Download PDF
J Pediatr Genet
DOI: 10.1055/s-0042-1758872
Original Article

A Cytogenetic Study of Turkish Children with Global Developmental Delay

Osman Demirhan 
1   Department of Medical Biology and Genetics, Faculty of Medicine, Çukurova University, Balcali-Adana, Turkey
,
Özlem Hergüner
2   Department of Child Neurology, Faculty of Medicine, Çukurova University, Balcali-Adana, Turkey
,
Erdal Tunç
1   Department of Medical Biology and Genetics, Faculty of Medicine, Çukurova University, Balcali-Adana, Turkey
› Author Affiliations Funding This study was conducted by means and allowances of Cytogenetic Laboratory of Medical Biology and Genetics Department at Çukurova University.
› Further Information
    Permissions and Reprints

Abstract

Global developmental delay (GDD)/intellectual disability (ID) is common in children and its etiology is unknown in many cases. Chromosomal abnormalities are predominant genetic causes of GDD/ID. The aim of this study is to determine the genetic risk factors that may be involved in the etiology of GDD/ID. In this study, 810 children with moderate to severe, clinically unexplained GDD/ID for whom cytogenetic analysis were performed were retrospectively rescreened. The results showed that GDD/ID affected more females than males (2 girls:1 boy). A total of 54 children (6.7%) with GDD showed chromosomal aberrations (CAs): 59.3% of these CAs were structural aberrations, and the rest were numerical aberrations (40.7%). Specifically, inversions, deletions, and reciprocal and robertsonian translocations, which were detected in 1, 0.7, 0.8, and 0.4% of the children, respectively, constituted important categories of structural CAs. Among numerical CAs, classic Turner and mosaics were detected in 1.2% of all children. Trisomy 21 and mosaic trisomy 21 were detected in 1% of the children. Marker chromosomes and 47,XXY karyotypes were found in two children each. Our results suggest that female sex is more affected by CAs among GDD/ID cases, and cytogenetic analysis is useful in the etiological diagnosis of GDD/ID.

