Neurofibromatosis Type 1: Causes, Symptoms & Treatment

Neurofibromatosis type 1 is a genetic disorder for which malformations of the central nervous system and skin are characteristic. With approximately one in 3000 newborns, neurofibromatosis type 1 is one of the most common genetic disorders.

What is neurofibromatosis type 1?

Neurofibromatosis type 1 (also known as Recklinghausen’s disease) is a genetic phakomatosis with malformations of the skin and central nervous system. Neurofibromatosis is manifested by pigmentary abnormalities that appear as early as infancy, such as patches of coffee-brown coloration (café-au-lait patches or latte patches) and axillary and inguinal lentigines (freckle-like pigmentation in the axillary and inguinal regions). Another leading symptom of neurofibromatosis type 1 are the neurofibromas found all over the affected person’s body. Neurofibromas are benign (benign) tumors that occur in most cases in childhood and can lead to pain and neurological deficits such as paresthesias when internal organs, especially spinal cord nerves and the brain, are affected in addition to the skin. In addition, in neurofibromatosis of this type, bone abnormalities such as scoliosis (spinal curvature), iris amartomas (Lisch nodules on the iris and the anterior eye), and learning and concentration deficits are possible symptoms.

Causes

Neurofibromatosis type 1 is due to mutational gene changes, and in Recklinghausen disease there is a mutation of the so-called NF-1 gene (neurofibromatosis 1 gene) on the 17th chromosome, which leads to uncontrolled cell proliferation (cell proliferation and growth). In this case, the mutation responsible for the manifestation of the disease is either passed on from one parent to the child via autosomal dominant inheritance or develops as a result of new mutations as spontaneous changes in the genome of the affected person (in about 50 percent of cases). It is not yet known which factors trigger these mutative processes. It is suspected that the size of the affected chromosome, which increases the probability of mutations, plays a decisive role.

Symptoms, complaints, and signs

Neurofibromatosis type 1 is primarily characterized by variously expressed, usually benign skin changes. These include excessive pigmentation of the skin, which can already occur in babies and newborns. Their shape is often oval, while the color is remotely reminiscent of latte. Therefore, these are also known in medicine as café-au-lait spots. Freckle-like speckles occasionally appear in the armpits, groin area or even in the oral mucosa. In advanced stages of the disease, benign nodules grow on the skin surface, sometimes with a considerable size of several centimeters, from the age of ten. These neurofibromas also appear spontaneously during pregnancy. As a rule, the tumors and skin changes do not cause any pain or other discomfort. Affected persons can therefore expect a healthy and painless life apart from the aesthetic impairment. The growth of neurofibromas is not limited to the skin surface. Their formation is also possible on the iris or within the body. Benign tumors on the optic nerve obstruct vision (opticuzsgliomas). Similarly, nerve fiber tumors and bone curvatures (scoliosis) then burden the performance capacity. Learning problems and loss of concentration are the result. In extreme cases, the growths also cause epileptic seizures. In milder forms, visual disturbances, signs of paralysis or a general tendency to insensitivity can be observed. Very rarely, neurofibromas of type 1 develop further into malignant tumors and accordingly cause sufferers pain depending on their localization.

Diagnosis and course

Neurofibromatosis type 1 is diagnosed on the basis of symptoms characteristic of the disease, such as café-au-lait spots, neurofibromas, multiple lentigines, Lisch nodules. DNA analysis can detect the underlying mutation on chromosome 17 (NF-1 gene). Familial clustering of the disease may also indicate neurofibromatosis. If the specific mutation present in the family is known, it can be detected prenatally by chorionic villus sampling or amniocentesis.Imaging techniques such as X-ray (scoliosis) or electroencephalography (impairment of the brain) are used to determine involvement of internal organs. Although the courses can diverge greatly even within families, neurofibromatosis has a mild course in the majority of cases (about 60 percent). If left untreated, neurofibromatosis can lead to marked impairments such as tumors of the optic nerve or brain.

Complications

Whether or not neurofibromatosis type 1 results in complications varies exceedingly. For example, some cases of the disease take a mild course, while serious sequelae are possible in others affected. For this reason, regular check-ups are extremely important, because they allow the doctor to detect any effects requiring treatment at an early stage. Among the most common sequelae of neurofibromatosis type 1 are the so-called partial performance disorders. In this case, children who actually have normal intelligence experience learning difficulties. About half of all children with the disease are affected by learning problems. It is not uncommon for behavioral disorders, attention deficits or hyperactivity to occur in parallel. However, the learning difficulties do not worsen. Support for the affected children should take place even before they start school. Another consequence of neurofibromatosis type 1 is the appearance of neurofibromas under the skin. In some patients they already appear in childhood, in others not until puberty. Neurofibromas that are already present can grow during puberty. Depending on which part of the body the growths appear, neurological disorders or pain are possible. Also common among neurofibromatosis patients are curvatures of the spine or scoliosis. They occur more frequently in neurofibromatosis than in healthy people. Brain tumors or tumors of the optic nerve such as optic gliomas are considered serious complications. In addition, epileptic seizures are conceivable.

When should you see a doctor?

