original articles medical complications of...

JtMed Genet 1998;35:705-712

Original articles

Medical complications of achondroplasia: amulticentre patient review

A GW Hunter, A Bankier, J G Rogers, D Sillence, C I Scott Jr

Department ofGenetics, Children'sHospital of EasternOntario, Departmentof Pediatrics,University of Ottawa,Ottawa, OntarioKIH 8L1, CanadaA GW Hunter

Department ofGenetics, RoyalChildren's Hospital,Parkville 3052,Melbourne, AustraliaA BankierJ G Rogers

Department ofPaediatrics and ChildHealth, University ofSydney, The NewChildren's Hospital,Parramatta, NSW2124, AustraliaD Sillence

Alfred I duPontHospital for Children,Wilmington, DE, USAC I Scott Jr

Correspondence to:Dr Hunter, Department ofGenetics, Children's Hospitalof Eastern Ontario, 401Smyth Road, Ottawa,Ontario K1H 8L1, Canada.

Received 19 December 1997Revised version accepted forpublication 2 March 1998

AbstractAchondroplasia is the most prevalentchondrodysplasia and numerous authorshave documented the varied social andmedical complications that maycompromise a full and productive life.Complications include cervicomedullarycompression, spinal stenosis, restrictiveand obstructive lung disease, otitis media,and tibial bowing, among others. Theseknown complications have led to recom-mendations for the anticipatory manage-ment ofsuch patients. There are relativelyfew data on the actual rates and timing ofthese problems. This paper reports dataon the rates and age of occurrence of sev-eral of these complications based on areview of recorded chart information of193 patients ascertained from several wellestablished genetic centres with a knowninterest in the chondrodysplasias. Thelength of follow up varied and the rates ofoccurrence at specific age intervals wereused to estimate the cumulative percent-age affected for each complication. Thereport includes information on otitismedia, ventilation tubes, hearing loss,tonsillectomy, speech problems, tibialbowing and osteotomy, ventricular shunt-ing, apnoea, cervicomedullary decom-pression, and neurological signsattributable to spinal stenosis.C7Med Genet 1998;35:705-712)

Keywords: achondroplasia; otitis media; tibial bowing;neurological signs

Achondroplasia has an estimated incidence of1/26 000' and is the most prevalent chondro-dysplasia. Although achondroplasia is generallyconsidered to be associated with normal intelli-gence and, in most cases, normal longevity2 andthus to be compatible with a full and productivelife, many authors have documented the variedmedical and social complications that may con-spire to compromise those prospects. The mostserious is narrowness of the cervical canal orforamen magnum or both, which may causecervicomedullary compression and consequentrisk of death,2 'central apnoea,4 and neurologicalsigns and symptoms including paraparesis.5Other of the more common complications

include respiratory signs as a result of either asmall chest4 6or upper airway obstruction,4 grossmotor delay associated with macrocephaly,hypotonia, and joint laxity, frequent otitis mediawhich may be accompanied by hearing loss anddelayed speech,7 bowing of the legs which mayrequire tibial osteotomies,5 hydrocephalus,9 andgenerally later onset neurological complaintsbecause of spinal stenosis.' '0 Obesity may alsooccur" and has the potential to exacerbate bothmedical problems and the difficulties ofpsycho-social adaptation."2 13

Recognition that there are many potentialcomplications for the patient with achondro-plasia has led to efforts towards a multidiscipli-nary approach'4 and anticipatory management,'5culminating in the position statement of theCommittee on Genetics of the American Acad-emy of Pediatrics (AAP).'6 Despite recognitionof these varied problems, there are relatively fewdata as to their age dependent rates ofoccurrence. This paper reports a chart review ofprospectively recorded data from 193 patientswith achondroplasia, often supplemented byinterview, which attempts to add to informationabout the age and incidence of a number ofthese complications and medical interventions.

MethodsThe conduct of this study and details ofpatientascertainment have been described previously.6The study was approved by the Research Eth-ics Review Committee ofThe Children's Hos-pital of Eastern Ontario. Most of the data pre-sented in this study were abstracted fromrecords in departments of genetics and fromhospital charts, and in about 40% of cases wassupplemented by direct interview (table 1).The greatest number of patients were fromWilmington, DE, and while few of thosepatients were directly interviewed, it was thepractice of that clinic to see the children everysix months to the age of 6 years and yearly

Table 1 Source ofpatients for this study

Total No interviewedSource patients at study

Wilmington, DE 108 7Sydney, NSW 47 36Melbourne, VIC 23 19Manchester, England 12 12Cardiff, Wales/Ottawa, ON 3 3Total 193 77

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Hunter, Bankier, Rogers, et al

Data were coded and entered in StatisticalPackage for the Social Sciences (SPSS/PC+)for data manipulation and descriptive analysis.