Keywords

global developmental delay - cytogenetic analysis - genetic abnormalities


Publication History

Received: 26 November 2021

Accepted: 20 September 2022

Article published online:
01 December 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Shevell MI, Majnemer A, Rosenbaum P, Abrahamowicz M. Etiologic yield of subspecialists' evaluation of young children with global developmental delay. J Pediatr 2000; 136 (05) 593-598
    CrossrefPubMedGoogle Scholar
  • 2 Bélanger SA, Caron J. Evaluation of the child with global developmental delay and intellectual disability. Paediatr Child Health 2018; 23 (06) 403-419
    CrossrefPubMedGoogle Scholar
  • 3 Yeargin-Allsopp M, Murphy CC, Cordero JF, Decouflé P, Hollowell JG. Reported biomedical causes and associated medical conditions for mental retardation among 10-year-old children, metropolitan Atlanta, 1985 to 1987. Dev Med Child Neurol 1997; 39 (03) 142-149
    CrossrefPubMedGoogle Scholar
  • 4 Grayton HM, Fernandes C, Rujescu D, Collier DA. Copy number variations in neurodevelopmental disorders. Prog Neurobiol 2012; 99 (01) 81-91
    CrossrefPubMedGoogle Scholar
  • 5 Majnemer A, Shevell MI. Diagnostic yield of the neurologic assessment of the developmentally delayed child. J Pediatr 1995; 127 (02) 193-199
    CrossrefPubMedGoogle Scholar
  • 6 Harris JC. Intellectual Disability: Understanding Its Development, Causes, Classification, Evaluation, and Treatment. Oxford: Oxford University Press; 2006
    Google Scholar
  • 7 Maulik PK, Mascarenhas MN, Mathers CD, Dua T, Saxena S. Prevalence of intellectual disability: a meta-analysis of population-based studies. Res Dev Disabil 2011; 32 (02) 419-436
    CrossrefPubMedGoogle Scholar
  • 8 Morrow EM. Genomic copy number variation in disorders of cognitive development. J Am Acad Child Adolesc Psychiatry 2010; 49 (11) 1091-1104
    PubMedGoogle Scholar
  • 9 Regier DA, Friedman JM, Marra CA. Value for money? Array genomic hybridization for diagnostic testing for genetic causes of intellectual disability. Am J Hum Genet 2010; 86 (05) 765-772
    CrossrefPubMedGoogle Scholar
  • 10 Savatt JM, Myers SM. Genetic testing in neurodevelopmental disorders. Front Pediatr 2021; 9: 526779
    CrossrefPubMedGoogle Scholar
  • 11 Uwineza A, Hitayezu J, Jamar M. et al. Cytogenetic studies of Rwandan pediatric patients presenting with global developmental delay, intellectual disability and/or multiple congenital anomalies. J Trop Pediatr 2016; 62 (01) 38-45
    CrossrefPubMedGoogle Scholar
  • 12 Mundhofir FE, Winarni TI, van Bon BW. et al. A cytogenetic study in a large population of intellectually disabled Indonesians. Genet Test Mol Biomarkers 2012; 16 (05) 412-417
    CrossrefPubMedGoogle Scholar
  • 13 Balkan M, Akbas H, Isi H. et al. Cytogenetic analysis of 4216 patients referred for suspected chromosomal abnormalities in Southeast Turkey. Genet Mol Res 2010; 9 (02) 1094-1103
    CrossrefPubMedGoogle Scholar
  • 14 Aboussair N, Jaouad IC, Dequaqui SC. et al. Cytogenetic analysis of 5572 patients referred for suspected chromosomal abnormalities in Morocco. Genet Test Mol Biomarkers 2012; 16 (06) 569-573
    CrossrefPubMedGoogle Scholar
  • 15 Kim SS, Jung SC, Kim HJ, Moon HR, Lee JS. Chromosome abnormalities in a referred population for suspected chromosomal aberrations: a report of 4117 cases. J Korean Med Sci 1999; 14 (04) 373-376
    CrossrefPubMedGoogle Scholar
  • 16 Dayakar S, Rani DS, Babu SJ. et al. Increasing role of cytogenetics in pediatric practice. Genet Test Mol Biomarkers 2010; 14 (02) 197-204
    CrossrefPubMedGoogle Scholar
  • 17 Thillainathan S, Sirisena ND, Kariyawasam KW, Jayasekara RW, Dissanayake VHW. Cytogenetic analysis of chromosomal abnormalities in Sri Lankan children. World J Pediatr 2015; 11 (04) 374-379
    CrossrefPubMedGoogle Scholar
  • 18 Duarte AC, Cunha E, Roth JM, Ferreira FLS, Garcias GL, Martino-Roth MG. Cytogenetics of genetic counseling patients in Pelotas, Rio Grande do Sul, Brazil. Genet Mol Res 2004; 3 (03) 303-308
    PubMedGoogle Scholar
  • 19 Curry CJ, Stevenson RE, Aughton D. et al. Evaluation of mental retardation: recommendations of a consensus conference: American College of Medical Genetics. Am J Med Genet 1997; 72 (04) 468-477
    CrossrefPubMedGoogle Scholar
  • 20 Hu T, Zhang Z, Wang J. et al. Chromosomal aberrations in pediatric patients with developmental delay/intellectual disability: a single-center clinical investigation. BioMed Res Int 2019; 2019: 9352581
    PubMedGoogle Scholar
  • 21 Flint J, Wilkie AO, Buckle VJ, Winter RM, Holland AJ, McDermid HE. The detection of subtelomeric chromosomal rearrangements in idiopathic mental retardation. Nat Genet 1995; 9 (02) 132-140
    CrossrefPubMedGoogle Scholar
  • 22 Knight SJ, Regan R, Nicod A. et al. Subtle chromosomal rearrangements in children with unexplained mental retardation. Lancet 1999; 354 (9191): 1676-1681
    CrossrefPubMedGoogle Scholar
  • 23 Wu Y, Ji T, Wang J. et al. Submicroscopic subtelomeric aberrations in Chinese patients with unexplained developmental delay/mental retardation. BMC Med Genet 2010; 11: 72
    CrossrefPubMedGoogle Scholar
  • 24 Evdokimova VN, Nikitina TV, Lebedev IN, Sukhanova NN, Nazarenko SA. Sex ratio in early embryonal mortality in man [in Russian]. Ontogenez 2000; 31 (04) 251-257
    PubMedGoogle Scholar
