Chromosome 22q11.2 deletion: world definition criteria, standards for diagnosis and monitoring

M.A. Gonchar, O.L. Logvinova, A.I. Strashok, N.V. Konovalova, D.A. Ivakhnenko

Abstract


The article presents own clinical observation of the chromosome 22q11.2 microdeletion syndrome in a child with congenital heart disease. Phenotype also includes facial skull anomalies, immune disorders, developmental delay and even cognitive deficits. The authors analyzed the current world definition criteria, standards for diagnosis and monitoring of patients to diagnose this syndrome. The epidemiology of 22q11.2 deletion syndrome is determined in the work. Its incidence varies between 1 : 3,000–1 : 6,000 newborns, the inheritance is autosomal dominant, however, in Ukraine the syndrome is rarely diagnosed, which in our opinion is due to the lack of neonatal screening and insufficient awareness of physicians of clinical features of the disease. Section 22q11.2 is one of the most structurally complex regions of the genome, primarily through several large blocks. The locus of low copy repeats in region 22q11.2 is prone to a genetic error, which is due to 96% identity. Attention is focused that clinical manifestations vary with age. In young children, typical symptoms include a combination of congenital heart disease, immunodeficiency, malformation of the palate, hypocalcaemia, difficulty in feeding, delayed mental and speech development, behavioral disorders, kidney and genital abnormalities, laryngo-tracheo-esophageal malformations, hypothyroidism, skeletal dysmorphology. In some children, the disease manifests in school-age by behavio­ral anomalies and mental retardation, and hypocalcaemia. The presence of facial features can contribute to identifying the syndrome at any age. At the same time, difficulties in diagnosis are associated with widespread phenotypic variability. The article describes in detail the genetic diagnosis of the syndrome using several methods (fluorescence hybridization in situ, multiplex ligation-dependent probe amplification and chromosomal microarray), the choice of which depends on the period of life and the expressiveness of phenotypic traits. To monitor the child with the syndrome of chromosome 22q11.2 microdeletion, the authors describe approaches that include multidisciplinary team approach and system after system method.

Keywords


chromosome 22q11.2 deletion; DіGeorge syndrome; pathophysiology; diagnosis; follow-up monitoring

References


McDonald-McGinn DM, Sullivan KE, Marino B, et al. 22q11.2 deletion syndrome. Nat Rev Dis Primers. 2015 Nov 19;1:15071. doi: 10.1038/nrdp.2015.71.

Grati FR, Molina Gomes D, Ferreira JC, et al. Prevalence of recurrent pathogenic microdeletions and microduplications in over 9500 pregnancies. Prenat Diagn. 2015 Aug;35(8):801-9. doi: 10.1002/pd.4613.

Chien YH, Chiang SC, Chang KL, et al. Incidence of severe combined immunodeficiency through newborn screening in a Chinese population J Formos Med Assoc. 2015 Jan;114(1):12-6. doi: 10.1016/j.jfma.2012.10.020.

Steinberg KM, Schneider VA, Graves-Lindsay TA, et al. Single haplotype assembly of the human genome from a hydatidiform mole. Genome Res. 2014 Dec;24(12):2066-76. doi: 10.1101/gr.180893.114.

Chaisson MJ, Huddleston J, Dennis MY, et al. Resolving the complexity of the human genome using single-molecule sequencing. Nature. 2015 Jan 29;517(7536):608-11. doi: 10.1038/nature13907.

Ellegood J, Markx S, Lerch JP, et al. Neuroanatomical phenotypes in a mouse model of the 22q11.2 microdeletion Mol Psychiatry. 2014 Jan;19(1):99-107. doi: 10.1038/mp.2013.112.

Mukai J, Tamura M, Fénelon K, et al. Molecular substrates of altered axonal growth and brain connectivity in a mouse model of schizophrenia. Neuron. 2015 May 6;86(3):680-95. doi: 10.1016/j.neuron.2015.04.003.

Earls LR, Zakharenko SS. A synaptic function approach to investigating complex psychiatric diseases. Neuroscientist. 2014 Jun;20(3):257-71. doi: 10.1177/1073858413498307.

Karpinski BA, Maynard TM, Fralish MS, et al. Dysphagia and disrupted cranial nerve development in a mouse model of DiGeorge (22q11) deletion syndrome. Dis Model Mech. 2014 Feb;7(2):245-57. doi: 10.1242/dmm.012484.

Pane LS, Zhang Z, Ferrentino R, Huynh T, Cutillo L, Baldini A. Tbx1 is a negative modulator of Mef2c Hum Mol Genet. 2012 Jun 1;21(11):2485-96. doi: 10.1093/hmg/dds063.

Diogo R, Kelly RG, Christiaen L, et al. A new heart for a new head in vertebrate cardiopharyngeal evolution Nature. 2015 Apr 23;520(7548):466-73. doi: 10.1038/nature14435.

Meechan DW, Maynard TM, Tucker ES, et al. Modeling a model: mouse genetics: 22q11.2 deletion syndrome, and disorders of cortical circuit development Prog Neurobiol. 2015 Jul;130:1-28. doi: 10.1016/j.pneurobio.2015.03.004.

Xu B, Hsu PK, Stark KL, Karayiorgou M, Gogos JA. Derepression of a neuronal inhibitor due to miRNA dysregulation in a schizophrenia-related microdeletion. Cell. 2013 Jan 17;152(1-2):262-75. doi: 10.1016/j.cell.2012.11.052.

Milgrom-Hoffman M, Michailovici I, Ferrara N, Zelzer E, Tzahor E. Endothelial cells regulate neural crest and second heart field morphogenesis. Biol Open. 2014 Jul 4;3(8):679-88. doi: 10.1242/bio.20148078.

