Leri-Weill dyschondrosteosis 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.

CC: Left wrist deformity CC: Left wrist deformity

F / 12Y

PHx: N-C

FHx: Mother & her brother--similar deformities on both wrists

P/E P/E

Left wrist: prominent dorsal dislocated ulna head, ulna deviation of the hand, ROM—WNL

P/E P/E

Short stature (150 cm, 25 percentile) with mild mesomelic shortening

RADIOGRAPHY RADIOGRAPHY

Radial inclination 35˙

Radial inclination 47˙

RADIOGRAPHY

RADIOGRAPHY

MRI MRI

MRI MRI

Madelung deformity 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

Madelung deformity 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

Madelung deformity 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

Tx of Madelung deformity Tx of Madelung deformity Splint & NSAIDOsteotomy of the distal radius & ulnar recessionE/F with radius osteotomy & lengtheningEpiphyseodesisEpiphysiolysis with fat interpositionDistal radioulnar joint arthrodesis with distal ul

nar pseudoarthrosis Ulnar resection + radius corrective osteotomy

Leri-Weill dyschondrosteosis Leri-Weill dyschondrosteosis

A skeletal dysplasia with mesomelic short stature and Madelung deformity

Cubitus valgus, coxa valga

Genu varum, ankle valgus

Leri-Weill dyschondrosteosisLeri-Weill dyschondrosteosisSHOX (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)

Leri-Weill dyschondrosteosis 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 S

HOX: 15%

Leri-Weill dyschondrosteosisLeri-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

Leri-Weill dyschondrosteosisLeri-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

Leri-Weill dyschondrosteosis 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

Langer mesomelic dysplasia (LMD)

Langer mesomelic dysplasia (LMD)

Caused by mutations in the SHOX gene.

The more severe LMD results from the homozygous loss of SHOX

DIFFERENTIAL DIAGNOSIS DIFFERENTIAL DIAGNOSIS

Traumatic distal radius physeal arrestCongenital anatomic variantMultiple exostosisOllier disease Turner syndrome Noonan's syndrome

Turner syndromeTurner 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.

Noonan's syndrome 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

Thank you for

your attention