Die Symptome einer Neurofibromatose können in allen Altersklassen
erstmals auftreten, häufig bereits in den ersten 3 Lebensdekaden,
teilweise mit sehr langsamer Entwicklung über Jahrzehnte oder rasch
progredient innerhalb weniger Monate. Unter anderem diese unterschiedliche
Entwicklungsdynamik kann die Diagnose einer Neurofibromatose ebenso wie die
Entwicklung eines individuellen Therapiekonzeptes erschweren.
Abstract
Background & Focus While the Neurofibromatoses have been observed and
classified by their phenotypes for several centuries, their great variability
constitutes a considerable challenge in diagnostics and therapy selection. This
article focuses on highlighting the three most frequent sub-types NF1, NF2 and
NF3.
Methods All three NF types are outlined by the following measures: the history
of their clinical detection, the typical appearance, the underlying genetic
constitution and its consequences, the official diagnostic criteria, the mandatory
diagnostic steps and finally the treatment opportunities and specific risks.
Results About 50% of NF patients have a positive family history and
the other 50% are the first symptomatic generations and suffer from new
mutations. A considerable (unknown) number of patients do not exhibit a complete
genetic NF constitution, but have a so-called mosaic sub-form with only a limited
number of cells being genetically affected and prone to tumorous changes. The
neurofibromatoses are neuro-cutaneous diseases with manifestations at the skin and
nervous system, except for NF 3, where the skin and eyes are never affected. Skin
and eye manifestations, especially pigmentation disturbances, mostly started early
in childhood and adolescence. The underlying genetic constitutions, on chromosome 17
in NF1 and on chromosome 22 in NF2 and NF3, cause a defect in tumor suppressor genes
and lead to excessive proliferation of Schwann cells. Major features are tumors of
the peripheral nerves, including cranial and spinal nerves leading to tumors with
considerable nerve, brain and spinal cord compression and resulting in pain, sensory
and motor deficits. A further variable disease feature may be neuropathy with
neuropathic pain, related to tumor formation or even independent of it.
Although benign by histopathology and growing rather slowly, those tumors often cause
progressive neurological deficit and loss of function. Loss of function may be
prevented by adequate timing of therapy such as nerve decompression by microsurgical
tumor resection or reduction, medication with immunotherapy or radiotherapy in
selected cases. To date it is unknown why some tumors remained silent and stable
while others progress and show periods of accelerated growth.
As a consequence, NF patients need to be accompanied by a specialized
interdisciplinary NF team at long-term, with a clear-cut standardized protocol for
clinical and imaging controls along with counseling and support in
decision-making.
Further, NF patients may suffer from reactive depression due to the danger of losing
essential neural functions, such as vision or audition or movement. And especially
NF1 patients show characteristics of ADHS and other cognitive compromise in at least
50% of cases.
Conclusions As the neurofibromatosis belong to the so-called rare diseases,
all patients with a suspicion or diagnosis of NF should get the opportunity to
present to an interdisciplinary NF Center, mostly situated at University Hospitals,
where competent counseling on the individual disease phenotype may be provided. Here
the patients will be informed on the necessary diagnostic steps, their frequency as
well as on practical steps in case of acute deterioration. Most NF centers are run
by neurosurgeons or neurologists or pediatricians, working in a network with
geneticists, neuro-radiologists, ophthalmologists, dermatologists, plastic and
general surgeons, psychologists, psychiatrists and social work experts. They
participate regularly in neuro-oncological tumor and sarcoma tumor boards, skull
base tumor centers, comprehensive hearing centers, and deliver all the treatment
opportunities provided by certified brain tumor centers, among those the inclusion
in special diagnostic and treatment studies or the contact information to patient
support groups.
