congenital escoliosis

7/27/2019 Congenital Escoliosis

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Congenital Scoliosis: PossibleCauses and Consequences in aSkeleton from NubiaLYNN KILGORE * AND DENNIS VAN GERVENDepartment of Anthropology, University of Colorado, Boulder, CO 80309-0233, USA

ABSTRACT Reports of congenital scoliosis (CS) are rare in the literature of paleopathology. This studydetails severe CS in the complete, well preserved skeleton of an adult male, dated to AD 550800, from the Sudanese site of Kulubnarti. This skeleton, designated as S-16, is the mostcomplete archaeologically derived example of CS to be documented. Copyright 2009 JohnWiley & Sons, Ltd.

Key words: congenital scoliosis; somites; somitogenesis; segmentation failure; vertebralanomalies

Introduction

Congenital scoliosis (CS) results from two formsof developmental abnormalities: failure of somites

(embryological precursors to vertebrae) to seg-ment and formation defects in individualvertebrae. There are numerous defects of bothtypes in the S-16 spine. Most important is a severeleft curve caused by posterior segmentationfailure and a probable unilateral bar betweenT8 and L1. These vertebrae are severely distortedand rotated to produce a secondary kyphosis.Other spinal defects include: agenesis of half ofthe C1 neural arch, agenesis of one cervicalvertebra, segmentation failure of T1-T2, T3-T5and T6-T7. There is also bilateral agenesis of the

styloid process of the temporal bone.Such a complete skeleton allows us to consider

some of the many ways severe scoliosis affectedthis mans life. For example, the associationbetween CS, genitourinary problems and cardio-

pulmonary insufciency indicate that he mayhave suffered from one or both of theseconditions. There are also a number of non-vertebral skeletal abnormalities that developed

secondarily to the scoliosis, and these arediscussed mainly in terms of how they affectedlocomotion. This skeleton provides a glimpseinto the life of a man who, in spite of extremedisabilities and possible pulmonary insufciency,actually lived longer than 63 per cent of the 399individuals excavated at Kulubnarti.

The goals of this study are to detail thepresence of severe CS and to consider its causesand consequences in the virtually completeskeleton of an adult male (designated S-16) fromthe medieval Nubian site of Kulubnarti (Figure 1).

CS is a lateral curvature of the spine caused byvertebral defects that form during the rst 4 weeksof embryological development. Because CS isuncommon, with an estimated prevalence of0.51 per 1000 live births in contemporarypopulations(Giampietro et al., 2003; Kaspiris et al.,2008), documented cases in the paleopatho-logical literature are rare (see below). Thus,the example reported here provides a rare

International Journal of OsteoarchaeologyInt. J. Osteoarchaeol.(2009)Published online in Wiley InterScience(www.interscience.wiley.com) DOI: 10.1002/oa.1085

* Correspondence to: Department of Anthropology, University ofColorado, Campus Box 233, Boulder, CO 80309-0233, USAe-mail: [email protected]

Copyright # 2009 John Wiley & Sons, Ltd. Received 31 July 2008 Revised 20 February 2009

Accepted 5 March 2009


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opportunity to examine the manifestations ofsevere CS in a well-preserved archaeologically

derived skeleton.The S-16 axial skeleton exhibits severaldevelopmental defects, all of which are familiarto orthopaedists and developmental biologists.The spinal deformation, which was present frombirth and progressively worsened throughout life,caused secondary changes in other parts of theskeleton and, quite possibly, compromised someorgan functions. In fact, the developmental errorsthat occurred during embryonic developmentmay have contributed to this mans death in hisearly to mid-twenties. Ultimately, given the

severity of the scoliosis and its probable con-sequences, it is remarkable that this man survivedas long as he did.

Materials and methods

This S-16 skeleton is one of 399 burials excavatedat Kulubnarti in 1979 by the Universities of

Colorado and Kentucky. Kulubnarti is located onthe west bank of the Nile River 80 miles south ofthe Egyptian-Sudanese border in an inhospitableregion called the Batn el Hajr . The archaeologicalremains at Kulubnarti consist of two cemeteriesand several partially ruined structures includinghouses, a church and a castle. There is also amonastery situated on a steep-sided islandseparated by a narrow channel from the shore.Based on analysis of textiles, pottery andarchitectural styles, Kulubnarti has been datedto Nubias Christian period from ca. AD 550 toca.1550. The S-16 burial is from the oldercemetery (ca. AD 550800), which is located onthe island. The more recent cemetery, on themainland, overlaps chronologically with theisland cemetery and was used by Christianinhabitants at least until the 16th century (VanGerven et al., 1995).

With the exception of four ribs and a few handphalanges, the S-16 skeleton is complete andpreservation is excellent. Investigation of theskeleton was accomplished by visual examinationand radiographic analysis following the removalof adhering mummied soft tissue from thevertebral column. The lower legs and feet werecompletely covered with mummied tissue andcould only be studied radiographically.