Keyte AL, Alonzo-Johnsen M, Hutson MR. Evolutionary and developmental origins of the cardiac neural crest: building a divided outflow tract. Birth Defects Res C Embryo Today. 2014 Sep;102(3):309-323. doi: 10.1002/bdrc.21076.

Guna A, Butcher NJ, Bassett AS. Comparative mapping of the 22q11.2 deletion region and the potential of simple model organisms. J Neurodev Disord. 2015;7(1):18. doi: 10.1186/s11689-015-9113-x.

Zheng P, Noroski LM, Hanson IC, et al. Molecular mechanisms of functional natural killer deficiency in patients with partial DiGeorge syndrome J Allergy Clin Immunol. 2015 May;135(5):1293-302. doi: 10.1016/j.jaci.2015.01.011.

Paronett EM, Meechan DW, Karpinski BA, LaMantia AS, Maynard TM. Ranbp1, deleted in DiGeorge/22q11.2 deletion syndrome, is a microcephaly gene that selectively disrupts layer 2/3 cortical projection neuron generation. Cereb Cortex. 2015 Oct; 25(10): 3977–3993. doi: 10.1093/cercor/bhu285.

Swillen A, McDonald-McGinn D. Developmental trajectories in 22q11.2 deletion syndrome. Am J Med Genet C Semin Med Genet. 2015 Jun;169(2):172-81. doi: 10.1002/ajmg.c.31435.

Fung WL, Butcher NJ, Costain G, et al. Practical guidelines for managing adults with 22q11.2 deletion syndrome Genet Med. 2015 Aug;17(8):599-609. doi: 10.1038/gim.2014.175.

Vergaelen E, Swillen A, Van Esch H, Claes S, Van Goethem G, Devriendt K. 3 generation pedigree with paternal transmission of the 22q11.2 deletion syndrome: intrafamilial phenotypic variability Eur J Med Genet. 2015 Apr;58(4):244-8. doi: 10.1016/j.ejmg.2015.01.008.

Widdershoven JC1, Bowser M, Sheridan MB, et al. A candidate gene approach to identify modifiers of the palatal phenotype in 22q11.2 deletion syndrome patients. Int J Pediatr Otorhinolaryngol. 2013 Jan;77(1):123-7. doi: 10.1016/j.ijporl.2012.10.009.

Stransky C, Basta M, McDonald-McGinn DM, et al. Perioperative risk factors in patients with 22q11.2 deletion syndrome requiring surgery for velopharyngeal dysfunction. Cleft Palate Craniofac J. 2015 Mar;52(2):183-91. doi: 10.1597/13-206.

Evers LJ, van Amelsvoort TA, Candel MJ, Boer H, Engelen JJ, Curfs LM. Psychopathology in adults with 22q11 deletion syndrome and moderate and severe intellectual disability. J Intellect Disabil Res. 2014 Oct;58(10):915-25. doi: 10.1111/jir.12117.

Vorstman JA, Breetvelt EJ, Duijff SN, et al. Cognitive decline preceding the onset of psychosis in patients with 22q11.2 deletion syndrome. JAMA Psychiatry. 2015 Apr;72(4):377-85. doi: 10.1001/jamapsychiatry.2014.2671.

Schneider M, Debbané M, Bassett AS, et al. Psychiatric disorders from childhood to adulthood in 22q11.2 deletion syndrome: results from the International Consortium on Brain and Behavior in 22q11.2 deletion syndrome. Am J Psychiatry. 2014 Jun;171(6):627-39. doi: 10.1176/appi.ajp.2013.13070864.

Grewal J, Silversides CK, Colman JM. Pregnancy in women with heart disease: risk assessment and management of heart failure. Heart Fail Clin. 2014 Jan;10(1):117-29. doi: 10.1016/j.hfc.2013.09.014.

Mercer-Rosa L, Pinto N, Yang W, Tanel R, Goldmuntz E. 22q11.2 deletion syndrome is associated with perioperative outcome in tetralogy of Fallot. J Thorac Cardiovasc Surg. 2013 Oct;146(4):868-73. doi: 10.1016/j.jtcvs.2012.12.028.

Hofstetter AM, Jakob K, Klein NP, et al. Live vaccine use and safety in DiGeorge syndrome. Pediatrics. 2014 Apr;133(4):e946-54. doi: 10.1542/peds.2013-0831.

Björk AH, Óskarsdóttir S, Andersson BA, Friman V. Antibody deficiency in adults with 22q11.2 deletion syndrome. Am J Med Genet A. 2012 Aug;158A(8):1934-40. doi: 10.1002/ajmg.a.35484.

Basta MN, Silvestre J, Stransky C, et al. A 35-year experience with syndromic cleft palate repair: operative outcomes and long-term speech function. Ann Plast Surg. 2014 Dec;73 Suppl 2:S130-5. doi: 10.1097/SAP.0000000000000286.

Wapner RJ, Babiarz JE, Levy B, et al. Expanding the scope of noninvasive prenatal testing: detection of fetal microdeletion syndromes Am J Obstet Gynecol. 2015 Mar;212(3):332.e1-9. doi: 10.1016/j.ajog.2014.11.041.

Pretto D, Maar D, Yrigollen CM, Regan J, Tassone F. Screening newborn blood spots for 22q11.2 deletion syndrome using multiplex droplet digital PCR. Clin Chem. 2015 Jan;61(1):182-90. doi: 10.1373/clinchem.2014.230086.




DOI: https://doi.org/10.22141/2224-0551.13.1.2018.127073

Copyright (c) 2018 CHILD`S HEALTH

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

 

© Publishing House Zaslavsky, 1997-2018

 

   Seo анализ сайта