4 Pseudopathology (deformation) and other abnormalities
Excluding the various cuts, and the possible congenital anomaly under discussion, a number of other pathological conditions were noted. The pelvis shows some long deep grooves on the left iliac blade which are probably due to post-mortem shrinkage and distortion. Two upper thoracic and four lumbar vertebrae show varying degrees of Schmorl’s nodes. They were originally thought to have no clinical significance, but may well be associated with osteoarthritic development, back stress and pain (Aufderheide & Rodríguez Martín 1998, 96-97; Capasso et al. 1999, 38).
The postcranial skeleton is almost entirely preserved, although a marked difference in size is observable between some bones of the left side of the body and their counterparts on the right side (i.e. the pelvis, the heel bones and the femora). Since these observations are not in accordance with any pathological disorder, post-mortem deformation is suggested as the main cause of these differences.
If asymmetry is indeed a post-mortem development, the specific shortening of the forearms and lower legs should possibly be classified as a pathological phenomenon known as dyschondrosteosis or Léri-Weill syndrome.
4.1 Possible anomaly of the forearms and lower limbsnext section
Both the proximal and the distal epiphyses of the right humerus and the preserved distal epiphysis of the left humerus are normal in shape and structure. The right and left forearms show partially deformed and underdeveloped epiphyses. The left and right radii are shorter than normal and moderately bowed.
The left femur is fractured and a small radiopaque body (1.5-2 cm, HF density between 1.000 and 2.000) is observable at the fracture edge of its distal epiphysis. This structure seems to be an intrusive stone (fig. 12).
Figure 12 Results of a CT scan performed on Zweeloo Woman’s skeletal remains. The viscera were positioned between the lower limbs.
Both the right femur and the right fibula show marked bowing. There are signs of coxa valga. The left leg appears to be shorter than its counterpart.
Both lower legs appear to be underdeveloped in comparison with the femora. This difference is however less evident than that observed in the forearms.
Proximal portions of the limbs, hands and feet show no abnormality of size, though there is possible evidence of reactive change in the bones of the feet caused by some degree of abnormal gait. There is no evidence of nutritional deficiency or infectious illness, and no other part of the skeleton appears to be affected.
The X-ray features of dyschondrosteosis in living patients and in dry bones are based on a spectrum of manifestations. The features typical of DCS patients that are observable in Zweeloo Woman include: 1) shortening of the radius extremity with hypodevelopment of both proximal and distal epyphises as compared with the normal standard for age and in relation to the size of the other bones; 2) double (lateral and dorsal) bowing of the radius which involves the entire diaphysis but is more marked at the distal end (Madelung’s deformity; Langer 1965); 3) shortening of the tibia in relation to the femur, which results in mild dwarfism. This pattern of shortening in the middle segment of extremities is referred to as mesomelia (Langer 1965).
The skull, the spine and the pelvis are radiologically normal in all cases described in the literature in which these bones have been studied, those of Zweeloo Woman included.
Surprisingly few bog bodies have been reported as showing anomalies and, where observed, the disease is mostly associated with adult individuals (Brothwell & Gill-Robinson, 2002, 120).
Following Lynnerup (2010, 444) “acid bog diagenetics mean that bone will be demineralised, become pliable and, upon subsequent excavation and drying out, also shrink and warp. This means that under these conditions, etiological attribution of pathology and trauma lack certainty”.
The greatest uncertainty in the case of Zweeloo Woman is essentially her ‘true’ stature. The great discrepancy between the value of 170 cm quoted shortly after her excavation (1952) and the values of 152 and 155 obtained in 1995 and 2009-2011 is clearly an issue.
No written records of the stature measurements carried out at the time of exhumation are available. The only scientific information is that provided by Stoddart, who interpreted the asymmetry identified between one side of the body and its counterpart as due to shrinkage.
The data obtained by means of AFM and histology provide evidence of slight degradation of collagen fibrils and moderate bone demineralisation, implying shrinkage. The possible diagnosis of Léri-Weill dyschondrosteosis should however not be totally rejected.
Since the taphonomic impact of the acidic peat bog environment on human remains is still not well understood (Janaway et al. 2003, 56-59; Gill-Frerking & Healey 2011, 69-74), the possibilities of taphonomy and pseudopathology must always be considered (Gill-Robinson 2003, 46). Similarly, bone abnormalities should not always be assumed to be due to bog taphonomy. The possibility of skeletal disorders pre-existing the taphonomic process should also be considered.