41099

85

Figure 1 Disease free rates for otitis media and ventilation tubes over time for patientswith prospective data. Numbers within columns are the actual numbers affected over thenumbers followed in that age category.

Table 2 Patients with retrospectively obtained histories of middle ear disease (OM)

No ofOM reported No of operations for tube placementNo of

Ages (y) cases None Several Chronic 0 1 2 3 >4 ?No

0-5 9 0 5 4 0 4 1 3 0 3>5-10 7 0 2 5 2 1 1 2 1 010-20 22 3 4 15 5 4 3 2 8 0>20 36 1 1 9 13* 24 3 4 1 3 1

*Plus to cases of serous OM.

thereafter. A standard set of medical historyquestions and a physical examination were car-ried out at each visit. While the approach at theother clinics was somewhat less systematic,regular follow up visits were the norm andmany of these patients were interviewed at thetime of this study. Patients seen at special clin-ics, for example at Little People of America Incmeetings, were excluded so as to avoidascertainment bias for medical problems. Thisstudy is partly cross sectional and includespatients from the first year of life to those intheir late 50s, but it also encompasses signifi-cant longitudinal data on individual patientsfollowed prospectively for a number of years.

Results (figs 1 to 10, tables 2 and 3)All patients on whom data were available whohad an affected parent were diagnosed at, or

occasionally before, birth. For the 134 patientswith no parent with achondroplasia, the age at

diagnosis was markedly skewed towards birthwith 79 diagnosed at birth and 94% by 1 year ofage. The mean age at diagnosis was 0.306 years

and the oldest ages at diagnosis were at 7 and 8years in patients who were born in 1965 and1958, respectively. There was a significantcorrelation between the age at diagnosis and theage ofthe patient (r=0.27, p=0.00 1), which sug-

gests that a diagnosis is more likely to be made ator around birth today than it was previously.The mean paternal age at birth of patients

who had no family history (34.85, n=134) was

older, but not statistically so, than patients whohad an affected parent (31.66, n=22)(0.05<p<0. 10).Fig 1 shows the percentage of patients with

achondroplasia who were followed prospec-

tively and remained free from OM and ventila-tion tubes (VT) at various age intervals. Retro-spective data (table 2) on OM are unlikely to beas reliable, especially as one gets further fromchildhood with its maximum rates of infection.However, they confirm the high childhoodattack rate while at the same time 14% ofpatients aged > 10 to 20 years claim not to havesuffered from OM.

Table 3 provides further data for the same

age groups concerning the frequency andchronicity of the middle ear problems in thepatients who were followed prospectively.The columns in figs 2-10 contain the actual

reported rates of the specific complication forthat age cohort. However, for most complica-tions the major interest for the patient, family,and physician is how often and at what age doesit occur. In other words, what is the "cumula-tive attack rate". Presentation of the data inthat way is compromised by the fact that thecomplication may occur at a variable time afterbirth, whereas the number ofpatients on whom

Table 3 Rates of otitis media and ventilation tube placement at different ages for patients with prospectively obtained data

Otitis media

0to <Iy I to <2y 2to <3y 3to <4y 4to <5y 5to <10y >10y

M F Total M F Total M F Total M F Total M F Total M F Total M F Total55 44 99 48 37 85 38 32 70 34 26 60 32 22 54 32 21 53 16 7 23

No of infections1 16 12 28 3 8 11 0 7 7 5 4 9 3 4 7 4 1 5 2 1 3

2 2 3 5 5 3 8 5 6 11 4 3 7 4 4 8 1 3 4 - - -3 1 1 2 3 2 5 1 2 3 2 1 3 - 2 2 4 2 6 - 1 1Several* 4 7 11 9 6 15 8 4 12 - 3 3 - - 1 1 2Chronic* 7 6 13 16 8 24 9 5 14 - 1 1 7 3 10 9 4 13 4 - 4

Serous - 1 1 2 1 3 1 - 1 1 - 1 1 0 1 2 4 6 1 - 1

Ventilation tubes

No of tubes surgery1 11 5 16 17 10 27 14 9 23 8 8 16 4 7 11 9 6 15 2 1 3

2 - - - 1 1 2 2 0 2 3 2 5 - - -3 - - - - - - - - - - - - - - - 1 1 2 - - -

>4 - - - - 1 1 - 1 1.1 1 2 - - -

*Several defined as more than three separately diagnosed infections. Chronic defined as where the otitis appears continual and one infection cannot be distinguishedfrom the next.

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Medical complications of achondroplasia

TonsillectomyHearing loss

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<4y 4<8y 8<12s 12<20v > 20 vFigure 2 Cumulative rates of tonsillectomy and of "conductive hearing loss". Numberswithin columns are the actual numbers affected over the numbers followed in that agecategory.

