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Tuberous sclerosis

This is part of Rare diseases.

Diagnosis: Tuberous sclerosis

Synonyms: Tuberous sclerosis complex, TSC, Bourneville disease

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Date of publication: 2010-04-19
Version: 3.3

The disease

Tuberous sclerosis is characterized by tumour-like changes in the brain and several other organs. The name means “root-like hardening,” which describes the changes in the cerebral cortex. The French neurologist Désiré-Magloire Bourneville gave the first complete description of the disease in 1880 and gave it its name. Major or minor changes can be found in one or several organs hence the name tuberous sclerosis complex (TSC). In some cases the only indication of the disease may be barely visible skin abnormalities. The following information primarily describes the forms of the disease that entail substantial disability.

Occurrence

Because mild cases of this disease are not always diagnosed, it is difficult to provide exact incidence figures. The estimated incidence of severe tuberous sclerosis is ten cases per 100,000 births, which means that approximately ten Swedish children are born with this form of the condition per year. In Sweden there are probably about 500 individuals with severe tuberous sclerosis, or approximately 60 individuals per million population. However, owing to the variety in clinical expression, many people remain ignorant of the fact that they have the disease. There is no difference in incidence between men and women.

Cause

Tuberous sclerosis is the result of a mutation on a gene controlling cell division and growth. Two different genetic changes have been found to cause the disease. Gene TSC1 is located on the long arm of chromosome 9 (9q34) and controls the formation of (codes for) a protein named hamartin.The other is gene TSC2, located on the short arm of chromosome 16 (16p13.3) and codes for the protein tuberin. These two proteins work together to inhibit the mTOR complex (mammalian Target Of Rapamycin) which in active form accelerates the creation, growth and development of cells. Uninhibited cell development and growth cause the many tumour-like growths characteristic of the disease.

In some families the mutated gene does not appear to be located on either chromosome 9 or 16, so there is/are presumably one or more genes which can cause tuberous sclerosis. Mutations on TSC2 are more common (approx. 70 percent) than mutations on TSC1 (approx. 30 per cent). There are also indications that TSC2 mutations may be associated with more severe symptoms. However, it is still not possible to determine the prognosis in individual cases by identifying the underlying mutation.

Heredity

The inheritance pattern of tuberous sclerosis is autosomal dominant. This means that only one copy of the mutated gene is needed in order to develop the disease. If one parent has the disease, the risk of passing it down to sons or daughters is 50 per cent. Children who do not inherit the mutated gene will neither develop the disease nor pass it down.

Figure: Autosomal dominant inheritance of genetic traits

Tuberous sclerosis can also be caused by a new mutation, meaning that the mutated gene has not been inherited and is not present in the affected individual’s family. The risk that parents of an affected child will have another child with the disease is therefore virtually non-existent. The new mutation, however, is hereditary and there is a risk that a person with a new mutation passes it down to the next generation.

If the parents have no symptoms there are two ways of confirming a new mutation. One way is for both parents to undergo an examination of brain, skin, eyes and kidneys. If all is normal the probability is that the mutation is new. A second way is to use a DNA analysis to try to find the mutation in the affected child and if that is positive, then to test the parents. If they do not have the mutation, a new mutation is indicated. Using contemporary techniques 70 per cent of those with definite symptoms of tuberous sclerosis are identified as having the mutation. Unfortunately however, the mutation does not always appear in all cells (mosaicism) and therefore may not appear in a blood test although this is uncommon. If the parents’ test results are normal, it is estimated that the risk of having another child with tuberous sclerosis is two per cent.

Symptoms

Tuberous sclerosis can affect most organs, but primarily the brain, kidneys, heart, eyes, lungs and skin. The most common symptoms are skin abnormalities, but the most marked symptoms are epilepsy, intellectual disability and autism.

