The most striking clinical features of Schmid metaphyseal chondrodysplasia which appear within the first 2-3 years of life are: moderate short limbs and short stature, a waddling gait, and increasing shortness of stature with age.
Given the homogeneity of mutations within the fibroblast growth factor receptor 3 (FGFR3) gene in the vast majority of patients with Ach, FGFR3 mutational analysis can be offered in every instance where a short-limb disorder is ultrasonographically detected in the latter stages of pregnancy.
Molecular analysis of the EVC and EVC2 genes is helpful in genetic counseling in cases with prenatally detected postaxial polydactyly, thoracic narrowness, short limbs and endocardial cushion defects.
Both Evc and Evc2 proteins localize to the basal bodies of primary cilia and analysis of an Ellis-van Creveld mouse model, which includes the limb shortening and tooth abnormalities of EvC patients, has demonstrated Hedgehog signaling defects in the absence of Evc.
Mutations of GDF5 are associated with several human and animal diseases that are characterized by skeletal deformity such as short digits and short limbs.
Metatropic dysplasia (MD), is a rare skeletal dysplasia occurring predominantly in infants characterized by a distinctive long torso and short limbs; it is as a result of mutations in the TRPV4 gene.
Consistent with strong tendon expression, Adamtsl2 conditional deletion in limb mesenchyme using Prx1-Cre led to tendon anomalies, albeit with normal collagen fibrils, and distal limb shortening, providing a mouse model for geleophysic dysplasia.
We show here that Gli2 mutant mice exhibit severe skeletal abnormalities including cleft palate, tooth defects, absence of vertebral body and intervertebral discs, and shortened limbs and sternum.
Disproportionate growth with short limbs has been documented in this condition, and a target gene of short stature homeobox, connective tissue growth factor (Ctgf), has been described.
Mutations in ROR2, encoding a receptor tyrosine kinase, can cause autosomal recessive Robinow syndrome (RRS), a severe skeletal dysplasia with limb shortening, brachydactyly, and a dysmorphic facial appearance.
Consistent with strong tendon expression, Adamtsl2 conditional deletion in limb mesenchyme using Prx1-Cre led to tendon anomalies, albeit with normal collagen fibrils, and distal limb shortening, providing a mouse model for geleophysic dysplasia.
Short stature in combination with ichthyosis or alopecia, cataracts, and limb shortening in an adult should prompt consideration of a diagnosis of CDPX2.