on vision and fshd - fsh society

F acioscapulohumeral muscular dys-trophy (FSHD) is rightly thought

of as a disease of muscle. As indeed itprimarily is. Thankfully, the vast major-ity of patients do not have any clinicalconsequences from disease affectingany other tissue. But there is an impor-tant corollary. A majority of FSHDpatients have an unusual, subclinicaland often subtle abnormal patterning(vascular telangiectasis) of the bloodvessels at the periphery of the retina,which is in all likelihood a develop-mental anomaly. The retina curvesround the back of the eye, and con-tains the cells which register light.

As these retinal vascular changesare usually benign, why are theyimportant? Two reasons. The firstrelates to treatment—for although thetelangiectasis (pronounced as tel-an-jee-ek-tuh-sis, chronic dilatation of thecapillaries and other small blood ves-sels) is usually asymptomatic, justoccasionally there can be serious leak-age from the abnormal blood vessels.When this happens the exudate (fluidthat has been released from a tissue orits capillaries) tracks centrally to theeye’s more capacious posterior pole,where it can cause the retina to detachfrom its moorings with loss of sight. Itis very important for individuals withFSHD to take special care if significantchanges in vision occur.

The second reason relates to whatthese vascular changes might be tellingus about the cause of the muscle dis-ease. What pathogenic factors mightthe muscle disease and the eye diseasehave in common? And what additionalfactor(s) might cause symptomatic eyeexudates in some patients?

The ‘retinal telangiectasis’ in FSHDcomprises areas of abnormally sparseand abnormally dilated retinal capillar-ies, sometimes with small outpouchings

called microaneurysms, par-ticularly in the retinal periph-ery. The presence of vascularabnormalities per se is not acause for alarm, althoughthere are certain situations, aswill be discussed below, whenit is as well to be alert.

Indeed very few FSHDpatients will have any abnor-malities visible on standard‘direct ophthalmoscopy,’ atechnique used to examine thecentral posterior pole (theback of the eye, usually refer-ring to the retina between theoptic disc and the macula). Or even on‘indirect ophthalmoscopy,’ a moresophisticated technique which alsoexamines the retinal periphery. Indeedthe vascular abnormalities can often

only be picked up with specializedfluorescein angiography, which high-lights tiny blood vessels. This is a verycommon technique in retinal diagnostic

FSH WatchFALL 2008

On vision and FSHD

A publication of the Facioscapulohumeral Muscular Dystrophy SocietyConnecting the community of patients, families, clinicians and investigators

continued on page 2

Exercise to improve health and fitness for patients with FSHDR. Ted Abresch, M.S., Research & Training Center for Neuromuscular DiseaseUniversity of California—Davis

At the Research and Training Center in Neuromuscular Disease at the Universi-ty of California—Davis, we are often asked what type of exercise programs

are appropriate for people with FSHD. Although this appears to be a simple ques-tion, there is not enough evidence-based information available to give a straightforward exercise prescription.

As everyone knows, there are many potential benefits of strength training andaerobic exercise in healthy subjects. Strength training increases muscle strengthand muscle mass and preserves independence. In addition, strength training andaerobic physical activity increases fitness level and capacity for exercise. Theyalso play a role in both primary and secondary prevention of cardiovascular dis-ease—they have been shown to reduce blood pressure, help prevent obesity, andreduce the risk of osteoporosis, arthritis, and type 2 diabetes.

The benefits derived from exercise would certainly be beneficial to individualswith FSHD. We have performed several studies which have shown that subjectswith FSHD and other slowly progressive neuromuscular diseases (SP-NMD) havemuscle wasting and weakness that limits physical activity and aerobic fitness.

Over the years, the sedentary lifestyle leads to weight gain, additional loss of

The photograph on the left shows a typical curved exudate at the posterior pole of an FSHD patient who was losing vision in this eye. Vision was substantially restored with laser photocoagulationtreatment. The picture on the right is a part of a fluorescein angiogram which shows abnormally patterned blood vessels and microaneurysms, which appear as bright dots.

Courtesy: Moorfields Eye Hospital, London, Professor Alan Bird

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continued on page 4

Robin B. Fitzsimons, M.B., B.S., B.Sc., (Med), Ph.D., FRACPUniversity of Sydney, Australia

2 FSH WATCH NEWSLETTER n FALL 2008

Board of DirectorsDaniel P. Perez, President & CEOWilliam R. Lewis, Sr., M.D., ChairmanHoward L. Chabner, J.D., Vice-ChairmanCarol A. Perez, M.Ed., SecretaryWilliam Michael, C.P.A., TreasurerE. Ann Biggs-WilliamsCorinne Bronfman, Ph.D.Robert H. Brown Jr., M.D./D.Phil. *James A. Chin, Sr.JoAnn P. ForanceDavid Glass, M.D.William S. Herzberg, M.D.Louis M. Kunkel, Ph.D.C. Larry Laurello, P.E.Richard A. Lefebvre, M.B.A.William R. Lewis III, M.D.Theodore L. Munsat, M.D. *Paul Schultz, M.D. *Robert F. Smith, Esq.Z. John Stekly, Sc.D.Christopher Stenmon, C.P.A.

Scientific Advisory BoardDavid E. Housman, Ph.D., ChairmanMichael R. Altherr, Ph.D.Robert H. Brown Jr., M.D./D.Phil. Rune Frants, Ph.D.David J. Glass, M.D.Louis M. Kunkel, Ph.D.William R. Lewis, M.D.William R. Lewis III, M.D.Katherine D. Mathews, M.D.Theodore L. Munsat, M.D. *George W. A. M. Padberg, M.D.Paul Schultz, M.D. *Kathryn Wagner, M.D., Ph.D.