The skin

Various skin abnormalities may present. The most common are depigmented patches, lighter than the surrounding skin and most readily visible under the blue light of a Wood’s lamp. Sometimes these patches may be shaped like ash leaves, but there are many variations. The patches exist from birth, although they may be difficult to discern in infants and fair individuals with little pigment.

In early childhood small red spots or bumps often appear on the face (facial angiofibromas), usually in a butterfly formation across the nose. Other possible skin abnormalities include shagreen patches on the lower back, i.e. skin lesions with a rough, leathery orange peel like appearance. Fibrous growths (fibromas) around the toenails and fingernails often appear in adults. Fibrous plaques, reddish-orange, slightly raised spots on the forehead are unusual but may appear in newborns. If fibrous plaques appear on the scalp, they are hairless and are sometimes surrounded by thin, white hairs. Tufts of white hair, or white eyelashes or eyebrows may be signs of tuberous sclerosis, but can also be found in individuals who do not have the disorder.

The brain

Changes can occur in the brain which may interfere with its functions. These are, above all, the uneven hardenings of the cerebral cortex (cortical tubers) which give the disease its name as well as the immature nerve cells which migrated to the wrong part of the brain during foetal development. These defects give rise to epilepsy and developmental problems, and they often occur with autism or autism spectrum disorders. Another type of abnormality, which is symptom-free, takes the form of small, often calcified nodules on the walls of the brain’s ventricles, the fluid-filled cavities of the brain (subependymal nodules). Abnormalities in the brain are present at birth but there are no subsequent changes. The exception is a tumour-like lesion, the giant-cell astrocytoma, which in rare cases presents in the ventricles in the front of the brain. These lesions may grow and block the outflow of fluid from the brain, causing hydrocephalus.

Figure: Cross-section of the brain, seen from above

1. Subependymal nodules
2. Cortical tubers
Figure: Cross-section of the brain, seen from above

The eyes

Certain abnormalities (hamartomas) may occur in the retina. They are usually located close to the point where the optic nerve enters the fundus, and seldom give rise to vision problems. Only when the abnormalities present in the most important area of vision, the macula, may there be any substantial impact on eyesight. In rare cases, retinal detachment and bleeding may result in vision problems. Depigmented areas, similar to those seen on the skin, may appear on the iris and retina.

The kidneys

Two different kinds of kidney disorders are found, sometimes simultaneously. The most common are non-malignant growths (benign angiomyolipomas), composed of blood vessels, and muscle and fat tissue. Angiomolipomas can sometimes bleed and cause pain in the kidneys or blood in the urine. It is also the only condition associated with tuberous sclerosis which is known to have the potential to give rise to malignant tumours although this is very rare. The other kind of kidney disorder is associated with the development of liquid-filled blisters (cysts), which may lead to renal failure and high blood pressure.

Figure: Cross section of the kidney

1. Angiomyolipoma
2. Cyst
Figure: Cross section of the kidney

The heart

Muscle nodules (rhabdomyomas) are often found in the heart at birth, but rarely give rise to complications. They decrease in size and number over time. In rare cases rhabdomyomas may disrupt the blood flow in the heart, or disturb the cardiac rhythm, in which case surgery may be required.

Figure: Cross section of the heart

1.Rhabdomyoma
Figure: Cross section of the heart

The lungs

Only a few individuals with tuberous sclerosis develop pulmonary lesions (lymphangioleiomyomatosis), which have a honeycomb appearance in an X-ray. These abnormalities are seen only in women, and appear after puberty. Symptoms may include coughing, breathing difficulties, and pulmonary failure.

Other symptoms

Fibromas (tissue nodules) may be found in the gums, particularly around the front teeth. The tooth enamel is often pitted. Cysts and abnormal tissue (hamartomas) may be found in the liver, pancreas, adrenal glands, ovaries and skeleton, but seldom if ever give rise to symptoms or problems. Rectal polyps may cause bleeding. Abnormal bulges may develop locally in blood vessels (aneurysms), for example aortic aneurysms.

