Neurocutaneous syndromes are inherited disorders characterized by neuroectodermal and mesenchymal abnormalities. In addition to the classic four phakomatoses (Bourneville-Pringle syndrome, neurofibromatosis, Sturge-Weber-Krabbe syndrome, Von Hippel-Lindau-Czermak syndrome) there are also a number of other diseases affecting the skin and the central nervous system manifest to the neurocutaneous syndromes.
What is Neurocutaneous Syndrome?
The diseases that belong to the neurocutaneous syndromes are all due to hereditary dysplasias that arise during the embryonic period. This can be explained by the fact that both neuroectodermal and mesenchymal malformations occur. The neuroectoderm is part of the outer germ layer (ectoderm). See nonprofitdictionary for Chronic Inflammatory Demyelinating Polyneuropathy (abbreviated as CIPD).
The nervous system develops from the neuroectoderm during the embryonic period. The mesenchyme is the “embryonic connective tissue”. Various structures of the human body develop from this – connective tissue, cartilage tissue, bones, tendons, muscle tissue, blood and fatty tissue.
These malformations, which develop during the embryonic period, explain why the skin and the central nervous system are affected. The neurocutaneous syndromes include both malignant and benign tumors.
Causes
Since the neurocutaneous syndromes are hereditary diseases, the cause is clear. There is a change in a gene that is inherited and is responsible for the dysplasia. The occurrence of the symptoms is then due to the malformations that occur in the course of the syndrome.
The malformations on the neuroectoderm and mesenchyme are already formed in the embryonic stage. The neuroectoderm develops into the nervous system during the embryonic period, which explains the neurological symptoms. Tumors can arise from the mesenchyme. These are called mesenchymomas. Malignant tumors of tissues arising from the mesenchyme are called sarcomas.
Symptoms, Ailments & Signs
The symptoms, signs and signs are different in the various diseases that are grouped together as neurocutaneous syndromes. For this reason, a distinction must be made here.
The neurocutaneous syndromes include the classic phakomatoses:
- Bourneville-Pringle syndrome (tuberous cerebral sclerosis)
- neurofibromatosis
- Von Hippel-Lindau Syndrome
- Sturge-Weber-Krabbe Syndrome
on the other hand, other diseases and syndromes:
- Bonnet-Dechaume-Blanc Syndrome
- Louis Bar Syndrome
- DeSanctis-Cacchione Syndrome
- McCune-Albright-Sternberg Syndrome
- Leschke syndrome
- Peutz-Jeghers Syndrome
- Bogaert-Divry Syndrome
- Gorlin-Goltz Syndrome
- Groenblad-Strandberg Syndrome
- Klippel-Trenaunay Syndrome
- Godfried-Prick-Carol-Prakken Syndrome
- Maffucci syndrome
- Osler-Weber-Rendu Syndrome
- Dysraphism Syndrome
In the following, the Bourneville-Pringle syndrome as a classic phakomatosis, the dysraphism syndrome as a “other neurocutaneous syndrome” and the Bonnet-Dechaume-Blanc syndrome as a disease that can possibly be assigned to the neurocutaneous syndromes are presented as examples.
Bourneville-Pringle syndrome is also known as tuberous sclerosis and is associated with a number of different symptoms. Tuberous cerebral sclerosis is inherited in an autosomal dominant manner. It can be assumed that there is a high spontaneous mutation rate and that 50 percent of those affected develop a new mutation.
The main symptoms of Bourneville-Pringle syndrome are adenoma sebaceum, epilepsy and mental retardation. With adenoma sebaceum, numerous small fibroadenomas of the sebaceous glands in the face develop. In addition to the symptoms described, numerous other symptoms can occur, which primarily affect the central nervous system, the skin and the kidneys.
The serious symptoms of the diseases are usually already noticeable in infancy. In computed tomography diagnostics, the visible periventricular calcifications are typical of tuberous cerebral sclerosis.
Dysraphy syndrome is a collective term for combined malformations that can be traced back to a defective spinal cord system or a disruption in the closing process of the primary neural plates. The syndrome is a hereditary constitutional anomaly.
