Koolen-de Vries Syndrome

What is Koolen-de Vries Syndrome?

Koolen-De Vries Syndrome (KdVS) is a rare genetic condition caused by partial loss of part of chromosome 17 [17q21.31 microdeletion], including the gene called KANSL1. It can also be caused by a change in the KANSL1 gene. These genetic changes can cause developmental delay, learning difficulties, and create possible health concerns. However, individuals vary, both in the degree to which they are affected and in other effects.

What are the symptoms of Koolen-de Vries Syndrome? 

• KdVS typically manifests as a developmental delay, and with mild to moderate intellectual disability
• Most babies and children with this disorder usually have weak muscle tone, and appear floppy (hypotonia)
• Weak muscle tone causes babies to hold their head up, sit, stand, move, and walk late
• Babies often have difficulty feeding and may require tube feeding
• Children often need learning support. Some children do well in mainstream schools, but others require special schooling
• Children and adults are generally friendly, cheerful, and cooperative
• About half of those with Koolen-de Vries have recurring seizures (epilepsy)
• Affected individuals often have distinctive facial features, including a pear-shaped nose, a long face and broad forehead, droopy eyelids, and prominent ears
• Patients with KdVS sometimes have heart defects, kidney problems, and skeletal and bone deformities

What causes Koolen-de Vries Syndrome? 

Koolen-de Vries Syndrome is an autosomal dominant condition, which means a deletion or mutation of one copy of the KANSL1 gene is enough to cause the disorder. Koolen-de Vries Syndrome is not typically inherited, but occurs randomly during the formation of reproductive cells, or during fetal development.

Most patients with Koolen-de Vries Syndrome are the first in their family to be diagnosed with the disorder. In most cases, the parents of children with Koolen-de Vries Syndrome don’t have the disorder. This means that neither parent has the microdeletion or the missing KANSL1 gene. The mutation or deletion happened randomly during fetal development. The likelihood that they will have another child with Koolen-de Vries Syndrome is very low. If patients with Koolen-de Vries Syndrome have children, there is a 50% chance their child will have the disorder.

How is Koolen-de Vries Syndrome diagnosed?

A technique known as microarray comparative genomic hybridization (array CGH) can show the loss of tiny amounts of DNA from a chromosome or a change in a particular gene. Using this technique, laboratory geneticists can see whether the 17q21.31 region including the KANSL1 gene is missing. Another technique known as FISH can also be used to show that DNA is missing, but these techniques do not show tiny changes in the KANSL1 gene. A technique known as DNA sequence analysis is used to identify small changes in KANSL1 at the base pair level.

What are the treatments for Koolen-de Vries Syndrome?

Currently, there is no cure for KdVS but there are several recommended therapies that most individuals will find beneficial. The earliest treatment is physiotherapy for feeding problems and motor delay, followed by physical therapy aimed at strengthening the muscles and core strength. As the child grows, the therapy focuses more on developing the child’s fine and gross motor skills with occupational therapy and continued physical therapy. Speech therapy help improve communication skills by using a multitude of techniques which can include sign language, pictures and Alternative and Augmentative Communication (AAC) or speech devices.

Patients should also seek orthopedic, cardiac, renal, and urologic care from physicians if those symptoms manifest. Neurologists can prescribe medication to help reduce epileptic seizures.

Where can I find out more about Koolen-de Vries Syndrome? 

• Koolen de Vries Syndrome Foundation 
• NIH
• National Organization for Rare Disorders 
• Medline Plus