Leri-Weill Disease

Michael W. Matchette, MD; Justin Q. Ly, MD; Douglas P. Beall, MD

August 03, 2005

Summary

A 5-year-old Hispanic girl was seen for evaluation of an unusual wrist deformity bilaterally that, according her parents, had gradually worsened since the age of 3. On examination, the child's wrist deformities were concerning for dorsal dislocation of the distal ulna bilaterally, which were nonreducible. The physical examination was otherwise normal and revealed an interactive patient with signs of age-appropriate cognitive development. The parents reported no history of trauma or prior hospitalizations. The parents appear to be of normal development, although the patient's mother is only 5 feet tall, which is much shorter than her siblings. The growth chart shows that the patient is in the 40th percentile for weight but only in the 5th percentile for height. The patient's short stature appears to be primarily related to under-development of the lower extremities. To better assess the apparent skeletal abnormalities, radiographs of the patient's extremities were obtained (Figures 1 and 2).

(A) Oblique radiograph of the left upper extremity shows an abnormally shortened humerus and radius, with mid-radius convex deformity and resultant widening of the interosseous space. At the distal radioulnar joint, there is abnormal widening. Similar changes are seen involving the contralateral extremity. (B) Anteroposterior radiograph of the right forearm shows similar shortening and bowing of the radius. The distal ends of the radius and ulna form a characteristic "V" shape. This appearance is consistent with Madelung's deformity, which is a bilateral finding.

(A) Oblique radiograph of the left upper extremity shows an abnormally shortened humerus and radius, with mid-radius convex deformity and resultant widening of the interosseous space. At the distal radioulnar joint, there is abnormal widening. Similar changes are seen involving the contralateral extremity. (B) Anteroposterior radiograph of the right forearm shows similar shortening and bowing of the radius. The distal ends of the radius and ulna form a characteristic "V" shape. This appearance is consistent with Madelung's deformity, which is a bilateral finding.

Anteroposterior radiograph of the distal left lower extremity reveals fibular shortening (also present on the right). Bilateral femur shortening or mesomelia (not shown) contributes to dwarfism in this patient.

Diagnosis and Imaging Findings

Leri-Weill disease.

The radiographic evaluation reveals bilaterally symmetric skeletal abnormalities that include Madelung's deformities and limb shortening (Figures 1 and 2). The constellation of clinical and radiographic findings is consistent with Leri-Weill disease (LWD).

Discussion

Leri-Weill disease, which has been described as a dyschondrosteosis, is a rare syndrome causing meso-melic shortening of the limbs. In 1998, Belin et al[1] discovered that Leri-Weill dyschondrosteosis was due to a haploinsufficiency of the short-stature homeobox-containing (SHOX) gene, which is located on the pseudoautosomal region of the short arm of both sex chromosomes.[1,2] Although LWD can affect males with a 45,X gene pattern, it primarily affects women. The higher prevalence and severity of disease in women has been postulated to be due to complementation of SHOX by a Y-specific growth gene, or by the regulatory role exerted on skeletal development by the sex steroids.[2]

Since Turner syndrome is also characterized by a haploinsufficiency due to a structural deformity of the X chromosome, it would therefore seem likely for these patients to commonly present with LWD. However, in the first systematic study of LWD in Turner syndrome, Binder et al[3] found that only 1 of 54 (2%) females with known Turner's syndrome had radiographic features consistent with LWD. It is thought that this may be due to an epiphyseal protective effect from estrogen deficiency. In the absence of Turner's syndrome, the diagnosis of LWD may not be made until late childhood or adolescence. Unlike children afflicted with Turner's syndrome, who are characteristically 2 standard deviations below the normal growth curve, patients with LWD may show relatively normal growth with a growth spurt during adolescence. The rate of growth after adolescence, however, can markedly decrease.

The predominant radiologic findings include triangularization of the distal radial epiphysis with shortening of the ulnar segment, dorsal dislocation of the distal ulna that cannot be easily reduced, pyramidalization of the distal carpal row, shortening and bowing of the distal radius, and widening of the distal radioulnar joint. This constellation of findings is known as Madelung's deformity. Moreover, LWD frequently involves shortening of the middle segment of the extremities (mesomelia), leading to a moderate degree of dwarfism.[4] Involvement of the lower extremity is common and the presence of body disproportion in an individual with Madelung deformities strongly suggests the diagnosis of LWD.

Differential considerations for this condition include multiple exostosis, enchondromatosis, multiple epiphyseal dysplasia, Turner's syndrome without LWD, achondroplasia, chondroectodermal dysplasia, and hypoparathyroidism.

Conclusion

Leri-Weill disease is a rare inherited disorder characterized by deformity of the wrist, known as Madelung deformity, and mesomelic short stature. Recognition of the described characteristic radiographic findings can aid in the diagnosis of this unusual and radiographically as well as visually striking entity.

References

  1. Belin V, Cusin, Viot G, et al. SHOX mutations in dyschondrosteosis (Leri-Weill syndrome). Nat Genet.1998;19:67-69.

  2. Shears DJ, Vassal HJ, Goodman FR, et al. Mutation and deletion of the pseudoautosomal gene SHOX cause Leri-Weill dyschondrosteosis. Nat Genet.1998;19:70-73.

  3. Binder G, Fritsch H, Schweizer R, Ranke MB. Radiological signs of Leri-Weill dyschondrosteosis in Turner syndrome. Horm Res.2001;55:71-76.

  4. Langer LO Jr. Dyschondrosteosis: A hereditable bone dysplasia with characteristic roentgenographic features. Am J Roentgenol Radium Ther Nucl Med. 1965;95:178-188.