1976, British Journal of Radiology, 49, 934-939

The radiology of sclerosteosisBy P. Beighton, M.D., Ph.D., F.R.C.P.Department of Human Genetics, Medical School, University of Cape Town, South AfricaB. J. Cremin, F.R.A.C.R., F.R.C.R.Department of Radiology, Groote Schuur Hospital, Cape Town, South Africaand H. Hamersma, M.B., Ch.B., M.D.University of Pretoria, South Africa(Received March 1976)

ABSTRACTSclerosteosis is an unusual disorder in which increased

skeletal density is associated with abnormalities of bonymodelling. The condition is progressive and complicationsarise due to cranial nerve involvement. Death from raisedintracranial pressure occurs in early adulthood.

In order to define the range and extent of the bonyabnormalities, the radiographic features of 18 affectedindividuals have been analysed. The recognition of character-istic changes permits diagnostic precision.

Increased skeletal density and abnormalities of bonymodelling are features of a number of uncommongenetic disorders. These conditions have often beengrouped together as "osteopetrosis", "Albers-Schonberg disease", or "marble bones". However,in recent years a number of entities with consistentand characteristic clinical and radiographic stigmatahave been separated from this general category.

Sclerosteosis is a disorder of this type which hasattained the status of a distinct entity. In order todefine the radiographic features of this condition,which is virtually confined to the Afrikaner popul-ation of Southern Africa (Beighton et al., 1976) wehave studied 18 affected individuals. The radio-graphic findings are presented and discussed in thispaper.

CLASSIFICATION

Understanding of the "osteopetrosis" group ofdisorders has been greatly facilitated by the classi-fication proposed by Gorlin et al. (1969), followingtheir critical review of the literature concerningthese conditions.

1. OsteosclerosisIn these conditions increased radiological density

of bone is the predominant feature. Abnormalities ofbony modelling, if present, are of minor degree. Theautosomal dominant and autosomal recessive formsof true osteopetrosis, together with pycnodysostosis,are the most important disorders in this group.

2. Craniotubular dysplasiasAbnormal modelling of the skeleton is the major

feature of this group of disorders, while increased

of lesser degree,may lead to nerve

radiological bony density i;Involvement of the craniumcompression and complications include facial palsyand deafness. Pyle's disease, the autosomal dominantand recessive types of craniometaphyseal dysplasia,and rarities such as craniodiaphyseal dysplasia andfrontometaphyseal dysplasia fall into this category.

3. Craniotubular hyperostosesOvergrowth of the cranium and tubular bones

predominate, while increased radiological density isless marked. Sclerosteosis, the subject of thispresentation, features in this group together withvan Buchem's disease, osteoectasia and Engel-mann's disease.

4. MiscellaneousDisorders which do not fall into any of the three

previous categories, but which have sometimes beenconsidered as forms of osteopetrosis include melor-rheostosis, osteopoikilosis and osteopathia striatum.

PATIENTS STUDIED

During the course of a nation-wide survey ofskeletal dysplasias in South Africa, 21 patients withsclerosteosis were examined. These individuals, whowere members of 15 separate kindreds, were all ofAfrikaner stock. The pattern of transmission of thecondition in these families was consistent withautosomal recessive inheritance.

Radiographic studies were undertaken in 18 ofthese patients, nine males and nine females, theirages ranging from nine months to 56 years. Thedescription of their radiographic features forms thesubject of this paper.

CLINICAL FEATURES

Individuals with sclerosteosis are unusually tall,adult males generally exceeding 198 cms. in height,while females may attain 183 cms.

Overgrowth of the cranium leads to distortion ofthe facies, the brow and lower jaw becoming massive.Facial palsies consequent upon cranial nervecompression contribute to the abnormal appearance

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and the affected individual's problems are compound-ed by the development of deafness and involvementof the optic nerve (Fig. 1). Death in early adulthoodis the usual consequence of progressive rise in intra-cranial pressure (Beighton et al., 1976).

Syndactyly of the 2nd and 3rd fingers is a promi-nent feature. This abnormality is variable in degree,ranging from cutaneous webbing to complete bonyfusion (Fig. 2). The digits are mis-shapen, withradial deviation of the terminal phalanges, and thenails may be dysplastic.

RADIOLOGICAL FEATURES

The outstanding radiographic changes in thef

affected individuals were massive increase in the size:

and density of certain components of the skeleton,the skull and tubular bones being predominantlyinvolved.

FIG. 1.The characteristic facies in sclerosteosis—a 45-year old malewith mandibular hyperplasia, facial palsy and proptosis.

The manifestations were age-related. The skullradiographs of three unequivocally affected childrenaged nine months, three and a half and five yearswere ostensibly normal, and their hand radiographsrevealed no bony changes other than syndactyly.However, definite thickening of the skull anddistortion of the phalanges were present in a seven-year-old girl. All the children examined had anormal epiphyseal age development.

In older individuals the bony density and abnormalmodelling became increasingly evident throughoutchildhood and early adult life before apparentlybecoming static by the end of the third decade.