* Board Member Emeritus

Executive & Development OfficeNancy Van Zant, Executive DirectorFSH Society, Inc.c/o BBRI R35364 Grove StreetWatertown, MA 02472 USA(617) 658-7878(617) 658-7879 [email protected]

Patient Resources OfficeCarol A. Perez, M.Ed.FSH Society, Inc.3 Westwood Road Lexington, MA 02420 USA(781) 860-0501 (781) 860-0599 Fax [email protected]

Research Programs OfficeDaniel Paul PerezFSH Society, Inc.11 Elmbrook Circle Bedford, MA 01730 USA(781) 275-7781 (781) 275-7789 Fax [email protected]

www.fshsociety.org

medicine: a fluorescent dye is injectedinto an arm vein, and photographs ofthe retina are rapidly taken as the dyecirculates through the eye before beingexcreted. That said, unusually tortuous(winding or twisting) retinal blood ves-sels can be very obvious ophthalmo-scopically in some cases of infantileFSHD.

If there are no abnormalities evi-dent on indirect ophthalmoscopy, it ishighly unlikely that the vessels willcause any visual problem—and certain-ly not imminently. Although angiogra-phy has been an invaluable researchtool in defining the relationshipbetween FSHD and retinal vascular dis-orders, it is now really only necessarywhen potentially sight-threatening exu-dates are seen on ophthalmoscopy, andfocused treatment is therefore beingconsidered. It is certainly not routinelyrecommended in FSHD patients.

The good news is that the retinalexudates can often be successfullytreated by targeted laser ablative pho-tocoagulation. In the case of FSHD thistreatment might have to be quite‘aggressive’ to be successful, but it canprevent or even reverse visual loss ifundertaken in a timely way, before per-manent nerve fiber damage hasoccurred. Although it is a very rarecomplication of FSHD, the fact that itis treatable means that timely detec-tion of sight-threatening exudates isimportant. Although patients withsevere ‘infantile onset’ FSHD seempeculiarly susceptible to clinical ‘CoatsSyndrome’ (as they are to clinical deaf-ness), no age group is entirely exempt.

Although retinal telangiectasisseems to be a general association ofFSHD, there may even be some predis-position to clinically severe retinal dis-ease in certain FSHD families, so if oneFSHD patient has needed treatment,experience suggests that it is importantfor their relatives with FSHD to beespecially alert to visual complications.

It is perhaps not surprising then thatmany of the papers reporting cases ofFSHD with retinal complications are inthe ophthalmological literature, wherethey are not necessarily always seen byneurologists. Indeed, the known associ-ation between Coats’ Disease or Syn-drome and FSHD has alerted

ophthalmologists to check for signs ofFSHD (such as facial weakness) whenthey see children with Coats’ Disease.Sometimes blindness in one eye due toCoats’ Disease in infantile FSHD hasprompted successful laser treatment tostop the leakage and preserve vision inthe other eye. Because of the relativerarity of visual loss in FSHD andbecause single case reports may notmake it to the medical literature, it islikely that the overall prevalence of thiscomplication will be underestimated.

Because visual loss is such a rare(albeit very real, and treatable) compli-cation of FSHD, there are legitimate dif-ferent clinical viewpoints about theimplications for visual screening. Mypersonal viewpoint is that preciselybecause it is treatable and devastating,it is worthwhile undertaking simple andnon-invasive ophthalmological screen-ing procedures of individuals, particular-ly young children who may notcomplain of visual loss, even if they areat very low risk. There are some U.S.clinicians who advise retinal ophthalmo-scopic examination under anaesthetic ofvery young infants who present withfacial weakness who might have FSHD.And of course infants will not be able tocomplain of losing sight. Adults andolder children need simply to be advisedto report visual symptoms immediately.

Parents of children at genetic risk ofFSHD should be aware that occasional-ly the eye disease presents before themuscle disease, even if this is more typ-ically seen in ‘sporadic’ FSHD.

The abnormal retina vascular patternin FSHD is identical to that which other-wise occurs in Coats’ Disease, which isusually a unilateral disease of youngboys. Semantic purists often prefer theterm Coats Syndrome when this retinaldisorder occurs in other contexts (suchas FSHD). In turn, Coats’ Disease is partof a group of developmental retinal vas-cular disorders with identical or virtual-ly identical patterns of peripheral retinalblood vessel abnormalities and whichcan be due to mutations affecting one ofseveral components of a signaling path-way (known as ‘Wnt’).

‘Wnts’ are secreted glycoproteinswhich act on the cell membrane and

On vision and FSHD, continued from front page

continued on page 4

3FSH WATCH NEWSLETTER n FALL 2008

Thank you very much.

Sincerely,

William R. Lewis, Sr., M.D.

Letter from the chairman, board of directors, FSH SocietyOctober 2008

Dear Friends,

I had the great privilege of attendingthe ribbon cutting and official open-

ing of the WellstoneCenter in Watertown,Massachusetts, onOctober 10. I knowyou share my excite-ment and that of myfamily: today there is aresearch centerfocused on facio-scapulohumeral musc-ular dystrophy (FSHD).

The FSH Society has a pivotalopportunity today, to provide gifts foradditional projects that will lead tomore research discovery. Your gifts will also enable us to continue ourlongstanding support of multifacetedFSHD research not included in theWellstone program.

The new center brings us closerthan ever to the development of a treat-ment for FSHD. You and your fellowFSH Society members have contributedto this progress to date. I hope you willcontinue to support these advances andgive another gift at this time.

William R. Lewis, Sr., M.D.

