An introduction totuberous sclerosis

complex

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An introduction totuberous sclerosis complex

Contents

P3 Introduction

P4 What is tuberous sclerosis complex (TSC)?

P5 Diagnosis

P6 How a person with TSC might be affected

Epilepsy

Intellectual ability, learning and academic skills in TSC

Behavioural difficulties

Skin

Kidneys

Heart

Eyes

Lungs

Teeth and mouth

Other organs

P15 Genetics of TSC

P16 Information and support

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IntroductionEvery month about 10 babies are bornin the UK with TSC. An estimated 1million people worldwide have TSC.Some will be diagnosed very early inlife while others may not bediagnosed until later childhood,adolescence or adulthood.

This booklet has been produced bythe Tuberous Sclerosis Association(TSA) to help the families andindividuals newly diagnosed, andprofessionals caring for them, tounderstand more about TSC. In thisbooklet we describe the various waysin which a person with TSC might beaffected.

It is important to keep in mind thatTSC varies from person to person andthat most people with the conditiondo not have all of the featuresdescribed.

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What is TSC?TSC is a genetic condition that can lead to growths in variousorgans of the body, but those most commonly affected are thebrain, eyes, heart, kidney, skin and lungs. These growths maybe referred to as benign (non-cancerous) tumours. When theycause problems it is mainly because of their size and wherethey are in the body. TSC growths have different namesdepending on which organ they are found in. The severity ofTSC varies greatly. Some people are so mildly affected that theyexperience very few problems. Others may be more severelyaffected and this can become apparent in childhood oradulthood.

It is important to know the possible effects of TSC on differentareas of the body and to follow the recommendations forscreening and evaluating TSC. Professionals and parents/carersshould be able to identify the early complications to ensureprompt and effective treatment.

Thanks to research findings and with improved medical care,the majority of people with TSC can expect to live healthierlives with a normal life expectancy.

The diagnosis of TSC is basedon a careful physical

examination in combinationwith imaging studies (scans)

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DiagnosisPeople with TSC may be diagnosed in the course ofinvestigation, during treatment for problems with specificorgans or during genetic screening of family members. Forexample, diagnosis may follow the finding of heart tumoursprenatally (during pregnancy) or in newborns, the onset ofinfantile spasms in babies, a diagnosis of autism in children, thedevelopment of skin problems in adolescents or the onset ofkidney problems in adults. It is important to know that TSCaffects each individual differently, even within a family.

There is no single clinical feature that is absolutely specific toTSC. Instead, a diagnosis of TSC is based on a careful physicalexamination in combination with imaging studies (scans). Thistesting does not cause pain to the patient. Published diagnosticcriteria exists for professionals to check against and certainfeatures need to be present or in combination to have adefinite diagnosis of TSC.

A small number of NHS TSC clinics exist throughout the UK.TSC guidelines provide guidance from TSC specialists on thescreening, monitoring and treatment of different aspects of TSC.

The specific tests that are performed depend on the age of theindividual who is suspected of having TSC and may include the following:

MRI (magnetic resonance imaging) scan of the brainCT (computed tomography) scan of the lungs liver and kidneysUltrasound scan of the kidneysEchocardiogram (ECG) ultrasound to examine the structures ofthe heartEye examination to look for abnormalities of the retinaSkin examination under ultraviolet lightGenetic testing to diagnose and/or confirm a diagnosis of TSC

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How a person with TSC might be affected

Several types of brain abnormalities may be seen in peoplewith TSC. Some people will have all of these changes, andothers will have none. However, the majority of people withTSC have one of these abnormalities. It is important to screenall individuals with TSC then tailor the monitoring plan for eachperson so that any problems can be treated should they arise.

The TSC guidelines include information on what age peopleshould be monitored and how often, this is then broken downby abnormality and size, and also includes recommendationsand actions.

Cortical Tubers Cortical tubers are disorganised areas of thebrain that contain abnormal cells and are best visualised by anMRI scan of the brain. Some people may have several tuberswhereas others may have one or none. Although these tubersmay become easier to see on scans over time, no new tubersdevelop after a child is born.

Researchers used to think that neurological difficulties werecaused by a combination of these:

The number and position of tumours (tubers) in the brain.

The types of seizures, age of onset and whether the seizurescan be controlled.

However, as researchers have done more work, is has becomeclear that the molecular abnormalities caused by the TSCmutation can directly lead to learning, behavioural and mentalhealth problems.