Symptoms include an “open back” (spina bifida), foot deformities, vertebral malformations with secondary kyphosis and/or scoliosis, sacral hypertrichosis, funnel chest, neurological disorders of the trophism, sensitivity and motor function of the lower extremities, spinal reflex anomalies, sphincter weakness, clefts in the pharynx and of the urogenital tract, foveola coccygea, four-finger furrow, hyperthelia and mental disorders.
Bonnet-Dechaume-Blanc syndrome is characterized by head and cerebral vascular malformations, facial changes, and retinal blood vessel abnormalities.
It should be noted that this syndrome is extremely rare and in 2009 only 132 cases were known worldwide. Both sexes were affected about equally often. Regarding the pathophysiology of the syndrome, there are numerous pathological connections between arterial and venous systems.
Furthermore, there are numerous so-called tendril angiomas and arteriovenous aneurysms in the area of the retina and in the central nervous system, especially in the mesencephalon, a part of the brainstem. The disease is congenital, the embryonic developmental disorder takes place in the seventh week of pregnancy. The cause is not yet known.
The majority of experts count the syndrome among the neurocutaneous syndromes, but some classify it differently. One aspect that speaks against the classification as a neurocutaneous syndrome is the fact that the syndrome is not a hereditary disease.
Changes in the face in the form of unnaturally protruding blood vessels are recorded as occurring symptoms, as are nystagmus, glaucoma and epistaxis. Exophthalmos (usually unilateral), retinal hemorrhage, vitreous hemorrhage, epilepsy, and cerebral hemorrhage can also occur. Cerebral hemorrhages are divided into subarachnoid hemorrhage and epidural hemorrhage.
The intraocular bleeding (here bleeding of the retina and the vitreous body) leads to blindness in the long term.
Diagnosis is by ophthalmoscopy, perimetry, MRI, CT and digital subtraction angiography. The syndrome can only be treated symptomatically. For this purpose, surgical treatments of the vascular malformations, laser coagulation and embolization are used.
Diagnosis & course of disease
Diagnosis and course of the disease depend on the respective syndrome or disease and cannot be given in general for all neurocutaneous syndromes.
Complications
Due to its diversity, the neurocutaneous syndrome can cause different complications. All diseases of this syndrome are known to be associated with malformations of the nervous system and skin. The complications that arise depend on the underlying disease. Every single neurocutaneous disease can lead to complications to a greater or lesser extent.
Bourneville-Pringle syndrome, also known as tuberous cerebral sclerosis, always leads to mental retardation in addition to epilepsy. In severe cases, malignant tumors sometimes develop here. The constant epileptic seizures and the tumors often drastically shorten the life expectancy of those affected. Neurofibromatosis type 1 can also lead to malignant degeneration of some of the many actually benign tumors (neurofibromas).
In addition, the optic nerve is sometimes affected by tumors. In half of the patients with this disease, bone cysts develop in addition to a curvature of the spine (scoliosis). The Sturge-Weber-Krabbe syndrome, in turn, is characterized by a vascular malformation that carries the risk of developing glaucoma and mental retardation due to the many epileptic seizures.
Epilepsy, glaucoma with the risk of blindness and other neurological deficits also occur in other diseases of the neurocutaneous syndrome. Some diseases can also lead to cerebral hemorrhage. In some cases, multiple skin tumors such as basal cell carcinoma occur. Hearing impairment or even deafness is also observed in some diseases of the syndrome.
When should you go to the doctor?
Medical advice should be sought if skin changes, neurological disorders and other symptoms suggestive of neurocutaneous syndrome or other serious medical conditions are noticed. It is best to consult a doctor immediately if the symptoms get worse or if typical complications such as movement disorders or skin bleeding are noticed. Medical advice must be sought at the latest when the symptoms affect well-being or there is a suspicion that the organs are involved.
