In other species: rock pigeon , chicken , turkey , dog , horse , pig , Arabian camel , guanaco , llama , Western roe deer , taurine cattle , goat , sheep , domestic guinea pig , alpaca , springbok

Categories: Limbs / fins / digit / tail phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 174500 (trait) , 605522 (gene) , 188740 (trait)

Links to MONDO diseases: No links.

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal dominant

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2008

Cross-species summary: Often called preaxial polydactyly (PPD)

Species-specific symbol: Pd

History: This trait occurs at a very high frequency in the population of cats that has long existed in the grounds of Ernest Hemingway's house in Key West, Florida (www.hemingwayhome.com). These "Hemingway" cats descend from a cat given to Hemingway by a ship's captain in the 1930s (Gwin, 2007).

Inheritance: Hamelin et al. (2020): "Polydactyly in Maine Coon cats is inherited as an autosomal dominant trait with incomplete penetrance and variable expressivity, and this trait is characterised by genetic heterogeneity in the Maine Coon breed."

Molecular basis: Polydactyly results from faults in the regulation of the developmental gene Sonic Hedgehog (SHH), which is expressed only at the border of the posterior limb bud, in a region called the zone of polarizing activity (ZPA). The faults in regulation result from mutations in an enhancer located in the LMBR1 gene, located about 1 MB upstream of SHH. The enhancer is called the ZPA regulatory sequence (ZRS). Thus polydactyly results from mutations in ZRS, which affect expression of SHH in the developing limb bud. Lettice et al. (2008) showed that polydactyly in cats is due to point mutations in the control region ZRS, whose product regulates the transcription and translation of the signalling molecule sonic hedgehog (SHH). All of the Hemingway polydactylous cats examined had the same point mutation; British polydactylous cats had two different point mutations in the same gene. Mutations in ZRS in humans and mice also give rise to polydactyly.

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

Clinical features: Polydactyly in cats is a congenital deformity, clinically characterized by the presence of more than 18 digits in total at birth, with the additional digit(s) on either their front and/or hind limb(s). A variety of combinations of different numbers of extra toes per paw have been observed, while the distribution of extra digits exhibits a non-continuous statistical pattern (Lange et al., 2013). Polydactyl cats not only have an unusual number and shape of digits, but they may also exhibit unharmful altered conformation of carpus and tarsus (Hamelin et al., 2016). IT thanks DVM student Ophelia Xinran Pan, who provided the basis of this contribution in May 2023.

Breeds: Domestic Shorthair, Maine Coon (Cat) (VBO_0100154), Pixiebob (Cat) (VBO_0100191).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below

Associated genes: