Bourneville-Pringle Syndrome: Causes, Symptoms & Treatment

Bourneville-Pringle syndrome is known as a triad of tumors of the brain with epilepsy and developmental delay, skin lesions, and growths in other organ systems. The disease is caused by a mutation of two genes, TSC1 and TSC2. Therapy is symptomatic with a focus on the epilepsy.

What is Bourneville-Pringle syndrome?

The medical term Bourneville-Pringle syndrome is a synonymous term for tuberous sclerosis. This pathological phenomenon falls into the group of hereditary diseases and is characterized by mostly benign tumors of the face, brain, and organ systems, mental retardation, and epileptic seizures. The prevalence of tuberous sclerosis for newborns is about one case per 8000 infants. French neurologists Désiré-Magloire Bourneville and Édouard Brissaud, along with British dermatologist John James Pringle, first described the condition in the 19th century. The name Bourneville-Pringle syndrome has become common for their sake. In English, the symptom complex is called the Tuberous Sclerosis Complex. Clinically, the complex is characterized by a symptomatic triad with the symptoms mentioned above. A special form of the syndrome is contiguous gene syndrome.

Causes

Familial clusters have been observed in association with Bourneville-Pringle syndrome, which appear to be based on an autosomal dominant inheritance. However, in half of all cases, the disease appears to be caused by a genetic new mutation. The rate of spontaneous mutations is thus at least as high as that of inherited mutations. In familial cases, mutations in the TSC1 gene at locus Chr.9q34 and in the TSC2 gene at locus Chr.16p13 have been observed with equal frequency. Sporadic occurrence is almost exclusively restricted to new mutations in the TSC2 gene. The two genes are tumor suppressor genes and thus involved in the suppression of cell proliferation. Their gene products are hamartin and tuberin, whose functions have not been conclusively clarified. The mutations in the context of a Bourneville-Pringle syndrome are distributed over all exons of the mentioned genes and can correspond to any mutation type. Only large deletions in the TSC2 gene on one or more exons have not been observed so far. The special form of contiguous gene syndrome affects both the TSC2 gene and the PKD1 gene.

Symptoms, complaints, and signs

Tuberous sclerosis is characterized by multiple areas of abnormal tissue differentiation called hamartia, which occur at variable locations with respect to organ systems. The main criteria of the disease include facial angiofibromas and connective tissue nevi in the frontal area, non-traumatic angiofibromas, at least three hypomelanotic patches, connective tissue nevi of the sacrum, and multiple hamartomas on the retina. In addition to cortical dysplasias, other findings include subependymal nodular formations, subependymal giant cell symptoms, and rhabdomyomas of the heart. In addition, pulmonary lymphangiomyomatoses and angiomyolipoma of the kidneys can be designated as major criteria. Concomitantly symptomatic, patients usually present with dental enamel defects, rectal polyps, or osseous cyst formations. In addition, concomitant symptomatology may include unusual stiffness of the cerebral white matter. The same is true for gingival fibromas, depigmentation, and cysts of the kidneys. The triad of the syndrome is broken down into symptomatic skin lesions, malformations of the brain with developmental abnormalities and epilepsy, and symptoms of other organ systems.

Diagnosis and course

To diagnose tuberous sclerosis, the physician demonstrates to the patient either two major criteria of the disease or one major symptom with two minor criteria. The brain changes are usually the earliest to be proven and are usually visualized by imaging such as MRI. Molecular genetic analysis can confirm the suspected diagnosis of the syndrome and exclude differential similar syndromes. The prognosis is good for patients of more mild Bourneville-Pringle syndrome. Many patients with mild BPD lead largely normal lives. Those affected by severe BPD and thus severe epilepsy, extreme cognitive impairment, and a large amount of tumors have a poorer prognosis and may face life-shortening effects.

Complications

In Bourneville-Pringle syndrome or tuberous sclerosis, various organ systems are affected and may have various complications. First, this disease primarily affects the central nervous system and brain. Those affected suffer from epilepsies, especially in childhood. So-called partial seizures are most common, but generalized seizures can also occur. If left untreated, childhood epilepsy can develop into Lennox-Gausaut syndrome. In this case, the affected person suffers a mostly tonic seizure and absences several times a day, which can also turn into status epilepticus, a medical emergency, in the worst case. Sometimes mental developmental disorders can also be observed in the child. Furthermore, one patient may develop increased intracranial pressure during the course of the disease. This leads to severe headaches and impaired consciousness. In the worst cases, important control centers in the area of the medulla oblongata can become trapped, which can lead to respiratory arrest. Furthermore, tuberous sclerosis can be the cause of kidney cysts or malignant tumors, which can be responsible for kidney failure (renal insufficiency). This severely limits the quality of life, and the patient may have to undergo dialysis or transplantation. In the heart, intracardiac rhabdomyoma may occur, which may be responsible for cardiac arrhythmias (arrhythmias) or even cardiac death.