Parents who notice the typical skin changes in their child should immediately consult the pediatrician. At the latest when growths or nodules form on the skin, medical advice is needed. The doctor can diagnose neurofibromatosis type 1 and initiate treatment immediately. If the skin lesions become infected, the child will need medical attention the same day. If fever and other accompanying symptoms are added, an inpatient examination in the hospital is necessary. In addition to the family doctor or pediatrician, neurofibromatosis type 1 may be seen by a dermatologist, neurologist, neurosurgeon, or other internist. The actual therapy usually takes place in a specialized clinic for skin diseases. To ensure optimal care, multidisciplinary consultation may be useful. Since the disease can also be a considerable burden for the parents, therapeutic counseling is always useful as well. After completion of treatment, the child must be examined by a physician at least once a year. The physician can clarify whether new tumors have developed and examine the internal organs as well as the eyes and ears for further damage.

Treatment and therapy

Because the underlying cause of neurofibromatosis type 1 is genetic or mutational, it cannot be treated causally. Accordingly, therapeutic measures are aimed at reducing the specific presenting symptoms and preventing potential secondary symptoms. Neurofibromas that cause the affected person disabling pain and/or have a risk of degeneration are usually removed by (micro)surgery. The tumors can be removed with a scalpel, laser or electrocautery. While neurofibromas located above the skin level are excised with a scalpel, cutaneous tumors or tumors located at the skin level can be removed with a laser or by electrocautery. The latter simultaneously enables an acceleration of hemostasis due to the effect of heat, which is a decisive advantage especially in the case of neurofibromas rich in blood vessels.However, in principle, a comprehensive risk-benefit analysis should take place in all cases prior to surgery, since any surgical intervention may result in paralysis due to a loss of function of the proximal nerves. In addition, tumors in the central nervous system may be unfavorably localized, so that healthy tissue structures may also be damaged by surgical intervention. Likewise, radiotherapeutic measures for degenerated tumors should be carefully considered because of the increased risk for further degeneration. Last but not least, additional existing symptoms of neurofibromatosis type 1 such as epilepsy (carbamazepine, clonazepam), poor concentration (dietary changes concentration exercises) or scoliosis (physiotherapy, corset, surgery) must be treated.

Outlook and prognosis

People who have neurofibromatosis type 1 suffer from an incurable disease. A genetic defect has been identified as the cause of the health disorder. As interventions and changes in human genetics are not allowed due to legal regulations, no cure can take place. This represents a considerable burden for the affected person as well as his or her relatives. Doctors concentrate their medical care on alleviating the existing and individually severe symptoms. In addition, one goal of treatment is to control the progress of the disease. Thanks to medical advances, there are nowadays various treatment approaches that lead to a significant alleviation of symptoms. Regular medical monitoring is also used to prevent any complications. In many cases, sensory impairments as well as motor disturbances are to be expected. If medical treatment is not sought, the risk of serious sequelae increases. In addition, the general quality of life is considerably impaired. In many cases, those affected require intensive daily care, as it is not possible for them to cope with everyday life on their own. Patients usually have to undergo repeated surgical interventions in the course of their lives. In these, tissue growths are to be removed so that deficits can be reduced or regression of existing symptoms can occur.

Prevention

Because neurofibromatosis type 1 is a genetic or mutational disease, it cannot be prevented directly. However, regular checkups should be performed to prevent complications so that therapeutic measures can be initiated in a timely manner, especially in the presence of neurofibromas that can degenerate into lymphomas or neurofibrosarcomas.

Follow-up

In most cases of neurofibromatosis type 1, the affected person has very few and also very limited measures and options for aftercare. For this reason, the affected person must see a doctor very early in this disease to avoid other complications or complaints. As a rule, self-healing is not possible. Due to the genetic nature of the disease, there is also no complete cure. Therefore, if the affected person wishes to have children, he or she should in any case undergo genetic testing and counseling to prevent the recurrence of neurofibromatosis type 1 in the children. During treatment, the affected person is usually dependent on the help and also the support of his or her own family. It is not uncommon that psychological support is also necessary to prevent depression and other psychological upsets. In many cases, children with neurofibromatosis type 1 also require intensive support at school to prevent complications in adulthood. Likewise, measures of physiotherapy and physiotherapy are very important, although many of the exercises from these therapies can also be performed at home.

This is what you can do yourself

The pigmentary changes that often occur in connection with neurofibromatosis type 1 can be treated cosmetically by the patient himself, for example with appropriate creams. Areas of the body that are prone to the pigmentary change should definitely be avoided from intense sunlight.The mental impairments that sometimes accompany neurofibromatosis type 1 (e.g. partial performance disorders, behavioral problems or motor impairments) can be treated with appropriate therapies – after guidance by a therapist, also independently. Self-help groups are the most important pillar in addition to conventional medical care. Self-help groups offer patients a wide range of services, such as arranging therapies, providing information about the course of the disease and its forms of treatment, and offering advice and support, for example, in the case of a genetic examination of a fetus during pregnancy. There are self-help groups in every federal state. Neurofibromatosis type 1 progresses differently in each patient; living with uncertainty – when will neurofibromatosis type 1 break out, what exactly will happen then – is thus inevitably part of the patient’s life. It is recommended, possibly with the support of an appropriate therapist, to find ways out of this unsatisfactory situation in order to be able to integrate the uncertainty into everyday life.