The Tuberous sclerosis ( ET ) or Bourneville disease Is a pathology of genetic origin that produces the growth of beningnos tumors (hamartomas) and diverse anatomical malformations in one or several organs: skin, brain, eyes, lungs, heart, kidneys, etc... (Sáinz Herández and Vallverú Torón, 2016).
At the neurological level, it usually significantly affects the central nervous system (CNS) and peripheral (SNP) and may also result in a combination of symptoms including seizures, generalized developmental delay, behavioral disorders, skin malformations and Renal pathologies (National Institute of Neurological Disorders and Stroke, 2016).
The incidence and severity of symptoms vary considerably among those affected. Many people with tuberous sclerosis quality of life (National Association of Tuberous Sclerosis, 2016).
The pathology that puts the life of the affected person at greater risk is the renal involvement. A large proportion of patients die as a result of renal problems And not by the neurological or cardiac (Curatolo, 2003).
The Tuberous sclerosis Is a medical condition that is usually detected in the early stages of life, usually during childhood. However, in some cases the absence of a significant clinical course delays diagnosis until adulthood (Mayo Clinic, 2014).
Currently, there is no specific curative treatment for tuberous sclerosis. All medical interventions will be conditioned to specific pathologies and clinical manifestations in each case (Sáinz Herández and Vallverú Torón, 2016).
Characteristics of tuberous sclerosis
Tuberous sclerosis (ET) is a medical condition described more than 100 years ago (Argüelles and Álvarez-Valiente, 1999).
In 1862, Von Recklinghausen published a clinical report describing a case of a newborn whose death was due to the presence of cardiac tumors and numerous brain sclerosis (Gerogescou et al., 2015)
Although the French neurologist Bourneville in 1880 first described the brain lesions characteristic of this pathology, it was not until 1908 that Vogt accurately defined the clinical course characterized by the presentation of the classic triad: Sebaceous adenoma , Mental retardation And convulsive episodes (Argüelles and Álvarez-Valiente, 1999).
In addition, in 1913 it was Berg, who demonstrated the hereditary nature of the transmission of this pathology (Gerogescou et al., 2015).
The term naming this disease, tuberous sclerosis, refers to the appearance of tumor lesions (calcified, with a similar shape to a tuber ) (Sánchez Hernández and Vallverdú Torón, 2016).
However, in the medical literature we can also find other names such as Bourneville disease, tuberous sclerosis complex, tuberous sclerosis facomatosis, among others.
Tuberous sclerosis (ET) is a genetic disease that is expressed variably, characterized by the presence of benign tumors or benign tumors in various organs, especially the heart, brain and foot (Arango et al., 2015).
Frequency
Tuberous sclerosis is a disease that affects both men and women and all ethnic groups (Gerogescou et al., 2015).
In addition, it presents a frequency of 1 case per 6,000 people (Curatolo, 2003).
However, other statistical studies estimate the prevalence of this pathology in one case for every 12,000-14,000 people under the age of ten. While the incidence is estimated in 1 case per 6,000 births (Gerogescou et al., 2015).
It is estimated that about one million people worldwide suffer from tuberous sclerosis (Tubeorus Sclerosis Association, 2016).
In the United States, tuberous sclerosis is thought to affect approximately 25,000-40,000 citizens (National Institute of Neurological Disorders and Stroke, 2016).
It has an autosomal dominant genetic origin in 50% of cases, while the other 50%, this pathology is due to a de novo genetic mutation (Curatolo, 2003).
Signs and symptoms
The clinical features of tuberous sclerosis are primarily based on the presence of non-cancerous tumors or other types of growths in various parts of the body, being more common in the skin, heart, lungs, kidneys and brain (May Clinic, 2014).
Skin affection
In the case of skin lesions, some of the most frequent manifestations are (Sáinz Herández and Vallverú Torón, 2016; National Association of tuberous sclerosis, 2016):
- Facial angiofibromas: Small benign tumors consisting of connective and vascular tissue. They usually appear on the nose and cheeks, and, in addition, at the beginning usually appear as small reddish bumps that have to increase in size over time. They usually appear in 70-80% of cases.
