Download PDF
CC BY-NC-ND 4.0 · Neuropediatrics
DOI: 10.1055/a-2430-0494
Original Article

Diagnostic Approach to Children with Unexplained Global Developmental Delay in Pediatric Neurology Outpatient Clinic

Airin Veronese
1   Department of Pediatric Neurology, University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia
,
Damjan Osredkar
1   Department of Pediatric Neurology, University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia
2   University of Ljubljana, Faculty of Medicine, Center for Developmental Neuroscience, Ljubljana, Slovenia
,
Luca Lovrečić
3   Clinical Institute for Genomic Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia
4   Department of Gynaecology and Obstetrics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
,
Anja Troha Gergeli
1   Department of Pediatric Neurology, University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia
› Author Affiliations
› Further Information
Also available at
   Permissions and Reprints

Corrected by:

Corrigendum: Diagnostic Approach to Children with Unexplained Global Developmental Delay in Pediatric Neurology Outpatient ClinicNeuropediatrics eFirst
DOI: 10.1055/s-0044-1801763

Abstract

Background Global developmental delay (GDD) is a common pediatric disorder that affects up to 3% of children. Due to the heterogeneous etiology of GDD, diagnostic procedures and algorithms are complex and diverse. The aim of our study was to investigate the diagnostic yield of genetic, metabolic, and imaging studies in establishing the etiology of unexplained GDD (UGDD).

Methods In this retrospectively observational study, we examined the medical records of all children diagnosed with UGDD at the Department of Pediatric Neurology, University Medical Centre Ljubljana, Slovenia, between January and December 2019. We evaluated the effectiveness of various genetic, metabolic, and magnetic resonance imaging (MRI) tests in identifying the underlying cause of GDD. Additionally, we assessed subgroups of patients to determine whether any of the studied tests were particularly beneficial based on their clinical symptoms.

Results A total of 123 patients met the inclusion criteria, with a median age of 4.3 years (range, 0–16 years), of which 71 (57.7%) were males. Genetic diagnosis was established in 47.1% (58/123) of patients. Metabolic laboratory testing did not identify a metabolic disease in any of the tested participants (114/123) and MRI was critical for diagnosis in only 1/81 (1.2%) patient.

Conclusion Our findings strongly suggest that genetic testing surpasses MRI and metabolic testing in establishing the etiology of UGDD in a pediatric neurology outpatient setting. This information will help guide the diagnostic evaluation of these children.

Keywords

unexplained global developmental delay - diagnostic yield - genetics - MRI - metabolic screening

Note

The work was performed at the Department of Pediatric Neurology, University Children's Hospital, University Medical Centre Ljubljana.


Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.