SENSs and SEGAs Subependymal nodules (SENs) are smallaccumulations of cells located on the walls of the cerebralventricles (the spaces in the brain that contain cerebrospinalfluid). The nodules often accumulate calcium, and are theneasily identified on CT imaging of the brain.

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Subependymal giant cell astrocytoma (SEGA, also known asSGCT) are growths that occur in up to 15% of people with TSC.SEGAs do not usually grow until later childhood, teenage yearsand young adulthood. They rarely grow beyond the mid 20s.The growth may be removed by surgery, or in certaincircumstances it may be possible to shrink the growth using adrug treatment. More information about this drug treatmentcan be found by contacting the TSA.

Epilepsy

Epilepsy is the most commonneurological feature of TSC.

About 40% of children, usuallyunder the age of two with TSCwill have a type of epilepsycalled 'infantile spasms'. It isimportant that carers are aware ofthe symptoms of infantile spasmsand seek medical advice early ifthey have concerns. They can bedifficult to identify at first and areoften mistaken for other conditionssuch as colic or reflux by both parents and healthcareprofessionals.

At first the seizures may be as subtle as a gentle head nod orthrust of the chin. Over time these tend to become moreobvious jerking movements. The movements themselves areusually brief and occur several to many times in a row. Mostcommonly these happen either first thing in the morning or onwaking from a nap. The child will often seem sleepy againafterwards despite having only just woken up.

Once children begin to have infantile spasms you may noticethat their development slows down. They may lose skills they

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had previously learned and become less interested in peopleand their surroundings. Their sleep pattern may becomedisrupted and they may seem irritable, distant or just differentfrom their usual self. Spasms are different from child to child,but as a parent/carer you are the best person to notice changesin your child and it is important that your concerns are takenseriously.

Older children and adults may develop other types of seizures.In some children with TSC developmental progress maydepend on how severe their epilepsy is and how well it iscontrolled. In order to reduce the potential impacts of epilepsyit is vital that it is promptly diagnosed and treated. Throughoutthe UK there are specialist epilepsy centres and several epilepsyorganisations that have comprehensive advice and support onall aspects of epilepsy. Some NHS TSC clinics have a particularspeciality in TSC and epilepsy.

More than 50% of people with TSC who have epilepsy will notrespond to standard antiepileptic medicines and may need analternative form of treatment. Specialist epilepsy centres exist inthe UK that are able to support families with complex epilepsyand advise on drug treatment, dietary options and surgery.

In order to reduce thepotential impacts of epilepsy

it is vital that it is promptlydiagnosed and treated.

Make sure you know who to contact if youthink your child is having seizures. In the UK this

will either be your GP or ‘open access’ to your localpaediatric ward.

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Intellectual ability, learning and academic skills in TSC

In TSC there is a very largerange of intellectualabilities, from very high toextremely low.

About 30% of people withTSC will fall within theprofoundly impaired range,approximately 20% of people withTSC will have an IQ slightly belowthe normal range and about 50%of individuals with TSC will havean IQ in the same range as thegeneral population.

There are two main recommendations regardingassessments in TSC:

1. Perform regular assessment of cognitive developmentand behaviour to identify and treat emerging difficultiesand to establish a baseline for evaluating any laterchanges.

2. Perform a comprehensive assessment when there arechanges in cognitive development or behaviour toidentify and treat the underlying causes ofneurobehavioral change.

Refer to the ‘Behaviour and learning in TSC’ to guide youon the type of assessments, monitoring and supportavailable. They are available on the TSA’s website here:

www.tuberous-sclerosis.org/factsheets.html

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Behavioural difficulties

This refers to the problems that can be observed at home, atschool or in a clinic. Some of these behavioural difficulties aremore common in people with TSC who also have anintellectual disability. Some examples of difficult behavioursthat are common in people with TSC are:

Poor eye contact

Aggression

Temper tantrums

Self-injury

Sleep difficulties

Anxiety

Repetitive and ritualistic behaviour

Speech and language delay

Overactivity

Restlessness

Impulsivity

Depressed mood

Extreme shyness

Developmental delay is the term used when a younger childrenare slower to reach milestones than other children. Delay mayoccur in the way a child moves, communicates, thinks andlearns, or behaves with others. If the delay is ongoing, the childmay be diagnosed with a developmental disability. Specificdevelopmental disabilities include autism and ADHD (attentiondeficit and hyperactivity disorder )

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Skin

A range of skin featuresmay develop as a result ofTSC. A person with TSCmay have none, some or allof the following:

Hypomelanotic macules(also known as ash leafspots) are areas of skinthat contain lesspigment than surrounding skin and therefore they appearlighter in colour. Ultraviolet light is used to identify these asthey may otherwise be hard to see in babies or people withfair skin.

