© 2018, GENASSIST, Inc.

By Keith S. Wexler, MBA, CFO, Business Development Director GENASSIST, Inc.

Paul Wexler, M.D., F.A.C.O.G., Medical Director, GENASSIST, Inc.

Clinical Professor, Department of OB/GYN, University of Colorado Health Sciences Center

Clinical Professor, Division of Genetics/Dept. of Pediatrics, Univ. of Colorado/The Children’s Hospital

Leri-Weil Dyschondrosteosis is inherited in an autosomal dominant manner and is due to a deletion or mutation in the SHOX gene, also called the Short Stature Homeobox gene which is on each X chromosome (Xp22.33) and

Y chromosome (Yp11.3).

The SHOX gene plays a major role in stature and development of the skeleton particularly the arms and legs. Both males and females have two copies of the SHOX gene.  The disease is often more severe in females.  A mutation in one of the SHOX genes can cause the disorder. 

Family members affected with Leri-Weil Dyschondrosteosis can have short stature and shortened long bones and each family member can present differently with symptoms from [mild to severe].

As with most autosomal dominant disorders, the severity may be variable and might explain the difference in family members.

It is believed that SHOX gene deficiency is probably more common than previously diagnosed perhaps affecting as many as 1:2000 individuals.

Wrist deformities known as the Madelung Deformity often serves as a clue to a SHOX gene deletion or mutation and is a more severe manifestation of the disorder. 

Other cases with findings similar to Leri-Weil Dyschondrosteosis have been described without evidence of the SHOX gene mutation.

The risk to each child to inherit one X chromosome with the SHOX gene mutation is 1:2 or 50%. Some individuals with the disease will have a SHOX gene mutation on each of their sex chromosomes giving a mother a 100% risk for passing an abnormal gene to all children, male or female.

A SHOX mutation on one X chromosome and the condition in a child inheriting that X chromosome may be variable in severity.

Recommend ultrasound at 4-6 week intervals during the pregnancy to monitor bone growth and evaluate the wrists.