Supplementary Material



Publication History

Received: 30 May 2024

Accepted: 25 August 2024

Accepted Manuscript online:
07 October 2024

Article published online:
19 October 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Mithyantha R, Kneen R, McCann E, Gladstone M. Current evidence-based recommendations on investigating children with global developmental delay. Arch Dis Child 2017; 102 (11) 1071-1076
    Search in Google Scholar
  • 2 O'Byrne JJ, Lynch SA, Treacy EP. et al. Unexplained developmental delay/learning disability: guidelines for best practice protocol for first line assessment and genetic/metabolic/radiological investigations. Ir J Med Sci 2016; 185 (01) 241-248
    Search in Google Scholar
  • 3 Michelson DJ, Shevell MI, Sherr EH, Moeschler JB, Gropman AL, Ashwal S. Evidence report: Genetic and metabolic testing on children with global developmental delay: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology 2011; 77 (17) 1629-1635
    Search in Google Scholar
  • 4 Bélanger SA, Caron J. Evaluation of the child with global developmental delay and intellectual disability. Paediatr Child Health 2018; 23 (06) 403-419
    Search in Google Scholar
  • 5 Lee JS, Hwang H, Kim SY. et al. Chromosomal microarray with clinical diagnostic utility in children with developmental delay or intellectual disability. Ann Lab Med 2018; 38 (05) 473-480
    Search in Google Scholar
  • 6 Vasudevan P, Suri M. A clinical approach to developmental delay and intellectual disability. Clin Med (Lond) 2017; 17 (06) 558-561
    Search in Google Scholar
  • 7 van Karnebeek CDM, Scheper FY, Abeling NG. et al. Etiology of mental retardation in children referred to a tertiary care center: a prospective study. Am J Ment Retard 2005; 110 (04) 253-267
    Search in Google Scholar
  • 8 AlMutiri R, Malta M, Shevell MI, Srour M. Evaluation of Individuals with non-syndromic global developmental delay and intellectual disability. Children (Basel) 2023; 10 (03) 414
    Search in Google Scholar
  • 9 van Karnebeek CDM. Evaluation of the child with developmental impairments. Continuum (Minneap Minn) 2018; 24 (1, Child Neurology): 228-247
    Search in Google Scholar
  • 10 Trakadis Y, Shevell M. Microarray as a first genetic test in global developmental delay: a cost-effectiveness analysis. Dev Med Child Neurol 2011; 53 (11) 994-999
    Search in Google Scholar
  • 11 Srivastava S, Love-Nichols JA, Dies KA. et al. NDD Exome Scoping Review Work Group. Meta-analysis and multidisciplinary consensus statement: exome sequencing is a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders. Genet Med 2019; 21 (11) 2413-2421
    Search in Google Scholar
  • 12 Lampret BR, Remec ŽI, Torkar AD. et al. Expanded newborn screening program in Slovenia using tandem mass spectrometry and confirmatory next generation sequencing genetic testing. Zdr Varst 2020; 59 (04) 256-263
    Search in Google Scholar
  • 13 Bergant G, Maver A, Lovrecic L, Čuturilo G, Hodzic A, Peterlin B. Comprehensive use of extended exome analysis improves diagnostic yield in rare disease: a retrospective survey in 1,059 cases. Genet Med 2018; 20 (03) 303-312
    Search in Google Scholar
  • 14 Lovrečić L, Rajar P, Volk M. et al. Diagnostic efficacy and new variants in isolated and complex autism spectrum disorder using molecular karyotyping. J Appl Genet 2018; 59 (02) 179-185
    Search in Google Scholar
  • 15 Richards S, Aziz N, Bale S. et al. ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015; 17 (05) 405-424
    Search in Google Scholar
  • 16 D'Arrigo S, Gavazzi F, Alfei E. et al. The diagnostic yield of array comparative genomic hybridization is high regardless of severity of intellectual disability/developmental delay in children. J Child Neurol 2016; 31 (06) 691-699
    Search in Google Scholar
  • 17 Misra S, Peters G, Barnes E. et al. Yield of comparative genomic hybridization microarray in pediatric neurology practice. Neurol Genet 2019; 5 (06) e367
    Search in Google Scholar
  • 18 Moeschler JB, Shevell M. Committee on Genetics. Comprehensive evaluation of the child with intellectual disability or global developmental delays. Pediatrics 2014; 134 (03) e903-e918
    Search in Google Scholar
  • 19 Xiang J, Ding Y, Yang F. et al. Genetic analysis of children with unexplained developmental delay and/or intellectual disability by whole-exome sequencing. Front Genet 2021; 12: 738561
    Search in Google Scholar
  • 20 Savatt JM, Myers SM. Genetic testing in neurodevelopmental disorders. Front Pediatr 2021; 9: 526779
    Search in Google Scholar
  • 21 Djordjevic D, Tsuchiya E, Fitzpatrick M, Sondheimer N, Dowling JJ. Utility of metabolic screening in neurological presentations of infancy. Ann Clin Transl Neurol 2020; 7 (07) 1132-1140
    Search in Google Scholar
  • 22 Griffiths PD, Batty R, Warren D. et al. The use of MR imaging and spectroscopy of the brain in children investigated for developmental delay: what is the most appropriate imaging strategy?. Eur Radiol 2011; 21 (09) 1820-1830
    Search in Google Scholar
  • 23 Shevell M, Ashwal S, Donley D. et al. Quality Standards Subcommittee of the American Academy of Neurology, Practice Committee of the Child Neurology Society. Practice parameter: evaluation of the child with global developmental delay: report of the Quality Standards Subcommittee of the American Academy of Neurology and The Practice Committee of the Child Neurology Society. Neurology 2003; 60 (03) 367-380
    Search in Google Scholar