Achondroplasia

Achondroplasia is the most common disproportionate skeletal dysplasia, characterized by rhizomelic limb shortening, macrocephaly, midface hypoplasia and lumbar lordosis. Major complications include foramen magnum and spinal stenosis, sleep-disordered breathing, recurrent otitis and orthopedic problems. More info

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Genetics

Autosomal dominant gain-of-function variants in FGFR3; more than 98% of affected individuals carry p.Gly380Arg. Most cases are de novo, with a paternal-age effect. Biallelic achondroplasia is usually lethal.

Molecular Mechanism

Constitutive FGFR3 signaling, primarily through RAS-MAPK and STAT pathways, suppresses growth-plate chondrocyte proliferation and differentiation. This selectively impairs endochondral ossification while intramembranous bone formation is relatively preserved.

Therapy

Multidisciplinary surveillance and treatment address neurologic, respiratory and orthopedic complications. Vosoritide, a C-type natriuretic peptide analogue that counteracts FGFR3-MAPK signaling, is approved for growing children with open epiphyses; it does not correct established adult anatomy.

CCP Activity

Mechanistic and preclinical research is conducted in collaboration with Dr. Pavel Krejci at Masaryk University. The programme evaluates small-molecule modulation of FGFR3-dependent signaling using disease-relevant cellular and in vivo growth-plate endpoints.