<unk>  is caused by a mutation in fibroblast growth factor receptor 3 (FGFR3) gene. This gene is mainly responsible for making the protein, fibroblast growth factor receptor 3. This protein contributes to the production of collagen and other structural components in tissues and bones. When the FGFR3 gene is mutated it interferes with how this protein interacts with growth factors leading to complications with bone production. Cartilage is not able to fully develop into bone, causing the individual to be disproportionately shorter in height. In normal development FGFR3 has a negative regulatory effect on bone growth. In<unk> , the mutated form of the receptor is constitutively active and this leads to severely shortened bones. The effect is genetically dominant, with one mutant copy of the FGFR3 gene being sufficient to cause<unk> , while two copies of the mutant gene are invariably fatal (recessive lethal) before or shortly after birth (known as a lethal allele). This occurs due to respiratory failure from an underdeveloped ribcage. A person with<unk>  thus has a 50% chance of passing dwarfism to each of their offspring. People with<unk>  can be born to parents that do not have the condition due to spontaneous mutation.<unk>  can be inherited through autosomal dominance. In couples where one partner has<unk>  there is a 50% chance of passing the disorder onto their child every pregnancy. In situations where both parents have<unk>  there is a 50% chance the child will have<unk> , 25% chance the child will not, and a 25% chance that the child will inherit the gene from both parents resulting in double dominance and leading to severe or lethal bone dysplasia. Studies have demonstrated that new gene mutations for<unk>  are exclusively inherited from the father and occur during spermatogenesis; it has been theorized that sperm carrying the mutation in FGFR3 have a selective advantage over sperm with normal FGFR3. The frequency of mutations in sperm leading to<unk>  increase in proportion to paternal age, as well as in proportion to exposure to ionizing radiation. The occurrence rate of<unk>  in the children of fathers over 50 years of age is 1 in 1,875, compared to 1 in 15,000 in the general population.Research by urologist Harry Fisch of the Male Reproductive Center at Columbia Presbyterian Hospital in 2013 indicated that in humans this defect may be exclusively inherited from the father and becomes increasingly probable with paternal age, specifically males reproducing after 35. There are two other syndromes with a genetic basis similar to<unk> : hypochondroplasia and thanatophoric dysplasia.
Achondroplasia
Pseudoachondroplasia
Thanatophoric dysplasia
Hypochondroplasia
Cartilage–hair hypoplasia
Metaphyseal dysplasia
Rachischisis
Cranioschisis