Neurocutaneous syndromes are inherited disorders characterized by neuroectodermal and mesenchymal malformations. In addition to the classic four phakomatoses (Bourneville-Pringle syndrome, neurofibromatosis, Sturge-Weber-Krabbe syndrome, Von Hippel-Lindau-Czermak syndrome), neurocutaneous syndromes also include a number of other disorders that manifest on the skin and central nervous system.
What is a neurocutaneous syndrome?
The disorders that are neurocutaneous syndromes are all due to hereditary dysplasias that develop during the embryonic period. This can be explained by the fact that both neuroectoderm and mesenchymal malformations occur. The neuroectoderm is a part of the outer cotyledon (ectoderm). The nervous system develops from the neuroectoderm during the embryonic period. The mesenchyme is the “embryonic connective tissue“. From this, various structures of the human body develop – connective tissue, cartilage tissue, bones, tendons, muscle tissue, blood and fatty tissue. These malformations, which develop during the embryonic period, can be used to explain why the skin and central nervous system are affected. Neurocutaneous syndromes include both malignant and benign tumors.
Causes
Because neurocutaneous syndromes are hereditary disorders, the cause is clear. There is a change in a gene that is inherited and is responsible for the dysplasias. The appearance of the symptoms is then caused by the malformations that occur in the course of the syndrome. Already in the embryonic stage the malformations are formed on the neuroectoderm and the mesenchyme. The neuroectoderm develops into the nervous system during the embryonic period, which explains the neurological symptoms. Tumors can develop from the mesenchyme. These are referred to as mesenchymomas. Malignant tumors of tissues arising from the mesenchyme are called sarcomas.
Symptoms, complaints, and signs
Symptoms, complaints, and signs differ among the various diseases grouped as neurocutaneous syndromes. For this reason, a differentiation must be made here. The neurocutaneous syndromes include, first, 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
- Dysraphia syndrome
The following are examples of Bourneville-Pringle syndrome as a classic phacomatosis, dysraphia syndrome as an “other neurocutaneous syndrome” and Bonnet-Dechaume-Blanc syndrome as a condition that may be classified as neurocutaneous syndromes. Bourneville-Pringle syndrome is also known as tuberous cerebral sclerosis and is associated with a number of different symptoms. Tuberous cerebral sclerosis is inherited in an autosomal dominant manner. It is thought that there is a high rate of spontaneous mutation and, as a result, 50 percent of those with the disease have a new mutation. The main symptoms of Bourneville-Pringle syndrome are adenoma sebaceum, epilepsy and mental retardation. Adenoma sebaceum results in the development of numerous small fibroadenomas of the sebaceous glands around the face. In addition to the described symptoms, numerous other symptoms may occur, mainly affecting the central nervous system, skin and kidney. The severe symptoms of the diseases are usually noticed in infancy. On computed tomographic diagnosis, the visible periventricular calcifications are typical of tuberous cerebral sclerosis. Dsyraphia syndrome is a collective name for combined malformations resulting from a deficient spinal cord anlage or a disorder of the closing process of the primary neural plates. The syndrome represents a hereditary constitutional anomaly.Symptomatic are an “open back” (spina bifida), foot deformities, vertebral malformations with secondary kyphosis and/or scoliosis, sacral hypertrichosis, funnel chest, neurological trophic disorders, sensibility and motor function of the lower extremities, spinal reflex anomalies, sphincter weakness, clefts of the pharynx and urogenital tract, foveola coccygea, four-finger furrow, hyperthelias, and mental disorders. Bonnet-Dechaume-Blanc syndrome is characterized by malformations of the head and cerebral vessels, changes in the face, and abnormalities of the blood vessels of the retina. It should be noted that this syndrome is extremely rare and only 132 cases were known worldwide in 2009. Here, both sexes were affected with approximately equal frequency. Regarding the pathophysiology of the syndrome, numerous pathological connections between arterial and venous systems are present. Furthermore, numerous so-called tendril angiomas and arteriovenous aneurysms are found in the retinal area and in the central nervous system, especially in the mesencephalon, a part of the brain stem. The disease is congenital, with the embryonic developmental disorder occurring in the seventh week of pregnancy. The cause is not yet known. The syndrome is classified by the majority of experts as a neurocutaneous syndrome, but some make a different classification. One aspect that speaks against the classification to the neurocutaneous syndromes is the fact that the syndrome is not a hereditary disease. The symptoms are changes in the face in the form of unnaturally protruding blood vessels, nystagmus, glaucoma and epistaxis. Exophthalmos (usually unilateral), retinal hemorrhages, vitreous hemorrhages, epilepsy, and cerebral hemorrhage may also occur. Cerebral hemorrhages are divided into subarachnoid hemorrhage and epidural hemorrhage. The intraocular hemorrhages (in this case, hemorrhages of the retina and vitreous humor) lead to long-term blindness. Diagnosis is made by ophthalmoscopy, perimetry, MRI, CT and digital subtraction angiography. The syndrome can only be treated symptomatically. For this purpose, surgical treatments of vascular malformations, laser coagulation, and embolization are used.
