Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

Léri-Weill Dyschondrosteosis (LWD), Langer Mesomelic Dysplasia (LMD), Idiopathic Short Stature

Dipl.-Biol. Christina Sofeso

Scientific Background

Léri-Weill dyschondrosteosis (LWD) is a pseudo-autosomal dominant inherited disproportionate short stature syndrome characterized by mesomelic shortening of the limbs. Madelung’s deformity of the wrists is typical, developing throughout life but usually during puberty. In most cases, the disease is caused by a haploinsufficiency of the SHOX gene, which is located in the pseudo-autosomal region (PAR1) on the short arm of both sex chromosomes. The SHOX (short stature homobox) gene codes for a transcription factor that has a role in chondrocyte function in the growth plate and is important for normal development of the limbs.

Pathogenic mutations in the SHOX gene have an incidence of approximately 1 in 1,000 among Caucasians and causal mutations in the SHOX gene are detected in up to 70% of all LWD cases. Over 80% of these mutations are deletions of the entire gene or large sections and its regulatory elements. The complete loss of SHOX activity due to homozygous or compound heterozygous changes in the SHOX gene results in Langer mesomelic dysplasia (LMD). LMD has a considerably more severe course than LWD.

As well as LWD and LMD, a SHOX deficiency has also been associated with the skeletal changes of Turner syndrome as well as with 2-5% of cases of idiopathic short stature. This can make it significantly more complicated to distinguish between LWD and other types of short stature. Moreover, the clinical phenotype of SHOX mutations varies strongly and even within a family with carriers of the same mutation may range from severe disproportionate short stature to mild short stature, with or without clinically and radiologically detectable anomalies. Molecular genetic diagnostics helps with the timely diagnosis of a SHOX deficiency and possible treatment of the growth disorder with growth hormone.


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