The FSH Watch is published by theFSH Society and distributed by mail toits members and supporters. All materialis copyrighted and may not be repro-duced without written permission. To beplaced on the mailing list or to submit anarticle, please write to: Nancy Van Zant,Executive Director, FSH Society, Inc.,c/o BBRI R353, 64 Grove Street. Water-town, MA 02472 USA. Articles may beedited for space and clarity. Every efforthas been made to ensure accuracy in thenewsletter. If you wish to correct anerror, please write to the above address.Look for us on the internet at:

www.fshsociety.orgEditors: Nancy Van Zant and Daniel

Paul Perez. Editorial Assistance: CarolPerez, Jenny Lazzaro, Howard L. Chabner & Charles C. Perez. Graphicdesign and editorial assistance: Susan L.Stewart, StewartBusinessStrategies.com

It is the editorial policy to report ondevelopments regarding FacioScapu-loHumeral Muscular Dystrophy(FSHD), but not to endorse any of the drugs or treatments discussed. We urge you to consult with yourown physician about the procedures

mentioned.

F F F

Dr. Lewis and other Society members enjoyed this event:


muscle mass, diminished walkingendurance, increased fatigue and pain.As a result, individuals with FSHD andother SP-NMDs have significantly high-er risk factors for metabolic syndrome(the combination of medical disordersthat increase the risk of developing car-diovascular disease and diabetes) andchronic disease resulting from obesityand a sedentary lifestyle.

Unfortunately, even FSHD subjectswith normal weight and body massindices also have problems with

thence via a highly complex series of interacting ‘signals’ to control the nucleartranscription of genes for other proteins, especially during development. Wnt sig-naling is crucial in the development of both muscle and the retina and its bloodvessels—as well as in muscle regeneration and in many other tissues.

Most cases of Coats’ Disease are idiopathic—meaning we do not know thecause. But some are due to mutation of ‘norrin,’ a Wnt activator, which is alsomutated in Norrie Disease, a much more severe and X-linked disorder of infants.Norrin mutation also causes yet another inherited vascular disorder, familial exuda-tive vitreoretinopathy (FEVR). FEVR can also be caused by mutations for genes ofother proteins in the Wnt pathway, called ‘frizzled 4’ and lipoprotein related protein5 (LPRP5). Quite clearly, FSHD is not due to any of these three proteins, but it willbe important to consider whether some other crucial component in Wnt signalingmight be affected in FSHD. This is especially so given that Wnt proteins interactwith members of the PITX family during developmental patterning and that Wntpathways also play a critical role in the development of muscle tissue and in the dif-ferentiation of the ‘satellite cells,’ from which muscle regenerates in adult life.

There was a certain focused serendipity about the discovery of retinal vascularabnormalities in FSHD. Whereas there had been occasional reports of eyes beingenucleated (removed) because of Coats’ Disease in children with FSHD, there hadbeen no consideration of the broader implications. But Coats’ Disease is known tobe due to leakage from small blood vessels. So when I was working at Hammer-smith Hospital in London and saw a patient with a retinal scar which had beenattributed to infection with toxoplasmosis, I wondered whether it might insteadactually be due to leakage from blood vessels, and if that were the case whetherher other visually asymptomatic FSHD relatives might also have abnormal retinalblood vessels. So I collaborated with Professor Alan Bird and Dr. Eric Gurwin atMoorfields Eye Hospital in London. When ‘fluoresceins’ showed that all four FSHDaffected members of that family had abnormal peripheral retinal blood vessels, wedecided to undertake a formal research study of FSHD patients at The NationalHospital for Neurology in London. Our study which showed that a majority ofpatients had demonstrable, albeit often subtle, peripheral retinal vascular changeswas later confirmed by Professor George Padberg’s group in Leiden.

It is also important to bear in mind that early-onset FSHD can be associatedwith clinical hearing impairment; and, if the general clinician is not very alert, theabsence of facial expression combined with hearing loss can sometimes lead to amisdiagnosis of mental retardation.

FSHD patients/families that have had visual complications of FSHD areinvited to contact the FSH Society or the author, who is interested in collectingexperiences of FSHD retinal complications for compilation.

Dr. Fitzsimons can be reached at [email protected] G

On vision and FSHD, continued from page 2

increased body fat. A recent study byAndrew Skalsky, M.D., in our Centerrevealed FSHD subjects had 14% lesslean muscle tissue in their trunk, but76% more fat in the trunk than an age-,weight-, and height-matched controlgroup. In addition, the FSHD subjectssignificantly lost muscle mass and hada concomitant increase in fat mass asthey aged, which was not seen in thecontrol population. We don’t know ifthese changes further increase the riskfor metabolic syndrome for individuals

with FSHD. We also do not knowwhether these risks can be reversedwith strengthening exercise orincreased physical activity. No well-controlled studies have been performedthat can answer these questions.

If there are so many benefits tophysical activity, why haven’t doctorsprescribed exercise for FSHD patients?It is because physicians have beenconcerned that exercise might causeoverwork weakness in patients with SP-NMDs. Back in the 1950s, during thelast of the polio epidemics, there were aseries of reports that showed thatpatients who were recovering fromacute polio got significantly weaker afterthey had started exercising. Thesestudies raised an alarm—physiciansreacted by telling their patients to limitexercise because strenuous exercisecould put patients back in a wheelchair.

These concepts were further rein-forced by studies that showed that indi-viduals with Duchenne musculardystrophy had the greatest muscledegeneration in muscles used duringsustained physical activity. Otherreports showed that individuals withFSHD who carried heavy loads duringwork or performed unsupervisedweightlifting had increased weaknessin the arms on their dominant side ascompared to their non-dominant side.The researchers hypothesized that theobserved weakness that was evidentin the dominant limb was caused bythe extra stress from overwork injuriesas a result of extra stress placed onthe dominant limb. As a result, mostphysicians when asked about exercisefor their patients with FSHD say thingslike, “Don’t over do it, and be very gen-tle” or “Go sub-maximal and use verylow resistance.” Patients do not knowhow to interpret this advice, and moreoften than not, they do not want to doanything. As a result patients becomesedentary and deconditioned, whichleads to additional muscle loss fromdisuse and increased levels of obesity.

