MIDWEST REGIONAL BONE DYSPLASIA CLINICRichard M. Pauli, M.D., ph.D., Director

Nnrunar Hrsrony: Rsv. 6 / 97

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Mnotcar Issuns AND Panaurar CoNcnRNs ro BE ANTTcTpATED

INlTnootrcrtoN: Unlike many bone dysplasias, multiple epiphyseal dysplasiamaY. be delaye{ in presentation and frequently diignoiir is not

-iOuuntil an individual is between 2 and 10 years of age. Diagnosis is some-times even delayed beyond these ages. First indicalors ofihe presence ofthis disorder are waddling gait, difficulties running, limping, joint stiff-ness, joint pain and/or subtle slowing of growth velocity.Multiple lPiphy-seal dysplasia is a descriptive diagnosis, simply im-plying that an individual has an intrinsic bone dysplasia limited tb [freends (epiphyses) of the long bones and with littla or no spine involve-

rye_nt. In general, there is profound delay in epiphyseal maturation and Jdeformity of epiphyses. The best described of ttre various forms of mul-tiple e^piphyseal dysplasia is sometimes termed the Fairbank type. Most ofthe information outlined here is most specifically applicable to those withthis type of multiple epiphyseal dysptaiia.

PnosrnNl: GnowruExprctartoNs: Initial growth in infancy and early childhood is often normal. Minimalto moderate short stature is usual, with adult heights ranging from about 135 cmto 155 cm. Head growth is normal.MoNnonluc: There are no growth charts available. Plotting linear growth on regulargrowth standards may provide some guide to whether growth ielocity is beingmaintained.IvrnRvEvmoN: No known treatment. Growth hormone etc. is not likely ro be effectivesince this disorder is secondary to intrinsic abnormality of bone growth. 1imblengthening has been used nccasionally but remains controversiai.

I' if,lf, T; I,XTlli Y;o; f!;g i ",," .,,",.rev.6/97

Pnonrru: HrpsExpnctarloNs: Hip pain is often the first presenting symptom. Stiffness, abnormal

gait (waddling) and limping may also be the first recognized characteristics inearly childhood. In addition to the intrinsic and constant abnormalities of the hip,avascular necrosis (Legg-Perthes disease) develops in a substantial minority. Hipdegeneration and premature osteoarthritis is nearly uniform often arising in earlyadolescence. Many will have total hip replacement, often in the 30s or 40s.

MoNnontNG: Radiologic assessment with symptoms.INrrRvEurIoN: Limitations of repetitive weight bearing activities and other activities

that result in repetitive stress on the hips, such as rope jumping, trampoline useetc., can slow degenerative arthritic change; [f avascular necrosis develops this istreated with traditional methods (a period of non-weight-bearing and physicaltherapy followed by abduction bracing). .Use of a motorized scooter for longdistance rnobility is warranted whenever osteoarthritic problems become severe -,sometimes as earlv as adolescence.

PnosrEr'a: OruEn Lnncn JorNr SyuprousExpECrRrtONS: More generalized osteoarthritis is not uncommon. This is particularly

common in the knees and the shoulders. As with Legg-Perthes developing in thehips, osteochondritis dessicans may develop in the khtes.

MorurroruNG: Clinical monitoring. Radiologic assessment may help predict theseverity of problems that can be expected - for example, the shape of theproximal humerus and humeral head is an excellent sign to assess likelihood ofand severity of shoulder arthritis later in life; likewise the degree of fragmentationof the femoral head allows prediction in late childhood of how severeosteoarthritic changes will become in the ensuing decades.

ImrnvrvrtoN: The usual treatments for osteoarthritis are applicable, but may need tocommence in adolescence and young adult life.

PnoslEl"r: [rc PoslrroNAl ABNoRMALTTTESExpecrRrtoNS: Beginning after orthograde weight bearing, nearly all develop some

knee and leg position abnormality, but these are usually relatively mild. Eithervarus deformity (bowleg) or valgus deformity (knockknee) may develop.Progressive deformity may arise and may be sufficiently severe in some olderchildren to warrant surgical intervention.

MoNtroRlNc: Clinical monitoring for alignment, development of chronic knee pain,limitation of ambulation (usually secondary to pain).

IvreRvevrloN: Surgery should be reserved for those with severe and symptomaticmal-alignment.

Richard M. Pauli, M.D., Ph.D.,N{idwest Regional Bone Dysplasia Clinicrev.6/97

Pnoslalur: Sunrr JorNr CHRNcnsExpectAnoNSl Hands are short with particularly short fingers. There is often mild

generalized hypermobility.MoNIronrNG: Function is usually fine, but some individuals may experience moderate

fine motor difficulties or fatigue secondary to efforts to stabilize intrinsicallyunstable small joints.

INrgnvnNrtoN: Usually none. Minor adaptations for fine motor activities in schoolmay be needed.

PnosrENa: ApRpuvrExpnCfaftoNs: In general short stature is not so severe that major environmental

adaptations are needed.MoNIronlNG: Assess for age appropriate needs.INrEnvtNrtoN: School adaptations, stools, etc. if needed.

Gnunrrcs AND MorncuLAR BroLocY

Multiple epiphyseal dysplasia is relatively common, arising in around 1 inevery 10,000 individuals. Multiple epiphyseal dysplasia is usually causedby an autosomal dominant gene abnormality. This means that an adultwith this disorder will have a 5Oo/o chance to pass this poorly functionalgene on to each child. Infrequently an individual with this disorder willbe born to average statured parents. It is not yet known whether this isbecause there are autosomal recessive forms of multiple epiphysealdysplasia or if this arises because of a new chance change (mutation) in .tonly the single egg or single sperm giving rise to the affected individual.Given the complexities of accurate diagnosis of subtypes of this disorder, 'diagnostic evaluation in a bone dysplasia center prior to any counselingregarding recurrence risk is essential.

Thusfar, changes in at least two different genes are known to be capableof causing multiple epiphyseal dysplasia. At least some instances ofmultiple epiphyseal dysplasia arise secondary to mutations in a genewhich codes for Cartilage Oligomeric Matrix Protein (the same gene that isinvolved in a similar but more severe bone dysplasia called Pseudoachon-droplasia). In other families multiple epiphyseal dysplasia arises,becauseof mutation within one type IX collagen gene (Col9A2). Thusfar, there isnot enough information available to know if finding lvhich gene isinvolved is of prognostic benefit.