I Curren tReview

Psychosocial aspectsof osteogenesis imperfecta

Glenda L. Shea-Landry, BA, MADavid E.C. Cole, MD, PhD, FCCMG

Osteogenesis imperfecta is a heterogeneousgroup of inherited disorders characterized bybone fragility and recurrent fractures. It is cur-rently classified into four types on clinicalgrounds and appears to arise from differentdisorders of bone collagen synthesis. The bio-chemical identification of disturbances in colla-gen metabolism and the genetic delineation ofnew mutations of collagen genes have madeprenatal diagnosis by molecular methods feasi-ble in some cases. Most people with osteogene-sis imperfecta suffer frequent fractures (andsometimes consequent serious disability), forwhich there are few effective preventive mea-sures. This disorder may have a profound psy-chosocial influence on patients and their fami-lies. In this report the extent of this influence isreviewed and aspects important to the medicalcommunity are highlighted; these include theemotional burdens imposed by unfounded sus-picions of child abuse, the social and financialcosts of repeated hospitalization and immobili-ty, and the frustrations generated by the lack ofhelpful, practical information for families andhealth care workers. An important social out-

From the Department of Pediatrics, Dalhousie University,Halifax

Dr. Cole is an assistant professor of pediatrics at DalhousieUniversity and the recipient of a scholarship from the CanadianLife and Health Insurance Association.

A portion of this work was submitted as a master's degreethesis in the Department of Sociology, Dalhousie University, forwhich Ms. Shea-Landry received a graduate studentship.

Reprint requests to: Dr. David E.C Cole, Rm. 415, Izaak WaltonKillam Hospital for Children, 5850 University Ave., Halifax, NSB3J 3G9

come has been the rise of self-help organiza-tions, exemplified by the Canadian Osteogene-sis Imperfecta Society. For Canadian familiesthe society has been an important vehicle forexchange of information and an active, positiveresponse to a lifelong, often severely disablingdisorder.

L'osteogenesis imperfecta, ou fragilite essentiel-le des os, constitue un groupe heterogene demaladies hereditaires predisposant la plupartdes sujets atteints aux fractures repetees. On enreconnait actuellement quatre formes cliniquesdont chacune semble representer une anomaliedistincte de la synthese du collagene osseux. Laconnaissance de ces anomalies et la notion deneomutations des genes concernes en permettentdans certains cas le diagnostic biochimiqueprenatal. On a peu de mesures preventives aopposer aux fractures et aux graves infirmitesqui en resultent parfois. Elles ont sur les mala-des et leurs familles de profondes incidences quifont l'objet du present article, ou l'accent est missur leur interet pour le medecin: les tensionsaffectives causees par d'injustes soupcons demauvais traitements aux enfants, les consequen-ces sociales et pecuniaires de l'hospitalisationrepetee et de l'immobilisation, la frustrationengendree chez les familles et les professionnelssoignants par le manque d'information utile.Aussi doit-on considerer comme une acquisitionimportante la naissance des organismes d'entrai-de, comme la Canadian Osteogenesis ImperfectaSociety, qui d'ores et deja assiste les famillesconcernees par l'echange d'information et favo-rise un point de vue positif sur ces maladies, quidurent toute la vie et causent souvent de redou-tables infirmites.

CMAJ, VOL. 135, NOVEMBER 1, 1986 977- For prescribing information see page 1034

O steogenesis imperfecta is a group of Men-delian genetic disorders that are definedby brittleness or fragility of the bones and

impaired collagen metabolism.' Recent advances indiagnosis and biochemical analysis have begun toclarify the complex relation between the geneticmutations and their clinical presentations.

