects the early morphogen-esis of the pharyngeal arches, heart, skeleton, and brain. TBX1 is the most important gene for 22q11DS. This syndrome can ultimately affect many organs or systems; therefore, it has a very wide phenotypic spectrum. An increasing amount of information is available related to the pathogenesis, clinical phenotypes, and management of this syndrome in recent years. This review summarizes the current clinical and genetic status related to 22q11DS.

[1]  A. Mussa,et al.  Teriparatide (rhPTH) treatment in children with syndromic hypoparathyroidism , 2019, Journal of pediatric endocrinology & metabolism : JPEM.

[2]  S. Eliason,et al.  TBX1 protein interactions and microRNA-96-5p regulation controls cell proliferation during craniofacial and dental development: implications for 22q11.2 deletion syndrome. , 2015, Human molecular genetics.

[3]  Jianbo Wang,et al.  Loss of Wnt5a disrupts second heart field cell deployment and may contribute to OFT malformations in DiGeorge syndrome. , 2015, Human molecular genetics.

[4]  E. Zackai,et al.  Perioperative Risk Factors in Patients with 22q11.2 Deletion Syndrome Requiring Surgery for Velopharyngeal Dysfunction , 2015, The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association.

[5]  Brian Chung,et al.  Practical guidelines for managing adults with 22q11.2 deletion syndrome , 2015, Genetics in Medicine.

[6]  A. Laquérriere,et al.  Fetal phenotype associated with the 22q11 deletion , 2014, American journal of medical genetics. Part A.

[7]  G. Repetto,et al.  Case fatality rate and associated factors in patients with 22q11 microdeletion syndrome: a retrospective cohort study , 2014, BMJ Open.

[8]  K. Mesbah,et al.  Tbx1 Coordinates Addition of Posterior Second Heart Field Progenitor Cells to the Arterial and Venous Poles of the Heart , 2014, Circulation research.

[9]  E. Zackai,et al.  22q11.2 Deletion syndrome and obstructive sleep apnea. , 2014, International journal of pediatric otorhinolaryngology.

[10]  D. Zheng,et al.  Mammalian TBX1 Preferentially Binds and Regulates Downstream Targets Via a Tandem T-site Repeat , 2014, PloS one.

[11]  P. Graham,et al.  Live Vaccine Use and Safety in DiGeorge Syndrome , 2014, Pediatrics.

[12]  R. Kirschner,et al.  Surgical considerations in 22Q11.2 deletion syndrome. , 2014, Clinics in plastic surgery.

[13]  T. de Ravel,et al.  Presenting symptoms in adults with the 22q11 deletion syndrome. , 2014, European journal of medical genetics.

[14]  H. Firth,et al.  Towards a safety net for management of 22q11.2 deletion syndrome: guidelines for our times , 2014, European Journal of Pediatrics.

[15]  A. Bassett,et al.  Prevalence of hypocalcaemia and its associated features in 22q11·2 deletion syndrome , 2014, Clinical endocrinology.

[16]  A. LaMantia,et al.  Anatomy and Regenerative Biology Faculty Publications Anatomy and Regenerative Biology Dysphagia and Disrupted Cranial Nerve Development in a Mouse Model of Digeorge/ 22q11 Deletion Syndrome Recommended Citation , 2022 .

[17]  Ekaterina Rogaeva,et al.  Association between early-onset Parkinson disease and 22q11.2 deletion syndrome: identification of a novel genetic form of Parkinson disease and its clinical implications. , 2013, JAMA neurology.

[18]  K. Sullivan,et al.  The diverse clinical features of chromosome 22q11.2 deletion syndrome (DiGeorge syndrome). , 2013, The journal of allergy and clinical immunology. In practice.

[19]  B. Amendt,et al.  Understanding the Role of Tbx1 as a Candidate Gene for 22q11.2 Deletion Syndrome , 2013, Current Allergy and Asthma Reports.

