Genetic Etiology of Adult Intellectual Disability (ID) of Unknown Cause in Qatar: a Retrospective Study

Overview

Journal Qatar Med J

Specialty General Medicine

Date 2022 Jun 27

PMID 35756865

Authors

Hesham Rustom

Yassin Hassan Eltorki

Mohamed Adil Shah Khoodoruth

Oraib Abdallah

Noriya Al-Khuzaei

Noriya Iqbal

Noriya Alabdulla

Affiliations

Soon will be listed here.

Abstract

Background: Intellectual disability (ID) is a common condition that consists of a heterogeneous group of clinical conditions with different etiologies, including genetic conditions. Identifying those with a genetic cause results in better clinical management.

Aim: To identify the genetic etiology of ID in adult patients with unknown etiology presenting to a specialist learning disability service in Qatar.

Methods: Retrospective review of chart notes of patients referred for ID service from January 1, 2015 to January 1, 2020.

Results: Of the 228 patients, 82 had a known cause of ID and did not require genetic testing, 22 had an unknown cause and underwent genetic testing, and 124 had an unknown cause and did not undergo genetic testing. Of the 82 patients with a known cause of ID, about one-half had an autistic spectrum disorder (ASD) and 18 patients had a genetic disorder. Of the 22 patients who underwent genetic testing, 2 were positive for the Fragile-X mental retardation 1 gene, 3 underwent chromosomal microarray, and 7 underwent whole-exome sequencing. Seven abnormal genes were identified.

Conclusions: Identifying the underlying genetic etiology of patients with ID has major implications for diagnostic and therapeutic approaches. Additionally, it guides a prediction of the natural history of the disease and makes it possible to test at-risk family members.

References

Hochstenbach R, Buizer-Voskamp J, Vorstman J, Ophoff R . Genome arrays for the detection of copy number variations in idiopathic mental retardation, idiopathic generalized epilepsy and neuropsychiatric disorders: lessons for diagnostic workflow and research. Cytogenet Genome Res. 2011; 135(3-4):174-202. DOI: 10.1159/000332928. View

Stankiewicz P, Beaudet A . Use of array CGH in the evaluation of dysmorphology, malformations, developmental delay, and idiopathic mental retardation. Curr Opin Genet Dev. 2007; 17(3):182-92. DOI: 10.1016/j.gde.2007.04.009. View

Ropers H . Genetics of intellectual disability. Curr Opin Genet Dev. 2008; 18(3):241-50. DOI: 10.1016/j.gde.2008.07.008. View

Taylor M, Jirikowic J, Wells C, Springer M, McGavran L, Lunt B . High prevalence of array comparative genomic hybridization abnormalities in adults with unexplained intellectual disability. Genet Med. 2009; 12(1):32-8. DOI: 10.1097/GIM.0b013e3181c83de0. View

Sagoo G, Butterworth A, Sanderson S, Shaw-Smith C, Higgins J, Burton H . Array CGH in patients with learning disability (mental retardation) and congenital anomalies: updated systematic review and meta-analysis of 19 studies and 13,926 subjects. Genet Med. 2009; 11(3):139-46. DOI: 10.1097/GIM.0b013e318194ee8f. View

Yavarna T, Al-Dewik N, Al-Mureikhi M, Ali R, Al-Mesaifri F, Mahmoud L . High diagnostic yield of clinical exome sequencing in Middle Eastern patients with Mendelian disorders. Hum Genet. 2015; 134(9):967-80. DOI: 10.1007/s00439-015-1575-0. View

Snowling M, Muter V, Carroll J . Children at family risk of dyslexia: a follow-up in early adolescence. J Child Psychol Psychiatry. 2007; 48(6):609-18. DOI: 10.1111/j.1469-7610.2006.01725.x. View

Raffan E, Hurst L, Al Turki S, Carpenter G, Scott C, Daly A . Early Diagnosis of Werner's Syndrome Using Exome-Wide Sequencing in a Single, Atypical Patient. Front Endocrinol (Lausanne). 2012; 2:8. PMC: 3356119. DOI: 10.3389/fendo.2011.00008. View

Worthey E, Mayer A, Syverson G, Helbling D, Bonacci B, Decker B . Making a definitive diagnosis: successful clinical application of whole exome sequencing in a child with intractable inflammatory bowel disease. Genet Med. 2010; 13(3):255-62. DOI: 10.1097/GIM.0b013e3182088158. View

10.

Choi M, Scholl U, Ji W, Liu T, Tikhonova I, Zumbo P . Genetic diagnosis by whole exome capture and massively parallel DNA sequencing. Proc Natl Acad Sci U S A. 2009; 106(45):19096-101. PMC: 2768590. DOI: 10.1073/pnas.0910672106. View

11.

Li M, Andersson H . Clinical application of microarray-based molecular cytogenetics: an emerging new era of genomic medicine. J Pediatr. 2009; 155(3):311-7. DOI: 10.1016/j.jpeds.2009.04.001. View

12.

Ng S, Turner E, Robertson P, Flygare S, Bigham A, Lee C . Targeted capture and massively parallel sequencing of 12 human exomes. Nature. 2009; 461(7261):272-6. PMC: 2844771. DOI: 10.1038/nature08250. View

13.

Al-Dewik N, Al-Mureikhi M, Shahbeck N, Ali R, Al-Mesaifri F, Mahmoud L . Clinical genetics and genomic medicine in Qatar. Mol Genet Genomic Med. 2018; 6(5):702-712. PMC: 6160705. DOI: 10.1002/mgg3.474. View

14.

McNamara R, Randell E, Gillespie D, Wood F, Felce D, Romeo R . A pilot randomised controlled trial of community-led ANtipsychotic Drug REduction for Adults with Learning Disabilities. Health Technol Assess. 2017; 21(47):1-92. PMC: 5592429. DOI: 10.3310/hta21470. View

15.

Snowling M, Gallagher A, Frith U . Family risk of dyslexia is continuous: individual differences in the precursors of reading skill. Child Dev. 2003; 74(2):358-73. DOI: 10.1111/1467-8624.7402003. View

16.

Zolezzi M, BenSmail N, Zahrah F, Khaled S, El-Gaili T . Stigma associated with mental illness: perspectives of university students in Qatar. Neuropsychiatr Dis Treat. 2017; 13:1221-1233. PMC: 5431692. DOI: 10.2147/NDT.S132075. View

17.

Savatt J, Myers S . Genetic Testing in Neurodevelopmental Disorders. Front Pediatr. 2021; 9:526779. PMC: 7933797. DOI: 10.3389/fped.2021.526779. View

18.

Bilguvar K, Ozturk A, Louvi A, Kwan K, Choi M, Tatli B . Whole-exome sequencing identifies recessive WDR62 mutations in severe brain malformations. Nature. 2010; 467(7312):207-10. PMC: 3129007. DOI: 10.1038/nature09327. View

19.

Salvador-Carulla L, Bertelli M . 'Mental retardation' or 'intellectual disability': time for a conceptual change. Psychopathology. 2007; 41(1):10-6. DOI: 10.1159/000109950. View

20.

Maulik P, Mascarenhas M, Mathers C, Dua T, Saxena S . Prevalence of intellectual disability: a meta-analysis of population-based studies. Res Dev Disabil. 2011; 32(2):419-36. DOI: 10.1016/j.ridd.2010.12.018. View