At present the classification of Sillence andcolleagues2 provides the best means of distin-guishing among the various clinical entities andoffering the patient or family reasonable prognosticadvice.4 Type I, the tarda or mildest form ofosteogenesis imperfecta, is distinguished by blue-ness of the sclera, perinatal or postnatal onset offractures and a pattern of autosomal dominantinheritance. Type II, the lethal congenita or prena-tal form, is now considered a genetically heteroge-neous category of both autosomal recessive condi-tions and disorders due to new, spontaneouslyarising, dominant mutations.3 - Since there is arecurrence risk for subsequently born siblings of25% with the former and OO% with the latter,distinguishing between the two groups is impor-tant in the counselling of prospective parents.Prenatal diagnosis of this uniformly lethal condi-tion can often be made in the second trimester byultrasonography.8 9 Type III, a rarer disorder, isalso genetically heterogeneous and may displayeither a dominant or a recessive pattern of inheri-tance.5 Its chief distinguishing features are themore severe and more frequent fractures comparedwith type I, the progressive limb deformities andthe absence of blueness of the sclera. Type IV isuncommon and has been less well defined. Pater-son and associates10 consider it to be milder thantype I, the patients having normal sclera and onlymoderate deformities of the long bones; however,it is more likely to be associated with dentinogen-esis imperfecta.

It is ironic that our knowledge of the individu-al molecular defects in patients with osteogenesisimperfecta is growing more rapidly than our un-derstanding of the pathogenesis of the bony abnor-malities and their relation to the natural history ofthe condition. Studies of collagen biosynthesis incultured fibroblasts have shown that osteogenesisimperfecta type I cells produce the different typesof collagen molecules in abnormal proportions:production of the bone form of collagen is reduced,whereas production of the skin collagen fraction isincreased.11 With the isolation and cloning ofcertain collagen genes it is now possible in somecases to identify the specific genetic defect. Thereare reports of at least a dozen different mutationsthat result in either decreased collagen synthesis orthe formation of an unstable collagen moleculethat does not integrate with other forms of colla-gen or other matrix components and ultimatelyundermines the mechanical strength of bone.712,1As our understanding of these molecular eventsgrows, our ability to make an accurate geneticdiagnosis is improving. Thus, patients with os-teogenesis imperfecta and their families should be

encouraged to undergo skin biopsy for fibroblastculture in an attempt to delineate the biochemicalor molecular defect. This may be particularlyimportant in calculating recurrence risks and estab-lishing an accurate prenatal diagnosis.4,1

Unfortunately, efforts to treat this conditionhave been frustratingly unsuccessful. Althoughdaily intramuscular injections of calcitonin mayreduce the number of fractures in some cases,14 thebone fragility is unresponsive to any form ofmedical intervention in most cases.' In infants andchildren with progressively deforming disease,minimizing the extent of disability is a formidablechallenge; prompt and effective orthopedic care isof paramount importance. In some patients theseverely deformed limb bone may be sawn intosmall hollow segments through which a metal rodis inserted in shish-kebab fashion, thereby straight-ening and lengthening the limb.1 In others thesephysical measures may not be possible or may notprove sufficient to prevent disability.

Little has been written about the family settingand psychosocial consequences of osteogenesisimperfecta. This review will draw on the availableliterature and on the results of a study conductedby one of us.1"

Psychosocial factors

Parents and family

The behaviour of the parents of a child bornwith osteogenesis imperfecta is strongly condi-tioned by their immediate reactions to the deformi-ty and disability of their child.', ' Initial shock andimmobility may be followed by anger, often be-cause there is no knowledgeable person availableto counsel them about the disorder. Feelings ofguilt may surface. As Schild"8 put it, "a fear thatone possesses a defective gene causes a momen-tous insult to the ego and fosters inadequateparental functioning". Further, some parents fearthey will not be able to provide adequate care forthe child. However, the child born into a familythat already has an affected member may enter amore secure environment.

As the family begins to accept the child'sdisorder an imbalance may develop in which themother becomes overinvolved in an intense rela-tionship with the child while the father and thesiblings are pushed outside the "magic circle".19Nevertheless, the rest of the family is expected tomake considerable lifestyle and financial sacrifices.Members of the extended family are sometimesseen as a hindrance to the family's interaction.Grandparents, aunts and uncles may deny thecondition or even reject the child. More distantrelatives may show undue concern, perhaps be-cause they believe that the disorder reflects un-favourably on their own genetic constitutions.

Children less severely affected with os-teogenesis imperfecta may suffer repeated fractures

978 CMAJ, VOL. 135, NOVEMBER 1, 1986

before the diagnosis is made. The unexplainedfractures may raise the suspicion of child abuse inthe minds of hospital personnel and others.' Whilethese suspicions linger, the parents must contendwith feelings of guilt and unfocused anxiety.