Cortical tubers in the brain may give rise to various severe functional disabilities, primarily epilepsy, cognitive impairment and autism. There is a strong association between these disabilities, and they may reinforce one another. Motor disabilities may present, but they are rare. When they do occur, their character will depend on the area of the individual’s brain which is damaged.

It is difficult to state exactly what percentage of individuals with tuberous sclerosis has epilepsy. Depending on whether or not individuals with mild forms of the disease are included, studies indicate between sixty and ninety per cent. The epilepsy often appears early and is frequently difficult to treat. The most severe forms are infantile spasms and Lennox-Gastaut syndrome.

Infantile spasms appear during the first year of life as a series of seizures where the child’s body is bent double (“jackknife seizures”). The child may become partially or completely unconscious and the EEG shows a characteristic pattern. In Lennox-Gastaut syndrome, a severe form of epilepsy that appears in children of preschool and school age, there is a combination of several types of seizures such as: tonic (resulting in stiffness), myoclonic (causing muscle jerks), atonic (where muscles suddenly lose strength) and absence seizures (which cause brief episodes of staring). In adults, the most common types of seizures are generalized tonic-clonic seizures (formerly known as grand mal) and complex partial seizures (formerly known as psychomotor seizures).

Intellectual abilities vary from normal intelligence to severe cognitive impairment. Fewer than 50 per cent of individuals diagnosed with tuberous sclerosis have delayed development. Individuals with intellectual disability require more time to understand and learn, have problems sorting information, adapting to new situations, distinguishing between the overall picture and the details, and understanding and interpreting cause and effect. Therefore, it may take them longer to express their desires, thoughts and feelings.

Autism and autism spectrum disorders are very common. The symptoms of autism are divided into three main categories:

  • Impaired ability to participate in reciprocal social interaction, including difficulties in empathizing with the perspective and feelings of others.
  • Impaired reciprocal verbal and non-verbal communication, including muteness and echolalia (repeating words and phrases or questions without understanding their meaning).
  • Limited imagination and interests, repetitive behaviour, stereotypical movements and impaired social and play skills.

Hyperactivity is a major problem in nearly 50 per cent of all individuals with severe tuberous sclerosis, particularly when there are also learning difficulties and autism. Extremely hyperactive children need to be constantly supervised, otherwise chaos ensues. Poor impulse control and frequent mood swings are also common.
Difficulties in speech and communication are frequently seen. Language ability is often more severely affected than motor development.
Sleep disturbances are common, including problems falling asleep, and a reduced need for sleep. These problems may be associated with epilepsy, and may also have a negative impact on functional abilities as well as increasing daytime behavioural problems.

Diagnosis

To date, no simple and effective test has been developed to establish whether or not a person has tuberous sclerosis. The diagnosis is made on the basis of observing one or several characteristic indications of the disorder. The diagnosis may be more or less definite. The diagnosis of tuberous sclerosis is considered definite if two of the primary criteria or one primary and two secondary criteria are fulfilled. Probable tuberous sclerosis is determined on the basis of the fulfillment of one primary and one secondary criterion, and possible tuberous sclerosis if either one primary or two or more secondary criteria are fulfilled. International diagnostic criteria for tuberous sclerosis, which were agreed on at a conference in the late 1990’s, were revised in 2004.

Primary criteria:

  • Facial angiofibroma or fibrous patches on the forehead
  • Nail fibromas (not resulting from injury)
  • White, pigment-free skin patches (three or more)
  • Shagreen patches (connective tissue nevus*)
  • Several retinal hamartomas
  • Tuberous abnormalities of the cerebral cortex
  • Subependymal nodules
  • Subependymal giant cell astrocytomas
  • Cardiac muscle nodules (one or more)
  • Honeycomb-like abnormalities of the lungs (lymph angiomyomatosis)
  • Angiomyolipomas in the kidneys

Secondary criteria:

