Endocrine Abstracts

Leri-Weill Dyschondrosteosis (LWD) is a skeletal dysplasia resulting in short stature and mesomelic limb-shortening; Madelung deformity of the wrist is often present. Mutation or deletion of the SHOX gene is the underlying cause of LWD. SHOX plays a role in regulating proliferation and maturation of chondrocytes. It is located in the pseudoautosomal region of the sex chromosomes (Xp22.3/Yp11.3); males and females usually have 2 functioning copies. Turner syndrome (TS) affects approximately 1 in 2500 girls and haploinsufficiency of SHOXcauses the short stature associated with TS; moreover Madelung deformity is sometimes seen. SHOX deletions may additionally be associated with proportionate ‘idiopathic’ short stature. The overlapping skeletal phenotypes can cause diagnostic uncertainty. Molecular and cytogenetic analysis can be required in order to distinguish LWD and TS. We present 3 cases which demonstrate the diagnostic challenges of differentiating these conditions.

1. Adult female with a diagnosis of mosaic TS made in childhood. Further investigation demonstrated a normal karyotype and a SHOXmutation consistent with LWD.

2. Teenage female under investigation for short stature and suspected skeletal dysplasia. Found to have mosaic TS with a complex structural rearrangement of the second X with significant reproductive implications.

3. Adult female presenting with Madelung deformity of the wrist. Karyotype revealed a diagnosis of mosaic TS with deletion of SHOX on the second X. Correct diagnosis is important as it has implications for both management and genetic and reproductive counselling. Referral to Clinical Genetics should be considered for patients with features of either condition.