Sex determination was based on assessment of

the subpubic angle, greater sciatic notch and theauricular surface of the ilium. Estimated age atdeath was based on epiphyseal closure, andmorphology of the pubic symphasis and sternalend of the right fourth rib. Epiphyseal union wascomplete, with no visible epiphyseal lines, on alllong bones and the sternal end of the clavicle.There was also complete fusion of all vertebralepiphyseal rings, iliac crests and the basilar sutureof the occiput. There was some erosion of thepubic symphyseal faces; thus, their usefulness wassomewhat limited. However, the presence of

partially obliterated ridges and furrows wasconsistent with a Suchey-Brooks Phase IIdesignation. This phase indicates an age rangeof 1934 years with a mean age of 23.4 (Brooks &Suchey, 1990). The morphology of the sternalend of the right fourth rib was consistent withIs can Rib phase 2 (age range 2023) (I s can et al.,1984). Based on these criteria, the age at death ofS-16 was estimated to be early to mid twenties.

Figure 1. Anterior view of the S-16vertebral column show-ing the severe left curvature produced by segmentationand formation defects from T8 to L1. The right curvaturein the cervical region is partly compensatory but mayalso have resulted from formation defects of the cervicalvertebra.

Copyright # 2009 John Wiley & Sons, Ltd. Int. J. Osteoarchaeol.(2009)DOI: 10.1002/oa

L. Kilgore and D. Van Gerven


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Examination of femoral cortical thickness wasfacilitated by the fact that, for purposes of aprevious study, thin sections of the femoral shaftshad been taken. Thus, the bone cortex wasavailable for visual inspection.

In clinical practice, the severity of scolioticcurves is determined by measuring the Cobbangle, the standard measurement approved by theScoliosis Research Society (Goldstein & Waugh,1973; Facanha-Filho et al., 2001). This techniquedoes not take into account secondary kyphosis oraxial rotation, but it does calculate the degree ofcurvature by measuring the tilt of the two endvertebrae of a scoliotic curve. The end vertebraeare those farthest from the apex with maximal tiltinto the curve (Lonstein, 1995). Unfortunately,identifying the end vertebrae in CS is moredifcult than in idiopathic scoliosis because theyfrequently are not obvious. However, thetechnique has been improved for CS in recentyears (Facanha-Filho et al., 2001).

Using X-rays, the Cobb angle is determined bydrawing a line parallel to the superior endplate ofthe cranial end vertebra of a scoliotic curve.Another line is drawn parallel to the inferiorsurface of the caudal end vertebra, and the angleof intersection of these two lines is the Cobbangle. Because this can sometimes be difcult toread, perpendiculars to these lines are also drawn

and the angle formed by their intersection alsoprovides the Cobb angle (Figure 2).Because determination of the end vertebrae in

CS can be difcult, the Cobb angle for S16 wascalculated twice, using T7 and L1, and T6 and L2as the end vertebrae. In order to do this, the spineand pelvic girdle were articulated and layers offoam were inserted to approximate intervertebraldiscs. The specimen was photographed andconverted to a line drawing on which the Cobbangle was then determined. Additionally, a cast ofthe entire specimen was X-rayed and the Cobb

angle was calculated at the Arkansas SpecialtySpine Center at Little Rock.

The embryology of the vertebralcolumn and spinal defects

Several paleopathological reports have discussedthe embryological development of the spine with

reference to vertebral defects (Barnes, 1994;Merbs, 2004), and the clinical literature on thetopic is vast. However, because it is impossible todiscuss CS without considering developmentalprocesses, they are reviewed here in order to

provide insights into the etiology of CS in thisindividual.Three weeks after conception, a human

embryo is a disc composed of three layers, theectoderm, mesoderm and endoderm. There isalso a rod shaped mass of cells, the notochord,that extends longitudinally along much of themidline through the mesoderm. The notochord isthe structure around which the precursors tovertebrae (somites) develop, and notochordalcells also produce several molecules that areinstrumental in somite formation (Christ et al.,

1998, 2000; Fleming et al., 2001; Carlson, 2004;Tabata & Takei, 2004).The medial portion of the mesoderm, the

presomitic mesoderm (PSM), consists of twothickened, parallel, columns that lie adjacent toeach side of the notochord and also thedeveloping neural tube (Lonstein, 1995; Scheuer& Black, 2000; Ganey & Ogden, 2001; Carlson,2004). Over a period of a few days, the PSM

Figure 2. The Cobb angle of the left thoracic curve show-ing the measurement using T6 and L2 as end vertebrae.


Congenital Scoliosis in a Nubian Skeleton


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segments into somites, a series of paired,sequentially formed, transient cell masses. Thesomites, in turn, give rise not only to thevertebrae, but also the entire axial skeleton,muscles of the trunk and the dermis of the back(Huang et al., 2000).

In its most basic sense, somite formation(somitogenesis) is a process whereby boundariesare formed between cell clusters. These bound-aries eventually dene not only individualsomites, but also the cranial and caudal compart-ments of each somite (Iulianella et al., 2003).Anything, including genetic mutations andepigenetic factors, that interferes with theestablishment of these boundaries can lead tovertebral segmentation failure and malformedvertebrae.