[20]  A. Bassett,et al.  Neonatal hypocalcemia, neonatal seizures, and intellectual disability in 22q11.2 deletion syndrome , 2013, Genetics in Medicine.

[21]  A. Auton,et al.  Enhanced maternal origin of the 22q11.2 deletion in velocardiofacial and DiGeorge syndromes. , 2013, American journal of human genetics.

[22]  Í. Lopes-Cendes,et al.  Defining new guidelines for screening the 22q11.2 deletion based on a clinical and dysmorphologic evaluation of 194 individuals and review of the literature , 2013, European Journal of Pediatrics.

[23]  S. Berra,et al.  [Di George syndrome: not always a pediatric diagnosis]. , 2013, Recenti progressi in medicina.

[24]  Anna Gambin,et al.  Inverted Low‐Copy Repeats and Genome Instability—A Genome‐Wide Analysis , 2013, Human mutation.

[25]  R. Shprintzen,et al.  Genomic disorders on chromosome 22 , 2012, Current opinion in pediatrics.

[26]  C. Persson,et al.  Speech and hearing in adults with 22q11.2 deletion syndrome , 2012, American journal of medical genetics. Part A.

[27]  K. Jones,et al.  Growth charts for 22q11 deletion syndrome , 2012, American Journal of Medical Genetics. Part A.

[28]  V. Friman,et al.  Antibody deficiency in adults with 22q11.2 deletion syndrome , 2012, American journal of medical genetics. Part A.

[29]  J. Ruda,et al.  A review of the evaluation and management of velopharyngeal insufficiency in children. , 2012, Otolaryngologic clinics of North America.

[30]  K. Baker,et al.  Is there a core neuropsychiatric phenotype in 22q11.2 deletion syndrome? , 2012, Current opinion in neurology.

[31]  Y. Roth,et al.  Head and neck manifestations of 22q11.2 deletion syndromes , 2012, European Archives of Oto-Rhino-Laryngology.

[32]  E. Husebye,et al.  Hypoparathyroidism and autoimmunity in the 22q11.2 deletion syndrome. , 2011, European journal of endocrinology.

[33]  I. Chinn,et al.  Induction of tolerance to parental parathyroid grafts using allogeneic thymus tissue in patients with DiGeorge anomaly. , 2011, The Journal of allergy and clinical immunology.

[34]  Z. Şıklar,et al.  Case Report: Two Patients with Partial DiGeorge Syndrome Presenting with Attention Disorder and Learning Difficulties , 2011, Journal of clinical research in pediatric endocrinology.

[35]  A. LaMantia,et al.  Three phases of DiGeorge/22q11 deletion syndrome pathogenesis during brain development: Patterning, proliferation, and mitochondrial functions of 22q11 genes , 2011, International Journal of Developmental Neuroscience.

[36]  K. Momma.  Cardiovascular anomalies associated with chromosome 22q11.2 deletion syndrome. , 2010, The American journal of cardiology.

[37]  M. Mcmaster,et al.  Spinal Deformity in Patients With DiGeorge Syndrome , 2010, Journal of spinal disorders & techniques.

[38]  M. Genuardi,et al.  Thyroid function and morphology in subjects with microdeletion of chromosome 22q11 (del(22)(q11)) , 2009, Clinical endocrinology.

[39]  A. Bassett,et al.  Extracardiac features predicting 22q11.2 deletion syndrome in adult congenital heart disease. , 2008, International journal of cardiology.

[40]  J. Lupski,et al.  Mechanisms for human genomic rearrangements , 2008, PathoGenetics.

[41]  A. F. Stewart,et al.  Hypoparathyroidism: is it time for replacement therapy? , 2008, Journal of Clinical Endocrinology and Metabolism.

[42]  K. Strömland,et al.  Facial features in children with the 22q11 deletion syndrome , 2008, Acta paediatrica.