So where does this leave us now?What type and intensity of exercisemay be beneficial and what types aredetrimental for patients with FSHD?About ten years ago investigators from

Exercise to improve health and fitness, continued from front page

continued on page 5

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our Center examined the effect of amoderate resistance, home-basedstrengthening exercise program on 27people with FSHD and other SP-NMDs. During the first week of a 12-week exercise program the patientswere instructed to strengthen theirknee extensors by performing threesets of four repetitions and at 30% oftheir maximum strength, which is prettylow for that muscle. The subjects grad-ually increased their exercise regimenand by week 12, they were performingthree sets of eight repetitions at 40%of their maximal strength. Even thoughthis exercise regimen was very moder-ate, it was enough to produce a signifi-cant increase in strength. However,subjects who had less than 15% nor-mal strength were unable to get anystrength gains from strengtheningexercise. Because we found improve-ments in a moderate resistance pro-gram, we wanted to see if we couldget greater effects with a maximumresistance exercise training program.The subjects didn’t get any strongercompared to the group who performedthe moderate exercise. Therefore, werecommend against high resistanceexercise for individuals with FSHD.

A recent study by E. L. van derKooi et al, in the Netherlands, (see theCochrane Reviews) also reported thatmoderate-intensity exercise strengthtraining appears to do no harm inpatients with muscle disease, but thereis insufficient evidence to show that itincreases strength. Nevertheless, thereis some work that suggests that mod-erate aerobic training programs mightimprove fitness and reduce the risksassociated with obesity and inactivityin FSHD patients. Most aerobic train-ing programs have demonstrated thatindividuals with FSHD have similarbeneficial cardio respiratory adapta-tions to sub maximal aerobic exercisetraining as able-bodied persons.

Investigators from our Center per-formed a 12-week home-based aero-bic walking program in subjects withFSHD and other SP-NMDs. Althoughwe did not see any improvements intheir fitness (no change in peak VO2, akey measure of your body’s exercisepotential), we did find that SP-NMD

Exercise to improve health and fitness, continued from page 4

patients had some beneficial effects,including a reduction in heart rate andsystolic blood pressure. Recently, weperformed a study to determine whethera 6-month home-based activity anddietary intervention can increase activitylevel, reduce caloric intake, and impactpositively components of metabolic syn-drome. The FSHD and other SP-NMDsubjects increased their activity by 27%above their baseline value, significantlyreduced their body fat percentage anddecreased their caloric intake over300kcal/d (the calories referred to in dietand exercise). However, this exerciseregimen did not reduce the risk factorsassociated with metabolic syndrome.

Although the direct benefits of exer-cise have not been proven scientifically,there are many other potential benefitsfrom exercise, such as restoring energyand reducing fatigue. Exercise has beenshown to reduce depression, increaseself-esteem, reduce pain and reducesocial isolation and loneliness. Based onthese results, we recommend thatpatients with FSHD perform moderatestrength training and regular aerobicexercise to maintain cardiovascular fit-ness. Studies with longer duration are

needed to assess the long-term effectsof training on disease progression inpatients with FSHD. The general exer-cise recommendations that we suggestfor individuals with FSHD are listedbelow and were adapted from a con-sensus conference of experts (Fowleret al Am J Phys Med Rehabil 2002:81(Suppl):S187-S195).

• Adopt an active lifestyle for itsphysical and psychological benefits.

• Perform moderate-intensityresistive strengthening exercise duringthe early stages of the disorder in mus-cles that have antigravity or greaterstrength. High intensity exercisesshould be avoided.

• Perform moderate-intensity aer-obic training programs to maintain orimprove aerobic capacity.

• Individuals will have a variableresponse to training depending upontheir degree of weakness and fatigue,their rate of progression, and their levelof conditioning.

• Stretching and range-of-motionexercises may be helpful in decreasingthe discomfort attributable to the limit-ed mobility of the joints secondary tomuscle weakness. G

F F FThese exercise recommendations come from the National Center on Physical Activity andDisability (NCPAD). The mission of the NCPAD is to promote substantial health benefitsthat can be gained from participating in regular physical activity.

Important considerations before exercising• Obtain a complete medical evaluation and physician consent before beginning an

exercise program.• Work with your cardiologist to determine cardiovascular complications, such as

cardiac arrhythmias, congestive heart failure, and right and left ventricular dilationwhich may limit your ability to exercise or the intensity at which you exercise.

• Obtain a specialized prescription for spinal deformities, such as scoliosis,kyphoscoliosis and lordosis.

• Respiratory problems: be aware of possible complications associated with weak-ness in the respiratory muscles.

• If you experience exercise-related cramps or fatigue, rest and decrease intensity.• Log your daily activities so that you can determine the appropriate intensity for

your exercise program.• Set reasonable goals with activities that are fun and game-oriented.• Nutritional counseling coupled with the exercise program will help prevent weight

gain.

Cardiovascular training guidelines• Set an exercise pace that feels good to you. Rate your level of exertion by the Rat-

ing of Perceived Exertion scale (range of 6 to 20 where 6 = very light, and

continued on page 6


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Exercise recommendations, continued from page 5

20 = very, very hard); 12 to 14 is agood target zone.

• Focus on the duration, rather than theintensity of your workout.

• Engage in brief walking sessions (20to 30 meters) several times daily, toincrease cardiovascular endurance.The walking surface must be level.

• Perform exercises that utilize multiple,rather than single, muscle groups.

Types of cardiovascular training: Arm and leg ergometry; walking, cycling,

swimming.

Strength training guidelines• Strength training should help you

retain strength in your arms, shoul-ders, legs, and hips. Your balanceand trunk stability can indicate thepreferred type of strengthening pro-gram.

• Splints or braces can assist in astrengthening program if you experi-ence muscle weakness or atrophy.

• If possible, perform multi-joint ratherthan single-joint exercises.

• Note that it may be necessary to limit

your use of weights so that you haveenergy left over for other tasks.