As somites form, the cells within themdifferentiate, eventually forming three regions.The ventromedial portion, which is of concernhere, becomes the sclerotome, which gives rise tothe vertebrae and ribs, and also contributes to theintervertebral discs (Monsoro-Burq, 2005). Scler-otome formation is followed by a secondsegmentation process during which the caudalhalf of one sclerotome separates from its cranialhalf and is joined to the rostral half of thesubjacent somite (Bagnall et al., 1988; Christ et al.,1998; Huang et al., 2000). Consequently, all

vertebrae, with the exceptions of C1 and C2,which are more complicated, are composed of thecaudal and cranial halves of two adjacentsclerotomes (Figure 3). After sclerotome reseg-mentation, cells at the margins of the area ofseparation give rise to the annulus of theintervertebral disc and, eventually, the notochor-dal cells that are now enclosed by the newlyformed structure develop into the nucleuspulposus (Larsen, 1997). While the process ofresegmentation is generally accepted, severalauthors have argued in favour of a one-

segmentation process (Keynes & Stern, 1988;Lonstein, 1995). Others have proposed a some-what modied resegmentation model (Morin-Kensicki et al., 2002.)

Beginning in the fourth embryonic week,proliferating cells of paired sclerotomes migrateuntil they join dorsal to the neural tube andventral to the notochord so that the dorsal andventral portions give rise to the vertebral arches

and vertebral centra, respectively. But even as thesclerotomal cells are migrating to assume their

nal position, they begin to produce moleculescharacteristic of cartilage (such as chondroitansulphate). These, in turn, give rise to chondro-cytes and form the cartilaginous anlagen ofvertebrae.

Developmental defects and congenital scoliosis

CS, which accounts for approximately 15 percent of all scoliosis cases (Riseborough &

Herndon, 1975), is variably expressed. CS iscaused by vertebral defects that form during therst 4 weeks of embryonic development. Thesedefects fall into two basic categories: segmenta-tion failure and abnormal formation.

Segmentation failure is one of the mostcommon causes of CS and it occurs when somitesor sclerotomes fail to segment properly. Seg-mentation failure can occur on any aspect of two

Figure 3. Diagrammatic representation of somitogenesis.Somitogenesis occurs at the cranial end of the developingparaxial or presomitic mesoderm. Once a somite formsand buds off, its dorsoventral portion becomes the scler-otome, which subsequently resegments. During reseg-mentation, the caudal half of one sclerotome separatesfrom its cranial half and is joined to the cranial half of thesubjacent sclerotome.




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or more adjacent developing vertebrae. When itoccurs both anteriorly and posteriorly, the resultis a block segment (Figure. 4). In the absence ofother conditions, such as partially formedelements, block vertebrae are usually asympto-matic (Winter, 1973; Hall, 1985).

Unilateral, anterolateral or posterolateral seg-mentation failure, however, results in the devel-opment of a vertebral bar which tethers adjacentvertebrae together and inhibits growth where itoccurs (Figure 4). However, growth continuesnormally on the opposite side, producing wedge-shaped vertebrae that lead to visible spinalcurvature by late infancy (Emans, 2005). Unilat-eral vertebral bars cause severe scoliosis, especi-ally if they involve several vertebrae.

There are also many developmental errors thatproduce incomplete or malformed individualvertebrae. The most common of these is partialor complete failure of one side of a vertebra todevelop, resulting in the formation of hemi-vertebrae.

Hemivertebrae occur in a number of forms,some of which are unsegmented and incorporatedinto adjacent vertebrae that are modied toaccommodate them (Figure 4). These usuallycause no serious deformity (McMaster, 2001).However, in fully segmented hemivertebrae,some disc material is present both cranially and

caudally. Moreover, adjacent vertebral bodieshave not been altered and consequently, thehemivertebra grows normally, producing a wedgethat increases in size between two non-accom-modating adjacent vertebrae. In such cases, there

is a progressive scoliosis that increases at a rate of1 o r 2 8 per year (McMaster, 2001). Moreover, thistype of wedging in the presence of a unilateralvertebral bar on the opposite side produces themost severe form of CS. If several segments areinvolved, this abnormality can lead to extremedeformity accompanied by genitorurinary andcardio-pulmonary problems even when treatedwith the advanced surgical techniques that areavailable today.

Cleft vertebrae (Figure 4) constitute one othertype of developmental defect and they have beenreported in archaeological material (Anderson,1963; Merbs, 1980, 2004; Pfeiffer et al., 1985;Rocek & Speth, 1986; Mann & Verano, 1990;Barnes, 1994). Clefting may occur coronally orsagitally when a portion of the centrum fails todevelop. In sagittal clefting, the central portion ofthe vertebral body is either partially or com-pletely unformed (Barnes, 1994; McMaster &Singh, 1999; Merbs, 2004). When the cleft occursin the sagittal plane, the defect is frequentlyreferred to as a buttery vertebra. Butteryvertebrae frequently cause an angular deformitythat eventually leads to kyphosis or kyphosco-liosis (McMaster & Singh, 1999).

Once a developmental defect has initiated theformation of a curve, compression of theendplates on the concave side further inhibits

growth, while the convex side continues to grownormally. Without intervention, the curvaturebecomes increasingly pronounced and, even aftergrowth has ceased, it may continue to develop ata rate of approximately 1 8 per year (Riseborough

Figure 4. Some of the vertebral abnormalities that result from segmentation and/or formation errors that occur duringembryonic development (McMaster, 2001).