The Shagreen Patch is a patch of skin similar in colour tosurrounding skin but which is rough and dimpled likeorange peel. It is usually found on the back but may beenseen on other parts of the body.

Facial angiofibromas can appear across the cheeks, nose andchin. These small reddish bumps often appear at the age of4 or 5 and may increase in size with age. If facialangiofibromas become problematic, a dermatologist cantreat them.

A forehead plaque is flesh-coloured and are soft orcompressible or doughy to hard lesion. They are found onthe forehead and scalp. At the initial examination, a Wood’slamp (an ultraviolet light) will be used to better visualise theplaque, especially on infants and people with pale skin. Atthe same time, the skin should be carefully examined forother manifestations of TSC.

Ungual fibromas are smooth, firm, flesh-coloured growthsthat arise next to or from underneath the nails.

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Kidneys

Although many kidneyabnormalities inpeople with TSC causeno problems, somecan have an effect onthe proper functioningof the kidney. Themost common kidneyproblems in peoplewith TSC areangiomyolipomas(AMLs). These occur inup to 80% of peoplewith TSC. Regularmonitoring by a consultantnephrologist (kidneyspecialist) is essential to thecare of people with TSC.

AMLs begin to grow inchildhood but may not causea problem until earlyadulthood. Once identifiedAMLs require monitoring.More information on renalAMLs and treatment optionscan be found by contactingthe TSA.

People with TSC may alsohave simple cysts (fluid-filledbumps) in one or bothkidneys. Usually these causeno problems. A small number(2%) of people with TSC alsohave polycystic kidneydisease (PKD), which cancause high blood pressureand impairment of kidneyfunction. It is important thatpeople with TSC and PKD areunder the care of a kidneyspecialist and centre.

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Heart

Heart tumours (cardiacrhabdomyomas) occur in about 50% of babies born with TSC. Specialistsrecommend that everyone diagnosedwith TSC have an echocardiogram andan electrocardiogram (ECG) when theyare diagnosed with TSC or if TSC issuspected. This will help them see their size, location andnumber. These tumours are at their largest at the time of thebaby’s birth and get smaller over time, eventually disappearing.A few individuals will have long-term problems with heartrhythm that will need to be monitored throughout their lives.

Lungs

Lymphangioleiomyomatosis (LAM) is a lung complication ofTSC caused by an overgrowth of cells in the airways, bloodvessels and lymph vessels. LAM is more common in womenthan in men and so the female hormone oestrogen is thoughtto play a part in its development. Therefore LAM occursbetween puberty and the menopause. LAM occurs inapproximately 30% of women with TSC but only causesbreathing problems in a small number of women. Women withTSC and LAM who are considering pregnancy should discussthis with their doctor first.

Recommendations from TSCexperts include a high resolutionCT scan followed closely by anassessment by a respiratoryconsultant familiar with TSC/LAM.Contact the TSA for moreinformation on LAM screening,monitoring and treatment.

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Eyes

Nearly 50% ofindividuals with TSChave benign (non-cancerous) tumoursaffecting the eyes.However, growth andchange is rare so usuallyno treatment is required.Opthalmologists (eye doctor)are able to check for thesegrowths.

Teeth and mouth

People with TSC may have an overgrowth of the gums(fibromas) and dental pits (weakened enamel of the teeth). As aresult, the teeth and gum tissue are slightly different andrequire a little more care to keep healthy. The tooth enamel willhave random pits that occur on any surface and can be thespot where decay can start. The enamel pits can be easily seenby the dentist. Meticulous dental hygiene, including regularbrushing and flossing are important.

Other organs

Cysts and AMLs may occur in other organs such as thepancreas, ovaries or liver. They usually do not cause anyproblems and therefore do not need treatment. If they docause symptoms they need to be treated by the appropriatespecialist.

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Genetics of TSC Two genes, TSC1 and TSC2 have beenidentified and changes in these cancause TSC. If one parent has TSC, theirchildren will have a 50:50 chance ofinheriting the faulty gene. About onein three people who have TSC haveinherited a faulty gene from anaffected parent. In two out of threechildren with TSC, neither parent isaffected. In these cases it isthought the cause is a'spontaneous' or new mutation,with this child being the firstperson in the family to haveTSC. The cause of these newmutations is not known.