  • Tooth enamel defects (multiple, random locations)
  • Rectal polyps of hamartoma type*
  • Skeletal cysts**
  • Aberrant nerve cells migrate wrongly in the white brain tissue, taking the form of radiating lines**
  • Gum fibromas
  • Hamartomas in internal organs other than the kidneys*
  • Colourless (pigment-free) patches in the retina
  • Confetti-like skin patches
  • Renal cysts (multiple)

* = Established by microscopic examination
** = Established by magnetic resonance imaging (MRI)/X-ray examination

In most cases a thorough physical examination is sufficient to establish a diagnosis. In small children, the combination of autism, delayed development and epilepsy indicate the need to investigate whether the underlying disorder might be tuberous sclerosis.

In rare cases there may be no external indications of the disorder, but the diagnosis may still be established on the basis of abnormalities of the brain, eye fundi, heart or kidneys.

X-ray or computer tomography may be used to determine whether there are abnormalities of the internal organs indicating tuberous sclerosis. Magnetic resonance imaging increases the ability to see brain abnormalities, including tuberous sclerotic sites in the cerebral cortex and migratory disturbance (erroneously migrating nerve cells). Nodules on the walls of the liquid-filled cavities of the brain (subependymal nodules) are often calcified, and can best be detected with a computer tomography scan. The kidneys, heart and other internal organs are usually examined using ultrasound. Other methods of investigation include ECG for the heart, and when epilepsy is suspected, EEG for the brain. There are also more specific examination methods for the brain. Retinal abnormalities are detected in a fundus examination.

DNA-based diagnostics may be possible in some cases. If a TSC1 or TSC2 mutation has been identified, prenatal diagnosis is possible. At the time the family is given the diagnosis, genetic counselling should be offered.

Treatment/interventions

As yet there is no cure for tuberous sclerosis. However, medication which inhibits mTOR, sirolimus och everolimus, has proved to be effective. mTOR inhibitors reduce the size of giant-cell astrocytomas which otherwise may require neurosurgery, and angiomyolipomas which can cause kidney dysfunction and haemorrhaging. Lung and kidney abnormalities may also be affected. Research is under way into the development of ointment containing sirolimus,which can reduce the size of facial angiofibromas. Investigations are also under way to determine whether mTOR inhibitors can affect epileptic seizures and behavioural abnormalities.

Other treatments for tuberous sclerosis are directed at treating different symptoms. It is important for the individual to have long-term contact with a physician who is familiar with the disease and its many signs and symptoms. Symptoms associated with the brain, kidneys, heart and lungs may require treatment from a specialist. 

The brain

If new symptoms arise, such as headache, lethargy, vomiting, more frequent convulsions or behaviour changes, tomography or an MRI (magnetic resonance imaging) scan should be considered. It is important to observe giant cell astrocytomas carefully as they may increase in size, and result in hydrocephalus (excessive quantities of cerebral fluid in the brain). The pressure on the brain then increases, and surgery may be necessary.

The kidneys

Angiomyolipomas may bleed and, in rare cases, lead to kidney cancer. Renal cysts may interfere with renal function, resulting in high blood pressure and renal failure. Ultrasound examination, urine tests, blood pressure checks and kidney function tests are therefore needed. When abnormalities are extensive, or difficult to identify, tomography, or an MRI scan should be considered.

The heart

If muscle nodules are found (cardiac rhabdomyomas), or if the individual has arrhythmia, the condition of the heart should be examined using, for example, ultrasound and ECG examinations. Muscle nodules may disrupt the blood flow in the heart, affecting both cardiac rhythm and the ability of the heart to act as a pump, but surgery is only necessary in exceptional cases. The size and number of nodules decrease over time.

Skin

Laser treatment may be helpful in cases of cosmetically-displeasing facial angiofibromas. Disfiguring or painful nail fibromas may be surgically removed.

The mouth

In cases of severe multi-disability, it is particularly important to provide supplementary preventive dental care.