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& Herndon, 1975). Eventually the vertebraecollapse along the concavity and, in long-standing cases, even in the absence of a vertebralbar, they become ankylosed, a process that mayobstruct intervertebral foramina.

Lateral bending of the spine is always coupledwith axial rotation of motion segments. Duringlateral exion of a normal spine, the ventralsurfaces of vertebral bodies rotate toward theconcavity. However, in a scoliotic spine, thespinous processes are increasingly orientedtoward the concave surface while the ventralsurfaces point toward the convex surface (Whiteand Panjabi, 1990). As the severity of a lateralcurvature increases, so does the amount ofrotation of individual vertebrae, eventuallyproducing what clinicians refer to as crankshaftdeformity (Figure 5).

If the abnormal curvature occurs in the thoracicregion, distortion and malformation of ribs alsodevelop because, as thoracic vertebrae rotate,they carry their associated ribs along with them.Because the proximal end of growing ribs arecontinuously pressed against the vertebral trans-verse processes, they develop a sharper than

normal angle dorsally on the convex side(Figure 6). Moreover, as the proximal ends ofthese ribs continue to move dorsally, theyprotrude from the patients back producing therib hump characteristic of scoliosis. Conversely,on the concave side of the curve, the ribs arepushed anterolaterally and develop a wider thannormal angle. Appositional growth in these ribscan be severely inhibited so that they are muchthinner than normal and lie in a more horizontalplane.

The paleopathology of congenitalscoliosis

While a few cases of idiopathic scoliosis orscoliosis associated with evidence of otherabnormalities have been published, denitivereports of CS are rare in the paleopathological

Figure 5. Block segment consisting of T8-L1 resultingfrom complete posterior non-segmentation and probablyalso from a right unilateral vertebral bar. Severe axialrotation has produced a marked crankshaft deformityso that the anterior surface of the T9 body is oriented in atleast a 50 8 angle to that of L1.

Figure 6. The ribs of S16 are characteristic of ribs thatdevelop in the presence of severe scoliosis. Note theabnormally sharp dorsal angle in the left ribs and the widedorsal angle in the right ribs.




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literature. Brothwell (1961) reported on a case ofscoliosis in a British skeleton dated to about 2000BC. In this report, he attributed the scoliosis tothe presence of hemivertebrae, a factor thatstrongly supports a diagnosis of CS.

Jarcho (1965) described vertebral anomalies ina skeleton from Peru. His diagnosis of KlippelFeil syndrome, which is always associated with atleast two fused cervical vertebrae, was based onthe presence of segmentation defects betweenC6-C7 and C7-T1. There were also twohemivertebrae on the right side in the upperthoracic region, and these had produced anangular deformity. Additionally the rst four ribswere fused proximally, a common occurrence inCS. Thus, this case is almost certainly an exampleof CS associated with KlippelFeil syndrome, asthese related conditions frequently occurtogether (Hensinger et al., 1974; Winter et al.,1984; Thomsen et al., 1997).

Cybulski (1992) reported on a denite and veryinteresting case of CS in a male aged 2228 yearsfrom the Greenville Burial Ground in BritishColumbia, dated to AD 7291220. The spine ofthis individual exhibited developmental defectsfrom T3 to L5, which included hemivertebrae andblock vertebrae. There were also secondaryalterations in other parts of the skeleton. Inaddition, this individuals cranium displayed two

fractures, one of which may have resulted from afatal blow to the head, a fact that makes this caseeven more intriguing.

In addition to CS, there are several reports ofisolated developmental defects of the axialskeleton (Bourke, 1971; Barnes, 1994, 2004;Merbs, 1980, 2004; Gonza lez-Reimers et al.,2001). Isolated malformed vertebrae are certainlyinteresting, and they may provide very generalestimates of prevalence in archaeological popu-lations; nevertheless, they usually offer noinformation as to how severely individuals were

affected or even if they were symptomatic.

The S16 skeleton

The axial skeleton of S-16 displays an assortmentof anomalies produced by segmentation defectscombined with formation errors in individualvertebrae, which are detailed in Table 1. The

most obvious manifestation is the major leftthoracic curve beginning at T6 and continuingthrough L1. (In standard terminology, thedirectional term refers to the convex surface ofthe curve). This curve consists of a block ofunilaterally compressed, extremely distortedvertebrae that includes T8-L1 with T9 at theapex of the curve (Table 1, Figure 5). The Cobbangles derived from measurements taken at T6-L2and T7-L1 were 104 and 120 8 , respectively(Figure 2). These gures substantiate that thiscurve would have been very debilitating.Deformities measuring 51100 8 are consideredsevere, and those with angles greater than 100 8

are extremely severe (Young, 1998).Concomittant with the left curve there is a

severe kyphosing scoliosis. The term kyphosingscoliosis is used to refer to secondary kyphosisthat results from the axial rotation of the spineand it occurs at the apex of the scoliotic curve(Winter, 1995).