• Focus on increasing the number ofrepetitions rather than increasing theweight. Do not use the overload prin-ciple.

• If you do use weights, utilize lightweights or no resistance. Begin withone set of five to 10 repetitions, andwork up to three sets of eight to 12repetitions, three sessions per week.

• Do not strength-train the same mus-cle groups on consecutive days.

Types of strength training: Weight machines; dynamometer for

grip strength or back/leg strength; thera-band (elastic resistance bands).

Flexibility training guidelines• The goal of flexibility training is to

improve range of motion, balanceand coordination.

• Perform a complete warm-up andcool down stretching program beforeand after each exercise program.Ideally, stretches should be held for10 to 30 seconds, repeated three

Gifts of stock to the FSH Society

As you begin to review your financialaffairs as 2008 draws to a close, it

will be important for you to considerwhether investment market conditionsmake it advantageous for you to makea gift of stock to the FSH Society atthis time.

Consider the tax benefitsA gift of appreciated securities held

for more than one year may providesignificant benefits to you as a contrib-utor, such as:

• Providing you a charitableincome tax deduction for the fairmarket value of the gifted secu-rities as of the date of gift.

• Eliminating capital gains tax thatwould ordinarily become due if you had sold the appreciated securities on the open market and donated the proceeds from the sale to charity.

• Claiming your charitable deduc-

tion against up to 30% of youradjusted gross income. Anyunused deductions can be car-ried forward over the next fiveyears.

• Providing a way to help you toachieve your long-term financialobjective of reducing yourincome and estate taxes.

Caution—Tax benefits are lost if:• the stock is sold and then pro-

ceeds given;• the stock is worth less than you

paid for it;• the stock has been held for one

year or less.For more information, contact the

FSH Society at (617) 658-7878, or goto the website, www.fshsociety.org andclick on Contribute and Gifts of Stock.You should also consult with yourfinancial advisor before initiating acharitable gift of stock. G

Charitable IRARollover opportunity

On Friday, October 3, Congressapproved and the President signed

legislation that includes the immediateand retroactive extension of the popu-lar Pension Protection Act of 2006 pro-vision which allows taxpayers over70-1/2 to make tax-free distributionsfrom their traditional and Roth IRAs(Individual Retirement Accounts)directly to charity in 2008 and 2009.

Check with your advisors about the best ways to take advantage of thisopportunity to give to the FSH Society.As always, the FSH Society will also be pleased to assist you in any waypossible. G

F F F

The FSH Society would like to thank youfor your support as we carry on the fight

for excellent research, treatment and a cure. We cannot do it without you!

times, and performed three to fourtimes daily.

• Focus on main muscle groups, espe-cially those more likely to develop con-tractures, such as those in your arms,wrists, fingers, shoulders, legs, andhips.

• Perform all stretches in a fluid manner.• AVOID overstretching or hypermobility.

Types of flexibility training: Active stretches-stretches you perform on

your own; passive stretches-stretchessomeone helps you perform. ____________________Note: The information provided here isoffered as a service only. The NationalCenter on Physical Activity and Disability,University of Illinois at Chicago, the NationalCenter on Accessibility, and the Rehabilita-tion Institute of Chicago do not formally rec-ommend or endorse the equipment listed.As with any products or services, con-sumers should investigate and determineon their own which equipment best fits theirneeds and budget.National Center on Physical Activity andDisability: http://www.ncpad.org G


On September 14, a beautiful day bythe Long Island Sound in Mamaro-

neck, New York, FSH Society member,Beth Johnston and a very energeticcommittee held a family picnic to raisefunds for FSHD.

Early in the summer, Beth gathereda group of FSH Society members, fami-ly members and friends, to plan thepicnic. Judy and Ken Seslowe gracious-ly offered their home and gardens forthe event, and work began.

By Sunday, September 14, over 150adults had purchased tickets for them-selves and 100 children! Dozens moreindividuals could not attend but sentcontributions. Everyone enjoyed boxlunches or a table of special foodincluding snow cones for children. Asilent auction entertained adults, whilechildren were occupied with wander-ing through a maze. Clowns and facepainters also entertained them.

Special thanks to Beth, her husbandJeff, and other volunteers who servedon the committee: Carrie Baumgartner,Kari McGovern, Jamie Seslowe, EmilyRosenfeld, Susannah Van Dyke, DebbieYounger, David Younger, DeborahSchwartz, and some great Girl Scoutswho want to help again in 2009! Beth isalready planning for next year.

The picnic netted $37,000 for a newpost-doctoral research fellowship.

Thanks to Alisa Dornau and Jen-nifer Egert for photos. G

FSH Society members and friends have a picnic in New York

Ken and Judy Seslowe with Beth Johnston

Jeff and Beth Johnston

Auction

Sandy Batkin and Rosalind Devon

Snow cones!

Face painting

The picnic netted $37,000

for a new post-doctoral

research fellowship.


Tenth Biennial International Patient and Researcher Network Meeting brings people from near and far to Iowa

In late July, nearly 130 people gath-ered in Coralville, Iowa, for the FSH

Society’s tenth biennial Patient andResearcher Network Meeting. Youngpeople and young families joined us ingreater numbers than before, as did people from Iowa, Minnesota, Kansas,Wisconsin, Nebraska, Missouri, Illinois,Michigan, North Dakota, and Texas. Old friends returned and new friendsalso arrived from California, New Jer-sey, Maryland, Florida, Ohio, Virginia,Kentucky, Mississippi, Arizona, NorthCarolina, and New York. Everyone wel-comed attenders from France, Australia,and Canada.

We had great concern for ourfriends in Iowa when the area experi-enced floods in June. Although manypeople experienced much personal and economic hardship, eastern Iowarecovered to a reasonable point for thisand other conferences by late July.

