Syndrome of the month

Journal of Medical Genetics 1988, 25, 200-203

SclerosteosisPETER BEIGHTONFrom the MRC Unit for Inherited Skeletal Disorders, Department of Human Genetics, Medical School,University of Cape Town, Observatory, South Africa.

Sclerosteosis is a severe autosomal recessivedisorder in which progressive bone overgrowth leadsto gigantism, cranial nerve entrapment, and raisedintracranial pressure. About 60 affected personshave been documented, the vast majority in theAfrikaner population of South Africa. In addition,sporadic cases or affected sibs have been reportedfrom the USA, Switzerland, Japan, and Brazil.

Sclerosteosis was first recognised as a distinctentity in 1958 when Truswell' described twounrelated South African girls with "osteopetrosiswith syndactyly; a morphological variant of Albers-Schonberg disease". Subsequently Hansen2 in 1967used the term 'sklerosteose', which in its anglicisedform 'sclerosteosis' has gained general acceptance.The manifestations in 25 affected Afrikaners werereviewed by Beighton et al3 in 1976 and a further 17patients were reported by Beighton andHamersma.4

Clinical features (figs 1 to 3)

Mandibular prognathism and frontal prominencebecome evident by the age of five years. Thesedeformities progress and in adulthood the face isseverly distorted, with dental malocclusion, prop-tosis, and relative mid-facial hypoplasia. Affectedchildren are tall for their age and adults with thecondition may have gigantism. The majority havepartial or total syndactyly, usually of the second andthird fingers, with deviation of the terminal phal-anges and hypoplasia of the nails of the corres-ponding digits. The bones are resistant to traumaand fractures are infrequent.

Transient palsy of the seventh cranial nerveoccurs during infancy and bilateral facial paralysis isusually permanent by adulthood. Progressive bonyencroachment upon the middle ear cavities andauditory nerve canals often causes deafness in mid-

Received for publication 20 October 1987.Acceptcd for publication 5 Novcmber 1987.

childhood. Compression of the optic nerves is aninfrequent late complication.Overgrowth of the calvarium leads to progressive

diminution of the capacity of the cranial cavity withraising of intracranial pressure. Severe headachedue to this mechanism often develops in earlyadulthood and several patients have died suddenlyfrom impaction of the medulla oblongata in theforamen magnum.

Radiographical features (figs 4 to 6)

Sclerosteosis is progressive; cranial sclerosis may beevident in infancy and the changes are usually wellestablished by the age of five years.5 In adulthood

FIG 1 Asymmetrical overgrowth of the mandible andproptosis are evident. This young woman has bilateralfacialpalsy and deafness.

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Sclerosteosis

the calvarium is widened and uniformly sclerotic.The base becomes very dense and the cranial nerveforamina may be obliterated. The sinuses remainpatent and the sella turcica may be expanded. Themandible is dense and massive, with asymmetricaldistortion and dental malocclusion. In the spine, thevertebral end plates and pedicles are sclerotic but

FIG 2 Many affected persons have gigantism. This man,who shows the characteristic facial distortion, is well over2 m in height.

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FIG 4 Lateral skull radiograph showing massive calvarialhyperostosis with sclerosis of the base.

Fl(i 3 A brother anid sister withmandibular expansion and Jacialpalsy. Partial sojt tissue svnda(ctylvofthe second and third digits atndradial deviation of the terminalphalanges of these fingers isevident.I

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P Beighton

the outlines of the bodies are not disturbed. Theclavicles and ribs are widened and dense and thescapulae and pelvis are sclerotic but not expanded.The long bones are massive, with cortical hyper-

ostosis and moderate alteration of their externalcontours. All the tubular bones, including those ofthe extremities, are involved in this process.Irregular cortical thickening is a mild but variablefeature and is apparently age related. Syndactyly,which is most often present in the second and thirdfingers, ranges from complete bony union to

FIG 5 The pelvis is sclerotic butthe bony contours are undisturbed.Thefemoral cortices are dense andexpanded and the modelling ofthese bones is disturbed.

FIG 6 AP radiograph of thehands. The tubular bones areundermodelled and their corticesare sclerotic.

minimal skin webbing. Radial deviation of theterminal phalanges may be radiologically evident.The toes are not syndactylous.