25 I Speech delayArticLlation problem

L Speech therapy

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Figure 3 Cumulative rate ofpatients reported as having speech delay, articulationproblems, or speech therapy. Numbers within columns are the actual numbers affected overthe numbers followed in that age category.

follow up information is available falls withincreasing age. In order to provide a cumulativeincidence, the rate at which a complicationoccurred in a specific age group was applied aswell to that part of the total previouslyunaffected patient sample not available at thatfollow up interval as if all had been available forstudy. For example, assume that 10 of 100patients followed for a year have a certain com-plication, but only 50 patients in the 1 to 2 year

group are available and that four of them havethe problem. The rate of 4/50 is then applied tothe 40 "unavailable unaffected from year 1"patients giving 7.2/100 in year 2, and a cumu-lative risk of 17.2/100. Factors which may

compromise the validity of this approach willinclude any temporal change in the occurrenceof the complication and any bias in either theascertainment, or lack of ascertainment,among those who continue to be followed ver-sus those who are lost to follow up. Also, thenumber of adults available for follow up is lim-

ited allowing a large margin of error in the esti-mates, especially for adult onset conditions.These factors need to be taken into accountseparately for each complication when consid-ering the estimated rates.

Fig 2 suggests that almost 40% of patientswill undergo tonsillectomy, the majority beforethe age of 8 years, but some in their teens oreven adulthood. Conductive hearing loss ap-pears to affect about 38% with about half ofthose detected before the age of 8 years.

Fig 3 provides data on the incidence ofspeech problems. Virtually all speech delay andarticulation difficulties are recognised betweenthe ages of 2 and 5 years and reach a rate of 19and 11% respectively, with about 10% of sub-jects receiving speech therapy.

Fig 4 shows the rates at which patients weretreated by orthodontics or were recorded ashaving a degree of malocclusion for whichorthodontics were planned. The total of thetwo is also shown.

Fig 5 presents data on the frequency ofintracranial shunts and whether they were car-ried out because of increasing head circumfer-ence or because ofneurological signs attributedto hydrocephalus. About 1 1% of patientsreceived shunts and these tended to beperformed early in childhood.

Fig 6 shows that about 8% of children arereported as having apnoea by 1.5 years and thatthe rate continues to rise to about 16% by theteenage years. Foramen magnum and uppercervical surgery, which is often related toapnoea as a sign, is uncommon below 6 monthsand then continues to occur into adulthoodwith a cumulative rate of about 16%.Neurological signs attributed to the cervicalarea are shown in fig 7.

Tibial bowing (fig 7) is generally notrecorded until after the child begins to walkand while the incidence appears to continue torise into adulthood it seems likely that this rep-resents a degree of under-recording at youngerages and thus late recognition. Fig 8 shows thatpatients with significant tibial bowing are sub-ject to tibial osteotomy beginning in mid child-hood and that the cumulative rate rises toabout 17% with the occasional procedurebeing carried out in adulthood.The rates of leg and back pain and

neurological symptoms ofthe arms and legs aresummarised in figs 8 and 9. The latter wastaken to include parasthesias, claudication,numbness, and limitation in walking.

Fig 10 presents the rate of spinal surgery andof patients diagnosed as having symptomaticspinal stenosis but who had not had surgery.The rate of formal recognition of spinal steno-sis clearly lags behind the onset of symptomsattributable to spinal stenosis. Six patientsreported loss of bladder function, and delay intreatment of symptomatic spinal stenosis mayhave consequences in terms of reversibility ofsymptoms.

DiscussionOTITIS MEDIA, SPEECH, AND HEARINGOtitis media has been long recognised as acomplication in achondroplasia,'7 but there are

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Figure 4 Cumulative rate ofpatients reported as having orthodontics, malocclusionneeding orthodontics, and the total of the two. Numbers within columns are the actualnumbers affected over the numbers followed in that age category.

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Figure 5 Cumulative rate ofpatients reported as having shunts for either increasing hecsize orfor neurological signs and the total of the two. Numbers within columns are theactual numbers affected over the numbers followed in that age category.