To sum up, the bone morphology and radiological findings indicate a possible case of Léri-Weill dyschondrosteosis.
4.2 Differential diagnosis
Differential diagnosis should include other deformities of the distal forearm (Langer 1965; Leiber & Olbrich 1981, 1135). Post-traumatic fusion of the ulnar aspect of the distal radial epiphysis may closely simulate the deformity of dyschondrosteosis, but Zweeloo Woman does not show any signs of such traumatic lesions.
Less commonly, infection may result in a similar deformity. The deformity is almost always unilateral in such cases. As is evident from all the published cases, dyschondrosteosis may be asymmetric as regards involvement, but, invariably, the criteria of dyschondrosteosis are radiologically observable, in both the forearms and the wrist regions (Langer 1965).
This is not a case of hypopituitary dwarfism, since it is not a generalised developmental failure. In achondroplasia, the most common form of skeletal dysplasia, the limbs are all shortened – the femur the most, then the humerus, then the bones of the lower legs and forearms. Adult stature rarely exceeds 140 cm (Aufderheide & Rodríguez Martín 1998, 360).
Achondrogenesis and thanatomorphic and camptomelic dysplasia are excluded from a differential diagnosis, because affected people die stillborn or at birth, and within the first year, respectively. Pseudoachondroplasia is also excluded as it is prominent at the hips (femora) and shoulder (humeri), with irregular epiphyses and widened metaphyses resulting in premature degenerative joint disease (Aufderheide & Rodríguez Martín 1998, 360-361).
Similarly, it is not a phocomelic type of dwarfism, since only a specific segment of each limb is involved and the skull is unaffected. The normal hands and feet argue against an effect of the ‘thalidomide injury’ type, for example following a viral infection. An ‘anti-Marfan’ type of syndrome can also be excluded, because the equivalent segment is involved in each limb, and the skull, hands and feet are spared (Langer 1965; Stoddart 1995, 9).
4.3 Genetic and clinical aspects of Léri-Weill dyschondrosteosis
Léri-Weill dyschondrosteosis (LWD) is a dominantly inherited skeletal dysplasia marked by disproportionate short stature and the characteristic Madelung’s wrist deformity. LWD is inherited in a pseudo-autosomal dominant manner with each child of an affected individual having a 50% chance of inheriting the mutation. Prevalence is unknown.
Short stature is present from birth with mesomelic shortening of the limbs (shortening of middle segments of the forearms and lower legs). Madelung’s deformity may only be detected at puberty. The wrist deformity is bilateral and is characterised by shortened and bowed radii and ulnae leading to dorsal dislocation of the distal ulna and limited mobility of the wrist and elbow (Langer 1965).
LWD was first described by Léri and Weill in 1929 in a French paper and since then occasional reports have appeared in the French, German and Spanish literature (Léri & Weill 1929; Langer 1965). Although the disorder occurs in both sexes, it is usually more severe in females, possibly due to sex differences in oestrogen levels (Lichtenstein et al. 1980).
However, pubertal development and fertility are generally normal in both sexes with the disorder (Ross et al. 2003). Intelligence is normal. In around 70% of cases, LWD is caused by haploinsufficiency of the short stature homeobox (SHOX) gene, which maps to the pseudoautosomal region 1 (PAR1) of the sex chromosome (Xp22.23 and Yp11.32) (Belin et al. 1998; Shears et al. 1998; Ross et al. 2001, 2003; Huber et al. 2001 ; Grigelioniene et al. 2000; Benito-Sanz et al. 2005).
Haploinsufficiency results from heterozygous mutations and deletion of SHOX, or of the downstream PAR1 (where SHOX enha"ncer elements are located). The molecular defect remains unknown in the remaining 30% of LDW cases. SHOX-associated LWD is part of a spectrum of disorders (ranging from the most severe Langer mesomelic dysplasia (LMD) to LWD, isolated Madelung’s deformity and so-called idiopathic short stature) all associated with SHOX/PAR1 abnormalities. The prevalence of SHOX/PAR1 mutation is estimated at 1/1000.
Diagnosis of suspected LWD in the Zweeloo Woman on the basis of the clinical and the radiologic findings will be attempted by means of molecular analysis in a follow-up study. However, we are aware of the fact that in some cases in which the degree of preservation may seem remarkably good, the chances of aDNA having survived in these acid wetland bodies will be very low.