Once the diagnosis is made, most parentslearn to cope with new fractures, and hospitalpersonnel may become less certain about how tohandle the infant and insensitive to practical sug-gestions the parents offer. Use of the bed cardprovided by the Canadian Osteogenesis ImperfectaSociety (COIS) (Fig. 1) is one way of protecting thechild from improper handling.

Like all parents of the severely disabled,parents of children with osteogenesis imperfectaneed an abundance of patience, courage and faith.They may find it difficult to persuade others thattheir child has real limitations for which specificallowances have to be made. Constant awarenessof their child's fragility makes routine activities asource of crisis in everyday living. And they musthelp the child resist the cultural imperatives toparticipate in sports and to take physical risks.

Growing up

Going to school is particularly frightening forchildren with osteogenesis imperfecta, and for theirparents, who must struggle to accept that thebenefits of academic and social growth outweighthe physical risks. However, children with severe

Fig. 1 Bed card provided on request by theOsteogenesis Imperfecta Foundation, Inc., through theCanadian Osteogenesis Imperfecta Society to familieswith members who have osteogenesis imperfecta.

handicaps will find it harder to realize thesebenefits if they are excluded from activities andinteractions with their peers because of their func-tional restrictions and episodes of illness or be-cause of the reactions of their peers or parents.19

Severely affected older children comment onthe general immobility of being confined to awheelchair, the social problems associated withshort stature, and the pain and specific immobilitydue to recurrent fractures, which may be moreprevalent at the time of the growth spurt inadolescence. As well, physical disability often ob-scures concerns over such matters as physicalappearance, sexual development and peer accep-tance, concerns that the handicapped child shareswith other children.

Adulthood

After early childhood the problems of immo-bility and of social and financial dependence con-tinue to beset the person severely affected withosteogenesis imperfecta.18 Patients come to dependheavily on family, friends and neighbours formobility, yet many potential helpers are deterredfrom assisting those in greatest need by the fearthat they will be "responsible" for new fractures.Lack of easy access to public transportation andbuildings enhances the patients' physical and so-cial isolation and limits their occupational andeducational choices and their ability to contributeeconomically to increasing their own mobility.Some have experienced discrimination in theworkplace, and employers rarely offer them morethan a subsistence income.

Patients with milder forms of osteogenesisimperfecta have unique problems arising from theconflict between their outwardly normal appear-ance and their underlying fragility. As adults theyface the certainty of new fractures and hospitalstays. They must compete on an equal footing withtheir physically healthy counterparts yet oftenencounter difficulty in obtaining insurance or get-ting dispensation for legitimate absences fromwork. Despite their often serious medical andorthopedic problems, they may be excluded fromcommunity support or special aid programs.

The physician's role

When first confronted with a newborn whohas multiple fractures and skeletal deformities thephysician may feel somewhat at a loss, if onlybecause of the very limited medical literaturedealing with osteogenesis imperfecta. Initially thedifferentiation between a lethal (type II) and a

nonlethal (type III) form of osteogenesis imperfectawill be the critical issue. Helpful in this context is a

careful evaluation of respiratory and neurologicfunction, since patients with significant pulmonaryhypoplasia or a major intracranial insult usually

CMAJ, VOL. 135, NOVEMBER 1, 1986 979

FRAGILE!HANDLE ME WITH CARE

Have Osteogenesis ImperfectaMy bones break very easily

NEVER push, pull, twist, turn, bend, apply pressure, or try tostraighten my limbs.

AVOID trying to turn my head.

AVOID lifting my legs to change a diaper.

ALWAYS place hands under my buttocks and slide diaperunder.

ALWAYS handle me gently with slow methodical movements,supporting my head, torso, and buttocks evenly.

ALLOW my parents to accompany me in X-ray rooms andexaminations. They know how to handle me.

OfvProvided by

; 0st_zon-azzii _qm#tfzcta qoun,d2tio,A

have type II osteogenesis imperfecta and, hence, aguarded prognosis. On the other hand, infantswith type III osteogenesis imperfecta and adequatepulmonary reserve may thrive despite markedlydeformed limbs and multiple rib or skull fractures.In either case it is important to be completelycandid with the parents from the very start,emphasizing the extreme heterogeneity of thesedisorders and the impossibility of accurately pre-dicting the ultimate outcome until the pattern ofthe fractures and bone growth is established. Atthe same time, one can point to the extraordinaryachievements of adults with severe but nonlethalosteogenesis imperfecta and can support the par-ents' natural inclination to see their infant as a"terrific fighter", overcoming what seem to beconsiderable odds against survival.