few published data on the incidence of tiproblem. Hall'5 apparently found that 75%150 patients in an unpublished seriespatients with achondroplasia had suffered 0and that the rate fell to 1 1% over the age ofyears. Berkowitz et at' used the indirtmeasure of the insertion of ventilation tut(VTs) to assess the impact of OM and foizthat 33 of 61 (54%) patients, 48 ofwhom weless than 5 years old, had had tubes insertePart ofthat series was from the Alfred I duPcHospital for Children and thus some of thcpatients may be included in this report.For purposes of this review, a record of oti

media in the interval since the last follow up viwas accepted as an event, although this clearelies on the abilities of the primary caphysician and does not allow any distincti,between serous OM and an acute infecticprocess. Sixty percent ofpatients had been dianosed as having OM within their first year a

only 10% remained disease free by the age of 2years. The respective figures for VT were 16%/aand 58%. The data suggest that about 7% olpatients have not suffered OM by the age of 3years and that about 5% of achondroplasticpatients may not experience OM. However, theplacement of VTs continues throughout child-hood so that only 22% of those patients over 10years had not had VTs. Of the 60% who wereinfected within the first year of life, more thanhalfhad more than one infection and 24/99 hadeither several infections or were considered tohave chronic OM. Multiple infections andchronic OM had their maximal impact duringthe first three years, although chronic diseasecontinues to be a factor for a significant minor-ity of patients, even beyond the age of 10. Thereappear to be more males than females withchronic OM. Table 3 also shows that 30/85(35%) of 1-2 year olds and 26/70 (37%) of 2-3year olds received at least one set of ventilationtubes and, while the rate per year fell with age,47% of 5-10 year olds received at least one set oftubes. There is no reason to expect that thepatients in this series would be selected by theoccurrence of middle ear disease and, while it ispossible that the known propensity for OM inachondroplasia may have led to some overdiag-nosis, the data suggest that the incidence ofOMand placements ofVTs is even higher that previ-ously thought. This high rate of OM has beenconsidered secondary to the orientation and sizeof the eustachian tube'9 as well as impaired nasalairflow and temporal bone abnormalities,7 al-though Pinelli et a!2 considered the latter rare inachondroplasia. Stura et at' provided evidencefor cochlear anomalies as the cause for the mildsensorineural impairment they observed in threecases.The cause of hearing loss in patients with

achondroplasia is most often conductive but therate of sensorineural impairment may also beincreased."8 20 21 MacDonald et af' discussed 12patients with conductive hearing loss and attrib-uted seven to acute changes while five were con-

zd sidered to result from ossicular chain stiffness,either congenital or acquired owing to pastchronic middle ear disease. Malformations ofthe ossicular chain have been reported from sin-

of gle patients in two previous series.7 22 While0 these previous studies have the advantage ofof more complete audiological evaluations, they1M are limited by relatively small numbers (18-2818 patients), a paucity of paediatric data,'8 orect selected referral to an ENT department.22 The)es cumulative figures for conductive hearing loss innd the present study show that by adulthood aboutore 38% ofpatients will have had this diagnosis. Not.d- included are an additional two patients recordednt as having sensorineural impairment. Audio-se grams were not available and it is very possible

that a greater proportion of the hearing loss wasitis sensorineural. While only 4% are diagnosedisit before the age of 4 years, the time ofmost activerly OM, the jump to 17% by the age of 8 is to berxe expected because of investigation of speech dif-on ficulties (see below) and detection of schoolus associated problems. The data do not allow anyig- assessment of the permanency of the loss (muchnd is likely to be temporary) or the underlying

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Em Apnoea!m~ Cervicomedullary

decompression

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Figure 6 Cumulative rates of clinical apnoea and of cervicomedullary decompressionsurgery. Numbers within columns are the actual numbers affected over the numbers folloin that age category.

L~ Tibial bowingil]Cervical neurological signs

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Figure 7 Cumulative rates of tibial bowing and neck neurological signs. Numbers withcolumns are the actual numbers affected over the numbers followed in that age category.

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Figure 8 Cumulative rate ofpatients complaining of leg pain and of those having tibicosteotomy. Numbers within columns are the actual numbers affected over the numbersfollowed in that age category.

aetiology. The continued placement ofVTs andoftonsillectomy into late childhood suggests thatin many cases it was considered associated withmiddle ear disease. Even transient hearingimpairment may have an important impact onthe acquisition of language and learning.

SPEECH AND LANGUAGEDelay in the acquisition ofspeech is a recognisedcomplication in achondroplasia. The AmericanAcademy of Pediatrics (AAP) guidelines'6 rec-ommend speech evaluation by 2 years of age andit is part of their anticipatory care. Emphasis isplaced upon ruling out conductive hearing lossas a cause. Hall'5 includes tongue thrust, result-ing from the abnormal maxillomandibular rela-tionship, as a component of this delay, and pre-sumably also for articulation problems. Theredo not appear to be published data on the over-all significance of these problems. From this

y review it appears that about 20% of childrenwith achondroplasia are delayed in acquiring