Epilepsy

The forms of epilepsy associated with tuberous sclerosis are often difficult to treat, and medication may need constant readjustment, particularly during childhood and adolescence. Treatment for epilepsy is often a problematic balancing act between effective seizure management and negative side effects of pharmaceuticals on behaviour, contact and receptivity. In spite of the fact that epilepsy in tuberous sclerosis is often caused by lesions in several parts of the brain, surgery may be helpful.

A neuropsychiatric examination should be carried out to assess autistic symptoms, hyperactivity and other behavioural disorders. A neuropsychological examination is also important to assess the level of mental development. As children with tuberous sclerosis may range from being very intelligent to having severe learning difficulties, and may also have more or less pronounced autism and other functional disabilities, it is impossible to make any general statement about what kind of assistance and schooling are most suitable.

Hyperactivity and poor impulse control, with resulting temper tantrums, are often difficult to manage. In addition to educational and psychological habilitation initiatives, medication may also be necessary.

Brief periods of medication may be necessary to alter sleep patterns and give the child and the parents the opportunity to catch up on lost sleep. It is also important to control epilepsy as far as possible, as it may otherwise have a negative impact on sleep patterns.

Children with tuberous sclerosis may require habilitation measures to compensate for loss of functions and to stimulate their development. For this reason the family should have early contact with a habilitation team. Such a team should provide specialised knowledge of specific disabilities and how they affect everyday life. They should also provide expertise in the areas of motor skills and psychological, linguistic and social development. Habilitation means assisting the child to develop skills. The goal is that both children and adults shall have the opportunity to participate in the life of the community on their own terms.

Assessments, investigations, assistance with the choice of aids, information about disabilities and counselling are examples of habilitation initiatives. The habilitation team can also offer support to parents and siblings as well as information about the support offered in the community.

Meeting the needs of people with disabilities often means their surroundings have to be adapted. The team can give advice on changes to the home and other environments. Sometimes the child’s social environment also requires some adjustment which may mean that those in immediate contact with the child or young person receive information on the best way to work with him or her. This is particularly important in the case of behavioural abnormalities which occur in cases of delayed development and autism. To stimulate development and reinforce positive behaviour in the child, the team can provide guidance for parents and others in the child’s immediate network. Information, education and all training programmes must be very well structured.

In the case of speech and language difficulties it is essential that a communication assessment is carried out. This is the basis for systematic training in speech and communication. Alternative forms of communication may be needed, such as symbol and sign systems. (AAC, Augmentative and alternative communication.)

Problems with eating and swallowing affect nutrition. A team consisting of, among others, a speech therapist and dietician, can assess whether the child is having problems swallowing and therefore runs a risk of becoming undernourished, and can give advice on how to prevent malnutrition.

Support and treatment are based on the individual needs of the child and are planned in close partnership with the child’s network: they can vary over time. There is also close collaboration with the local authority on the different initiatives needed to make the everyday life of the family easier, for example by offering personal assistance, a contact family or respite care. The family may also require help in coordinating different care initiatives.

Adults with tuberous sclerosis

Tuberous sclerosis does not necessarily imply any disabilities for individuals with mild forms of the disease, nor does it necessarily impact on life expectancy. In more severe forms, with symptoms involving the heart, brain and kidneys, monitoring and treating complications can improve both the quality of life and life span. Women who have problems with their lungs may need hormone treatment or surgery.

Adults with autism and delayed development continue to require habilitation measures and a great deal of support in their everyday lives. Support and care, along with organized daily activities, may be provided by staff in special accommodation.

Practical advice

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National and regional resources in Sweden

All regional hospitals in Sweden should have sufficient knowledge and resources to diagnose this disease.

The Queen Silvia Children’s Hospital in Göteborg has a team in neuropsychiatry and neuropaediatrics for children and young people with rare diseases and disabilities. Tuberous sclerosis is one of the diagnoses covered by their remit. The team has drawn up a checklist for the diagnosis and monitoring of tuberous sclerosis.