- Ungual fibromas or Köenen tumors : Fleshy formations that develop under the nails or around.
- Fibrous plates : Pink spots or formations located on the face, especially on the forehead or cheeks.
- Hypochromic stains (Color lighter than the skin) or acromic (total absence of cutaneous pigment): This type of cutaneous involvement occurs in approximately 90% of cases of tuberous sclerosis.
Renal Impairment
In the case of the kidneys, some of the most frequent manifestations are (Sáinz Herández and Vallverú Torón, 2016; National Association of Sclerosis Tuberosa, 2016):
- Renal angiomyolipomas (AMLs) : They are formations Benign tumor . It usually appears and childhood and develop slowly, so do not usually cause major medical problems until they reach adulthood. It is a common clinical manifestation, appears in 70-80% of cases. Some of the symptoms they are going to cause are: hypertension, kidney failure, or blood in the urine, among others.
- Renal cysts: Kidney cysts are sacks or fluid sacs that form in different areas of the kidneys. Although in many cases they do not usually have a great clinical relevance, in other cases they can be due to a Renal carcinoma (A type of kidney cancer).
Cardiac Impairment
Cardiac lesions, if present, tend to be of a higher size, more serious in the early stages of life, and have to be reduced with the normal development of the organism (Mayo Clinic, 2014).
- Cardiac Rhabdomyomas : It is the most frequent cardiac affectation, usually appears in approximately 70% of the cases. They are benign tumor formations that usually reduce their size or disappear with the increase of the age. As a consequence, other cardiac symptoms may appear as Arrhythmias or Tachycardia (Sánchez Hernández and Vallverdú Torón, 2016, National Association of Tuberous Sclerosis, 2016)
Pulmonary affectation
Lung signs and symptoms are more common in women than in men. In addition, it is usually associated with the presence of lymphangioleiomyomatosis (LAM), a type of degenerative pathology that affects the lungs (Sáinz Herández and Vallverú Torón, 2016).
The clinical consequences of lung involvement usually consist of respiratory failure, pneumothorax Spontaneous, pulmonary collapse, among others (Sáinz Herández and Vallverú Torón, 2016).
Neurological affectation
Tuberous sclerosis is a pathology that affects a wide variety of structures of our organism, however, the most remarkable and the main area affected is the nervous system. Neurological involvement usually occurs between 80% and 90% of cases (Curatolo, 2003).
Some of the medical conditions that usually affect the neurological sphere are: (Sáinz Herández and Vallverú Torón, 2016; National Association of Tuberous Sclerosis, 2016):
- Corneal tufts: Corneal tufts or tuberosities are small tumor formations that are usually located in frontal and parietal areas. In addition, they are usually made up of abnormal or disorganized cells.
- Subependymal glial nodules: This type of involvement is constituted by an abnormal accumulation of cells in different areas of the cerebral ventricles. They usually present an asymptomatic clinical course.
- Subcommittee Giant Cell Astrocytomas: They are tumoral formations derived from subependymal glial nodules. When they reach a high size they can block the drainage of cerebrospinal fluid and consequently lead to the development of Endocranial hypertension .
The involvement of each of these areas will produce a series of medical complications or secondary symptoms, among which are:
- Convulsive episodes : The presence of tumor formations at the neurological level can lead to epileptic discharges in approximately 92% of the cases. When this type of crisis is not effectively controlled, cumulative brain damage may appear.
- Motor symptoms : Tumor formations at the cerebral level can also lead to the development of Hemiplegia , Motor incoordination, presence of involuntary movements, among others.
- Intellectual disability : Brain alterations and the persistence of convulsive episodes can have a strong impact both on general intellectual functioning and on the different cognitive domains in particular.
- Behavioral alterations : In many cases of tuberous sclerosis the presence of autistic features, hyperactivity, aggressive behavior, obsessive-compulsive traits, lack or absence of verbal communication, irritability, psychic lability, lack of initiative, among others.
