Identifying the genetic causes of Chronic Recurrent Multifocal Osteomyelitis


Dr. Daire O’Leary is a clinical research fellow in Children’s Health Ireland, Crumlin and the UCD Centre for Arthritis Research, under the supervision of Prof. Gerry Wilson and Dr. Orla Killeen. Daire’s research aims to identify the genetic causes of chronic recurrent multifocal osteomyelitis.

Chronic recurrent multifocal osteomyelitis (CRMO) is an auto-inflammatory disease of childhood.  Auto-inflammatory diseases lead to recurrent episodes of inflammation in specific parts of the body with no obvious trigger. In CRMO, this inflammation occurs in bone leading to localised pain, swelling and difficulty using the affected parts of the body.  Daire explains “When someone gets CRMO, their bones get inflamed without a good reason.  This can make them painful, swollen and hard to use”.

CRMO affects one or many bones and symptoms usually recur over many years. Poor growth or fractures in the affected bones can lead to unequal limb length or abnormal curvature of the spine (scoliosis) which are serious long-term problems. “If we don’t treat CRMO, it can cause poor growth, fracture or an abnormally curved spine (scoliosis)”. CRMO is an extremely rare condition. As Daire explains “There are about 60 children and teenagers living with this condition in Ireland right now. There is also a smaller number of adults. Around the world, we think that about 1 in every 100,000 children is living with the condition”.

The cause of CRMO is not known but it is likely that there is a genetic basis because it sometimes affects more than one member of a family. Studies have looked at a small number of genes which are known to cause other auto-inflammatory diseases but have failed to find a genetic cause of CRMO in most of the children who took part. “If we know why CRMO happens, we might be able to treat it better.  If we know why CRMO is worse in some people than others, we might be able to treat those people differently at the beginning and stop problems like poor growth or fractures from happening”.

To date, 43 patients have been diagnosed with CRMO at the National Centre for Paediatric Rheumatology (NCPR) at Children’s Health Ireland, Crumlin.  Instead of only examining specific genes known to be associated with other auto-inflammatory diseases, Daire is analysing the entire exome of patients with CRMO “The NCRC has funded us to use state-of-the-art technology to look at the genes of people with CRMO in detail.  This is called whole exome sequencing.  It looks at the parts of genes which make proteins.  Proteins are the building blocks of the body.  We want to see if there are small changes in genes which happen more often in people with CRMO.  This might help us figure out why CRMO happens”.

Daire has identified several genetic changes in children with CRMO. “These results show about 20,000 small changes for each person which is a lot of information.  So far, we have used software programmes to make a shortlist of genes which might have something to do with CRMO.  I’m working to see if there is a relationship between these genes and how bad someone’s CRMO is (this is measured in a number of ways, including quantifying how many bones are affected).

A better understanding of the underlying causes of CRMO would lead to better treatments and outcomes for patients with CRMO “If we know why CRMO happens, we might be able to treat it better.  If we know why CRMO is worse in some people than others, we might be able to treat those people differently at the beginning and stop problems like poor growth or fractures from happening”.

This work was funded through the National Children’s Research Centre Innovation Award scheme (Principal Investigators; Prof. Gerry Wilson and Dr. Orla Killeen).

Information on all UCD Centre for Arthritis Research studies are available at http://www.ucd.ie/car/research/

Further patient/parent information on CRMO can be found through the following links:

http://crmoawareness.org/wp-content/uploads/2018/01/CNO_CRMO_CaregiverLong_Final.pdf

http://crmoawareness.org/wp-content/uploads/2018/01/CNO_CRMO_CaregiverShort_FINAL.pdf