Specialist knowledge in orofacial problems (problems associated with the mouth and face) is available at the Mun-H-Center, Faculty of Odontology, University of Gothenburg, Medicinaregatan 12A, SE-413 90 Göteborg, Sweden. Tel +46 31 750 92 00, fax +46 31 750 92 01, email: mun-h-center@vgregion.se,  www.mun-h-center.se.

Resource personnel

Professor Paul Uvebrant, The Queen Silvia Children's Hospital, SE-416 85 Gothenburg, Sweden. Tel: +46 31 343 40 00.

Senior physician Suzanne Steffenburg, Paediatric Neuropsychiatry Unit, The Queen Silvia Children’s Hospital, Otterhällegatan 12A, SE-411 18 Göteborg, Sweden. Tel +46 31 343 59 50, fax +46 31 84 89 32.

TSC Sweden has an advisory council whose members are: Professor Christopher Gillberg (paediatric neuropsychiatry), Assistant Professor Sverker Hansson (paediatric nephrology), and Professor Paul Uvebrant (paediatric neurology). All work at The Queen Silvia Children’s Hospital, SE-416 85 Göteborg, Sweden.

Courses, exchanges of experience, recreation

Ågrenska is a national competence centre for rare diseases. The centre arranges stays for children and young people with disabilities and their families. Ågrenska is open to families from the whole of Sweden and focuses particularly on the needs of children and young people with rare diseases. A number of programmes are also provided for adults with rare diseases. For information, please contact the Ågrenska National Competence Centre, for Rare Diseases, Box 2058, SE-436 02 Hovås, Sweden. Tel: +46 31 750 91 00, fax: +46 31 91 19 79, email: agrenska@agrenska.se, www.agrenska.se.

TSC Sweden arranges annual theme days and family weekends. Contact the association for information (see under “Organizations for the disabled/patient associations”).

Organizations for the disabled/patient associations

TSC Sweden- Tuberous sclerosis complex, c/o Annika Hallberg Juhlin, tel: +46 76 800 11 81. Email: annika@tsc-sverige.se, or info@tsc-sverige.se, www.tsc-sverige.se. TSC Sweden is an organisation offering support for people with tuberous sclerosis and their parents, other relatives and personnel. The Association's newsletter, TS-bladet (in Swedish only) is published three times a year.

Rare Diseases Sweden, Sturegatan 4C, Box 1386, SE-172 27 Sundbyberg, Sweden. Tel: +46 8 764 49 99, email: info@sallsyntadiagnoser.se, www.sallsyntadiagnoser.se. Rare Diseases Sweden is a federation of rare disease organizations, serving the interests of people with rare disorders.

FUB, The Swedish National Association for Persons with Intellectual Disabilities, Gävlegatan 18 C, Box 6436, SE-113 82 Stockholm, Sweden. Tel: +46 8 508 866 00, fax: +46 8 508 866 66, email: fub@fub.se, www.fub.se.

The Autism and Asperger Association, Bellmansgatan 30, SE-118 47 Stockholm, Sweden. Tel: +46 8 702 05 80, fax: +46 8 644 02 88, email: info@autism.se, www.autism.se.

The Swedish Epilepsy Association, Sturegatan 4 A, Box 1386, SE-172 27 Sundbyberg, Sweden. Tel: +46 8 669 41 06, fax: +46 8 669 15 88, email: info@epilepsi.se, www.epilepsi.se

Courses, exchanges of experience for personnel

TSC Sweden arranges annual meetings on various themes. Contact the association for information (see under “Organizations for the disabled/patient associations”).

Research and development (R&D)

Currently, intensive research into this condition is taking place successfully all over the world, but primarily in the USA and Great Britain. In Sweden research areas include the areas of neuropsychiatry, and surgery to cure or control epilepsy. Information may be obtained from Professor Christopher Gillberg and Professor Paul Uvebrant, The Queen Silvia Children’s Hospital, SE-416 85 Göteborg, Sweden. Tel +46 31 343 40 00.

