Clinical Genetic Evaluation of the Child With Mental Retardation or Developmental Delays

Abstract

This clinical report describes the clinical genetic evaluation of the child with developmental delays or mental retardation. The purpose of this report is to describe the optimal clinical genetics diagnostic evaluation to assist pediatricians in providing a medical home for children with developmental delays or mental retardation and their families. The literature supports the benefit of expert clinical judgment by a consulting clinical geneticist in the diagnostic evaluation. However, it is recognized that local factors may preclude this particular option. No single approach to the diagnostic process is supported by the literature. This report addresses the diagnostic importance of clinical history, 3-generation family history, dysmorphologic examination, neurologic examination, chromosome analysis (≥650 bands), fragile X molecular genetic testing, fluorescence in situ hybridization studies for subtelomere chromosome rearrangements, molecular genetic testing for typical and atypical presentations of known syndromes, computed tomography and/or magnetic resonance brain imaging, and targeted studies for metabolic disorders.

Aetiology of intellectual disability in paediatric outpatients in Northern India

“…5 However, the diagnostic yield of chromosomal or cytogenetic testing in this study was essentially nil as the four children with Down syndrome had clinically obvious features. In the rest of the 28 children, karyotyping and cytogenetic studies did not yield any abnormalities.…”

“…5 In an Indian study in 47 patients with intellectual disability of unknown origin, Pandey et al found that 19 (42.2%) had specific findings useful in reaching an aetiologic diagnosis. 32 This is borne out by our study on unselected patients, where 48 (42.1%) had equivalent specific diagnostic findings on neuroimaging.…”

“…3,4 The reported frequencies of aetiological categories of intellectual disability are remarkably variable, with exogenous and endogenous (genetic) causes both ranging roughly between 17% and 47%. 5 Again, variations may be explained by differences in setting, the severity of intellectual disability, patient selection, technological advances over time, and definitions used. Studies from industrialized countries have consistently shown that prenatal and genetic causes predominate.…”

Genome-wide UPD screening in patients with intellectual disability

“…2 Several studies reported causative submicroscopic chromosomal aberrations that were only detectable by chromosomal microarray analysis (CMA) 3 and a consensus statement was published that CMA is recommended as first-tier clinical diagnostic test for patients with DD/ID. 4 Besides the detection of submicroscopic deletions and duplications, SNP microarrays can be used for detection of uniparental disomy (UPD).…”

Dysmorphology at a distance: results of a web-based diagnostic service

“…The rarity of these conditions means that even within these centres, experience may be limited, resulting in a delayed or uncertain diagnosis, reported to occur in 38% of the cases in a study by Moeschler et al 3 Access to specialists in dysmorphology varies widely across the EU. To date, there has been no formal network for dysmorphology, and though there is considerable knowledge and experience within the existing European Centres of Expertise, the channels of communication between Centres are informal and inconsistent.…”