Page 14 - Demo

Chapter 112From neurodevelopment to neurodegeneration An interesting aspect of GNDs is that their phenotype is often associated with precocious aging.9 For example, individuals with Down syndrome have an increased risk of developing early-onset Alzheimer’s disease and presbycusis (age-related hearing loss) that, on averages, occurs about 30 years earlier compared to individuals in the general population.10, 11 Another example is found in women with Turner syndrome, who show hearing loss comparable to what is seen in women from the general population aged 20-25 years older.12 Likewise, while Parkinson’s disease in the general population is rare under the age of 50 years,13 individuals with 22q11.2DS are known to have an increased risk of early-onset Parkinson’s disease with motor onset at a mean age of 40 years.14 However, the prevalence of Parkinson’s disease in individuals with 22q11.2DS is still unclear.This co-existence of neurodevelopmental and early-onset neurodegenerative disorders, may indicate shared cellular and molecular mechanisms caused by the same genetic susceptibility.9 Abnormal development of neurons may partly be responsible for an increased vulnerability to neurodegenerative disorders.9 Approaching these neurodevelopmental and neurodegenerative disorders as a continuum, with origins early in life that can be influenced across the life span, stresses the importance of natural history studies in GNDs.922q11.2 deletion syndrome 22q11.2DS is a recurrent GND that is relatively common within the group of rare diseases,3 with an estimated prevalence of 1:2148 live births.4 It is a multisystem disorder with variable expression of associated manifestations including, but not limited to, congenital heart disease, intellectual disability, palatal defects and psychiatric disorders such as schizophrenia (Figure 1).1522q11.2DS was previously also known as DiGeorge syndrome, Shprintzen syndrome, velocardiofacial syndrome and conotruncal anomaly face syndrome,15 named after clinicians who recognized it as an entity, and after clusters of the clinical manifestations.