[43]  K. Sullivan,et al.  Chromosome 22q11.2 deletion syndrome: DiGeorge syndrome/velocardiofacial Syndrome. , 2008, Immunology and allergy clinics of North America.

[44]  K. Miller.  FISH Diagnosis of 22q11.2 Deletion Syndrome , 2008 .

[45]  K. Sullivan,et al.  Velocardiofacial syndrome, DiGeorge syndrome: the chromosome 22q11.2 deletion syndromes , 2007, The Lancet.

[46]  A. Gentles,et al.  Traffic of genetic information between segmental duplications flanking the typical 22q11.2 deletion in velo-cardio-facial syndrome/DiGeorge syndrome. , 2005, Genome research.

[47]  P. Lapunzina,et al.  Comparative study of three diagnostic approaches (FISH, STRs and MLPA) in 30 patients with 22q11.2 deletion syndrome , 2005, Clinical genetics.

[48]  M. Hurles.  How homologous recombination generates a mutable genome , 2005, Human Genomics.

[49]  G. Tsangaris,et al.  Detection of 22q11.2 deletion among 139 patients with Di George/Velocardiofacial syndrome features. , 2004, In vivo.

[50]  Lorenzo D Botto,et al.  A population-based study of the 22q11.2 deletion: phenotype, incidence, and contribution to major birth defects in the population. , 2003, Pediatrics.

[51]  G. Passos,et al.  Recurrent 22q11.2 deletion in a sibship suggestive of parental germline mosaicism in velocardiofacial syndrome , 2002, Clinical genetics.

[52]  P. Scambler.  The 22q11 deletion syndromes. , 2000, Human molecular genetics.

[53]  K. Devriendt,et al.  The annual incidence of DiGeorge/velocardiofacial syndrome. , 1998, Journal of medical genetics.

[54]  S. Tezenas du Montcel,et al.  Prevalence of 22q11 microdeletion. , 1996, Journal of medical genetics.

[55]  N. Franck,et al.  [Neurocognitive and psychiatric management of the 22q11.2 deletion syndrome]. , 2015, L'Encephale.

[56]  Dalyir I. Pretto,et al.  Screening newborn blood spots for 22q11.2 deletion syndrome using multiplex droplet digital PCR. , 2015, Clinical chemistry.

[57]  C. Leopold,et al.  Laryngeal abnormalities are frequent in the 22q11 deletion syndrome. , 2012, International journal of pediatric otorhinolaryngology.

[58]  R. Rosa,et al.  Hematological abnormalities and 22q11.2 deletion syndrome , 2011, Revista brasileira de hematologia e hemoterapia.

[59]  A. Gennery.  Immunological aspects of 22q11.2 deletion syndrome , 2011, Cellular and Molecular Life Sciences.

[60]  P. Scambler.  22q11 Deletion Syndrome: A Role for TBX1 in Pharyngeal and Cardiovascular Development , 2010, Pediatric Cardiology.

[61]  M. Digilio,et al.  Cardiac defects and results of cardiac surgery in 22q11.2 deletion syndrome. , 2008, Developmental disabilities research reviews.

[62]  B. Emanuel.  Molecular mechanisms and diagnosis of chromosome 22q11.2 rearrangements. , 2008, Developmental disabilities research reviews.

[63]  T. van Amelsvoort,et al.  Involvement of hyperprolinemia in cognitive and psychiatric features of the 22q11 deletion syndrome. , 2007, Human molecular genetics.

[64]  D. Driscoll.  Molecular and genetic aspects of DiGeorge/velocardiofacial syndrome. , 2006, Methods in molecular medicine.

[65]  S. Weinzimer.  Endocrine aspects of the 22q11.2 deletion syndrome , 2001, Genetics in Medicine.

[66]  E. Zackai,et al.  Lack of correlation between impaired T cell production, immunodeficiency, and other phenotypic features in chromosome 22q11.2 deletion syndromes. , 1998, Clinical immunology and immunopathology.