Genetics of Achondroplasia

Abstract

Achondroplasia is an autosomal dominant disorder, which results in abnormal bone growth and leads to short stature. This disease occurs approximately in 1 in 25,000 births, and is common in all races. Achondroplasia is one of the oldest genetic disorders described: some of the ancient Egyptian medical texts depict patients with Achondroplasia. Achondroplasia affects bone growth, especially of the long bones of arms and legs. The meaning of the word Achondroplasia is "without cartilage". Even though in affected persons cartilage is formed, it develops into bones very slowly. This results in short stature and reduced height, approximately 1.22 meters (4'0"), in adults. Achondroplasia is usually diagnosed after birth by a physical exam and X-rays. The patients have relatively normal size torso and shortened arms, legs, fingers and toes. Babies with Achondroplasia have difficulties sitting, standing and walking without support. 99% of the affected individuals have a single point mutation in the Fibroblast Growth Factor Receptor gene 3 (FGFR 3), which is located on chromosome 4. As a result of this mutation, glycine is substituted for arginine at codon 380 of FGFR 3. Such a mutation results in an abnormal cartilage and fibrous connecting tissue formation. Therefore, not only bones, but the ligaments, tendons and muscles of the patient with Achondroplasia are affected.

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• Genes and mutations involved in development of Achondroplasia
• Hereditary vs. new mutations in Achondroplasia
• Connection between Achondroplasia and other disorders
• Prenatal screening and diagnosis
• Treatment options