What is Noonan syndrome?

Noonan syndrome is a hereditary physical development disorder (see below) that is also associated with learning disabilities and a slightly increased risk of malignant diseases. There are various specific forms of Noonan syndrome and Noonan-syndrome-like diseases:

Noonan syndrome with multiple lentigines: Along with the changes typical of Noonan syndrome, this variant also manifests dark spots (lentigines) on the skin. Those affected are often hard of hearing and generally have specific heart defects (e.g. hypertrophic cardiomyopathy).

Noonan-syndrome-like disease with loose anagen hair: Those affected exhibit changes typical of Noonan syndrome but have a slightly darker pigment and loose hair.

CBL syndrome: With this Noonan-syndrome-like disease, the changes typical of Noonan syndrome take on a milder form and are easily missed. Patients may develop vascular inflammation (vasculitis) and are at a high risk of a malignant blood disease during childhood (juvenile myelomonocytic leukemia).

How is Noonan syndrome diagnosed?

People with Noonan syndrome exhibit typical characteristics that can be identified by experienced human geneticists, pediatricians, or others who are familiar with this disease. The following changes present in a variety of ways:

  • Striking facial features with low-lying ears that are rotated towards the back

  • Wide-set eyes

  • Drooping eyelids

  • Dwarfism (short stature)

  • Broad neck with a low hairline

  • Congenital heart defects (especially pulmonary stenosis and hypertrophic cardiomyopathy)

  • Deformed rib cage

  • Changes in the skin and hair

  • Vision problems

  • Undescended testicles

  • Learning difficulties

  • Tendency to bleed

A suspected diagnosis based on clinical symptoms can be followed by a genetic test to confirm that the diagnosis is correct, which is almost always the case.

What is the risk of cancer?

The risk of cancer in children with Noonan Syndrome is around 8 times higher. Since cancer in children is very rare, the risk is still not very great, and the majority of children with Noonan syndrome do not develop cancer. The cancer spectrum lists the following types of cancer (not exhaustive): low-grade glioma (a relatively benign brain tumor), acute leukemia, neuroblastoma, and rhabdomyosarcoma.

Specific mutations in PTPN11 are associated with an increased risk of excess blood formation during the first months of life. This myeloproliferative disorder sometimes progresses in an aggressive manner, and requires treatment. In such cases, it is important to consult experienced pediatric oncologists.

Noonan-syndrome-like CBL syndrome is associated with a high risk of juvenile myelomonocytic leukemia. Even though this is malignant, not everyone who is affected requires treatment, as the clinical progression can be benign. Here as well, it is important to involve an experienced pediatric oncologist.

What causes Noonan syndrome?

Noonan syndrome develops because of a hereditary change in a gene of the RAS signaling path. The following genes may be affected: PTPN11, SOS1, RAF1, RIT1, KRAS, NRAS, BRAF, MAP2K1, RRAS, RASA2, A2ML1, SOS2, LZTR1, CBL, SHOC2, PPP1CB.

Is there a treatment?

There is no treatment for Noonan syndrome itself. However, it makes sense to address the individual problems associated with Noonan syndrome (heart, hearing, vision, etc.) together with the treatment team and also to focus on promoting patient education.

If cancer develops, the treatment should be discussed with the principal investigator concerned. In children with juvenile myelomonocytic leukemia, it may be possible to forgo aggressive treatment. However, this should be decided on a case-by-case basis and after consulting with the EWOG MDS Study.

Surveillance Recommendations for the Early Detection of Cancer

Surveillance Recommendations

Since the risk of cancer is only slightly increased, no general surveillance measures are necessary. However, any medical problems that occur should be cleared up right away.

The following screening can be offered for children 0 to 5 years of age who are at risk of excess blood formation (particularly PTPN11 or KRAS mutations) or for children with CBL syndrome: a physical examination that pays particular attention to the size of the spleen and to the blood count, making comparisons every 3-6 months.

Self-Care and Support

What should I pay special attention to?

If your child feels unwell, is listless, fatigued, or pale, has a palpable change or unusual outward bulge in the abdomen, or if you notice anything else that is unusual, it is important for this to be evaluated right away.

Support Groups and Additional Information