Parents

Defects in a gene called EXTL3 are responsible for a neuro-immuno-skeletal syndrome.

The protein encoded by EXTL3 is involved in the generation of a cellular surface for adhesion properties as well as professional extracellular matrix to let tissue cells bind and grow normally.

The syndrome shows an autosomal recessive inheritance. We have two genes – one from our father – one from our mother. If one gene is affected and the other not, this condition does not cause disease. The person is called a healthy carrier. The syndrome will only become clinically overt in case a pathogenic mutation carried by each of the healthy parents is inherited by the child, i.e. both EXTL3 genes are mutated.

The main clinical features consist of skeletal dysplasia. These manifestations are universal and present as disproportionate short stature with progressive kyphosis, meaning a bowed back and short legs and arms.

The children also show neurodevelopmental delay, which may be mild (school-going, learning defects), to severe with limited psychomotor development (not sitting , walking, talking).

Recurrent infections may occur early in life, being caused by an incomplete immune system. One important white blood cell type is insufficiently formed in the early months-years, which may however show spontaneous recovery over time, with a protective response by normal antibody generation upon vaccinations. This may in the end be true for the killed ‘dead’ vaccines as well as over time for the live-attenuated vaccines (measles-mumps-rubella). The latter should be avoided until the disease has shown sufficient immune recovery.