"Legius Syndrome" – What Is It?
Legius syndrome is a disease caused by mutations, i.e., genetic changes in the SPRED1 gene. It is clinically similar to neurofibromatosis type 1 (NF1) due to the numerous café-au-lait spots on the skin (benign, light brown, uniform pigment spots). However, other manifestations of NF1 do not occur.
How Is "Legius Syndrome" Diagnosed?
Suspected Diagnosis
Legius syndrome is suspected if the following findings are present:
- Café-au-lait spots with or without intertriginous freckling (similar to freckles in the armpit or groin region)
AND - Absence of other clinical manifestations of NF1 such as Lisch nodules (small brownish-white to yellowish sharply defined spots of the iris of the eye), neurofibromas (nerve tumors), optic glioma (benign nerve tumor of the optic nerve) or specific bone changes (sphenoid dysplasia, dysplasia of the long bones)
AND - Parent with numerous café-au-lait spots without other signs of NF1
Genetic Diagnostics
The diagnosis of “Legius syndrome” is confirmed by detecting a mutation, i.e., a genetic change in the SPRED1 gene.
What Is the Risk of Cancer?
In individual cases, leukemia has been reported in the context of Legius syndrome. It is known that various defects or changes in a specific signaling pathway (RAS/MAPK signaling pathway) within our body cells lead to an increased risk of cancer. The mutation responsible for Legius syndrome also affects this signaling pathway, which suggests an increased risk of cancer. However, this assumption has not yet been verified due to the small number of patients.
Legius syndrome is very similar to NF1 in terms of skin manifestations. Almost all patients have multiple café-au-lait spots, and many also have freckling of the axillary and/or inguinal region. However, other clinical features of NF1 are absent in Legius syndrome.
In some patients with Legius syndrome, psychomotor developmental delays are described, particularly in the language area and as learning disabilities. ADHD has also been reported as part of the disease. Overall, however, patients with Legius syndrome appear to be less cognitively impaired than patients with NF1.
In addition, some patients have vascular changes.
What Is Known About the Development of "Legius Syndrome"?
Legius syndrome is caused by mutations, i.e., genetic changes in the SPRED1 gene. This gene codes for a protein (SPRED1) of the so-called RAS/MAPK signaling pathway, which mediates information in our cells.
If the SPRED1 gene is now present in an altered form, the corresponding protein is also not produced correctly and can no longer fulfill its actual function. This results in incorrect information transfer within the cell, leading to skin changes and developmental delay, among other things.
The incidence of the disease is not yet known, but around 2% of patients who meet the NF1 diagnostic criteria have a SPRED1 mutation. The disease incidence of NF1 is 1:3000. Legius syndrome can be passed on from parents to their children, whereby the inheritance is autosomal dominant.
Is There Any Form of Treatment Available?
Physical or speech therapies can be carried out for developmental delay. Behavioral therapy or drug therapy may be considered for patients with ADHD. If a learning disability is present, individualized learning plans may be useful.
Diagnosis of " Legius Syndrome" What's Next?
If you have been diagnosed with this cancer predisposition syndrome, it is important to see a specialist. The following section explains whether cancer screening tests or other measures are needed and how they should be carried out. We also give you some valuable tips on what you can do yourself. If you have any questions, please do not hesitate to contact us or your doctor.
Diagnosis of " Legius Syndrome" What's Next?
If you have been diagnosed with this cancer predisposition syndrome, it is important to see a specialist. The following section explains whether cancer screening tests or other measures are needed and how they should be carried out. We also give you some valuable tips on what you can do yourself. If you have any questions, please do not hesitate to contact us or your doctor.
Medical Measures for Early Detection
Regular examinations should be carried out to detect developmental delays, behavioral changes, and learning disabilities.
Furthermore, regular clinical examinations with blood pressure measurements should be carried out to check for vascular changes.
Patients should be made aware of a possible increased risk of cancer. Targeted cancer screening is not recommended.
Legius Syndrome- What You Can Do Yourself
You Should Pay Attention to This
You should consult a doctor when there are any abnormalities in your child’s learning behavior, changes in development or other behavior. However, non-specific symptoms such as tiredness or a feeling of weakness should also be noticed and reported to a doctor. You should also consult a doctor if you notice any new abnormalities or complaints.
Further Information
Unfortunately, we are not yet aware of any support groups for patients with Legius syndrome. As soon as we have new information, we will add it here. However, patients can also register for the CPS registry at any time or have this done by the doctors looking after them.
Any further questions?
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