Diagnosing Achondroplasia (Short-Limbed Dwarfism)

Luca Santarelli, MD of Therachon discusses diagnosing Achondroplasia. Therachon's lead pipeline candidate, TA-46, a novel protein therapy in development for achondroplasia, the most common form of short-limbed dwarfism. Achondroplasia is an autosomal dominant disorder characterized by dwarfism and disproportionate shortness of limbs, accompanied by life-altering complications. Achondroplasia is caused by a gene alteration (mutation) in the FGFR3 gene. Approximately 97% of achondroplasia cases are caused by a single mutation in the fibroblast growth factor receptor 3 (FGFR3), a G380R substitution which results in a ligand dependent gain of function. This leads FGFR3 to send persistent rather than transient growth inhibition signals, preventing its down-regulation. The ensuing disrupted endochondral ossification, results in disproportionate shortness of limbs, and is associated with debilitating orthopedic, neurological and ENT (Ear Nose and Throat) complications. Children are typically diagnosed at birth, but increasingly parents are finding out via prenatal ultrasounds. Currently, the only available treatment / option for achondroplasia is limb lengthening, an extremely invasive surgical procedure that only addresses height but not achondroplasia-associated complications.