Léri-Weill dyschondrosteosis (LWD, also referred to as Léri-Weill syndrome [LWS]) is a heritable disorder characterized by short stature, mesomelic shortening of the limbs (shortening of the forearm and lower leg relative to the proximal limbs), and Madelung deformity (bowing of the radius
with dislocation of the proximal ulna). However, LWD is associated with significant phenotypic variability, and affected females are often more severely affected than males. The most frequent feature among LWD patients is mesomelia, which is often identified by an increased sitting height to
standing height ratio. The growth deficiency characteristic of LWD, which is typically evident in early childhood, leads to a mean adult height approximately 2.2 standard deviations (SD) below the mean. However, some children and adults with LWD are of normal stature (± 2 SD). In addition, the
development of Madelung deformity, which is often considered a hallmark feature of LWD, is not found in all LWD patients. In those with Madelung deformity, it generally becomes apparent in midto-late childhood and often worsens during puberty. Additional clinical features that may be present
in individuals with LWD include a highly arched palate, bowing of the tibias, increased carrying angle at the elbow (cubitus valgus), scoliosis, and the appearance of muscular hypertrophy. Overall, the clinical features of LWD become more apparent with age. As a result, the clinical diagnosis of LWD is often not made until late childhood or adolescence. The management of patients with LWD may include growth hormone therapy, the use of wrist splints and ergonomic devices for Madelung deformity, and potentially, surgery to help restore wrist function. LWD is inherited in a pseudoautosomal dominant manner and results from haploinsufficiency of the short stature homeobox (SHOX) gene. The SHOX gene (also known as PHOG for pseudoautosomal homeobox-containing osteogenic gene) is located in the pseudoautosomal region (PAR1) of the X and Y chromosomes (at Xpter-p22.32 and Ypter-p11.2) and encodes a homeodomain transcription factor. Most LWD patients are found to carry deletions of the entire SHOX gene; others carry partial SHOX gene deletions or deletions involving a recently identified downstream enhancer element. A minority of individuals with LWD have smaller intragenic SHOX sequence variants. Individuals with two nonfunctional copies of the SHOX gene have Langer mesomelic dysplasia, a more severe bone dysplasia characterized by severe short stature and an underdevelopment or absence of the ulna and fibula.