Patients with mild osteogenesis imperfecta(type I) may not come to the physician's attentionuntil after the first few fractures. Because of thefavourable prognosis and the natural improvementthat accompanies this disorder, the physician canpromote a very favourable point of view, empha-sizing the importance of normal peer relations, theneed for exercise (swimming is an excellent form ofvigorous exercise suitable for any patient withosteogenesis imperfecta who has access to a pooland adequate supervision) and the bright outlookfor normal adulthood.

For any patient with osteogenesis imperfectaappropriate referrals to a skilled orthopedic teamand a knowledgeable physiotherapy service will gofar to obviate complications due to suboptimalsetting of fractures or a poor recovery from surgicalrepairs. Patients with dentinogenesis imperfecta(Table I) or other dental complications should beseen by a dental team familiar with the disorder.20All patients should be seen by a cardiologist so asto identify any of the potentially troublesomecardiovascular complications of the collagen defect,

such as aortic valve incompetence accompanyingaortic root dilatation.21 All patients should alsoundergo a formal hearing test as soon as practicallypossible, and most should probably be retestedregularly to identify any hearing loss at an earlystage. Perhaps the most important referral one canmake is to another family with a child who hasosteogenesis imperfecta. The practical informationthat these parents accumulate with time cannot beacquired elsewhere, and most parents of a child inwhom osteogenesis imperfecta has just been diag-nosed are extremely grateful for this kind ofsupport.

The Canadian Osteogenesis Imperfecta Society

The medical response to osteogenesis imper-fecta is necessarily limited, and in view of thesubstantial social and physical problems associatedwith this disorder the spontaneous development ofrelated self-help organizations is hardly surpris-ing.22 The establishment of COIS in 1983 followedthe examples of the British Brittle Bone Society andthe American Osteogenesis Imperfecta Foundationin the 1970s.

Membership in COIS is open to anyone inter-ested in the welfare of people with osteogenesisimperfecta, including parents, friends, medical per-sonnel and other health care professionals. For amodest annual fee, members and other interestedparties receive several times a year the newsletterConnect. The self-professed aims of the society areas follows: to provide emotional support on apersonal level for parents and people with os-teogenesis imperfecta; to acquaint medical person-nel, hospitals, educational institutions and socialagencies with all facets of osteogenesis imperfecta;to encourage Canadian medical research into theunderlying causes of osteogenesis imperfecta; to

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keep an up-to-date library of literature, both medi-cal and general, pertaining to osteogenesis imper-fecta; to promote an understanding and awarenessof "brittle bones" by the general public; to estab-lish and maintain a confidential central registry ofpatients with osteogenesis imperfecta; and to solicitand receive funds to carry out the aims of thesociety.

Most families have expressed support for thesegoals, irrespective of their interest or direct in-volvement in the national organization. Localchapters of COIS have also provided families withseveral different kinds of informal aid, such asrelief from a sense of isolation, knowledge thatothers have similar problems, and the opportunityto exchange helpful information on methods ofhome management and treatment. Thus, physi-cians should contact the organization for assistancein finding centres with expertise in clinical andlaboratory diagnosis and for help in identifyingfamilies of patients with osteogenesis imperfecta inthe same community who can help with themanagement of the new patient.

Readers wishing to receive a copy of the COISnewsletter or to learn more about osteogenesisimperfecta are invited to contact the society at POBox 607, Station U, Toronto, Ont. M8Z 5Y9.

Conclusion

Osteogenesis imperfecta is an uncommon,complex genetic disorder with multiple modes ofinheritance. It cannot be cured. The inherent bonefragility that characterizes the condition leads tofrequent fractures and sometimes serious disabili-ties and thus places a considerable demand on ourhealth care system.