Causes
The origin of tuberous sclerosis is genetic. Clinical and experimental studies have been able to identify that this pathology is due to the presence of defects or mutations in two genes, TSC1 and TSC2 (National Institute of Neurological Disorders and Stroke, 2016).
- The TSC1 gene was discovered in the 1990s. It is present on chromosome 9 and is responsible for the production of a protein called hamartin (National Institute of Neurological Disorders and Stroke, 2016).
- The TSC2 gene, present on chromosome 16, is responsible for the production of tuberin protein (National Institute of Neurological Disorders and Stroke, 2016).
Diagnosis
The diagnosis of tuberous sclerosis is usually based on the clinical signs characteristic of this disease: mental retardation, seizures, formations Tumor (Argüelles and Álvarez-Valiente, 1999).
A conference in 1998 established a set of consensus diagnostic criteria for tuberous sclerosis (Gerogescou et al., 2015)
Currently, the diagnosis may be probable or possible and a genetic test must also be included (Gerogescou et al., 2015).
Genetic Testing
The results of genetic testing should show the presence of a mutation or pathogenic alteration in one of the TSC1 or TSC2 genes.
Generally, a positive result is usually sufficient for the diagnosis, however, a negative result does not exclude the presence. Approximately 10% to 15% of diagnosed cases have failed to identify a specific genetic mutation.
Major and minor clinical criteria
Major clinical criteria
The major clinical criteria include a great variety of medical affectations among which are: hypopigmented macules, Angiofibromas , Ungual fibroids, skin plaques, retinal hamartomas, cortical dysplasias, subependymal nodules, cardiac rhabdomyoma, Angiomyolopimas Renal And lifangioleimiomatosis.
Minor clinical criteria
Less clinical criteria include: dental depressions, cutaneous lesions, intraoral fibromas, retinal macules, multiple renal cysts, and extrarenal hamartomas.
Thus, according to the presence of major and / or minor criteria, the diagnosis of tuberous sclerosis may be (Gerogescou et al., 2015):
- Definitive diagnosis : Presence of two major criteria or a major increase and 2 or more minor criteria.
- Possible diagnosis : Presence of a higher criterion or two or more minor criteria.
- Probable diagnosis : Presence of a higher criterion and a lower criterion.
Treatment
Currently, there is no cure for tuberous sclerosis. Despite this, there is a wide variety of treatment available for symptom control.
In this way, the therapeutic interventions will depend fundamentally on the areas that are affected and the medical signs and symptoms that are present.
At the pharmacological level, one of the treatments most used are the drugs Antiepileptics . The basic purpose of these is the control of convulsive episodes to avoid the development of secondary brain damage.
On the other hand, it is also possible to use surgical procedures for the elimination of tumor formations. Normally, it is used to eliminate tumors that have a simple access.
In addition, significant advances are being made at the experimental level for the identification of curative treatments.
On the other hand, psychological intervention is also fundamental in cases of intellectual involvement.
References
- Argüelles, M., & Álvarez-Valiente, H. (1999). Clinical study of tuberous sclerosis. Rev Neurol .
- Clinic, M. (2014). Tuberous Sclerosis . Obtained from Mayo Clinic.
- Curatolo, P. (2004). Tuberous sclerosis complex. Rev Neurol .
- Georgescou, G., de la Vaissière, S., Castelnau, P., Halimi, J., & Toutain, A. (2015). Tuberous sclerosis of Bourneville. EMC-Dermatology .
- NIH. (2014). Tuberous sclerosis . Obtained from MedlinePlus.
- NIH. (2016). Tuberous Sclerosis . Retrieved from the National Institute of Neurological Disorders and Stroke.
- Sáinz Hernández, M., & Vallverdú Torón, H. (2016). Chapter XII. Tuberous Sclerosis.
- Tuberosa, A.N. (s.f.). Tuberous Sclerosis . Obtained from Tuberous Sclerosis.
- Tuberous Sclerosis Alliance. (2016). What is TSC? Obtained from Tuberous Sclerosis Alliance.
- Image source 1.