About VPS4a

The CIMDAG-syndrome (Cerebellar hypoplasia-intellectual disability-congenital microcephaly-dystonia-anemia-growth retardation syndrome) results in an ultra-rare neurodevelopmental disorder characterized by delayed motor development (such as inability to walk, hypotonia, and spasticity), epileptic seizures, problems speaking and understanding, visual and cognitive impairment apparent from early infancy. Further hematologic abnormalities can occur leading to life threatening conditions. This novel syndrome was firstly described by Catherine Rodger in 2020 [1].

Interestingly other VPS variants, e.g. VPS11 can cause similar symptoms and features [2], [3].

Little information is available from research and no therapy strategies exist actually.

[1]: De Novo VPS4A Mutations Cause Multisystem Disease with Abnormal Neurodevelopment

[2]: Vision and sensorimotor defects associated with loss of Vps11 function in a zebrafish model of genetic leukoencephalopathy

[3]: Characterization of the Expression of Vacuolar Protein Sorting 11 (Vps11) in Mammalian Oligodendrocytes

The VPS4a [1] variant occurred randomly and was not caused by lifestyle, diet, or other environmental factors. It happened either in the sperm or egg of a parent, or during early development of the embryo. If your child is affected, please know that YOU DID NOTHING WRONG!

We all have two copies of VPS4a. A variant in a single copy can cause the disorder (“autosomal dominant”). If you want to learn more about genetics please click here: https://rarechromo.org.

[1]: VACUOLAR PROTEIN SORTING 4 HOMOLOG A; VPS4A

In most people diagnosed so far, neither parent has the same genetic change in VPS4a. Such novel genetic changes are called “de novo” variants and it means that the likelihood of another child being affected is very low (1-2%). If neither parent has the variant in any of their cells, the risk is ~0.1% (1 in 1’000).

For further questions or advice, you should talk to your clinical geneticist!

Very common:

• Severe mobility issues: not reaching the milestones of development
• Eye problems: from visual impairment to full blindness
• Severe feeding problems

As the condition is so new and the number of cases is very low, we don’t know much yet about its prognosis - we want to help change that! If your child was diagnosed with a VPS4a (or at least VPS) variant anywhere in the world, please contact us via the Facebook group “VPS4A Mutation”.