Achondroplasia Aswad Habeeb Hameed Al-Obeidy FICMS GE & Hep

This is a relatively common form of short-limb dwarfism occurs in 1 in 15,000 to 1 in 40,000 live births The disease is caused by a mutation of the fibroblast growth factor receptor 3 (FGFR3) gene that results in a gain-of-function state Most cases are sporadic mutations However, when the disorder appears in families, the inheritance pattern is consistent with an autosomal dominant disorder

The primary defect is abnormal chondrocyte proliferation at the growth plate Causes development of short but proportionately thick long bones Other regions of the long bones may be relatively unaffected

Patients with achondroplasia have mutations in the gene for receptor for fibroblast growth factor (FGFR3) The syndrome is the most common cause of short-limbed dwarfism accompanied by macrocephaly and dysplasias of the metaphyses of long bones The same single-base mutation in the gene that converts glycine to arginine at position 380 in the FGFR3 gene is present in over 90% of patients

Most patients represent sporadic new mutations, and this nucleotide change must be one of the most common recurring mutations in the human genome The mutation causes unregulated signal transduction through the receptor and inappropriate development of cartilage Mutations that alter other domains of FGFR3 have been found in patients with the more severe disorders of hypochondroplasia and thanatophoric dysplasia and in a few families with a variant of craniosynostosis

The disorder is manifest by the presence of short limbs (particularly the proximal portions) Normal trunk Large head Saddle nose An exaggerated lumbar lordosis Severe spinal deformity may lead to cord compression

The homozygous disorder is more serious than the sporadic form and may cause neonatal death Pseudo-achondroplasia clinically resembles achondroplasia but has no skull abnormalities