Page 14 - Characterization of genetic neurodevelopmental disorders at adult age, with a focus on 22q11.2 deletion syndrome - Emma Boersma

Chapter 1
From 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.9
22q11.2 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).15
22q11.2DS 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.
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