Currently, intensive research is under way internationally into the molecular biological workings of mTOR , and to gain more information into what happens when the proteins hamartin and tubertin, coded for by gene TSC, are absent. The aim of this research is to develop further medications with an effect on the symptoms and progression of tuberous sclerosis.

Information material

An information booklet on tuberous sclerosis, which summarises the information in this database, is available free of charge from the customer service department of the Swedish National Board of Health and Welfare (in Swedish only, article number 1998-126-1074). Address: SE-120 88 Stockholm, Sweden. Tel: +46 75 247 38 80, fax: +46 35 19 75 29, email: publikationsservice@socialstyrelsen.se. Postage will be charged for bulk orders.

The Ågrenska National Competence Centre for Rare Diseases has published a newsletter on tuberous sclerosis, nr. 380, 2010 (in Swedish only). The newsletter contains adapted summaries of lectures given at Ågrenska family stays or adult programmes. Order from: Ågrenska, Box 2058, SE-436 02 Hovås, Sweden. Tel: +46 31 750 91 00, fax: +46 31 91 19 79, email: agrenska@agrenska.se. The newsletter can also be downloaded from their website: www.agrenska.se.

Information on rare diseases. Tuberous sclerosis. Order from: Center for Små Handicapgrupper, Bredgade 25 F, 5. sal, DK-1260 Copenhagen, Denmark. Tel +45 33 91 40 20, fax +45 33 91 40 19, email: csh@csh.dk, www.csh.dk.

A review of tuberous sclerosis complex with differential diagnosis. Orders: Tuberous Sclerosis Alliance, 801 Roeder Road, Suite 750, Silver Spring, MD 20910, tel (301) 562-9890, fax (301) 562-9870, e-post: info@tsalliance.org, www.tsalliance.org. See website for further information.

Leaflet on tuberous sclerosis (in Norwegian) from The Norwegian Association for Tuberous Sclerosis. Order from: The Secretary/ Torbjørn Hodne, N-4532 Øyslebø, Norge, www.nfts.no.

“Tuberous Sclerosis – more than just skin deep,” a brochure from The Tuberous Sclerosis Association of Great Britain can be ordered from TSC Sweden, www.tsc-sverige.se. There is more information on the British association’s website. www.tuberous-sclerosis.org.

Video

Tuberous Sclerosis – a disease with many faces, (in Swedish only). Order from TSC Sweden, www.tsc-sverige.se

About autism

Information on autism can be found on the Autism Forum’s web site www.autismforum.se. The Autism Forum is a website and library run by “Handikapp och Habilitering” within the auspices of Stockholm's municipal health authority.

Literature

Ahlsén G, Gillberg IC, Lindblom R, Gillberg C. Tuberous sclerosis in western Sweden. A population study of cases with childhood onset. Arch Neurol 1994; 51: 76-81.

Bolton P, Griffiths P. Association of tuberous sclerosis of temporal lobes with autism and atypical autism. Lancet 1997; 349: 392-395.

Curatolo P. Tuberous Sclerosis Complex: From Basic Science to Clinical Phenotypes, International Review of Child Neurology Series. Cambridge University Press on behalf of Mac Keith Press, 2003. ISBN1 898683-39-5.

Curatolo P, Portofino MC, Manzi B, Seri S. Autism in tuberous sclerosis. Eur J Paediatr Neurol 2004; 8: 327-332.

CuratoloP, Bombardieri R, Jozwiak S. Tuberous sclerosis. Lancet 2008; 372: 657-668. Review.

Franz DN, Bissler JJ, McCormack FX. Tuberous sclerosis complex: Neurological, renal and pulmonary manifestations. Neuropediatrics 2010; 42: 199-208.

Gillberg IC, Gillberg C, Ahlsén G. Autistic behaviour and attention deficits in tuberous sclerosis: a population-based study. Dev Med Child Neurol 1994; 36: 50-56.