wved speech and that, as expected, the vast majorityare noted between the ages of 2 and 5 years.Recognition of articulation problems whichwere reported in 1 1% of patients, some ofwhomalso experienced speech delay, followed thesame age pattern. It would appear that less thanhalf of the children who experience these prob-lems are receiving formal therapy. The data donot allow the cause of the speech delay orarticulation problems to be identified. Whileseveral children were ultimately considered asslow learners (9) or mentally retarded (4), thosechildren were a minority of those with delayedlanguage acquisition. While the nature of thesedata do not allow for statistical evaluation of thepossible association of speech delay and articu-lation problems with hearing loss or dentalmalocclusion, examination of our data did notshow any evidence that hearing loss or malocclu-sion was more common in the children withspeech problems than in those without such dif-ficulties. While craniofacial anomalies andtongue thrust might be considered more impor-tant in the articulation than in the acquisition ofspeech, we have posited that disproportion ofthe tongue may be resposible for the delay inspeech seen in some children with Beckwith-Wiedemann syndrome.23 It is to be hoped thatspeech therapy will become more readily avail-able in the current era.

DENTALThe dental concern in achondroplasia is for aclass III malocclusion because of the dispropor-tionate growth of the cranial base which leads tosevere maxillary retrusion and a decreased max-illary vertical height.24 Furthermore, the teethmay be crowded and a narrow upper jaw maylead to a crossbite (D E Engst, personalcommunication). It is recommended that allchildren with achondroplasia be evaluated forpossible orthodontic needs by the age of 5 or 6years'6 (D E Engst, personal communication).Only 3% of the children in this review wererecorded as having a significant orthodontic

zl need before the age of 10 years and in manycases treatment did not occur until the late teensor early adulthood. Ultimately, over 50% of

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Figure 9 Cumulative rate ofpatients reported as having back pain, neurological signs in the legs, and neurological signs inthe arms. Numbers within columns are the actual numbers affected while those in brackets above the columns are thenumbers followed in that age category.

patients were noted to have an orthproblem and 40% received treatment.problems are significantly under-repomedical charts and these figures may rean underestimate of the problem.

VENTRICULAR SHUNTINGHurko et af5 have pointed out thatenthusiasm for ventricular shuntiachondroplasia has, to a large exten'replaced by the view that hydrocephalinot occur to a degree that requires shurmost cases of achondroplasia. While aqtal stenosis has been reporteachondroplasia,26 it is unusual and (

distinguished from the common veni

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Figurel10 Cumulative rates of symptomatic spinal stenosis and of spinal surgery.Numbers within columns are the actual numbers affected over the numbers followedage category.

iodontic megaly seen in achondroplasia by the lack ofDental prominent sulci and frontal subarachnoidrted in space characteristic of achondroplasia. Whenpresent hydrocephalus does occur, it is almost always

communicating and may relate to venous out-flow at the cranial foramen or at the cervicotho-racic junction.9 The diagnosis ofhydrocephalus

earlier in achondroplasia is not trivial given the back-ing in ground macrocrania and ventriculomegaly, butt, been there appears to be a consensus5 25 that carefulus does monitoring of head circumference and devel-ating in opment, including gait, against the publishedueduc- norms for achondroplasia will distinguish~d in patients with symptomatic hydrocephalus.can be Hurko et arP5 go further and suggest thattriculo- surgery should be reserved for those patients

whose increased intracranial pressure has beenshown by either extra- or intracranial monitor-ing. It is not known whether any of the patientsin this series had such monitoring. The statedcriteria for surgery were evenly split betweenthe head circumference crossing centiles andneurological signs attributed to hydrocephalus(fig 5). About 1 % of patients underwentshunting with the rate per year remaining quitesimilar throughout childhood. Only one teen-ager and no adult was shunted. It was not pos-sible to determine from the data whether thepatients benefited from the shunting or whetherthere were children who were overlooked whenshunting would have been appropriate.

CERVICOMEDULLARY COMPRESSIONNarrowness and related anatomical variationof the foramen magnum and upper cervicalspine in achondroplasia have potential to

in that cause significant complications.4 5 25 27 It hasbeen shown that the average adult with

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achondroplasia has a foramen magnum that isequivalent to that of a newborn in transverseand that of a 2 year old in sagittal diameter.5This reduced area is further compromised byanterior placement of the foramen whichresults in superior displacement of the brain-stem, causing the upper cervical cord totraverse the foramen, and concurrent hyperex-tension of the brainstem, even at a neutral headposition.25 Cervicomedullary compression isconsidered to account for a significant pro-portion of the early excess mortality,2 28apnoea,42' and progressive paraparesis5 21 inachondroplasia. Hurko et al25 raised the pro-vocative notion that it might play a role in thevirtual universal early hypotonia and motordelay seen in affected infants.There are not universally agreed upon criteria