Differential diagnosis

Sclerosteosis must be differentiated from theosteopetroses and other sclerosing bone dysplasias.In this context the severity of the condition and thepresence of syndactyly are the most importantdiagnostic discriminants. In view of the high

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Sclerosteosis

TABLE Distinguishing features ofBuchem disease.

sclerosteosis and van

Sclerosteosis r,an Buchemn disease

Reported cases 60 15Age of clinical

presentation Early childhood PubertyPrognosis Potentially Comparatively

lethal benign

Habitus Gigantism Normal statureFacies Gross Prominent

distortion mandible

Teeth Irregular, with Normalmalocclusion

Torus palatinus Sometimes Absentpresent

Cranial nervepalsy Very common Inconsistent

Intracranialpressure Raised Normal

Syndactyly Frequent AbsentNail hypoplasia Frequent AbsentCranial

hyperostosis Gross ModerateDistortion of

tubular bones ofhands and feet Marked Mild

prevalence of sclerosteosis in the Afrikaner popula-tion of South Africa, the condition should besuspected in any member of this community whopresents with syndactyly or facial palsy.

Sclerosteosis is very similar to the autosomalrecessive form of endosteal hyperostosis(van Buchem disease) and as many of the Afrika-ners of South Africa had their origins in Holland,where van Buchem's patients were studied, it seemspossible that there might be some fundamental linkbetween these disorders.6 They are both inherited as

autosomal recessives and the clinical and radio-graphical manifestations are similar. No absolutediagnosti-c marker has yet been recognised, andchanges such as periosteal excrescences or raisedlevels of serum alkaline phosphatase are unhelpful,as they may occur in both conditions (table).

Management

Prophylactic craniectomy in early adulthood isnecessary in most affected persons. Decompressionof the seventh and eighth cranial nerves gives incon-sistent results. An external hearing aid may bebeneficial. Syndactyly requires cosmetic repair.

Orthodontic measures are indicated for dentalmalalignment.

Genetics

Analysis of pedigree data confirms that sclero-steosis is an autosomal recessive condition. Thegene frequency in the Afrikaner people is estimatedat 0-0035, with 10 000 clinically normal hetero-zygotes in this population. Heterozygote detectionmay be possible on the basis of recognition of minorchanges which are apparent on skull radiographs.7

Prenatal diagnosis has not yet been achieved, butit might be possible to recognise syndactyly in apotentially affected fetus by means of fetoscopictechniques.

I am grateful to Gillian Shapley for typing themanuscript. Material in this review appeared inSclerosing bone dysplasias and in my monographInherited disorders of the skeleton and I am gratefulto the publishers, Springer Verlag and ChurchillLivingstone, for their permission for these to bereproduced. My research into this disorder has beensupported by grants from the Medical ResearchCouncil of South Africa, the Mauerberger Founda-tion, the Harry Crossley Foundation, and theUniversity of Cape Town Staff Research Fund.

References

Truswell AS. Osteopetrosis with syndactyly. A morphologicalvariant of Albers-Schonberg disease. J Bone Joint Surg (Br)1958;40:208-18.

2 Hansen HG. Skierosteose. In: Opitz H, Schmidt F, eds.Handbuch der Kinderheilkunde. Vol 6. Berlin: Springer, 1967:351.

3 Beighton P, Durr L, Hamersma H. The clinical features ofsclerosteosis. A review of the manifestations in 25 affectedindividuals. Ann Intern Med 1976;84:393-7.

4 Beighton P, Hamersma H. Sclerosteosis in South Africa. S AfrMed J 1979;55:783-8.

5 Beighton P, Cremin BJ, Hamersma H. The radiology ofsclerosteosis. Br J Radiol 1976:49:934-40.

6 Beighton P, Barnard A, Hamersma H, van der Wouden A. Thesyndromic status of sclerosteosis and van Buchem disease. ClinGenet 1984;25:175-81.

7 Beighton P, Davidson J, Durr L, Hamersma H. Sclerosteosis:an autosomal recessive disorder. Clin Genet 1977;11:1-7.

Correspondence and requests for reprints toProfessor P Beighton, Department of HumanGenetics, Medical School, University of CapeTown, Observatory 7925, Cape Town, SouthAfrica.

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