When should you see a doctor?

If there are recurrent epileptic seizures and cognitive impairment, a doctor must be consulted. The latter can determine whether Bourneville-Pringle syndrome is causative by means of an ultrasound examination. However, a specific diagnosis of the tumor disease is only possible after a comprehensive medical history has been taken. The hallmark epilepsy can be detected as early as the first few months of life. The pediatrician will then arrange for a routine examination and quickly diagnose Bourneville-Pringle syndrome. If the epileptic seizures do not occur, the diagnosis is more difficult. Any developmental disorders and behavioral abnormalities often develop during childhood or adolescence. As a general rule, if the child behaves in a conspicuous manner, has difficulty learning or shows other impairments, the pediatrician must be consulted. Other warning signs that require medical clarification are increasing skin changes such as reddish poplars or the characteristic leaf-shaped spots on the skin. As the disease progresses, skin tumors, nodules and other abnormalities may be added. If one or both parents have Bourneville-Pringle syndrome, medical evaluation during pregnancy is recommended.

Treatment and therapy

Bourneville-Pringle syndrome cannot yet be treated causally because only gene therapy approaches can be considered as causal therapy, and although these approaches are currently the subject of research, they have not yet received approval for use. For this reason, only symptomatic therapies are currently available for treatment. The treatment of epilepsy is the focus of therapy, since it is precisely this symptom that severely impairs the quality of life of those affected and, in the worst case scenario, causes a severe deterioration in their state of health, even leading to death. Epilepsy is treated either with medication or, in severe cases, as far as possible surgically. For example, separation of the two cerebral hemispheres by surgical removal of the corpus callosum has recorded success in epilepsy therapy in the past. For milder forms, administration of anti-epileptic drugs is often sufficient. In addition to these treatment steps, the tumors must be removed from the organ systems. Since most of the tumors are benign, subsequent radiation is usually not indicated. However, close monitoring is indicated for the large number of tumors in order to detect possible changes towards malignancy in good time. Since those affected often suffer from mentally delayed development, measures such as early intervention can also be appropriate therapeutic steps. Speech development can be supported in logopedic care. The motor developmental delays can be countered with physical and occupational therapy measures.If the disease causes psychological stress for the patient, additional psychotherapy may be useful.

Outlook and prognosis

Currently, there is no curative therapy for Bourneville-Pringle syndrome. Only symptomatic treatment is possible. The severity of the disease varies in individual patients. As a rule, there is a normal life expectancy. However, this may be reduced by frequent epileptic seizures, severe mental retardation, and malignant degeneration of the existing tumors. Therapy is particularly limited to the treatment of epileptic seizures. All seizure forms of epilepsy occur in the course of the disease. A correlation between cognitive development and seizure frequency has been observed. Adults mainly experience secondary generalized focal seizures. Overall, there are developmental disturbances that manifest as speech, movement, and learning disorders. The intelligence quotient of the individual affected can develop differently. While this is normal in half of the patients, approximately 31 percent of those with the disease achieve a quotient of 21 or less. Skin changes also vary and depend on age. These are sebaceous gland adenomas. The cosmetic treatment of adenomas is surgical removal or laser irradiation. Angiomyolipoma, a benign tumor in the kidney tissue, is also common. Furthermore, a benign tumor may also form in the transverse striated muscles of the heart. Tumors can also affect other organs such as the lungs. Malignant degeneration is very rare.

Prevention

To date, Bourneville-Pringle syndrome can be prevented only to the extent that couples in family planning can use molecular genetic testing to assess their risk of having children with the disease and, if necessary, decide against having children of their own if the risk is elevated.

Here’s what you can do yourself

Tuberous sclerosis, also known as Bourneville-Pringle syndrome, is a genetic disease that currently has no causal treatment. Therapeutic measures therefore address the symptoms. One of the most troublesome accompanying symptoms, which usually severely impairs the quality of life of those affected, is epilepsy. In addition to medication with antiepileptic drugs, patients can often help to reduce the frequency or severity of seizures through their lifestyle. Patients should keep an epilepsy diary to find out whether factors from their everyday life trigger the seizures. Such factors can be of a completely different nature. Certain foods, alcohol, mind-altering drugs as well as lack of sleep, stress, strong feelings of anxiety or, in women, menstruation. Critical factors should be avoided as far as possible. Many sufferers and their relatives are also helped by joining a self-help group for epileptics, which now exist in numerous German cities. Very often, persons affected by tuberous sclerosis also suffer from delayed mental development. The negative consequences can be counteracted by adequate early intervention. Parents can seek advice here from pediatricians or the youth welfare office. If the development of motor skills is also impaired, ergo- and physiotherapeutic measures can help. In the case of delayed speech development, a speech therapist should be consulted.