Genetic diseases passed on from one generation to the next, caused by mutations in a gene or genes, have become an issue of great interest to obstetricians, not only because anyone caring for a pregnant woman should make future parents aware of the risk of passing on the disease, but also present them with diagnostic options and further management.
Table of contents:
- Diagnosis and symptoms
- Prevention
- Conditions of pregnancy in Recklinghausen's disease
- Care and treatment
Recklinghausen 's disease is a rare genetic condition inherited in an autosomal dominant manner. It is also known as neurofibromatosis type I, as well as neurofibromatosis type I. It belongs to a group of conditions known as phacomatoses referred to as neurocutaneous dysplasias. It occurs once every 2,500 to 3,500 births and is caused by a mutation of the NF-1 tumour suppressor gene (a gene that prevents tumours from developing) on chromosome 17, arising during embryonic development. Damage to this gene therefore carries an increased risk of dangerous cancerous lesions developing during the course of the disease.
Diagnosis and symptoms
Recklinghausen's disease is sometimes difficult to diagnose due to the variety and complexity of its symptoms and their varying severity. The main symptoms suggesting the existence of the disease are skin lesions and neurological symptoms. The skin lesions appear as subcutaneous nodules, containing elements of nerve and connective tissue, located just under the skin, and skin discolouration in the form of spots, no less than 15 mm in diameter and coffee-coloured or resembling large freckles in the groin area. These spots are often a symptom that precedes the onset of nodules and may already appear in newborns, but are more often observed in the later months and years of life. As the nodules are often located along the course of peripheral nerves or cranial nerves, causing compression of the nerves and neighbouring organs, various organ and neurological symptoms can be found in the course of the disease.
Depending on the size and location of the lesions , neuralgia of the peripheral nerves, occasional epileptic seizures, sacral pain, abnormal innervation in the limbs, hydrocephalus, and psychomotor and mental retardation may occur. Nodular lesions can grow in size over time and some of them develop into neoplastic lesions. Skeletal changes, e.g. lateral curvatures of the spine, bone defects and deformities, as well as hormonally active tumours or embryonal tumours, are also common. Neurofibromatosis type I often coexists with other malformations such as heart defects or intestinal anomalies. In Recklinghausen's disease, ocular symptoms may also occur. These include so-called Lisch nodules in the iris in the form of hardly noticeable whitish spots, optic nerve gliomas or optic neuritis, which can lead to poor vision or irreversible damage to the eyes. An adrenal tumour is also a common symptom of this disease, resulting in a hormonal surge that causes blood pressure spikes.
The severity of the symptoms, as well as the course of the disease, can vary widely. They range from a mild form, where there are no visible symptoms apart from skin discolouration or visual disturbances, to a severe form with neurological disorders, bone deformities or malignant neoplastic lesions. The variation in the severity of the clinical condition probably depends on the type of mutation, the effect of the environment on gene expression or the presence of modifier genes, and depends, among other things, on the location and dynamics of the disease process. Therefore, the first symptoms of the disease are often misdiagnosed and the correct diagnosis is made at a later stage, e.g. when tumours appear. The diagnosis of the disease is made primarily on the basis of history, neurological examination, funduscopic examination and histopathological examination of the surgically removed nodule. It is made when at least two of the most common symptoms of the disease are found.
Prevention
Since the risk of passing on the mutated gene to the next generation if one of the parents carries it is approximately 50%, every woman planning a pregnancy should carefully take a family history and pay particular attention to genetic diseases in the family, as well as to symptoms in family members that may indicate the presence of any of these diseases. It is worth remembering that in some family members, as well as in the parents-to-be, the symptoms of Recklinghausen's disease may not have been diagnosed as a genetic disease. This may have been due, for example, to a lack of diagnostic possibilities in genetics or the knowledge of doctors at the time about certain diseases. Symptoms, especially in the abortive form, may not have been associated as a disease. If no one in the family has shown symptoms of the disease then it is possible that the disease is the result of a new gene mutation. This means that the disease may arise spontaneously in the family and none of the family members is a carrier of the affected gene.