People who lead an unhealthy lifestyle or are under stress are particularly prone to developing neurocutaneous syndrome. Tumor patients and people who already suffer from sarcomas are also among the risk groups and should always have the symptoms mentioned checked out. Parents who notice changes in their child’s appearance or posture a few weeks to months after birth should consult their pediatrician . Possible bone damage or fractures indicate a serious condition that needs to be clarified immediately.
Neurocutaneous syndrome can be diagnosed by a neurological specialist. Depending on the symptoms, dermatologists, ophthalmologists, orthopedists and other specialists can be involved in the treatment. Patients must be examined and treated in a specialist clinic in any case, as it is a progressive disease.
Treatment & Therapy
Treatment and therapy also depend on the respective clinical picture. What the various syndromes have in common is that causal therapy is not possible.
Outlook & Forecast
The hallmark of neurocutaneous syndrome is a change in human genetics. This is the main reason for the health problems. At the same time, doctors and medical professionals are not permitted to modify a person’s genetic material. Legal requirements prevent this possible step. Therefore, sufferers of this syndrome do not experience a cure.
Due to the circumstances described, the prognosis can be described as unfavorable. The existing malformations are individually pronounced in each patient. Overall, they lead to severe limitations in coping with life. Its intensity is a decisive factor for the further course of the disease and the treatment options. Under favorable conditions, numerous changes and improvements in the quality of life can be achieved through interventions. Possible movement restrictions are corrected and the well-being of the patient is improved.
However, the disease is also associated with mental impairments. Despite all efforts and early support, these cannot be completely regenerated. In most cases, the patients need lifelong therapeutic support as well as daily support in organizing everyday life.
Optical changes often occur, and dysfunctions of various systems or organs are observed. Seizures are also possible complaints. If there is no regular medical care, the risk of premature death and the possibility of a life-threatening condition increases. The overall situation is so demanding that subsequent psychological disorders are to be expected.
Prevention
Since these are hereditary diseases, prevention is not possible.
Aftercare
The neurocutaneous syndrome requires lifelong follow-up care in affected patients. It must always be noted that a causal therapy is not possible, since the diseases are hereditary. Only symptoms can be treated more or less successfully.
After the treatments, constant follow-up examinations must take place in order to prevent further complications and to maintain or, to a certain extent, improve the quality of life of those affected. However, follow-up care always depends on the underlying condition. It is therefore necessary to continuously monitor patients with constant epileptic seizures in order to be able to provide emergency aid quickly in an emergency.
In the case of certain phakomatoses, the skin should also be monitored continuously for the rapid detection of any malignant degeneration that may occur. With timely diagnosis, skin cancer can usually be treated successfully. Patients with mental retardation also require constant care. Physical deformities sometimes require surgery.
In the healing phase after such operations, the patient is dependent on particularly intensive follow-up care because there is always a risk of serious complications. The other organs should always be checked for possible damage. Many of those affected also need psychological support. In the context of psychotherapy, strategies for the best possible way of dealing with the illness can then be developed with the patient.
You can do that yourself
Depending on the type and severity of the neurocutaneous syndrome, patients can do a number of things themselves. Basically, with phakomatoses, one must pay attention to the signals of the body, since the symptoms can manifest themselves in different areas. In consultation with the doctor, the sick person should keep a complaints diary and note all unusual symptoms and manifestations in it.
In the case of skin problems, such as those that occur with neurofibromatosis, strict personal hygiene applies. Irritating substances and foods that could worsen the complexion should be avoided. In the event of seizures, such as those that occur as part of Sturge-Weber syndrome, the emergency services must be alerted. The patient must be monitored around the clock so that immediate action can be taken in the event of accidents or falls. Close monitoring is also important in the case of cognitive disorders or severe vascular malformations with a risk of thrombosis.
The additional measures that patients with neurocutaneous syndrome can take depend on the type of disease. After a comprehensive diagnosis, the family doctor can give tips and rules of conduct for dealing with the condition. In addition, aids such as walking aids and wheelchairs usually have to be organized and bureaucratic tasks such as contact with health insurance companies, nursing services, etc. have to be taken on. Those affected can find support from a therapist or in self-help groups.
