Abstract Intellectual disability, occurring in 1%-3% of the general population, is a common disease of the nervous system in children. Since diverse genetic and environmental factors contribute to its pathogenesis, the etiological diagnosis of intellectual disability is challenging with respect to the selection of diagnostic tests. It is important to determine the etiology of intellectual disability for the assessment of prognosis, treatment and the family plan. This paper summarizes the research progress in etiology and diagnosis for intellectual disability and introduces the recommended clinical genetics diagnostic approach from the American Academy of Pediatrics.
Schalock RL, Luckasson RA, Shogren KA, et al. The renaming of mental retardation:understanding the change to the term intellectual disability[J]. Intellect Dev Disabil, 2007, 45(2):116- 124.
[2]
Shevell M, Ashwal S, Donley D, et al. 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[J]. Neurology, 2003, 60(3):367-380.
[3]
Gmitrowicz A, Kucharska A. Developmental disorders in the fourth edition of the American classification:diagnostic and statistical manual of mental disorders (DSM IV-optional book)[J]. Psychiatr Pol, 1994, 28(5):509-521.
[4]
van Bokhoven H. Genetic and epigenetic networks in intellectual disabilities[J]. Annu Rev Genet, 2011, 45:81-104.
[5]
Moeschler JB, Shevell M. Comprehensive evaluation of the child with intellectual disability or global developmental delays[J]. Pediatrics, 2014, 134(3):e903-918.
[6]
Guo L. Etiological analysis of neurodevelopmental disabilities:single-center eight-year clinical experience in south China[J]. J Biomed Biotechnol, 2011, 2011(doi:10.1155/2011/318616).
Gilissen C, Hehir-Kwa JY, Thung DT, et al. Genome sequencing identifies major causes of severe intellectual disability[J]. Nature, 2014, 511(7509):344-347.
[9]
de Ligt J, Willemsen MH, van Bon BW, et al. Diagnostic exome sequencing in persons with severe intellectual disability[J]. N Engl J Med, 2012, 367(20):1921-1929.
[10]
Rauch A, Wieczorek D, Graf E, et al. Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability:an exome sequencing study[J]. Lancet, 2012, 380(9854):1674-1682.
Flint J, Wilkie AO, Buckle VJ, et al. The detection of subtelomeric chromosomal rearrangements in idiopathic mental retardation[J]. Nat Genet, 1995, 9(2):132-140.
[13]
Wu Y, Ji T, Wang J, et al. Submicroscopic subtelomeric aberrations in Chinese patients with unexplained developmental delay/mental retardation[J]. BMC Med Genet, 2010, 11:72.
[14]
Shao L, Shaw CA, Lu XY, et al. Identification of chromosome abnormalities in subtelomeric regions by microarray analysis:a study of 5,380 cases[J]. Am J Med Genet A, 2008, 146A(17):2242-2251.
[15]
Knight SJ, Regan R, Nicod A, et al. Subtle chromosomal rearrangements in children with unexplained mental retardation[J]. Lancet, 1999, 354(9191):1676-1681.
[16]
Sagoo GS, Butterworth AS, Sanderson S, et al. Array CGH in patients with learning disability (mental retardation) and congenital anomalies:updated systematic review and metaanalysis of 19 studies and 13,926 subjects[J]. Genet Med, 2009, 11(3):139-146.
[17]
Hochstenbach R, van Binsbergen E, Engelen J, et al. Array analysis and karyotyping:workflow consequences based on a retrospective study of 36,325 patients with idiopathic developmental delay in the Netherlands[J]. Eur J Med Genet, 2009, 52(4):161-169.
[18]
Verkerk AJ, Pieretti M, Sutcliffe JS, et al. Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome[J]. Cell, 1991, 65(5):905-914.
[19]
Christodoulou J, Ho G. MECP2-Related Disorders[M]. GeneReviews(R), 2012, Seattle (WA).
[20]
Lubs HA, Stevenson RE, Schwartz CE. Fragile X and X-linked intellectual disability:four decades of discovery[J]. Am J Hum Genet, 2012, 90(4):579-590.
[21]
Hamamy HA, Masri AT, Al-Hadidy AM, et al. Consanguinity and genetic disorders Profile from Jordan[J]. Saudi Med J, 2007, 28(7):1015-1017.
[22]
Miller DT, Adam MP, Aradhya S, et al. Consensus statement:chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies[J]. Am J Hum Genet, 2010, 86(5):749-764.
[23]
Schaaf CP, Wiszniewska J, Beaudet AL. Copy number and SNP arrays in clinical diagnostics[J]. Annu Rev Genomics Hum Genet, 2011, 12:25-51.
[24]
Hook EB. Exclusion of chromosomal mosaicism:tables of 90%, 95% and 99% confidence limits and comments on use[J]. Am J Hum Genet, 1977, 29(1):94-97.
[25]
Conlin LK, Thiel BD, Bonnemann CG, et al. Mechanisms of mosaicism, chimerism and uniparental disomy identified by single nucleotide polymorphism array analysis[J]. Hum Mol Genet, 2010, 19(7):1263-1275.
[26]
Flore LA, Milunsky JM. Updates in the genetic evaluation of the child with global developmental delay or intellectual disability[J]. Semin Pediatr Neurol, 2012, 19(4):173-180.
[27]
Ellison JW, Ravnan JB, Rosenfeld JA, et al. Clinical utility of chromosomal microarray analysis[J]. Pediatrics, 2012, 130(5):e1085-1095.
[28]
Girirajan S, Rosenfeld JA, Cooper GM, et al. A recurrent 16p12.1 microdeletion supports a two-hit model for severe developmental delay[J]. Nat Genet, 2010, 42(3):203-209.
[29]
Vissers LE, de LJ, Gilissen C, et al. A de novo paradigm for mental retardation[J]. Nat Genet, 2010, 42(12):1109-1112.
[30]
BCABS Association. Special report:exome sequencing for clinical diagnosis of patients with suspected genetic disorders[J]. Technol Eval Cent Assess Program Exec Summ, 2013, 28(3):1-4.
[31]
Biesecker LG, Green RC. Diagnostic clinical genome and exome sequencing[J]. N Engl J Med, 2014, 371(12):1170.
[32]
Srivastava S, Cohen JS, Vernon H, et al. Clinical whole exome sequencing in child neurology practice[J]. Ann Neurol, 2014, 76(4):473-483.
[33]
Engbers HM, Berger R, van HP, et al. Yield of additional metabolic studies in neurodevelopmental disorders[J]. Ann Neurol, 2008, 64(2):212-217.
[34]
Lion-Francois L, Cheillan D, Pitelet G, et al. High frequency of creatine deficiency syndromes in patients with unexplained mental retardation[J]. Neurology, 2006, 67(9):1713-1714.
[35]
van Karnebeek CD, Shevell M, Zschocke J, et al. The metabolic evaluation of the child with an intellectual developmental disorder:diagnostic algorithm for identification of treatable causes and new digital resource[J]. Mol Genet Metab, 2014, 111(4):428-438.
[36]
van Karnebeek CD, Stockler S. Treatable inborn errors of metabolism causing intellectual disability:a systematic literature review[J]. Mol Genet Metab, 2012, 105(3):368-381.