In addition to the primary thoracic curve, thereis a less pronounced right curve from C1 to T5.This curve may be compensatory but it could alsohave resulted from formation defects of thecervical vertebrae (Table 1). Only six cervicalvertebrae are present and, given the excellentstate of preservation and the fact that all sixarticulate normally, one cervical element appar-

ently failed to develop. This explanation issupported by the fact that agenesis of cervicalvertebrae is a fairly common occurrence in CS.

The thoracic spine consists of four blocksegments: T1-T2, T3-T5, T6-T7 and T8-L1(Table 1). The T3-T5 segment is of particularinterest because, in addition to segmentationfailure, there are also formation defects (Table 1).The same developmental error that resulted in theT3-T5 block segment also led to partialsegmentation failure of the right fourth and fthribs so that these ribs are fused proximally.

The sixth and seventh thoracic vertebrae alsoconstitute a block vertebra. But, in spite of themarked developmental defects in the upperthoracic spine, the entire segment from T1 toT7 does not exhibit severe curvature. Had it notbeen for the need to compensate for the severelydistorted T8-L1 segment, the upper thoracicspine most likely would have had little or nodeformation.




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Table 1. Developmental anomalies in the S-16 skeleton

Cranium Bilateral agenesis of styloid process of temporal bonePresacral vertebrae Severe left thoracic curve with compensatory right cervicothoracic curve.

The Cobb angle of the thoracic curve was measured twice, using twodifferent pairs of end vertebrae. T7-L1 122 8 , T6-L2 104 8

Severe kyphosing scoliosis with apex of curve at T9. This is not

considered true kyphosis because it is caused by the crankshaftdeformity in left scoliotic curve.Agenesis of one cervical vertebra

C1 Agenesis of r ight half of vertebral arch posterior to superior articular facet,dens facet positioned to right of centre, osteophytic lipping aroundmargins of dens facet and right superior articular facet,anterior tubercle thickened

C2 Some osteophytic development on dens, left articular facets larger than r ight

C3 Left articular facets larger than right

C4 Left articular facets larger than right, left pedicle underdeveloped so thatthe left articular facets are immediately adjacent to left transverse process,spinous process is oriented slightly to left, agenesisof anterior and posterior tubercles of left transverse process

C5 Agenesis of anterior and posterior tubercles of right transverse process,poorly developed right articular process with inferior articular facet immediatelysubjacent to superior articular facet and shortening of left side of vertebralarch, spinous process tilted to right and vertebral foramen narrower on right

C6 Minimal development of right articular process with inferior facet immediatelysubjacent to superior facet, right lamina shorter than left with spinousprocess tilted to right and narrowing of right side of vertebral foramen

T1-T2 Block segment with complete segmentation failure on all sides and atarticular facets, agenesis of left lamina of T2 with displacement ofleft inferior facet to caudal surface of superior facet, incompletedevelopment of left articular processes of both vertebrae so that lefttransverse processes are fused medially and left side of segment is shorter(T2 left inferior facet 7 mm higher than right)

T3-T5 Block segment associated with formation defects. Anteriorly there is partial

segmentation with slight disc development between T3 and T4. Agenesisof T3 right lamina. T4 exhibits sagittal clefting at anterolateral surface of centrum.T4 and T5 exhibit complete non-segmentation posteriorly and anteriorly.Three transverse processes on left side of block and two on the right due toagenesis of T3 lamina. T5 transverse process shifted somewhat cranially.Partial sagittal cleft of T5 centrum

T6-T7 Block segment with complete non-segmentation of posterior elementsincluding articular facets. Vertebral bodies segmented with some discspace present. Severe distortion of vertebrae with shortenedright pedicles and laminae with spinous process angled to right. Thisdistortion is secondary to major left thoracic curve

T8-L1 Block segment that forms the severe left thoracolumbar lateral curve withT9 at its apex. Complete segmentation failure of all posterior elements andright unilateral bar from at least T8 to T10 but may extend to L1. Right halfof all elements collapsed with virtual destruction of T8 and T9. Axial rotation

of T9 is at least 508

relative to L5. Secondary kyphosis at level of T8-T9.Complete occlusion of T8-T9 and T10-T11 intervertebral foraminae

L2-L5 Defects in fusion of spinous processes at the midline probably due to alteredweight bearing. Spinous processes of L2, L3 and L5 are fused at the midlinebut the left half is lower than the right. L4 spinousprocess is unfused possibly due to the left half being lower than the right.L5 left inferior articular facet greatly enlarged

(Continued )




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L2 through L5 continue to tilt to the left at the

angle established by L1; consequently, there is nocompensatory curve in the lower lumbar area.The enlargements of the left inferior articularfacet and left superior articular facet of L5 and S1,respectively, are modications produced inresponse to the abnormal compression forcesexerted on them from a very early age. Thelaminae of L2 through L5 are slightly offset withthe left side lower than the right. This malalign-ment, most likely due to the imbalance and shiftin weight bearing caused by the T8-L1 primarycurve, probably prevented the fusion of the

spinous processes of L4 and asymmetries in thespinous processes of L2, L3 and L5 (Table 1).The sacrum exhibits the same pattern as seen in

the lumbar vertebrae with the left side beinglower than the right. The neural arch of S1 isfused but those of S2-S5 are not. Although it ispossible that this is an example of spina bidaocculta, it is also possible that the lack of fusion isdue to the fact that the right and left halves of the

sacral vertebrae were offset as were those in L2-

L5. Moreover, the arches of the sacrum may notfuse until age 7 (Scheuer & Black, 2000) by whichtime the effects of the thoracic curve on thesacrum were probably becoming more pro-nounced. Thus, the problems with fusion ofthe lumbar and sacral neural arches in thisindividual may indicate that, as early as lateinfancy, the T8-L1 curve had a signicant impacton skeletal development.

