Defect In Gene Causes 'Neuralgic Amyotrophy'

Neuralgic Amyotrophy, a painful disorder of the nervous system

Hereditary Neuralgic Amyotrophy (HNA) is characterized byrepeated attacks of pain in a shoulder, arm, and/or hand, followed bytotal or partial paralysis of the affected area. The pain and the lossof movement usually disappear within a couple of weeks, but sometimesrecovery can take months or even several years. Many HNA patients alsohave particular facial features, such as eyes that are somewhat closertogether, a fold in the upper eyelid that covers the inside corner ofthe eye, and sometimes a cleft palate.

HNA is a relatively rare disorder: the disease appears in some 200families worldwide. There is also a non-hereditary form of HNA, calledthe Parsonage-Turner Syndrome. The clinical picture of this morefrequently occurring form - 2 to 4 cases per 100,000 persons - is notdistinguishable from that of the heritable form.

The attacks of pain are usually provoked by external factors such asvaccination, infection, operation, and even pregnancy or childbirth. Byvirtue of their genetic predisposition, carriers of the hereditary formof HNA run greater risk of having an attack. Its re-occurrence, and thefact that the disease is provoked by environmental factors, make thisdisorder unique in the group of peripheral nervous system disorders.Therefore, HNA is a genetic model for more frequently occurringdisorders such as the Parsonage-Turner Syndrome and neurologicaldisorders like Guillain-Barré Syndrome.

Genetic cause of HNA discovered

VIB researchers in Antwerp, under the direction of Vincent Timmermanand Peter De Jonghe, have discovered the genetic defect that underliesHNA. In this effort, the researchers, connected with the University ofAntwerp, have been working with colleagues from the universities ofMunster (Germany) and Seattle (USA).

The researchers studied several large families and identified the generesponsible for the disorder. They have now shown that HNA is linked tothe long arm of chromosome 17, and they have found mutations oralterations in the genetic code of the Septin 9 protein in the patientsbeing studied. HNA is the first mono-genetic disorder caused by adefect in a gene of the Septin family.

The researchers do not yet know exactly how Septin 9 functionsin the peripheral nervous system or why mutations give rise to HNA.They do know that other members of the Septin family are involved inthe cell division that forms the cytoskeleton and in the development oftumors. The fact that mutations in Septin 9 prevent cell division fromoccurring properly can perhaps explain why so many HNA patients alsohave facial abnormalities.

The first step toward treatment?

Today, no effective therapies yet exist to retard or prevent theprogress of Neuralgic Amyotrophy. The current treatment is merelysupportive. The findings of the researchers in Antwerp are a firstessential step in the development of a specific treatment. Now thatthey know the gene involved, scientists can acquire more insight intothe molecular processes of this disease, which may ultimately lead to atherapy.

VIB, the Flanders Interuniversity Institute for Biotechnology, is aresearch institute where 850 scientists conduct gene technologicalresearch in a number of life-science domains, such as human health careand plant systems biology. Through a joint venture with four Flemishuniversities (Ghent University, the Catholic University of Leuven, theUniversity of Antwerp, and the Free University of Brussels) and a solidfunding program for strategic basic research, VIB unites the forces ofnine university science departments in a single institute. Through itstechnology transfer activities, VIB strives to convert the researchresults into products for the benefit of consumers and patients. VIBalso distributes scientifically substantiated information about allaspects of biotechnology to a broad public.

Given that this research can raise a lot of questions forpatients, we ask you to please refer questions in your report orarticle to the email address that VIB makes available for this purpose:patienteninfo@vib.be. Everyone can submit questions concerning this and other medically-oriented research directly to VIB via this address.

Patients with hereditary peripheral nervous system disorders can also visit the following website:http://www.charcot-marie-tooth.be/