SkullThe major feature was a dense thickening of the

calvarium with complete obliteration of the diploicspace (Fig. 3). The increase in bone density andwidth commenced from the inner table of the cranialvault and progressed so that the internal diameter ofthe cranium was reduced by adulthood. The frontalsinuses were enlarged, the vascular markings wereprominent and the occipital venous sinuses wereoften well outlined. The bones of the base of the skullwere particularly dense and narrowing of the exitforamina was confirmed by tomography in threepatients. The sella turcica was enlarged and roundedin six of the 12 adults.

FIG. 2.Sclerosteosis in a 33-year-old female. Soft tissue syndactylyof the 2nd and 3rd fingers has been surgically corrected.

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FIG. 3.Skull radiograph, lateral. Increased density and width of thecalvarium is a major feature. The mandible is massively

enlarged.

The body of the mandible was massively enlargedin the adults, with resultant prognathism. The jawswere usually edentulous or deficient in teeth and thedensity of the bone was such that it was not possibleto recognise the lamina dura.

ThoraxThe clavicles were generally enlarged, the

thickening and widening being most markedmedially. The ribs were widened with increaseddensity so that the inner texture of the bones was notreadily visible (Fig. 4).

VertebraeChanges in the vertebrae were confined to their

posterior aspects, notably the pedicles and laminaeof the lumbar and sacral vertebrae (Fig. 5). Thevertebral bodies showed no increase in density. Theonly degenerative changes noted in the inter-vertebral disc spaces were present in a 35-year-oldmale.

FIG. 4.Chest radiograph. The clavicles and ribs are widened and

dense.

PelvisIncrease in density predominantly involved the

lower portions of the iliac bones and the ischialand pubic rami. Bony outlines were generally normalalthough relative hypoplasia of the iliac wings was aconsistent feature (Fig. 6.).

Tubular BonesThese bones were massive, with marked cortical

thickening and some degree of disturbance ofmodelling (Fig. 7). The thickening of the cortexgenerally extended along the whole length of theshafts. However, in the femora the cortical thicken-ing was confined to the upper two thirds, while thelower third had an abnormal configuration, the meta-physeal region being widened, with lack of normaldiaphyseal constriction (Fig. 8).

The hand changes were an outstanding feature ofthe condition (Figs. 9 and 10). Every patient hadsome degree of syndactyly and the tubular bones ofthe hands were enlarged, dense and distorted withradial deviation of the terminal phalanges. In theonly patient in whom the feet were X-rayed, themetatarsals and phalanges showed similar features.

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FIG. 5.Lumbar spine—lateral radiograph. The vertebral bodies arerelatively normal, increased bony density being of significant

degree only in the pedicles.

FIG. 6.Pelvis—antero-posterior radiograph. Density is increasedparticularly in the lower portions of the iliac bones and in the Knees—antero-posterior radiograph. Modelling defects areischial and pubic rami. The iliac wings are relatively hypo-

plastic.

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FIG. 7.Humerus—antero-posterior radiograph. The cortex is thickened

and bony modelling is disturbed.

particularly evident in the lower ends of the femora, wherethe metaphyseal region is widened.

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FIG. 9.Hands—antero-posterior radiograph. Changes in the bones ofthe hands are a prominent feature of sclerosteosis. Theshafts of the metacarpals and phalanges are distorted, with

increased cortical thickening.

FIG. 10.Hand—anterior-posterior radiograph. Syndactyly of the 2ndand 3rd fingers is variable in degree. This patient hasmarked soft tissue union and phalangeal malformation.

DISCUSSION

Although sclerosteosis is a rarity, there is nodoubt that it is a separate and distinct entity. In thepast, a few case reports appeared under the loosedesignation "osteopetrosis". Truswell (1958) firstrecognized that the condition was a unique disorder,to which Hansen (1967) later applied the designation"sclerosteose". Although by no means a truedescription of this condition, the appellation of"sclerosteosis" has now gained popular acceptance.

Other than the Afrikaner patients, the only othercase reports have concerned a kindred in New York(Kelley and Lawlah, 1946) and a girl in Japan(Sigiura, 1975).

Sclerosteosis is a potentially lethal disorder, andearly death is preceded by distressing complications.For this reason, diagnostic precision is of paramountimportance, as this will permit accurate prognos-tication and rational genetic counselling. At thepresent time therapy is limited to surgical de-compression of entrapped cranial nerves, craniotomyto relieve raised intracranial pressure, cosmeticsurgery to the face and hands,-and the provision of ahearing aid.

The radiological features of sclerosteosis bearsome resemblance to those of virtually all thedisorders mentioned in the classification section.However, the syndactyly and severe distortion of thephalanges serves to distinguish sclerosteosis fromthese conditions. Furthermore, sclerosteosis is theonly disorder in this group in which excessive heightoccurs. The facial changes and tall stature givessclerosteosis a superficial resemblance to acromegaly.Nevertheless, even in patients with enlargement ofthe sella, radiographic distinction is an easy matter,as cranial hyperostosis and modelling defects of thelong bones are not features of acromegaly. In thiscontext, it may be relevant that extensive investi-gations in two of our patients with sclerosteosis haverevealed no endocrine abnormality.

