Journal of Archaeology in the Low Countries 4-1 (October 2012)Raffaella Bianucci; Don Brothwell; Wijnand van der Sanden; Christina Papageorgopoulou; Paul Gostner; Patrizia Pernter; Eduard Egarter-Vigl; Frank Maixner; Marek Janko; Dario Piombino-Mascali; Grazia Mattutino; Frank Rühlis; Albert Zink: A possible case of dyschondrosteosis in a bog body from the Netherlands
4 Pseudopathology (deformation) and other abnormalities

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.