A small number of physicallyunaffected parents of a childwith TSC have a mutation only intheir egg or sperm cells; this is called germlinemosaicism.

The chance of unaffected parents of a child with TSC having asecond child with TSC is approximately 3% (or three in 100).

Genetic testing can be used to identify which mutation ineither the TSC1 or TSC2 gene is causing a person’s TSC. Testingcan only be undertaken at genetics centres who will provideadvice and counselling before any testing is performed. Thegene can be identified in approximately 80% of cases. Thisinformation may be helpful in certain circumstances. Regionalgenetics centres are available throughout the UK and all arefamiliar with TSC, its variability and complexity.

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Information and support The TSA is here to help and support you.

The first thing to understand is that TSC is a very complexdisease. TSC affects all individuals differently, so what youmight read about one person and how TSC impacts his or herlife may be quite different from how it impacts your life.

Another thing to remember is that different aspects of TSCaffect an individual’s life at different times. For example, youmay be concerned about the heart tumours in a newborn babywho has just been diagnosed with TSC, but people in their 40smay only need to be concerned about the kidney tumours.

The TSA can help you access the accurate and reliableinformation that you need, as and when you need it. The TSAcan liaise with, and signpost you to, specialist services and helpraise awareness and understanding of TSC amongprofessionals.

Please get it touch with the TSA at www.tuberous-sclerosis.orgor by calling 0207 922 7731.

Living with TSC can raise a number ofchallenges and uncertainties but much has been

learnt about TSC over the last decade and researchinto the condition has never been so active.

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TSA AdvisersWe have a team of TSA Advisers across the UK.

Examples of the ways in which we can help:

Supporting people attending meetings withprofessionals, school review meetings, health caremeetings, complaints processes and specialist hospitalvisits

Helping individuals liaising with social services andhealth care professionals

Liaising on your behalf with our professional medicaladvisers regarding complex TSC queries

Providing TSC awareness sessions to staff in residentialhomes, supported living accommodation, schools andto professional staff such as nurses, where appropriate

Helping to set up local regional support groups

Holding events and gatherings to exchangeinformation, share experiences and meet others insimilar situations

For more information please contact:support@tuberous-sclerosis.org

Find your regional TSA Adviser here: www.tuberous-sclerosis.org/tsa_advisers

The Tuberous Sclerosis AssociationTo provide hope for todayand a cure for tomorrow

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ReferencesA list of TSC scientific references, TSC clinics and TSCprofessional advisers is available on request.

We value your feedbackPlease help us improve the information we offer by sharingyour comments on this publication.Please email information@tuberous-sclerosis.org or write to us atthe address below.

Supporting the TSAThe TSA provides this information free of charge but if youwould like to help cover the cost please visit the fundraisingsection of our website to make a donation:www.tuberous-sclerosis.org/fundraising.html

Or send a cheque or postal order to:Tuberous Sclerosis Association, CAN Mezzanine,32-36 Loman Street, Southwark, London SE1 0EH.

Contact UsIf you would like support or further information about anyaspect of TSC, please contact us at:

Tuberous Sclerosis Association, CAN Mezzanine,32-36 Loman Street, Southwark, London SE1 0EH

By email: admin@tuberous-sclerosis.orgOn our website: www.tuberous-sclerosis.orgBy telephone: 0207 922 7731

Join the TSC community online:

www.facebook.com/thetsauk

www.twitter.com/UKTSA

www.youtube.com/TSAssociationUK

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Notes

Produced March 2017 - Review date March 2019

Tuberous Sclerosis Association is a Company Limited by Guarantee Registered in England and Wales No. 2900107English Registered Charity Number. 1039549 | Scottish Registered Charity No. SC042780 Registered Office:

CAN Mezzanine, 32-36 Loman Street London SE1 0EH

Disclaimer: We have made every effort to ensure that information in this publication is correct at the time of goingto print. We do not accept liability for any errors or omissions, and policy and practice may change.

We’re the only UK charity dedicated tosupporting people affected by TSC.

Our aim is to ensure that everyoneaffected by TSC has the care and

support they need.

TSCampaign: Our commitment toraising awareness and driving

forward positive change

TSCare: Our commitment toenhancing quality of life for all

people affected by TSC

TSCure: Our commitment to research

www.tuberous-sclerosis.org admin@tuberous-sclerosis.org Tel: 0207 922 7731

About the TSA