The 2008 conference program waswell circulated in advance and is not

repeated here. It added a dimension forteenagers and young adults by way oftwo workshops in the afternoon ses-sions. In addition to making the meetingmore accessible to midwesterners, weselected this location so that familiesand children with infantile FSHD couldparticipate in the clinic offered byKatherine Mathews, M.D., and staff, onMonday, following the meeting.

EvaluationAttenders evaluated their experience

at the meeting. Overall they were quitepositive, and they offer the Societygood advice for the future:

• They were most appreciative ofthe opportunity to meet otherslike themselves.

• They sometimes found the pre-sentations too technical, and theywished for copies of the presen-tations in advance.

• They suggested spreading themeeting out over 2-3 days.

• They would like more practicalinformation about disease man-agement.

• They suggested that we offermore age segmentation in organ-izing the program.

• They liked the convenient andless expensive location. (Ofcourse, the latter does not allowfor opinion for non-attenders whodid not like the location!)

Future meetingsThe next meeting will be in the latter

half of 2010. The Society will attempt torespond to the good suggestions that weheard. Especially, we will work toexpand the meeting, perhaps withoptional sessions the day before and theday after the core program, and we willtry to increase demographic segmenta-tion in the programming. We will alsocontinue to listen to your ideas for thefuture. Perhaps early in 2009, we willgive you an opportunity to vote for the

region of the coun-try where the 2010meeting will be held.

Special thanks tothe clinicians andresearchers whoprovided our pro-gram and to thegreat staff at theUniversity of IowaHospitals and Clinic.

William R. Lewis, Sr., M.D., chairman of the FSH Society Board of

Directors, opens patient/researcher network meeting on July 27

Teenagers and young adults workshop

Louis Kunkel, Ph.D., and panel of speakers

Save the DateA Festive Evening of Music and SongMarch 25, 2009

Concert and Silent Auctionto benefit the FSH Society

Merkin Concert Hall at Kaufman Center,New York. For more

information, go to www.fshsociety.org

FSH Society members plangatherings for 2009:

• Hobe Sound, Florida—Sundayafternoon—February 2009

• Los Angeles area—Brunch—Spring 2009

• Denver—Reception—Spring2009

• Cape Cod—Fundraising Walk—Summer 2009 G

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Thanks to Leslie Berkeley for photos.


Preparing for our first trip to theFSH Society conference in Iowa Citywas nerve-racking. It was obviouslynot a pleasure vacation but rather apainful journey to gain more informa-tion and find more people like us.People like us would include familieswith small children with infantileFSHD. In our case our son is three, sothe need to know more and talk topeople who “get it”was our driving force.

The night beforethe conference wefound ourselvesexplaining to ourthree year old thatyou are going to seepeople using wheel-chairs and some peo-ple that may not beable to smile backwhen you say “hello.”We tried to use theopportunity to talkabout different wayspeople get aroundand that people oftensmile on the inside,even if we cannot seeit on their faces. Aswe tried to prepare him for the expe-rience we realized it was just as mucha preparation for ourselves.

After registering, we startedsearching for other families withsmall children. We met an amazingfamily with another three year oldand would meet more families with

young children. While our stories aredifferent in relation to age when ourchildren were diagnosed, how they areprogressing related to issues aroundFSHD, it is a relief to know we are notalone. Just talking to someone, evenfor five minutes, who “gets it,” is anunbelievably comforting experience.

The start of the conference entailedpresentations made to the entire

group. The presentationswere helpful for us sincewe are new to the worldof FSHD. It was informa-tion that I know is avail-able somewhere, but tohave the experts review-ing it and answering ques-tions made it moreaccessible. Somehow sit-ting in a room with over100 other people who canrelate on some level withwhat you are dealing withmade it seem less fright-ening.

One of the sessions weattended for caregiversand friends of people withFSHD was also very help-ful. As we went around the

room and introduced ourselves wecouldn’t hold back and boldly stated“We don’t want to be here. And really,this sucks.” We went on to say thatwhile we are starting to learn to beokay with it, we need the space to voiceour fears, disappointments, and pain.As we looked around the room and

noticed nods from others again we realizedwe are not alone. Hearing how other fami-lies are coping and have been coping gaveus much needed reassurance we will beable to handle it (whatever it is), and intime it will be okay.

For us the greatest fear is not havingthe right information and contacts. TheFSH Society conference provided themuch-needed information about thespecifics of infantile FSHD plus provided apersonal network to talk to other familieswho understand, even if we at times do notunderstand. We are looking forward togoing back and would encourage others todo the same.

Stephanie O’Meara,freshman, Creighton University, on taking a big step

The most memorable part of the FSHSociety conference was the people I met. Icannot even remember what the presenta-tions were on but I can remember everyinteraction I had with the people at the con-ference. The first person to introduce her-self to me was a young girl. She was noolder than five with the cutest smile and amouth that did not stop. She was followedclosely behind by her younger sister whowas clearly affected by the disease. As theyounger sister ran towards us she stumbledand fell but quickly picked herself up andcontinued running like nothing had hap-pened. I was stunned to see such persever-ance in such a young child. When she got tous, she entered our conversation as any 3year old would. The two sisters jabbered onabout who knows what while I stood there

International Patient and Researcher Network Meeting

continued on page 10

Patients and researchers assembled in Coralville, Iowa Conference attenders & friend

Parents Michelle and John Hosp share their search—for information, for other families and for coping skills

“The FSH Societyconference providedthe much-neededinformation aboutthe specifics ofinfantile FSHDplus provided a personal network totalk to other familieswho understand,even if we at timesdo not understand.”

—Michelle & John Hosp


utterly amazed by these two younggirls. One was affected by a disease butdid not let it get in the way of what shewanted to do and the other would bethe first one to her sister’s side if sheneeded help.