for operative intervention in the face of assumedsymptomatology resulting from cervicomedul-lary compression. Rates of intervention as highas 34 and 42% have been reported from patientseries largely selected because ofsymptomatology.429 Pauli et a!'8 performedsurgery on five of 53 prospective cases andargued that measurements of the foramen mag-num, central hypopnoea, and hyperreflexia/clonus were the best predictors of the need forsurgery. Rimoin'0 countered that the argumentswere tautological and reported that 9/200 casesin his group had had surgery (including somewhose surgery was performed before referral)and with a series mortality of only 1/200. Hepredicted, based on unpublished experience,that lack of anterior and posterior CSF flow andthe presence of intracord lesions would prove tobe the best predictors of the need for surgery. Infact the surgical exposure rates between the twogroups were not statistically different. Short of alarge randomised multicentre trial it is difficultto see how intervention will be optimised. Thepatients in this study have been ascertainedthrough departments of genetics and are thusunlikely to be significantly selected for symp-tomatology. The rate of surgical intervention bythe age of 4 years (6.8%, fig 6) is intermediatebetween that of Rimoin,'0 who did not provideage data, and that of Pauli et al,28 whose patientswere of comparable age. However, it is impor-tant to emphasise that the apparent need forintervention, primarily because of progressiveneurological symptoms, may continue intoadulthood" and that ultimately about 17% ofpatients may undergo this surgery (fig 6).The rates of apnoea, neurological impairment

of the arms, or neurological signs attributed tothe cervical region are summarised in figs 6, 9,and 7, respectively. For two of the 21 patientswho underwent cervicomedullary decompres-sion, the indication was not recorded. Of theremainder, nine were recorded as having cervicalsigns, four apnoea, one with both, three withneurological impairment of the arms and legs,and two with impairment limited to the legs.The latter two groups tended to be older.

TIBIAL BOWINGTibial bowing is considered to be a hallmark ofachondroplasia and is one ofthree anomalies ofthe structure of the knee, which also include

tibial genu recurvatum and lateral torsion.'2 Itis believed to be secondary to the relative over-growth of the fibula as compared to the tibia,and it is considered clinically significant whenwhen the ankle +/- knee fall outside aplumbline dropped from the hip. Milder casesare common and the rate will to some extentdepend upon the definition used. For thisseries, a distance 5 cm between the knees,with the legs straight and the ankles apposed,was used and the rate in fig 7 shows theexpected jump at the time of onset of walking,but with continued significant numbers ofcases diagnosed into adulthood. There appearto be few published comparative data. Kopits8reported that 50% of patients had bowing butthat in only half was a joint outside the hipplumbline. No ages were given. Later he statedthat parents note a varus deformity in 40% ofthe children as they begin to stand and that93% of adults are affected.32 The adultsreported as unaffected were seen at the time ofthis survey and clearly a significant proportiondid not have tibial bowing as defined. The agegroupings shown are the ages at first recordingof the bowing and should not be construed torepresent the age of onset. Kopits8 found thatonly 10% ofhis patients offered surgery (2.5%)of the total group accepted. From this review itis estimated that about 22% of patients hadosteotomies, with most being carried out inchildhood but a significant number being per-formed on teenagers and young adults (fig 8).

SPINAL STENOSISThe average area of Li is said to be reduced by39% and of L5 by 27% in achondroplasia,"and yet the average age of onset ofsymptoms issaid to be 38 years.34 A number of factors asso-ciated with normal or specific achondroplasticageing are thus considered to play a role in theonset of symptoms. These include disc protru-sion, spondyloarthritic spurs, a kyphoticwedge, excess lumbar lordosis (perhaps excac-erbated by excess weight), a bulging annulusfibrosis, and vertebral malalignment/instability.5 1035 Leg (fig 8) and lower back(fig 9) pain (including the buttock) may beearly presenting signs of spinal stenosis. Theleg pain in early childhood is more likely a con-sequence of local changes at the knee, second-ary to fibular overgrowth.3'2 Kopits3" claims that70% of children with achondroplasia aged 4 to10 years have leg pain. This is far higher thanthe rate recorded here and may represent someselective bias to a surgical practice. By the ageof 12 years, only 20% of children wererecorded as having leg pain but this had risen toalmost 50% by adulthood with most of theincrease probably the result of symptomaticspinal stenosis. Less than 10% of 10 year oldshad neurological signs related to their legs butthis rises to 20% by the end of the teens and to80% by the 50s. Back pain showed a fairly par-allel rate of onset (fig 9). The numbers in theadult intervals are small and there could besome selection bias in seeking follow up.Comparison with published series is highly

age dependent. Hall'5 quotes a 1974 LPA surveywhere 20-30% ofpatients reported symptoms of

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stenosis and 10% were considered to requiresurgery. Bethem et al° reported that 7/30 of theirpatients with achondroplasia had claudication orflaccid paralysis because of spinal stenosis.Nelson36 reported three series of patients. In ahistoric group, 38/51 patients below the age of15 were asymptomatic, two had back pain, and11 a significant kyphosis. Three of sevenbetween 15 and 29 years had neurological signsand one had back pain. All 12 patients over theage of 30 had neurological signs. The secondsurvey comprised questionnaire replies aboutback pain from 67 members of the Associationfor Research into Restricted Growth (ARRG).Nineteen of 27 males aged 12 to 65 years, and31 of 40 females aged 12 to 75 years had backpain. In a personal series of 37 patients (fourwith hypochondroplasia), seven had back painalone and 10 had symptomatic spinal stenosis.