In pregnant women with a family history of neurofibromatosis type 1 or in her husband's family, genetic counselling is particularly important. It is advisable to refer her to a genetic counselling clinic for prenatal diagnosis. Early in pregnancy, this gene mutation can be detected with appropriate tests. However, these tests are not routinely carried out because the disease in the new family member may be mild and not cause health problems. If tests detect this genetic defect, it does not constitute grounds for a termination of pregnancy.
From the point of view of genetic counselling, the best solution would be to test the whole family, not only to determine the risk of passing the disease on to future generations, but also the risk of cancer for those carrying the defective gene. This would make it possible to classify these individuals as being at increased risk and to provide them with appropriate prophylaxis. Unfortunately, this is difficult to achieve in practice.
Making parents-to-be aware of the symptoms and risks associated with Recklinghausen's disease allows them to prepare adequately for the possibility of having a sick child. This is particularly important because parents need to be sensitive to the symptoms that their child may develop. Seeing a doctor as soon as the first symptoms appear, which may suggest the presence of the disease, allows an early diagnosis to be made and the child to receive prophylaxis and multispecialist care. Prevention is aimed primarily at reducing the risk of developing cancer and visual impairment.
Recklinghausen's disease, photo: panthermedia
Pregnancy conditions in Recklinghausen's disease
Pregnancy in women affected by neurofibromatosis type I should be treated as a pregnancy of special concern. The mother-to-be should not only be under the constant supervision of an obstetrician, but also doctors of other specialities, e.g. an ophthalmologist and a neurologist.
The treatment of pregnant women diagnosed with Recklinghausen's disease depends on the symptoms present and the severity of the clinical condition. Most often, therapy is limited to symptomatic treatment only. Due to the variety of symptoms of the disease, difficulties arise in differentiating them from symptoms resulting from pregnancy. Sacral pain, hypertension or visual disturbances often occurring during pregnancy should therefore be consulted for this disease.
Spikes in blood pressure are particularly dangerous for pregnant women, as are other complications resulting from the presence of an adrenal tumour, one of the symptoms of Recklinghausen's disease. The tumour can cause adrenal hyperfunction, posing a threat to the normal development of the pregnancy. In women with symptoms of hyperadrenalism, pregnancy can be complicated by miscarriage, preterm delivery, intrauterine growth disorders and even intrauterine fetal death. The coexistence of an adrenal tumour with pregnancy is very rare due to the fact that women diagnosed with a tumour often develop hormonal problems causing, among other things, blocked ovulation and thus difficulties in getting pregnant. As the amount of circulating blood and the minute ejection capacity of the heart increases during a physiological pregnancy, pregnant women often have problems with normal blood pressure. The additional burden of pressure surges due to the presence of a tumour increases the risk of abnormal placental blood flow and thus abnormal fetal oxygenation and nutrition, leading to intrauterine fetal stunting. Any sudden increase in pressure poses a risk to both mother and foetus. Its most dangerous complication is eclampsia, which is the most common cause of maternal and fetal death.
Care and treatment
Special care is required for pregnant women with neurofibromatosis type I who develop epileptic seizures as a result of nerve compression by nodules. A pregnant woman with epileptic symptoms requires appropriate pharmacological treatment and supervision by a neurologist. Epileptic seizures occurring during pregnancy or childbirth increase the risk of mechanical injury to the mother and the foetus and may also cause intrauterine hypoxia. The increased risk of malformations, most commonly defects of the nervous system and heart, in the children of mothers with epilepsy is most likely influenced by the teratogenic effects of certain antiepileptic drugs rather than the seizures themselves. Women with epilepsy are much more likely to have preterm births, as well as other complications of pregnancy, such as premature detachment of the placenta or spontaneous abortion. More often, pregnancies in women with epilepsy end in caesarean sections or surgical deliveries.
Recklinghausen's disease, like most genetic diseases, is incurable and no possibility of correcting this gene mutation has yet been found. Due to rapid advances in genetics, it may be possible in the future to correct the damaged gene with appropriate gene therapy. At present, the only option is to prevent the transmission of the defective gene to the next generation, to inform future parents of the risks associated with its transmission and to extend early prevention to those who have such a gene.