Diagnosis and course of the disease
Diagnosis and disease course depend on the particular syndrome or disease and cannot be stated generally for all neurocutaneous syndromes.
Complications
Neurocutaneous syndrome can cause different complications because of its diversity. All disorders of this syndrome are known to be associated with malformations of the nervous system and skin. The complications that occur depend on the particular underlying disease. Thus, each individual neurocutaneous disorder may lead to complications to a greater or lesser degree. For example, Bourneville-Pringle syndrome, also called 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). Furthermore, the optic nerve is sometimes affected by tumors. In half of the patients with this disease, bone cysts also develop in addition to a spinal curvature (scoliosis). Sturge-Weber-Krabbe syndrome, in turn, is characterized by vascular malformation, which carries the risk of developing glaucoma as well as mental retardation due to the many epileptic seizures. Epilepsies, glaucoma with the risk of blindness, and other neurological deficits also occur in other neurocutaneous syndrome disorders. Some diseases may also lead to cerebral hemorrhage. In some cases, multiple skin tumors occur, such as basal cell carcinoma, among others. Hearing loss or even deafness is also observed in some diseases of the syndrome.
When should one go to the doctor?
When skin changes, neurological disturbances, and other symptoms are noticed that may indicate neurocutaneous syndrome or another serious condition, medical advice should be sought. Affected individuals are best to consult a physician immediately if symptoms become more severe or typical complications such as movement disorders or skin bleeding are noticed.Medical advice must be sought at the latest when the signs of the disease affect well-being or when organ involvement is suspected. People who maintain an unhealthy lifestyle or are under stress are particularly susceptible to the development of neurocutaneous syndrome. Tumor patients and people who already suffer from sarcomas are also among the risk groups and should have these complaints clarified in any case. Parents who notice changes in their child’s appearance or posture a few weeks to months after birth must consult their pediatrician. Possible bone damage or fractures indicate a serious condition that should be clarified immediately. Neurocutaneous syndrome can be diagnosed by a specialist in neurological disorders. Depending on the symptoms, dermatologists, ophthalmologists, orthopedists and other specialists may be involved in treatment. Sufferers must always be examined and treated in a specialist clinic, as it is a progressively progressive disease.
Treatment and therapy
Treatment and therapy also depend on the particular syndrome. What the various syndromes have in common is that causative therapy is not possible.
Outlook and prognosis
The hallmark of the neurocutaneous syndrome is a change in human genetics. This is causally responsible for the health impairments. In parallel, physicians and medical professionals are not allowed to alter a person’s genetic material. Legal regulations prevent this possible step. Therefore, sufferers of this syndrome do not experience a cure. The prognosis can be described as unfavorable due to the described circumstances. The existing malformations are individually pronounced in each patient. Overall, they lead to severe limitation in coping with life. Their intensity is a decisive factor for the further course of the disease as well as the treatment options. Under favorable conditions, numerous changes and improvements in quality of life can be achieved through interventions. Possible movement restrictions are corrected and thus the patient’s well-being is improved. However, the disease is also accompanied by mental losses. These cannot be fully regenerated despite all efforts and early intervention. In most cases, patients require lifelong therapeutic support as well as daily assistance in managing their daily lives. Visual changes are common and dysfunction of various systems or organs is observed. Similarly, seizures are possible complaints. If regular medical care is not provided, the risk of premature death increases, as does the possibility of a life-threatening condition. The overall situation is so demanding that secondary mental disorders are to be expected.
Prevention
Because these are hereditary disorders, prevention is not possible.
Follow-up care
Neurocutaneous syndrome requires lifelong follow-up in affected patients. It must always be kept in mind that causative therapy is not possible, as these are hereditary diseases. Only symptoms can be treated more or less successfully. After the treatments, constant follow-up examinations must take place in order to prevent renewed 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. For example, it is necessary to monitor patients with continuous epileptic seizures on a permanent basis in order to be able to provide rapid emergency assistance in case of an emergency. In the case of certain phakomatoses, the skin should also be permanently observed for 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. In the case of physical deformities, surgical intervention is sometimes necessary. In the healing phase after such operations, the patient is then dependent on particularly intensive aftercare, because serious complications can always threaten. The other organs should always be examined for possible damage. Furthermore, many patients need psychological support.Psychotherapy can then be used to develop strategies with patients to best manage the condition.
What you can do yourself
Depending on the type and severity of the neurocutaneous syndrome, patients can do a few things themselves. Basically, with phakomatosis, attention must be paid to the body’s signals, as the symptoms can manifest in different areas. In consultation with the doctor, the sufferers should create a complaints diary and note down all unusual symptoms and manifestations in it. In the case of skin complaints, such as those that occur in neurofibromatosis, strict personal hygiene applies. Irritating substances and foods that could worsen the skin condition should be avoided. In the event of seizures, such as those that occur in 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 cases of cognitive impairment or severe vascular malformations with risk of thrombosis. The additional measures that patients of a neurocutaneous syndrome can take depend on the nature of the disease. After a comprehensive diagnosis, the family doctor can provide tips and behavioral rules 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, care services, etc. have to be taken on. Those affected can find support from a therapist or in self-help groups.