During the session I led, a sessionfor teens with FSHD, I met the mostamazing teenagers in my life. Each oneof them had their own stories andweren’t afraid to share them. I mayhave started the session leading, but bythe end we were just a group of friendssharing our experiences. There was agirl, a year older than me, whom Iimmediately clicked with. She sharedher problems and listened to mine.With me beginning my freshman yearshe gave me hope and courage to begina new experience. We still keep intouch through email today, and I knowthat she will always be there for me if Ineed her. Then there is the girl who isa couple years younger than me whomakes me laugh till my sides hurt. Sheshows me that, yeah having the diseaseis hard but it is just a tiny aspect of ourlives. And it is great to be able to share

my wisdom with her to make her highschool years the best. Although we justrecently reconnected, it is like we werenever apart. These are just a few of thepeople who influenced my life duringthat session.

I guess what I am getting at is thatthe FSH Society conference changedmy life. I met the greatest people. Theyknew what I was going through andwere eager to help. I was known as“the girl who is starting Creighton inthe fall” to the adults, a friend to thepeople my age, and a person to look upto for the children. I may be all thosethings to those people, but they haveno idea how much they influenced me.Over the course of a couple days, Igained hope, friendship, and an experi-ence I will never forget.

Sixto Garcia, soon to becomea junior at the University of California, Northridge

The Garcia family enjoyedimmensely the Iowa conference. First,having participated in the Boston con-ference two years earlier, we touchedbase with old friends and more impor-tantly, met new ones! Second, theorganization of the meeting was muchmore fluid, informative, and it was wellmanaged.

I am 21 years old, and still in myprime of developing a personality;being with others who may feel, look,and experience as I do is a key ingredi-ent in being able to not only cope withFSHD but also to adapt and live withit. In my first conference I was struckby the varying and many people that Icould relate to. Their experiences, feel-ings, and outlooks in life made me feelvery welcomed.

I came to the Iowa conferencemore prepared than I arrived at theBoston conference, as I knew I wouldsee familiar faces. But this time, mygoal was not just to find a place to fitin, but also to help others find what Ifound. I have learned a lot from thefirst conference and from the 2 yearssince then; as a psychology major, Ifelt the obligation to motivate thosewho were in my position at the firstconference.

International Patient and Researcher Network Meeting, continued from page 9

“The FSH Societyconference changed my life.I met the greatest people.They knew what I was goingthrough and were eager tohelp. I was known as ‘thegirl who is startingCreighton in the fall’ to theadults, a friend to the peoplemy age, and a person tolook up to for the children. Imay be all those things tothose people, but they haveno idea how much theyinfluenced me. Over thecourse of a couple days, Igained hope, friendship,and an experience I willnever forget.”

—Stephanie O’Meara

I want everyone to know that notonly is the conference a great experi-ence, but a necessity if you want tocope and adapt with FSHD. I am fortu-nate to be someone who is mildlyaffected by FSHD, and seeing thoseless fortunate, and speaking with themon how they conduct their own liveswith FSHD not only showed me what Istill have, but what I should do to main-tain it. I have heard stories and strate-gies on how to begin dealing withFSHD, but nothing is more provocativethan seeing and speaking with a personthat can tell you just how far FSHD cango. Looking into their eyes and seeingthem smile when a young personcomes up and asks them for knowledgeis a priceless experience. And what I’velearned from studying psychology isthat the best way to overcome an ill-ness or disadvantage in life is to helpthose affected. I saw that those I con-versed with at the conference felt need-ed, and that may be a change from theirdaily life of feeling dependent on oth-ers.

I wish all those I spoke with thebest of luck and I truly admire every-one’s strength by showing up to eitherone of the conferences. I hope to seeyou all again soon. Life is just an adap-tation of obstacles. I now see that life isbeautiful and regardless of FSHD. Idon’t think I would be the passionate,intelligent, sensible, and motivationalperson that I am today. I have left withmy head held high. Thank you to theFSH Society to make this wonderfulconference possible! G

“Life is just anadaptation of obstacles. I now see that life isbeautiful and regardlessof FSHD. I don’t think Iwould be the passionate,intelligent, sensible, andmotivational person that Iam today. I have left withmy head held high.”

—Sixto Garcia


Combined FederalCampaign (CFC)— Are you a federal, postal or military employee?

F ederal civilian, postal and militarypersonnel can donate to the FSH

Society through the Combined FederalCampaign during the campaign season,September 1 to December 15, 2008. TheFSH Society code is #10239.

For more information about theCFC, you may go to the official website:http://www.opm.gov/CFC/ G

Are you a member ofthe FSH Society? Haveyou made a gift to theSociety in 2008?

T he FSH Society is a world leaderin combating muscular dystrophy.

It has provided $2 million in seedgrants to pioneering research world-wide and it has created an internation-al collaborative network of patients andresearchers.

If you are not already a member,won’t you join in this effort? Pleasereturn your membership gift, or anothergift, in the envelope enclosed insidethis issue of Watch.

Or contribute online at: www.fshsociety.org.

Go to Contribute, and select thegift category you wish to make. Thankyou! G

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Above: Family and friends made gifts totaling more than $30,000 toestablish the Aubrie Lee Family Research Fund, to support researchin infantile FSHD. The Lees, their five sons and wives, and manygrandchildren are pictured above. Aubrie Lee is in the first row,third from the right.

Left: Aubrie Lee and herparents invited herfriend, Justin Cohen,together with his familyto her grandparents’anniversary dinner.

FSH Society Research Fellowships yielding fast forward dividends and insightsResearch summary

FSH Society research fellow, KyokoYokomori, Ph.D., is studying a com-

plex involved with D4Z4 (the FSHDarea at the end of chromosome 4) thatnormally modifies histones (proteins) atD4Z4 and recruits factors that areinvolved in gene silencing. Dr. Yoko-mori and her colleagues believe thatthis complex bound to D4Z4 spreads its

silencing effect to target gene(s) bylong-distance interactions. In FSHD,this process is disrupted and the silenc-ing is lost when only one strand of thechromosome is shortened. In addition,FSHD patients who are clinically affect-ed, but who do not have a deletion onchromosome 4, e.g., the non-4q-linkedvariety, are found to have a disruptionof this complex and the silencing isagain lost. Patients with four other dys-trophies do not experience this particu-lar over expression and the loss of genesilencing.