Non-vertebral manifestationsThere is one additional, developmental anomalythat does not involve the spine, and that is thebilateral agenesis of the styloid process of thetemporal bone. All other skeletal malformationsare the secondary results of abnormal growth dueto altered biomechanical forces imposed by thedeformed lower thoracic spine.

Sacrum Left superior articular facet of S1 greatly enlarged. Caudalward shift ofleft half of all segments results in left side being 5 mm lower than the right.There is complete fusion of the neural arch of S1 but little to no fusion of S2-S5.As in L2-L5, the right and left halves of the neural arches are offset and thereforenormal fusion was not possible

Ossa coxae Iliac breadth greater on right than left: Left 136mm, Right 141mm.Iliac height greater on left than right: Left 99 mm, Right 88 mm. Right iliumexhibits greater development of the anterior and posterior gluteal lines than left ilium.Slight bevelling of the superior rim of the right acetabulum indicative of somesubluxation of right femoral head and possible early stages of osteoarthritis.Left ilium ares more laterally than the right

Ribs Twenty ribs, 10 from each side, are present; those on the left (convex) sideof the thoracic curve, present a sharper than normal angle posteriorly withthe angle increasing caudally and most marked in ribs 8-10. When articulated,right 5th rib curves laterally to outside of ribs 6-8 and bends caudally so thatthe sternal end is inferior to that of rib 9. In contrast, the right ribs exhibit a widerthan normal angle. Right ribs 4 and 5 fused proximally corresponding todevelopmental defect in T3-T5 block segment. Ribs 8-10 compressedand underdeveloped (Figure 5)

Scapulae Right scapula longer and narrower than left. Maximum length(middle of superior border to inferior most point): Right 125.5 mm,Left 119.9mm. Maximum breadth (middle of dorsal border of glenoid fossa tomedial end of spine): Right 90.8 mm, Left 94.8 mm. Right spine and glenoidfossa more cranially oriented than left

Clavicles Left clavicle shorter than right: Left 137mm, Right: 143 mm

Femora Right femur has poorly developed linea aspera, AP/ML indices: Left 128;Right 91, lower right index due to underdeveloped linea aspera

Table 1. Continued




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Lastly, the right scapula is longer and narrowerthan the left (Table 1). It is not unusual in scoliosisfor the scapula on the convex side to be elevated ifthe curve extends above the level of T7.However, it is uncommon for there to be actualanatomical changes (Riseborough & Herndon,1975).

Distortions of the pelvis occur when con-genital anomalies of the spine lead to imbalancesin muscle action during growth (Dubousset,1997). Therefore, it is not surprising that there isa slight bilateral asymmetry of the S-16 pelvis(Table 1). It can also be assumed that there wassubstantial pelvic obliquity, a common featurenot only in severe scoliosis, but also in thepresence of most spinal abnormalities (Dubous-set, 1997; Riseborough & Herndon, 1975;McCarthy, personal communication). (Conver-sely, when the obliquity is caused by otherfactors, such as leg length inequality, it can causescoliosis.) In scoliosis patients, the pelvis iselevated on the concave side of the majorscoliotic curve. Therefore, in S-16 the right sideof the pelvis was higher than the left.

Both femora exhibit dense cortical bone andthe left linea aspera is normal. However, the rightlinea aspera, the area of insertion for the threemajor adductor muscles (adductor magnus,medius and brevis) is considerably underdeve-

loped.

Discussion

The specic etiologies of most developmentalerrors of the spine are unknown, but a number ofinherited and/or spontaneous somatic geneticmutations or environmental insults are involved(Kaspiris et al., 2008). Investigations into thespecic genetic mechanisms that underlie spinal

anomalies are providing new insights into theregulatory genes and pathways that inuenceskeletal formation (Zelzer & Olsen, 2003; Erolet al., 2004; Maisenbacher et al., 2005). Moreover,in the last 15 years specic genetic mutationshave been linked to particular syndromescharacterised by vertebral anomalies. Oneexample of a syndrome known to be associatedwith specic genetic mutations is spondylocostal

dysostosis (SCD), also referred to as JarchoLevin syndrome (Dunwoodie et al., 2002).

SCD is a diverse group of disorders charac-terised by abnormally formed vertebrae, ribdefects and block vertebrae distributed through-out the entire spine (Whittock et al., 2003). Onetype of SCD is caused by mutations in the Dll3gene located on chromosome 19. Dll3 is one ofmany genes involved in somitogenesis, and 17different mutations at the Dll3 locus alone havebeen identied in SCD patients so far (Turn-penny et al., 2003; Turnpenny & Kusumi, 2004).Moreover, in one report, 15 per cent of 46 CSpatients carried Dll3 mutations (Maisenbacheret al., 2005) but, given the number of genes thatdirect somitogenesis, mutations at dozens ofother loci can also cause abnormalities.