In our experience, the only condition which couldbe confused with sclerosteosis is van Buchem'sdisease (hyperostosis corticalis generalisata). One ofthe authors (H.H.) visited Holland to examineaffected individuals and concluded that the disordersdiffer in that patients with van Buchem's diseaseare of normal stature, have less distortion of the faceand have little involvement of the hands. Thiscontention is supported by the case descriptions ofeight patients published by van Buchem (1971),none of the individuals having syndactyly or othersignificant digital involvement.

As sclerosteosis is transmitted as an autosomalrecessive, an affected individual must inherit anabnormal gene from each of his parents in order todevelop the disorder. These "carrier" parents arethemselves clinically normal. On a basis of theprevalence of sclerosteosis in South Africa, it can becalculated that at least one in 140 individuals ofAfrikaner stock is a heterozygote or carrier of thegene.

This population prevalence is of practical sig-nificance for the radiologist, as it is possible that thecarrier might be detected by the recognition of

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minor degrees of widening and loss of trabeculationof the calvarium (Beighton and Hamersma, 1974).This problem is presently under investigation, as areliable technique for determination of carrierstatus would have far reaching implications foreventual control of the disorder.

ACKNOWLEDGMENTSWe are grateful to Sister Lecia Durr for assistance with

the family studies, to Mrs. R. S. Henderson for preparingthe illustrations and to Mrs. Greta Beighton for typing themanuscript.

Our thanks are due to Professor A. S. Truswell, Dr. G. K.Klintworth and many other colleagues for their kindness infacilitating access to affected idividuals.

The investigation was supported by grants from theSouth African Medical Research Council, the University ofCape Town Staff Research Fund and the Hettie de BeerFund.

REFERENCESBEIGHTON, P., DAVIDSON, J., DURR, L., and HAMERSMA, H.,

1976. Sclerosteosis-an autosomal recessive disorder (inpress).

BEIGHTON, P., DURR, L. and HAMERSMA, H., 1976. Theclinical features of sclerosteosis. Annals of InternalMedicine, 84, 393-397.

BEIGHTON, P., and HAMERSMA, H., 1974. Sclerosteosis inSouthern Africa. Proceedings of the XIV InternationalCongress of Paediatrics, Buenos Aires, 10, 59.

GORLIN, R. J., SPRANGER, J., and KOSZALKA, M. F., 1969.Genetic Craniotubular bone dysplasias and hyperostoses.In Birth Defects; Original article series, Vol. V, pp. 79-94.

HANSEN, H. G., 1967. Sklerosteose. In Vol. 6, Handbuch derKinderheilkunde, J. Opitz and F. Schmid eds. Berlin,Gorringen, Heidelberg, New York pp. 351-355.

KELLEY, C. H., and LAWLAH, J. W., 1946. Albers-Schon-berg disease-a familial study. Radiology, 47, 507-510.

SIGIURA, Y., 1975. Sclerosteosis. Journal of Bone and JointSurgery, 57A, No. 2, 273-276.

TRUSWELL, A. S., 1958. Osteopetrosis with syndactyly.Journal of Bone and Joint Surgery, 40B, No. 2, 208-218.

VAN BUCHEM, F. S. P., 1971. Hyperostosis CorticalisGeneralisata, Acta Medica Scandinavica, 189, 257-267.

Book reviewThe upper brain stem in the human: its nuclear configurationand vascular supply. By B. Schlesinger, pp. 266, illustrated,1976 (West Germany, Springer-Verlag) ?159.90.

This book describes the anatomy of the upper brain stemin great detail. It is based on painstaking anatomicaldissections performed by the author and on his study ofcollections of myelin stained specimens.

The author first describes in considerable detail hismethod of making and analysing oblique sections of thebrain stem in a way which allows him to reconstitute a threedimensional matrix which depicts the precise spacialrelationships of the structures in the sections. In this way hehas established the form, position and variation of nuclei,fibretracts and of the fine vascularization. In 36 specimensthe vessels were injected in various ways and then studiedby radiography and by anatomical sectioning. There is an

excellent discussion on the variations in vascular anatomy,which confirms that the usually described pattern is anidealized conception and that the exception to this pattern isthe rule. Finally, there is a short chapter on the syndromesassociated with specific vessel occlusions.

Unfortunately, some of the nomenclature varies from thatgenerally accepted by neuroradiologists, although the latteris usually referred to in discussion. The book is beautifullyillustrated with photographs of dissections, radiographs ofspecimens and excellent diagrams. A great deal of theminute anatomy is of much greater interest to neuro-surgeons and neuroanatomists than to neuroradiologists, butthe chapters on variation of the larger vessels are of neuro-radiological interest and will be useful for reference.

B. E. KENDALL.

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