In this study socio-demographic, deafness-related and diagnosticcharacteristicsofhearingimpairedchildrenandadolescentsreferred to... Show moreIn this study socio-demographic, deafness-related and diagnosticcharacteristicsofhearingimpairedchildrenandadolescentsreferred to anationalmentalhealthservicefordeafandhardofhearingchildrenandadolescentswere examined. Socio-demographic and diagnosticcharacteristicswere compared to correspondingcharacteristicsofhearingreferred peers with identifiedmentalhealthproblems. The difference incharacteristicsbetween them andhearingreferred peers with identifiedmentalhealthproblems was analyzed. A total of 389deafandhardofhearingand 3361hearingchildrenandadolescentswas extracted from a database, all first referrals of patients of a center for child and adolescent psychiatryovera15-yearperiod. Withdeafandhardofhearingpatients we found higher rates of environmental stress, as indicated by conditions such as more one parent families (38.6% versus 25.8%), and more parents with a low educational level (44.2% versus 31.1%). Moreover,deafandhardofhearingpatients were older at their first referral (10.8 versus 9.4years) and had higher rates of pervasive developmental disorders (23.7% versus 12.3%) andmentalretardation (20.3% versus 3.9%). Within the target group ofdeafandhardofhearingpatients, most patients weredeaf(68.9%; 22.3% was severelyhardofhearing), relatively few (13.7%) had a non-syndromal hereditaryhearingimpairment, and more (21.3%) had a disabling physicalhealthcondition, especially those with a pervasive developmental disorder (42.6%). These findings illustrate both the complexity of the problems ofdeafandhardofhearingchildrenandadolescentsreferred to specialistmentalhealthservices, and the need for preventive interventions aimed at early recognition. Show less
Conventional karyotyping has been used as the standard cytogenetic technique since the 1970s. With conventional karyotyping one can detect aberrations larger than 5 __ 10 Mb and it can detect... Show moreConventional karyotyping has been used as the standard cytogenetic technique since the 1970s. With conventional karyotyping one can detect aberrations larger than 5 __ 10 Mb and it can detect chromosomal aberrations in approximately 5% of patients with mental retardation (MR). To identify smaller copy number variants (CNVs) new molecular cytogenetic techniques have been developed. One of these techniques is the Single Nucleotide Polymorphism (SNP) array. This method allows the detection of SNP-genotype as well as the presence of small deletions and amplifications. In this thesis we have studied patients with MR and/or congenital malformations. The question we have tried to answer by studying the genome of the patient is whether we can find a cause for the signs and symptoms observed in the patient. The SNP array was successfully used for the detection of novel CNVs and has replaced the conventional karyotyping in the routine diagnostic flow in MR patients in our diagnostic setting. We are therefore able to make a diagnosis in a higher number of MR patients, thus improving medical care and genetic counselling. However, a major complexity is the finding of potentially pathogenic CNVs for which the clinical significance is not immediately clear. Show less
Copy number variations (CNVs) in the human genome are inherent in both evolutionary progression as well as the etiology of disease. The introduction of this thesis will review CNVs that appear to... Show moreCopy number variations (CNVs) in the human genome are inherent in both evolutionary progression as well as the etiology of disease. The introduction of this thesis will review CNVs that appear to be neutral as well as CNVs that appear to be related to a phenotypic trait. This will be followed by a review of the many different technical approaches that can be used for detecting genomic rearrangements. The articles (chapter II & III) describe several studies that have applied the rapidly evolving techniques for CNV detection to the clinical problem of unexplained mental retardation and congenital malformation(s). The availability of the new diagnostic tools will greatly increase our understanding of the genetic causes of mental retardation and congenital malformation(s), and might one day lead to therapeutic interventions in some cases. Show less