ConclusionThis study showed an encouraging trend toearlier diagnosis of achondroplasia and pro-vided data on the rates of some of the morecommon health concerns. Middle ear disease,with its attendant risk of hearing loss, was evenmore frequent than previously reported, andwhile a significant minority of patients experi-enced delay in the acquisition of speech orarticulation difficulties or both, only a minorityof those received speech therapy. The identifi-cation and treatment of orthodontic problemswas significantly delayed and the need prob-ably under-recognised. The rate of early cervi-comedullary decompression was comparableto reported series, but it appears that an equiv-alent proportion of patients require such inter-vention beyond childhood.The patients reported in this series were cared

for at a time before the promulgation of guide-lines for care, such as those of the AmericanAcademy of Pediatrics,"6 and before the trend tomutidisciplinary clinics. However, most suchefforts have a paediatric focus. Our data haveshown that a significant number of patients haveneurological complaints by their teens and thatthis becomes the majority in adulthood. Duringthese years, care is often fragmented with littleemphasis on prevention and early intervention.During the study many adults were interviewedwho had major physical limitations and painwhich seriously affected their quality of life. It isa clear challenge for the future to improve thecare provided to these people.

The people who helped with this study, both professional andthe patients and their families, are more thoroughly acknowl-edged in Hunter.6 We again wish to thank them all, for withouttheir selfless help this study would not have been possible. Thesupport of the Children's Hospital of Eastern Ontario for DrHunter's sabbatical leave is again acknowledged.

1 Oberklaid F, Danks DM, Jensen F, Stace L, Rosshandler S.Achondroplasia and hypochondroplasia. Comments onfrequency, mutation rate, and radiological features in skulland spine. J Med Genet 1979;16:140-6.

2 Hecht JT, Francomano CA, Horton WA, Annegers JF. Mor-tality in achondroplasia. Am 7Hum Genet 1987;41:454-64.

3 Pauli RM, Scott CI, Wassman ER Jr, et al. Apnea and sud-den unexplained death in infants with achondroplasia. JPediatr 1984;104:342-8.

4 Reid CS, Pyeritz RE, Kopits SE, et al. Cervicomedullarycompression in young patients with achondroplasia: valueof comprehensive neurologic and respiratory evaluation. JPediatr 1987;110:522-30.

5 Hecht JC, Butler IJ. Neurologic morbidity associated withachondroplasia. J Child Neurol 1990;5:84-97.

6 Hunter AGW. Craniofacial anthropometrics in several typesof chondrodysplasia. Am J Med Genet 1996;65:5-12.

7 Berkowitz RG, Grundfast KM, Scott C, Saal H, SternHrosenbaum K. Middle ear disease in childhoodachondroplasia. Ear Nose Throat J 1991 ;70:305-8.

8 Kopits SE. Orthopedic complications of dwarfism. ClinOrthop Rel Res 1976;114:153-79.

9 Steinbok P, Hall J, Flodmark 0. Hydrocephalus inachondroplasia: the possible role of intracranial venoushypertension. J Neurosurgery 1989;71 :42-8.

10 Bethem D, Winter RB, Lutter L, et al. Spinal disorders ofdwarfism. J Bone J7oint Surg (Am) 1981 ;63: 1412-25.

11 Hecht JT, Hood OJ, Schwartz RJ, Hennessey JC, BernhardtBA, Horton WA. Obesity in achondroplasia. Am J MedGenet 1988;31:597-602.

12 Scott CI Jr. Medical and social adaptation in dwarfing con-ditions. Birth Defects 1977;XIII(3C):29-43.

13 Stace L, Danks DM. A social study of dwarfing conditions.II. The experience of children with bone dysplasias and oftheir parents. Aust Paediatr J 1981;17: 172-6.

14 Nicoletti B, Kopits SE, Ascani E, McKusick VA, eds.Human achondroplasia. A multidisciplinary approach. NewYork: Plenum Press, 1988;48:3-9.

15 Hall J. The natural history of achondroplasia. In: NicolettiB, Kopits SE, Ascani E, McKusick VA, eds. Humanachondroplasia. A multidisciplinary approach. New York: Ple-num Press, 1988;48:3-9.

