Polydactyly is a congenital genetic disorder that causes the affected individual to exhibit additional digits on the hands and/or feet. These digits may just be a mass of tissue or a fully functional digit. HealthHearty explores and discusses the true genetic basis for the emergence of this particular condition.
Did You Know?
Akshat Saxena, from India, holds the world record for the highest number of digits. He possesses 7 digits on each hand, and 10 digits on each foot, making it a total of 34 digits.
Polydactyly or polydactylism is a term derived from the Greek words ‘polys’, meaning ‘many’, and ‘daktylos’, meaning ‘finger’. It is also called hyperdactyly, and involves the development of supernumerary fingers or toes in an individual. In other words, people affected by this condition exhibit more than 5 fingers/toes on each hand/foot. It has an incidence of 1 in every 500 live births, and is seen to be more common in people from African origins as compared to those of Caucasian descent. It is also more common in males than females.
The extra digit may present itself in three possible ways: a mass of tissue and muscle; tissue and a bony growth devoid of any joints; or tissue and bone with a joint, making it functional. The level of functionality increases with the increase in the level of bone development. This also increases the surgical difficulty in removing this outgrowth, if required. This condition can be diagnosed by carrying out physical examinations and X-rays of the additional digit. Ultrasound can be used to detect it during the course of pregnancy as well. The course of treatment is decided based on the degree of development of the digit.
The extra digit may appear in three locations along the hand or foot. It most commonly appears on the ulnar (little finger) side of the hand. Less common is its appearance on the radial (thumb) side of the hand, and it is extremely rare to be found within the middle three digits. These presentations are used as a basis to classify polydactyly into its various types: Ulnar or postaxial, radial or preaxial, and central polydactyly. The extra digit in these conditions is most often due to an abnormal forking in the existing digit during its development, or it may originate from the wrist itself, as in the case of a normal digit.
Genetic Basis of Polydactyly
Polydactyly can occur by itself, as a part of a congenital syndrome. Based on this, the inheritance pattern of this condition varies. If it is a single gene disorder, manifesting by itself, then it is most likely due to an error in the GLI3 zinc finger gene, and it shows an autosomal dominant inheritability. Hence, only one copy of the mutated gene is enough to induce this condition. Also, if at least one parent has this presentation, then each progeny has a 50% chance of inheriting the trait.
However, there have been multiple documented cases of polydactyly occurring in association with syndromic disorders. In such a case, the inheritance of the trait depends on the type of genetic errors, as well as the genes involved in that particular disorder. In other words, in case of a syndromic presentation, the condition may arise due to genetic mutation in genes other than GLI3. Also, the inheritance pattern will be determined by the genes associated with the particular syndrome. This multifactorial case may follow the patterns of autosomal recessive or X-linked trait. In case the trait is autosomal recessive, both parents must carry at least one copy of the mutated gene (carriers), for the child to develop this trait. If both or either one of the parents do not possess the mutated gene, then the child is born with a normal set of 5 digits on each hand and foot.
On the other hand, if the condition is sex-linked, there are two possibilities. The defunct gene may be X-linked or Y-linked. This discernment is important, as the X-linked inheritance pattern can be dominant or recessive. This is possible due to the fact that, both male and females possess at least one X chromosome. Here, if the trait is dominant, all progeny are affected, but if the trait is recessive, it will only be seen in case of females. On the other hand, in case of Y-linked inheritance, there is only dominant inheritance, hence, the males will show polydactyly, and so will their male offspring. It may sometimes be difficult to even decipher the mode of inheritance due to the interactions of the involved genes, and there have been cases of spontaneous cases of polydactyly.
This leads to the conclusion that, the condition follows a very varied pattern of inheritance, which is based on factors like family history, spontaneous mutations, nature of mutation, gene affected, etc. Hence, it is impossible to ascribe a universal genetic basis to the propagation of this condition in the population. The exact pattern can differ from individual to individual, based on his/her genetic makeup. The following table outlines a few syndromic and non-syndromic presentations of polydactyly, accompanied by the genes involved, and the mode of their inheritance.
