1. Leri-Weill dyschondrosteosis Department of Orthopaedic Surgery, College of Medicine, Dong-A University, Busan, Korea Sung Soo Kim, M.D. Jong Ill Kwak, M.D.

2. CC: Left wrist deformity F / 12Y PHx: N-C FHx: Mother & her brother-- similar deformities on both wrists

3. P/E Left wrist: prominent dorsal dislocated ulna head, ulna deviation of the hand, ROM—WNL

4. P/E Short stature (150 cm, 25 percentile) with mild mesomelic shortening

5. RADIOGRAPHY Radial inclination 35˙ Radial inclination 47˙

6. RADIOGRAPHY

7. MRI

9. Madelung deformity Developmental abnormality of the wrist Anatomic changes in the radius, ulna, and carpal bones, leading to palmar and ulnar wrist subluxation More common in female patients and is usually present bilaterally Evident clinically between the ages of 6 and 13 years

10. Madelung deformity Growth disturbance in the volar-ulnar distal radial physis leading to a typical appearance of the upper extremities The majority of Madelung deformity case caused by hereditary dyschondrosteosis of the wrist

11. Madelung deformity Often is associated with additional clinical abnormalities, particularly delayed puberty and menstrual disorders, as well as sexual chromosome aberrations Aesthetic deformity, functional problems, pain Corrective surgical procedures

12. Tx of Madelung deformity Splint & NSAID Osteotomy of the distal radius & ulnar recession E/F with radius osteotomy & lengthening Epiphyseodesis Epiphysiolysis with fat interposition Distal radioulnar joint arthrodesis with distal ulnar pseudoarthrosis Ulnar resection + radius corrective osteotomy

13. Leri-Weill dyschondrosteosis A skeletal dysplasia with mesomelic short stature and Madelung deformity Cubitus valgus, coxa valga Genu varum, ankle valgus

14. Leri-Weill dyschondrosteosis SHOX (short stature homeobox-containing gene) SHOX plays a role in chondrocyte function in the growth plate Deletions & point mutations lead to haploinsufficiency Autosomal dominant inherited SHOX haploinsufficiency have been found in LWD and in a variable proportion of patients with idiopathic short stature (ISS)

15. Leri-Weill dyschondrosteosis Defects in SHOX have been identified in approximately 60% of LWD cases Whereas, in the remaining approximately 40% the molecular basis is unknown This suggests either genetic heterogeneity or the presence of mutations in unanalyzed regions of SHOX, such as the upstream, intragenic, or downstream regulatory sequences PAR 1(Pseudoautosomal region 1) deletions downstream of SHOX: 15%

16. Leri-Weill dyschondrosteosis Abnormalities in the growth plate may lead to short stature and skeletal deformity including Leri Weill syndrome Which has been shown to result from deletions or mutations in the SHOX gene, a homeobox gene located at the pseudoautosomal region of the X and Y chromosome

17. Leri-Weill dyschondrosteosis At final height females were 14.4 cm shorter and males 5.3 cm shorter than normal siblings (135-170 cm) SHOX haploinsufficiency leads to short arms in 92%, bilateral Madelung deformity in 73% and short stature in 54% Females were more severely affected than males

18. Leri-Weill dyschondrosteosis Growth failure occurred during the first year of life Children with a severe degree of wrist deformity were significantly shorter than those with mild deformities. 24 months of rhGH was a safe and effective therapy and the effect of GH therapy varied between individuals

19. Langer mesomelic dysplasia (LMD) Caused by mutations in the SHOX gene. The more severe LMD results from the homozygous loss of SHOX

20. DIFFERENTIAL DIAGNOSIS Traumatic distal radius physeal arrest Congenital anatomic variant Multiple exostosis Ollier disease Turner syndrome Noonan's syndrome

21. Turner syndrome Swelling of foot & hand Cubitus valgus, genu valgum Short stature, scoliosis Clinical clues to the diagnosis of SHOX haploinsufficiency in childhood include short stature, short limbs, wrist changes, and tibial bowing.

22. Noonan's syndrome Craniofacial anomalies, i.e. ptosis, webbing of the neck and a deep nuchal hairline Skeletal deformities such as short stature, clinodactyly, pectus carinatum and funnel chest Other organ anomalies, mainly cardiac valve disease, less often testicular retention or kidney malformations Madelung like deformity of the wrist

23. Thank you for your attention