Progressive deformities are among the mostdaunting of prospects for severely affected patientsand their families. When immobility ensues, thefamily bears most of the enormous responsibilityfor making the patient's environment as normal aspossible. The health care system also providessome assistance, but a common effort is needed, ifonly to ensure that each patient attains his or hermaximum potential for social, intellectual andeconomic growth. COIS is a self-help organizationthat has arisen out of a perceived need of patientsand their families to achieve this potential. Devel-oping a better response to the social issues hasbeen a welcome counterbalance to current scientif-ic efforts to expand our understanding of thegenetic defects and their pathophysiologic conse-quences.

We thank Sheila Bannon for preparing the typescript,Sharon Digout for editorial assistance and ElizabethWinsor for critical review of the text. We also expresssincere appreciation to the participating families for theirpatience and their willingness to be frank and open intheir discussions of personal and family matters. Specialthanks go to the late Terry Saunders, whose struggle

with his disease and his disabilities was an inspiration tomany; his support and encouragement were invaluablecontributions to our study.

References

1. Smith R, Francis MJO, Houghton GR: The Brittle BoneSyndrome: Osteogenesis Imperfecta, Butterworths, London,1983

2. Sillence DO, Senn A, Danks DM: Genetic heterogeneity inosteogenesis imperfecta. J Med Genet 1979; 16: 101-116

3. Sillence DO, Barlow KK, Garber AP et al: Osteogenesisimperfecta type II: delineation of the phenotype withreference to genetic heterogeneity. Am J Med Genet 1984;17: 407-423

4. Byers PH, Bonadino JF, Steinmann B: Osteogenesis imper-fecta: update and perspective. Ibid: 429-435

5. Sillence DO, Barlow KK, Cole WG et al: Osteogenesisimperfecta type III: delineation of the phenotype withreference to genetic heterogeneity. Am J Med Genet 1986;23: 821-832

6. Paterson CR, McAllion S, Stellman JL: Osteogenesis imper-fecta after the menopause. N EnglJ Med 1984; 310: 1694-1696

7. Tsipouras P, Bonadino JF, Schwartz RC et al: Osteogenesisimperfecta type II is usually due to new dominant muta-tions [abstr]. Am J Hum Genet 1985; 37: A79

8. Shapiro JE, Phillips JA, Byers PH et al: Prenatal diagnosis oflethal perinatal osteogenesis imperfecta (OI type II). JPediatr 1982; 100: 127-133

9. Brown BSJ: The prenatal ultrasonographic diagnosis ofosteogenesis imperfecta lethalis. J Can Assoc Radiol 1984;35: 63-66

10. Paterson CR, McAllion S, Miller R: Osteogenesis imperfectawith dominant inheritance and normal sclerae. J Bone JointSurg[Br] 1983; 65: 35-39

11. Sykes B, Francis MJO, Smith R: Altered relation of twocollagen types in osteogenesis imperfecta. N Engl J Med1977; 296: 1200-1203

12. Prockop DJ, Kivirikko KI: Heritable diseases of collagen. NEnglJ Med 1984; 311: 376-386

13. Prockop DJ: Mutations in collagen genes: consequences forrare and common diseases. J Clin Invest 1985; 75: 783-787

14. Castells S, Colbert C, Chakrabarti C et al: Therapy ofosteogenesis imperfecta with synthetic salmon calcitonin. JPediatr 1979; 95: 807-811

15. Shea-Landry GL: The Adaptation of Families to Stigma-tized Chronic Illnesses, dissertation, Dalhousie University,Halifax, 1985

16. McCay V: Parental reactions to birth-defective children.Postgrad Med 1979; 35: 183-188

17. Kiely L, Sterne R, Witkop C: Psychological factors inlow-incidence genetic disease. Social Work Health Care1976; 1: 409-419

18. Schild S: The challenging opportunity for social workers ingenetics. Social Work 1966; 4: 22-28

19. Weitzman M: School and peer relations. Pediatr Clin NorthAm 1984; 31: 59-69

20. Schwartz S, Tsipouras P: Oral findings in osteogenesisimperfecta. Oral Surg 1984; 57: 161-167

21. Hortop J, Tsipouras P, Hanley JA et al: Cardiovascularinvolvement in osteogenesis imperfecta. Circulation 1986;73: 54-61

22. Katz A: Self-help organizers and volunteer participation insocial welfare. Social Work 1970; 15: 51-60

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