Genetics of childhood glaucoma in the Netherlands

Childhood glaucoma is a rare but sight threatening disease where an increased
intraocular pressure causes harmful changes to the eye. The genetic background
plays a role in the disease risk and severity for childhood glaucoma. In
primary congenital glaucoma (PCG), mutations in CYP1B1 gene are frequently
found (15-90% depending on the population). Patients with a CYP1B1 mutation
present often with a more severe phenotype of the disease, which is less easily
to treat. Quite a lot is known about the CYP1B1 gene in relation to childhood
glaucoma. However, other genes are also involved, and mutations in these other
genes might play a more prominent role in Caucasian and Azian children. Not
much is known about these other gene mutations, their prevalence and phenotype
effect. Furthermore, not all cases with childhood glaucoma can be explained
with the known (childhood) glaucoma genes. Knowledge and widening of the scope
of disease genes will help to better understand the disease and improve
treatment strategies.

The goal is to study the genetic background of childhood glaucoma in the
Netherlands. We aim to study which mutations play a role in the pathogenesis of
childhood glaucoma in the Netherlands and their prevalence. We will study the
genetic mutations in relation to the clinical findings. With this
phenotype-genotype study we will ultimately come to personalized medicine,
which make each treatment path per patient optimal and significant. Finally we
aim to find new gene mutations that are involved in childhood glaucoma.

diagnostic cohort study

The study's risk is minimal, and the burden is low, as most participants
already have stored DNA. If not, a small blood sample is taken, preferably
during planned surgeries for children.
Participation to the study might result in the finding of a gene mutation that
causes the disease. This finding could give more context of the disease and
more information about the heritability, which might be beneficial for
patients/parents.
Global research on childhood glaucoma may not fully apply to the Netherlands
due to differing surgical techniques and genetic factors. Deepening our
understanding of the genetic background in the Netherlands is important to
develop personalized medicine. It is important to include children into this
study, since it is a childhood disease and children need to be treated (usually
surgically) at young age. The childhood glaucoma population in the Amsterdam
UMC is relatively young and it would take around 8 years before half of these
patients are > 16 years old.