Neurodevelopmental disorders; yield of extended investigations

Abstract

Summary Chapter 1 addresses general aspects of neurodevelopmental disorders and gives an outline of this thesis. Neurodevelopmental disorders (NDD), are an important health care problem with a prevalence of 2-3% in the general population. The widespread etiological causes for NDD comprise exogenic factors (teratogens, infections and trauma) and genetic causes (including metabolic diseases). The complicated diagnostic work-up in NDD is described. Chapter 2 describes the importance of metabolic investigations in the diagnostic pathway of NDD. We studied the yield of metabolic investigations in patients with neurodevelopmental disorders of unknown origin and found a yield of 2.8 % despite performed metabolic investigations before referral. As seen in this study, additional metabolic investigations can even extend the metabolic yield in an already screened population. Chapter 3 describes the findings of MRI scans in patients with unexplained NDD. In 30.7 % of the patients abnormal MRI scans were observed and in 5.4 % the MRI scans lead to an etiologic diagnosis. This study shows in a large population of patients with NDD that neurological findings are indicative for having an abnormal or diagnostic MRI. In our specialised centre 5.4 % of the patients had a diagnostic MRI scan, despite initial metabolic and genetic investigations before referral. This study confirms for the first time in a large population of patients with unexplained NDD, the value of an MRI scan of the brain, in the diagnostic work-up for NDD. Chapter 4 describes the yield of MRI imaging in patients with NDD in association with dysmorphic features. Dysmorphic features could indicate an altered embryonic, foetal or post-natal development, likely to increase the chance of abnormal developmental patterning of the brain. This study showed a higher number of craniofacial dysmorphic features in patients with NDD increasing the yield of brain abnormalities of those patients. This might aid the search for an etiological diagnosis. In chapter 5 the frequency of specific pregnancy and delivery features in children with NDD was compared with the frequency of pregnancy and delivery features in children of the general Dutch population. The study established associations between NDD and gestational diabetes, polyhydramnion, postterm pregnancy, Low Birth Weight (LBW