What is Polydactyly?
Polydactyly is a genetic condition characterized by the presence of additional fingers or toes on at least one limb. [1] The most common types of polydactyly are called ‘postaxial’ and ‘preaxial.’ Postaxial polydactyly describes the development of an additional pinky finger/toe, while preaxial polydactyly describes the development of an additional thumb/big toe. [2] The additional digits range in functionality from small and entirely undeveloped to fully-functional. Polydactyly arises from genetic errors in early embryonic development. [3]
Examples of pre- and postaxial polydactyly
Polydactyly and the GLI3 Gene
One of the genes associated with polydactyly is GLI3, a transcription factor involved in the Hedgehog signaling pathway. [3] The Hedgehog pathway is essential to embryonic organ development in vertebrates. GLI3, lacking Hedgehog signaling, is post-transcriptionally modified into GLI3R, a repressor that blocks the transcription of genes involved in organ development. [4] When GLI3 receives Hedgehog signaling, it is converted into GLI3A, an activated form that promotes target gene expression. The ratio of GLI3R/GLI3A is crucial to proper organ development, including the development of the proper number of digits. [4] The biological mechanism determining digit number and placement (and GLI3's role in that mechanism) is currently unknown, as is the explanation for the broad range of polydactly phenotypes arising from GLI3 mutations. [3]
Figure 1. GLI3 is activated by the Hedgehog signaling pathway and travels into the nucleus, where it acts as a transcription factor
Diagnosis and Treatment
Polydactyly is typically discovered via ultrasound and, following birth, can be further characterized through X-ray imaging to view the extent of bone development in the extra digits. [5] Polydactyly is rarely harmful by itself, but is frequently associated with other, more serious genetic disorders, such as Grieg cephalopolysyndactyly syndrome and Pallister-Hall syndrome. Patients with these syndromes display polydactyly accompanied by developmental abnormalities of the head, eyes, brain, and kidneys, sometimes resulting in frequent seizures or neurodevelopmental delay. [3] Polydactyly of the toes can affect balance and gait when learning to walk. Surgery to remove the additional digits is usually performed in the first year of life, and ranges in complexity based on how well-developed the digits are. [5]
References
1 Patel, R., Singh, C. B., Bhattacharya, V., Singh, S. K., and Ali, A. (2016) GLI3 mutations in syndromic and non‐syndromic polydactyly in two Indian families. Congenital Anomalies, 56: 94– 97. doi: 10.1111/cga.12139.
2 Human Phenotype Ontology. (November 2019). Polydactyly HP:0010442. Retrieved from https://hpo.jax.org/app/browse/term/HP:0010442.
3 Crapster, J. A., Hudgins, L., Chen, J. K., & Gomez-Ospina, N. (2017). A novel missense variant in the GLI3 zinc finger domain in a family with digital anomalies. American journal of medical genetics. Part A, 173(12), 3221–3225. doi:10.1002/ajmg.a.38415
4 Carballo, G.B., Honorato, J.R., de Lopes, G.P. et al. A highlight on Sonic hedgehog pathway. Cell Commun Signal 16, 11 (2018). https://doi.org/10.1186/s12964-018-0220-7
5 Ahmed, H., Akbari, H., Emami, A., & Akbari, M. R. (2017). Genetic Overview of Syndactyly and Polydactyly. Plastic and reconstructive surgery. Global open, 5(11), e1549. doi:10.1097/GOX.0000000000001549
2 Human Phenotype Ontology. (November 2019). Polydactyly HP:0010442. Retrieved from https://hpo.jax.org/app/browse/term/HP:0010442.
3 Crapster, J. A., Hudgins, L., Chen, J. K., & Gomez-Ospina, N. (2017). A novel missense variant in the GLI3 zinc finger domain in a family with digital anomalies. American journal of medical genetics. Part A, 173(12), 3221–3225. doi:10.1002/ajmg.a.38415
4 Carballo, G.B., Honorato, J.R., de Lopes, G.P. et al. A highlight on Sonic hedgehog pathway. Cell Commun Signal 16, 11 (2018). https://doi.org/10.1186/s12964-018-0220-7
5 Ahmed, H., Akbari, H., Emami, A., & Akbari, M. R. (2017). Genetic Overview of Syndactyly and Polydactyly. Plastic and reconstructive surgery. Global open, 5(11), e1549. doi:10.1097/GOX.0000000000001549
Images
Header: https://www.brighthub.com/science/genetics/articles/62988.aspx
Image 1: https://www.medicalnewstoday.com/articles/321607.php#symptoms
Image 2: https://www.handsurgeryresource.com/polydactyly
Image 3: http://p0lycephaly.blogspot.com/2014/05/growth-evolution-supernumerary-body.html
Figure 1: https://www.novusbio.com/hedgehogpathway.html
Image 1: https://www.medicalnewstoday.com/articles/321607.php#symptoms
Image 2: https://www.handsurgeryresource.com/polydactyly
Image 3: http://p0lycephaly.blogspot.com/2014/05/growth-evolution-supernumerary-body.html
Figure 1: https://www.novusbio.com/hedgehogpathway.html
This website was last updated 5/10/2020, by Tanner Zocher, an undergraduate student at the University of Wisconsin-Madison studying genetics and genomics. You can contact him at [email protected].
This web page was produced as an assignment for Genetics 564, an undergraduate capstone course at UW-Madison.
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https://genetics564.weebly.com/