In addition to mutations in the DNA itself,in uteroenvironmental factors such as heat andmaternal hypoxia, are known to interfere withnormal gene function and thus disrupt somito-genesis in mice. In fact, studies of monozygotictwins have revealed low concordance for CS,suggesting that in uteroenvironmental inuenceson gene action play a substantial role in theappearance of developmental anomalies (Peter-son & Peterson, 1967; Hattaway, 1977; Pool,1986; McMaster, 2001; Kaspiris et al., 2008).

For some time, retinoic acid (RA), a metabolite

of vitamin A, has been known to be a powerfulteratogen. In uteroexposure to both excessive andinsufcient amounts causes developmentaldefects in vertebrae (Marin-Padilla & Ferm,1965; Maden et al. 2000) by interfering withthe expression of several genes that directsomitogenesis (Vermot et al., 2005).

The teratogenic effects of abnormal levels ofRA occur because RA is actually a signallingmolecule that is a key factor in somitogenesis.Thus, defects in RA signalling lead to bilateralasymmetry in the PSM and thus to the develop-

ment of the vertebral anomalies that cause CS(Duester, 2007). Although there is little in thecurrent literature regarding the role of vitamin Adeciency in the development of CS per se,Hornstein and Tabin (2005) speculate on thepotential for increased risk of skeletal defects ininfants born to vitamin A decient mothers.Today, vitamin A deciency is a public healthproblem in the Sudan and has been partly




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attributed to a diet that is high in sorghumand low in leafy green vegetables (el Bushra,1992).

Vitamin A and/or its precursor, carotene, arefound in yellow and leafy green vegetables, shoil, liver and dairy products, all of which (with thepossible exception of sh oil) were uncommonfood items at Kulubnarti. Instead, the Kulubnartidiet consisted primarily of ...sorghum, millet,barley, lentils, peas, dates and wheat, (VanGerven et al., 1995) and occasional meat derivedfrom domestic livestock. Consequently, althoughit cannot be demonstrated, maternal vitamin Adeciency can at least be considered as onepossible factor in the development of the spinaldeformity of S-16.

Due to the excellent preservation of the S-16skeleton, coupled with the fact that thisindividual survived well into adulthood, it ispossible to observe the effects of the spinalabnormalities on the appendicular skeleton as itdeveloped to accommodate drastically alteredspinal biomechanical relationships. Furthermore,we can also speculate on a few aspects of the lifeof this person, and perhaps on cause of death.

Typically in patients with thoracic scoliosis,cervicothoracic and thoracolumbar compensa-tory curves partially function to maintain thehead and centre of gravity in an approximation of

the normal position above the pelvis (Dubousset,1986). However, this accommodation was onlypartly feasible for S-16 because of the likelyinstability of the neck due to the hypoplasticC1 and other malformed cervical vertebrae.Moreover, there is no true lumbar compensatorycurve.

The fact that the femoral cortices arecomposed of dense bone indicates that S-16was ambulatory, but probably with the aid of awalking stick. The underdevelopment of the rightlinea aspera suggests that the major adductors of

the right thigh (magnus, longus and brevis) wereat least compromised if not paralysed. Paralysiscannot be completely ruled out as compression ofthe spinal cord occurs in some severe cases of CS.The adductors, working in opposition to theabductors gluteus minimus and medius, act asmedial rotators of the thigh when walking.However, perhaps more importantly, theystabilise the hip during the stance phase or when

standing. Thus, while S-16 appears to have beenambulatory, the stability of his right hip wasprobably compromised.

Pelvic obliquity is a very common result ofmost spinal abnormalities (Dubousset, 1997;McCarthy, personal communication). On theconcave side of the major curve, the muscles thatextend from the spine to the pelvis and proximalfemur are shortened (Riseborough & Herndon,1975; Dubousset, 1997). Many investigatorsbelieve that increased contracture of thesemuscles (iliopsoas, quadratus lumborum anderector spinae) elevates the concave side of thedeveloping pelvis (Riseborough & Herndon,1975; Shook & Lubicky, 1997). Likewise,abnormal contraction of gluteus minimus andmedius, the main abductors of the femur, whichextend from the ilium to the greater trochanter ofthe femur, also increase the elevation of the pelvisand femur. In S-16, the anterior and posteriorgluteal lines are considerably more pronouncedon the right ilium than on the left. Althoughgluteus minimus and medius do not attachdirectly to these two lines, they do attach tothe ilium in areas immediately adjacent to them.This raises the possibility that increased contrac-tion of the right gluteal muscles may have furthercontributed to pelvic obliquity. In more severecases, these factors can lead to some distortion of

the growing ilium during childhood, and sub-luxation or complete dislocation of the hip iscommon on the elevated side (Shook & Lubicky,1997). Slight bevelling of the superior surface ofthe right acetabulum suggests that the right hipmay have been subluxed, but there is no evidenceof complete dislocation.