  • 25 Morin SJ, Eccles J, Iturriaga A, Zimmerman RS. Translocations, inversions and other chromosome rearrangements. Fertil Steril 2017; 107 (01) 19-26
    CrossrefPubMedGoogle Scholar
  • 26 Shaffer LG, Jackson-Cook CK, Stasiowski BA, Spence JE, Brown JA. Parental origin determination in thirty de novo Robertsonian translocations. Am J Med Genet 1992; 43 (06) 957-963
    CrossrefPubMedGoogle Scholar
  • 27 Halgren C, Nielsen NM, Nazaryan-Petersen L. et al. Risks and recommendations in prenatally detected de novo balanced chromosomal rearrangements from assessment of long-term outcomes. Am J Hum Genet 2018; 102 (06) 1090-1103
    CrossrefPubMedGoogle Scholar
  • 28 Gorski JL, Kistenmacher ML, Punnett HH, Zackai EH, Emanuel BS. Reproductive risks for carriers of complex chromosome rearrangements: analysis of 25 families. Am J Med Genet 1988; 29 (02) 247-261
    CrossrefPubMedGoogle Scholar
  • 29 Vermeulen S, Menten B, Van Roy N. et al. Molecular cytogenetic analysis of complex chromosomal rearrangements in patients with mental retardation and congenital malformations: delineation of 7q21.11 breakpoints. Am J Med Genet A 2004; 124A (01) 10-18
    CrossrefPubMedGoogle Scholar
  • 30 Wu BL, Schneider GH, Sabatino DE, Bozovic LZ, Cao B, Korf BR. Distal 8p deletion (8)(p23.1): an easily missed chromosomal abnormality that may be associated with congenital heart defect and mental retardation. Am J Med Genet 1996; 62 (01) 77-83
    CrossrefPubMedGoogle Scholar
  • 31 Maurin ML, Brisset S, Le Lorc'h M. et al. Terminal 14q32.33 deletion: genotype-phenotype correlation. Am J Med Genet A 2006; 140 (21) 2324-2329
    CrossrefPubMedGoogle Scholar
  • 32 Spinner NB, Conlin LK, Mulchandani S, Emanuel BS. Deletions and other structural abnormalities of the autosomes. In: Rimoin DL, Pyeritz RE, Korf BR. eds. Emery and Rimoin's Principles and Practice of Medical Genetics. Oxford: Academic Press; 2013: 1-37
    Google Scholar
  • 33 Cho EK, Kim J, Yang A, Cho SY, Jin DK. 2q37 Deletion syndrome confirmed by high-resolution cytogenetic analysis. Ann Pediatr Endocrinol Metab 2017; 22 (02) 129-132
    CrossrefPubMedGoogle Scholar
  • 34 Theisen A, Shaffer LG. Disorders caused by chromosome abnormalities. Appl Clin Genet 2010; 3: 159-174
    PubMedGoogle Scholar
  • 35 Cornish KM, Cross G, Green A, Willatt L, Bradshaw JM. A neuropsychological-genetic profile of atypical cri du chat syndrome: implications for prognosis. J Med Genet 1999; 36 (07) 567-570
    PubMedGoogle Scholar
  • 36 Ropers HH. X-linked mental retardation: many genes for a complex disorder. Curr Opin Genet Dev 2006; 16 (03) 260-269
    CrossrefPubMedGoogle Scholar
  • 37 Carrel L, Cottle AA, Goglin KC, Willard HF. A first-generation X-inactivation profile of the human X chromosome. Proc Natl Acad Sci U S A 1999; 96 (25) 14440-14444
    CrossrefPubMedGoogle Scholar
  • 38 Feng Y, Zhang F, Lokey LK. et al. Translational suppression by trinucleotide repeat expansion at FMR1. Science 1995; 268 (5211): 731-734
    CrossrefPubMedGoogle Scholar
  • 39 Sasikala K. Occurrence of pericentric inversion in a group of children with multiple congenital abnormalities. The Indian Zoologist 1990; 14: 169-174
    PubMedGoogle Scholar
  • 40 Gardner RJ, Sutherland GR. Chromosomal abnormalities and genetic counseling. In: Gardner RJ, Sutherland GR. eds. Elements of Medical Cytogenetic. New York, NY: Oxford University Press; 1990: 6-9
    Google Scholar
  • 41 Demirhan O, Pazarbasi A, Suleymanova-Karahan D, Tanriverdi N, Kilinc Y. Correlation of clinical phenotype with a pericentric inversion of chromosome 9 and genetic counseling. Saudi Med J 2008; 29 (07) 946-951
    PubMedGoogle Scholar
  • 42 Kamnasaran D, Chen CP, Devriendt K, Mehta L, Cox DW. Defining a holoprosencephaly locus on human chromosome 14q13 and characterization of potential candidate genes. Genomics 2005; 85 (05) 608-621
    CrossrefPubMedGoogle Scholar
  • 43 Morgan T. Turner syndrome: diagnosis and management. Am Fam Physician 2007; 76 (03) 405-410
    PubMedGoogle Scholar
  • 44 van Karnebeek CD, Jansweijer MC, Leenders AG, Offringa M, Hennekam RC. Diagnostic investigations in individuals with mental retardation: a systematic literature review of their usefulness. Eur J Hum Genet 2005; 13 (01) 6-25
    CrossrefPubMedGoogle Scholar
  • 45 Sadek AA, Mohamed MA. Yield of karyotyping in children with developmental delay and/or dysmorphic features in Sohag University Hospital, Upper Egypt. Egypt J Med Hum Genet 2018; 19: 253-259
    CrossrefPubMedGoogle Scholar
  • 46 Chapman RS, Hesketh LJ. Behavioral phenotype of individuals with Down syndrome. Ment Retard Dev Disabil Res Rev 2000; 6 (02) 84-95
    CrossrefPubMedGoogle Scholar
  • 47 Kumin L. Speech and language skills in children with Down syndrome. Ment Retard Dev Disabil Res Rev 1996; 2: 109-115
    CrossrefPubMedGoogle Scholar
  • 48 Maurer B, Haaf T, Stout K, Reissmann N, Steinlein C, Schmid M. Two supernumerary marker chromosomes, originating from chromosomes 6 and 11, in a child with developmental delay and craniofacial dysmorphism. Cytogenet Cell Genet 2001; 93 (3–4): 182-187
    CrossrefPubMedGoogle Scholar
  • 49 Hu J, Madan-Khetarpal S, Russi AHS. et al. Three supernumerary marker chromosomes in a patient with developmental delay, mental retardation, and dysmorphic features. Genet Res Int 2011; 185271: 7
    PubMedGoogle Scholar