New criteria for the diagnosis of type 1 neurofibromatosis and Legius syndrome

19 May 2021

An international team under the supervision of prof. dr. Eric Legius of UZ Leuven has reached a consensus about new criteria for the diagnosis of type 1 neurofibromatosis and the Legius syndrome. The new guidelines allow a better distinction between the two related disorders, which is important for the follow-up and treatment of patients.

Foto van vader en kind op raadpleging bij arts

"In case of suspected type 1 neurofibromatosis or the Legius syndrome it is very important to have a correct diagnosis from an early age to follow and treat patients better." - prof. dr. Eric Legius, centre for human genetics at UZ Leuven

Type 1 neurofibromatosis (NF1) and the Legius syndrome are hereditary disorders caused by mutations in two different genes. In both disorders, patients have the same type of pigmentations marks on their skin (café-au-lait spots), making the clinical distinction between the two disorders difficult.

Until recently, the American NIH diagnostic criteria were used for NF1. These criteria date from 1987 and don't allow a distinction between the two disorders, because at that time the Legius syndrome had not been discovered yet. In addition, little was know about the underlying genetic causes for both disorders.

It is important to come to a diagnosis at an early age, because NF1 is a lot more serious and requires careful follow-up.
prof. dr. Eric Legius

Prof. dr. Eric Legius, head of the UZ Leuven centre for human genetics: “However, it is very important to come to a diagnosis at an early age, because NF1 is a lot more serious: the disorder comes with subcutaneous nerve tumours (neurofibromas) that can turn malignant is some cases and require careful follow-up. A minority of the patients develop eye or brain tumours. They can also encounter cognitive problems or other clinical symptoms. The Legius syndrome is rather mild and usually causes no other complication apart from from the pigmentation spots.”

Consensus between experts worldwide

So the diagnostic criteria needed updating. To reach a worldwide consensus within all parties involved, prof. Legius' team invited more than 60 international experts – researchers, physicians, patient associations, patients and their families – to anonymously fill out a questionnaire and give an indication as to what extent they agreed with certain assertions about neurofibromatosis and its diagnosis. Prof. dr. Catherine Cassiman (ophthalmology) and prof. dr. Jaan Toelen (paediatrics) also participated for UZ Leuven.

A genetic test is informative, but not requirede for a NF1 diagnosis. The clinical findings remain important.

Prof. dr. Legius: “We were able to determine which clinical and genetic criteria are relevant today for the diagnosis of NF1. We agreed that a genetic test could be informative but not required, because these tests are not available or reimbursed in every country. What's more, genetic tests are not conclusive: in exceptional cases false positive results can occur. Clinical findings remain important. When there is no genetic fault in the NF1 gene but only the typical pigmentations spots, a genetic test can point to the Legius syndrome.”

Treatments

In April 2021, the European Medicines Agency approved the first drug for NF1. The medicine, selumetinib, works on the deviating molecular cell signals which are at the base of the disease. It can reduce the growth of the congenital neurofibromas and even shrink them.

The new diagnostic criteria play an important role in determining which patients will need intensive follow-up and qualify for medication. They will also help develop new, more effective treatments.

More information

More about "Centre for human genetics"

Puzzle helps children to understand their rare genetic disorder

16 January 2020
The Leuven remedial educationalist Ann Swillen developed Piecing the puzzle together, an interactive information package for children with a rare genetic disorder. The object is primarily to stimulate the children, as well as the parents, brothers and sisters, to talk openly about the complex disease.
More info
Last edit: 1 June 2021