In scoliosis patients with pelvic obliquity, theleg on the concave side is effectively lengthenedwhile the leg on the convex side is shortened.Consequently, a person with pelvic obliquitystands with the functionally shortened leg on the

convex side bearing most of the weight of theupper body. Depending on the degree of pelvictilt, the leg on the opposite side is often exed atthe knee. When walking, however, more weightis distributed to the longer leg and someindividuals tip-toe on the convex side. We canassume these locomotor patterns, or somethingquite similar, for S-16. Thus, the picture we haveof S-16 is that of a disabled man with legs of




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functionally unequal length, probably using astick when traversing steep, rocky terrain.

In addition to severe skeletal deformities, S-16may have had problems that arose from defects ofvarious organs. CS (or even an isolated vertebralanomaly) is frequently associated with develop-mental abnormalities of organ systems that arisefrom other portions of the same somites that gaverise to the malformed vertebrae. Genitourinarytract abnormalities are common in CS patients,but prevalence varies between studies. Hall(1985) states that genitourinary defects are seenin 2030 per cent of CS patients. In threeseparate reports, prevalence ranged from 18 to 39per cent (Viko et al., 1972; Drvaric et al., 1987;Beals et al., 1993). MacEwen et al. (1972) reportedthat of 231 patients with vertebral anomalies, onethird had unilateral kidney agenesis.

Cardiovascular anomalies are also seen in CSpatients, with one study reporting a prevalence of15 per cent in 66 cases (Mohanty and Kumar,2000). There may also be neurological problemsand gastrointestinal malformations (McMaster,1984; Beals et al., 1993). Obviously neurological,genitourinary or gastrointestinal malformationscannot be substantiated for S-16, but it islikely that he suffered from cardio-pulmonaryinsufciency.

Impaired pulmonary function is common in

patients with severe scoliosis (Day et al., 1994)due to compression and displacement of thelungs. Indeed, curves of over 80 8 are associatedwith reduced pulmonary function and total lungcapacity is reduced to approximately 50 per centwith curves greater than 100 8 (Weinstein, 1986).Moreover, severe distortion of the rib cage, suchas is present in S-16, interferes with normal lungdevelopment. Increasing deformity during thegrowth period, particularly in the presence of aunilateral bar, can increase by as much as 5 8 peryear. This increase leads to a decrease in vital

capacity and can even result in death in earlyadulthood (McMaster, 2001).Cardiopulmonary function is compromised in

cases of severe kyphosis as well as scoliosis. Thisis due to the rigidity and malformation of the ribcage, and abnormal position of the diaphragm(Dubousset, 1985). In addition, hypertrophy ofthe right ventricle of the heart is common(McMaster, 2001). It is also possible that

impaired blood ow to the lungs from the rightventricle would have further reduced the oxygencarrying capacity of the blood.

The S-16 skeleton provides a fairly detailedlook at the life of an individual who suffered alifetime of disability and perhaps pain with nomedical care in uncompromising circumstances.As the left thoracic curve of his spine becameincreasingly severe during childhood, S-16 mayhave experienced intermittent bouts of pulmon-ary insufciency that worsened with age. It is alsoquite possible that he suffered from genitour-inary, neurological and/or gastrointestinal pro-blems. Yet, examining survivorship data forKulubnarti (Van Gerven et al., 1981) reveals thateven if he died at the age of 21 (and he almostcertainly survived beyond that age) S16 outlived63 per cent of the people represented in the entireKulubnarti sample ( n 399), and 74 per cent ofthose in the older cemetery ( n 214). There canbe little doubt that this individual receivedconsiderable care and support from family andfriends, and he was probably a well-integratedmember of the society.

Modern inhabitants of the Nile valley holddisabled persons in high esteem and accord thema favoured status. While this attitude is charac-teristic of Islamic beliefs in this part of the worldtoday, it may have predated Islam, and even

Christianity, in the region. If so, the disabilitiesthat aficted S-16 may have actually inclinedfamily members and other village inhabitants toprovide him some measure of additional care,without which he could not have survived as longas he did.

Conclusions

The S-16 spine provides one of the mostcomplete archaeologically derived examples of

CS so far described. Furthermore, becausevirtually the entire skeleton has been preserved,it is the only such specimen in which a spectrumof secondary consequences of CS can be seen.Thus, this remarkable skeleton provides a glimpseinto the life of a severely compromised individualwho lived more than 1000 years ago.

We have briey discussed the process ofsomitogenesis and the developmental errors that




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can occur as a result of mutations in develop-mental and/or regulatory genes during somiteformation. We have also mentioned in uteroenvironmental factors that, through their inu-ence on gene expression, may have beenimportant. While the precise causal factor cannotbe identied, one thing is certain. Beginning inthe third week of embryonic development, theprocess of somitogenesis went awry, leading to acascade of events that continued to increase inseverity throughout lifetime of this man. Thiscascade may have included genitourinary con-ditions and/or cardio-pulmonary insufciency,complications that may have contributed to hisdeath.

Acknowledgements

We express our appreciation and gratitude toDiane France, of France Casting, for makingthe exceptional cast of the S16 axial skeletonused in some of the analysis of the spine. Also, fortheir advice and assistance, we thank Robert Jurmain, Richard McCarthy, MD, and Anita Grif-fen of the Wardenberg Student Health Center,University of Colorado, Boulder.

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