16 American Academy of Pediatrics. Committee on Genetics.Health supervision for children with achondroplasia. Pedi-atrics 1995;95:443-51.

17 Cohen MM. Dysmorphic syndromes with craniofacialmanifestations. In: Stewart RE, Prescott G, eds. Oralfacialgenetics. St Louis: Mosby 1976:523-5.

18 Glass L, Shapiro I, Hodge SE, Bergstrom L, Rimoin DL.Audiological findings of patients with achondroplasia. IntrJPediatr Otorhinolarygol 1981;3: 129-35.

19 Crawford DB, Ensor RE, Dorst JP. The chondrocranium inachondroplasia. In: Bosma JF, ed. Development of the basi-cranium. Bethesda: US Department of Health Educationand Welfare Publication No NIH 76-989, 1976:301-8.

20 Pinelli V, Masi R, Partipilo P, Pierro V, Tieri L. Otologicimpairments in achondroplasia: a nosologic assessment. In:Nicoletti B, Kopits SE, Ascani E, McKusick VA, eds.Human achondroplasia. A multidisciplinary approach. NewYork: Plenum Press, 1988:149-52.

21 Stura M, Boero S, Origo C, Tarantino V. Evaluation of hear-ing in achondroplastic patients. In: Nicoletti B, Kopits SE,Ascani E, McKusick VA, eds. Human achondroplasia. Amultidisciplinary approach. New York: Plenum Press 1988:183-4.

22 MacDonald JM, Seipp WS, Gordon EM, Heroy J.Audiologic findings in achondroplasia. In: Nicoletti B,Kopits SE, Ascani E, McKusick VA, eds. Human achondro-plasia. A multidisciplinary approach. New York: PlenumPress, 1988:143-7.

23 Hunter AGW, Allanson JE. Follow-up study of patients withWiedemann-Beckwith syndrome with emphasis on thechange in facial appearance over time. Am J Med Genet1994;51: 102-7.

24 Dunbar JP, Goldin B, Subtelny JD. Correction of class Icrowding in an achondroplastic patient. Am J Orthod Den-tofac Orthop 1980;96:255-63.

25 Hurko 0, Pyeritz R, Uematsu S. Neurological considera-tions in achondroplasia. In: Nicoletti B, Kopits SE, AscaniE, McKusick VA, eds Human achondroplasia.A multidiscipli-nary approach. New York: Plenum Press, 1988:153-62.

26 Cohen ME, Rosenthal AD, Matson DD. Neurologicalabnormalities in achondroplastic children. J Pediatr 1967;71:367-76.

27 Aryanpur J, Hurko 0, Francomano C, Wang H, Carson B.Craniocervical decompression for cervicomedullary com-pression in pediatric patients with achondroplasia. J7 Neuro-surg 1990;73:375-82.

28 Pauli RM, Horton VK, Glinski LP, Reiser CA. Prospectiveassessment of risks for cervicomedullary junction compres-sion in infants with achondroplasia. AmJ Hum Genet 1995;56:732-44.

29 Francomano CA, Carson B, Seidler A, et al. Morbidity andmortality in achondroplasia: efficacy of prospective evalua-tion and surgical intervention. Am J Hum Genet Suppl1993;53:A1 12.

30 Rimoin DL. Cervicomedullary junction compression ininfants with achondroplasia: when to perform neurosurgi-cal decompression. Am J Hum Genet 1995;56:824-6.

31 Morgan DF, Young RF. Spinal neurological complicationsof achondroplasia: results of surgical treatment. Neurosur-gery 1980;52:111-13.

32 Kopits SE. Orthopedic aspects of achondroplasia inchildren. In: Nicoletti B, Kopits SE, Ascani E, McKusickVA, eds. Human achondroplasia. A multidisciplinary ap-proach. New York: Plenum Press 1988:189-97.

33 Lutter LD, Longstein JE, Winter RB, Langer LO. Anatomyofthe achondroplastic lumbar canal. Clin Orthop 1977;126:139-42.

34 Lutter LD, Langer LO. Neurological symptoms in achon-droplastic dwarfs-surgical treatment. Jf Bone Joint Surg(Am) 1977;59:340-4.

35 Fortuna A, Ferrante L, Acqui M, Santoro A, Mastronardi L.Narrowing of thoraco-lumbar canal in achondroplasia. JNeurol Sci 1989;33:185-96.

36 Nelson MA. Kyphosis and lumber stenosis in achondro-plasia. In: Nicoletti B, Kopits SE, Ascani E, McKusick VA,eds. Human achondroplasia. A multidisciplinary approach.New York: Plenum Press, 1988:305-11.

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