Hunt A. Development, behaviour and seizures in 300 cases of tuberous sclerosis. J Intellect Disabil Res 1993; 37: 41-51.

Krueger DA, Care M, Holland K, Agricola K, Tudor C, Mangeshkar P et al. Everolimus for subependymal giant-cell astrocytoma in tuberous sclerosis. N Engl J Med 2010; 363: 1801-1811.

Krueger DA, Franz DN. Current management of tuberous sclerosis complex. Paediatr Drugs 2008; 10: 299-313. Review.

Maria BL, Deidrick KM, Roach EC, Gutmann DH. Tuberous sclerosis complex: pathogenesis, diagnosis, strategies, therapies and future research directions. J Child Neurol 2004; 19: 631-642.

Miya R, Asato MD, Antonio Y, Hardan MD. Neuropsychiatric problems in tuberous sclerosis complex. J Child Neurol 2004; 19: 241-249.

Mc Daniel S, Rensing N, Thio L, Yamada K, Wong M. The ketogenic diet inhibits the mammalian target of rapamycin (mTOR) pathway. Epilepsia 2011; 52: e7-e11.

Moareva R, Cerminara C, Curatolo P. Epilepsy secondary to tuberous sclerosis: lessons to be learned and current challenges. Childs Nerv Syst 2010; 26: 1495-1504.

Napolioni V, Moavero R, Curatolo P. Recent advantages in neurobiology of Tuberous Sclerosis Complex. Brain Dev 2009; 31: 104-113.

Paul E, Thiele E. Efficacy of sirolimus in treating tuberous sclerosis and lymphangioleiomyomatosis. N Engl J Med 2008; 358: 190-192.

Perciak-Vance MA, Gardner RJM, Steingold S, Wall SL, Carter S, DiMario FJ et al. Confirmation of linkage of tuberous sclerosis to chromosome 16p. (Abstract) Am J Hum Genet 51(suppl): A198.1992.

Roach ES, Gomez MR, Northrup H. Tuberous sclerosis complex consensus conference: revised clinical diagnostic criteria. J Child Neurol 1998; 13: 624-628.

Roach SE, Sparagana SP. Diagnosis of tuberous sclerosis complex. J Child Neurol 2004; 19: 643-649.

Tuberous sclerosis complex. Genes,clinical features and therapeutics. Kwiatkowski DJ, Whittemore VH, Thiele EA editors. Wiley-Blackwell, Weinheim 2010. ISBN 978-3-527-32201-5.

van Slegtenhorst M, de Hoogt R, Hermans C, Nellist M, Janssen B, Verhoef S et al. Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. Science 1997; 277: 805-808.  

Database references

OMIM (Online Mendelian Inheritance in Man)
www.ncbi.nlm.nih.gov/omim 
Search: tuberous sclerosis

GeneReviews (University of Washington)
www.genetests.org (select GeneReviews)
Search: tuberous sclerosis complex

Document information

The Swedish Information Centre for Rare Diseases produced and edited this information material.

The medical expert who wrote the draft of this information material is Professor Paul Uvebrant, The Queen Silvia Children’s Hospital, Gothenburg, Sweden.

The relevant organisations for the disabled/patient associations have been given the opportunity to comment on the content of the text.

An expert group on rare diseases, affiliated with the University of Gothenburg, approved the material prior to publication.

Date of publication: 2010-04-19
Version: 3.3
Publication date of the Swedish version: 2009-06-24

For enquiries contact The Swedish Information Centre for Rare Diseases, The Sahlgrenska Academy at the University of Gothenburg, Box 400, SE-405 30 Gothenburg, Sweden, tel: +46 31 786 55 90, email: ovanligadiagnoser@gu.se.

 

About the database

This knowledge database provides information on rare diseases and conditions. The information is not intended to be a substitute for professional medical care, nor is it intended to be used as a basis for diagnosis or treatment.