Further, this lab has also found that continued on page 12

this disrupted complex causes overexpression of Pitx2, thought to be oneof the target genes in FSHD. They havefound that artificial over expression ofPitx2 in muscle cells leads to theincrease of another gene, known to behighly over expressed in FSHD patientmuscles, called Pitx1. (This is the workof Yi-Wen Chen, D.V.M., Ph.D., alsofunded by the FSH Society.) Pitx1 overexpression was found to cause muscleatrophy. Thus, the results suggest thatthe increase of Pitx2 indeed criticallycontributes to FSHD pathogenesis. If

Mary and Man So Lee, M.D., celebrated their 50th wedding anniversary, Staten Island, New York, August 9, 2008.

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Connectingwith other FSHSociety membersArticles in this issue and recent con-

versations remind me that manySociety members express an interestin meeting others with FSHD. In recentmonths, many of you have asked if wecould help you connect. Consider thefollowing:

• FSHD patient in New Jerseywho would like to meet othersnearby

• Parents with small children whowould like to connect by email orphone

• Los Angeles area membersplanning a winter or springbrunch

• Teenagers and young adultshave formed a virtual networkand welcome new friends

If you would like to participate in oneof the above, or if you have a network-ing request, email me, [email protected], with your permission togive your contact information to others,and we will help you connect!

—Nancy Van Zant

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Potential novel diagnostics For FSHD

Facioscapulohumeral Dystrophy(FSHD) is reported to have a 1 in

20,000 incidence. However, there isgreat concern that the actual number ofaffected individuals is significantly high-er due to undiagnosed cases (with alikely incidence of 1/7,000). A properdiagnosis of FSHD depends initially onrecognition of clinical signs and symp-toms and differentiation of FSHD casesfrom other muscular dystrophies.

Molecular studies have been usedto reinforce the clinical impression. Theprimary approach has been throughdetection of 4qD4Z4 repeat contractionby pulsed-field gel electrophoresis(PFGE) following restriction digestion.However, this method cannot identifyphenotypic FSHD patients who do nothave a chromosome 4 repeat contrac-tion, and certain band patterns canprove difficult to interpret. Our workfocuses on histones which are themain protein components of chromatin.Histones act as spools around whichDNA can wind, and influence and havea role in gene regulation. We haverecently discovered a specific change

in histone modification at the D4Z4repeat sequences (known to be asso-ciated with the disease) which isdetected in both 4q-linked (with D4Z4repeat contraction) and phenotypic (norepeat contraction) FSHD patient cells.

Importantly, this change is highlyspecific for FSHD; no significantchange of this histone modificationwas observed in Duchenne musculardystrophy (DMD), limb-girdle musculardystrophy (LGMD), oculopharyngealmuscular dystrophy (OPMD), inclusionbody myopathy associated withPaget’s disease of bone and fron-totemporal dementia (IBMPFD), or“immunodeficiency, centromeric insta-bility and facial anomalies” (ICF) syn-drome patient cells.

Furthermore, this change is seennot only in affected muscle cells orfibroblasts derived from patient musclebiopsy samples, but also in patientlymphoblasts (derived from blood).This suggests that this histone modifi-cation alteration occurs early in devel-opment and is therefore found in manycell types in an affected individual. This

is potentially very useful from a clinicaldiagnosis standpoint.

One could envision making a diag-nosis of FSHD by analyzing peripheralmononucleocytes that could beobtained significantly less invasively(and less painfully) than muscle biopsysamples. Detection of the histone mod-ification alteration is accomplished byperforming a chromatin immunoprecipi-tation (ChIP) analysis, which entailscrosslinking of cellular DNA andimmunoprecipitation with antibody spe-cific for a particular histone modifica-tion marking. We anticipate that asufficient number of patient cells couldeasily be acquired through a standardblood draw. Experiments are currentlyunderway to test this notion. If we candemonstrate that this is the case, ChIPcan be used to analyze the histonemodification markings in the patients’blood samples for FSHD diagnosis. G

Alexander R. Ball Jr., Ph.D., and Kyoko Yokomori, Ph.D.University of California, Irvine, California

the researchers can modulate Pitx2,which is a transcription factor protein,they can also modulate Pitx1 and in turncontrol and treat FSHD.

Finally, the researchers postulatethat Pitx2 is involved in early humandevelopment. To study these embryoniceffects, Dr. Yokomori is now developingembryonic mice models and humanembryonic cell model systems, the nextsteps in developing a treatment.

A key understanding here is thatpatients with several other dystrophiesdo not experience this particular overexpression and the loss of gene silenc-ing. It is very interesting that FSHDpatients with one strand of the chromo-some shortened, as well as the FSHDpatients with no shortening of the chro-mosome, the non-4 linked FSHD cases,

do experience this particular overexpression and the loss of gene silenc-ing.

Last, this particular histone complexcould lead to a new and novel methodto diagnostically and genetically testpatients with both types of clinicallydetermined FSHD e.g. those with ashortened D4Z4 region (the chromosme-4-linked) and those with no shorteningof the D4Z4 region (the non- chro-mosme-4-linked).

Drs. Ball and Yokomori wrote thefollowing on efforts to find a more rapidand efficient diagnostic and prenataltest for all types of FSHD.

Dr. Yokomori has support from theFSH Society Helen Younger and DavidYounger Post-doctoral Research Fel-lowship Award. G

FSH Society Research Fellowships, continued from page 11

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on vision and fshd - fsh society

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