|Associated Disorder||Genes Involved||Inheritance|
|Achondrogenesis, Type II||COL2A1||Autosomal Recessive|
|Acrocallosal Syndrome||GLI3||Autosomal Recessive|
|Apert Syndrome||FGFR2||Autosomal Dominant|
|Asphyxiating Thoracic Dystrophy||IFT80, DYNC2H1||Autosomal Recessive|
|Atelosteogenesis Type III||FLNB||Autosomal Dominant|
|Baller-Gerold Syndrome||RECQL4||Autosomal Recessive|
|Bardet-Biedl Syndrome||BBS1, BBS2, ARL6, BBS4, BBS5, MKKS, BBS7, TTC8, BBS9, BBS10, BBS11, BBS12||Autosomal Recessive|
|Basal Cell Nevus Syndrome||PTCH1||Autosomal Dominant|
|Beckwith-Wiedemann Syndrome||CDKN1C||Autosomal Dominant|
|Bloom Syndrome||RECQL3||Autosomal Recessive|
|Brachydactyly Type B||ROR2||Autosomal Dominant|
|Brachydactyly Type C||GDF5||Autosomal Dominant|
|Branchiooculofacial Syndrome||TFAP2A||Autosomal Dominant|
|C Syndrome||CD96||Autosomal Dominant|
|C-LIKE Syndrome||CD96||Autosomal Dominant|
|Carpenter Syndrome||RAB23||Autosomal Recessive|
|CHAR Syndrome||TFAP2B||Autosomal Dominant|
|CHARGE Syndrome||CHD7, SEMA3E||Autosomal Dominant|
|Chondrodysplasia, Grebe Type||GDF5||Autosomal Recessive|
|Chondrodysplasia Punctata 2||EBP||Sex-linked|
|De Smet Complex Synpolydactyly||FBLN1||Autosomal Dominant|
|Chondrodystrophy; Advanced Bone Age||CANT1||Autosomal Recessive|
|Diamond-Blackfan||RPS19, RPL5, RPL11||Autosomal Recessive|
|Duane-Radial Ray Syndrome||SALL4||Autosomal Dominant|
|Ellis-Van Creveld Syndrome||EVC, EVC2||Autosomal Recessive|
|Fanconi Pancytopenia Syndrome||FANCA, FANCB, BANCC, FANCD1, FANCD2, FANCE, FANCF, XRCC9, FANCI, FANCJ, PHF9, FANCM, FANCN, FANCO||Autosomal Recessive|
|Fibular Aplasia or Hypoplasia||WNT7A||Autosomal Recessive|
|Focal Dermal Hypoplasia||PORCN||Sex-linked|
|Frontonasal Dysplasia||ALX3||Multiple modes|
|Greig Cephalopolysyndactyly Syndrome||GLI3||Autosomal Dominant|
|Holt-Oram Syndrome||TBX5||Autosomal Dominant|
|Hydrolethalus Syndrome 1||HYLS1||Autosomal Recessive|
|Hydrops-Ectopic Skeletal Dysplasia||LBR||Autosomal Recessive|
|Joubert Syndrome||CXORF5, INPP5E, TMEM216, RPGRIP1L||Multiple modes|
|Lacrimoauriculodentodigital Syndrome||FGFR2, FGFR3, FGF10||Autosomal Dominant|
|McKusick-Kaufman Syndrome||MKKS||Autosomal Recessive|
|Meckel Syndrome||CC2D2A, CEP290, MKS1, TMEM67, RPGRIP1L||Autosomal Recessive|
|Nijmegen Immunodeficiency Syndrome||NBN||Autosomal Recessive|
|Oculo-dento-digital Syndrome||GJA1||Autosomal Dominant|
|Otopalatodigital Syndrome, Type II||FLNA||Sex-linked|
|Pallister-Hall Syndrome||GLI3||Autosomal Dominant|
|Polydactyly, Postaxial||GLI3||Multiple modes|
|Polydactyly, Preaxial||SHH, ZRS||Autosomal Dominant|
|Renal-Hepatic-Pancreatic Dysplasia||NPHP3||Autosomal Recessive|
|Robinow-Sorauf Syndrome||TWIST||Autosomal Dominant|
|Rubinstein-Taybi Syndrome||CBP||Autosomal Dominant|
|Schinzel-Giedion Midface-Retraction Syndrome||SETBP1||Autosomal Recessive|
|Simpson-Golabi-Behmel Syndrome, Type I||GPC3||Sex-linked|
|Smith-Lemli-Opitz Syndrome||DHCR7||Autosomal Recessive|
|Thanatophoric Dysplasia, Type I||FGFR3||Autosomal Dominant|
|Tibial Hemimelia-Polydactyly-Club Foot||PITX1||Autosomal Dominant|
|Townes-Brocks Syndrome||SALL1||Autosomal Dominant|
|Ulnar-Mammary Syndrome||TBX3||Autosomal Dominant|
|Weyers Acrofacial Dysostosis||EVC||Autosomal Dominant|
It must be noted, however, that the condition arises not only as a result of mutations in the genes themselves, but also due to errors in cis-regulatory elements responsible for the expression of a specific gene, or errors in signal transduction pathway molecules. Also, there are documented cases of sporadic occurrences of polydactyly caused due to disruption of cells during embryonic development. Such spontaneous cases are not heritable.
This condition occurs not only in humans, but also is cats and dogs. It is also a common trait in chicken and mice. Evolutionary research suggests that, such mutations cause a revertion to ancestral phenotypes, since approximately 375 million years ago, there existed tetrapods possessing as many as 8 digits per appendage. This suggests that somewhere along the evolutionary timeline, the extra fingers were shed off, and the five-finger plan emerged as the predominant form. This notion is supported by the fact that, various animals that have evolved in parallel to humans also possess the five-finger skeletal structure. These include dolphins, bats, cats, dogs, mice, etc.