Polysyndactyly

Polysyndactyly
Foot polysyndactyly
SpecialtyMedical genetics

Polysyndactyly is a congenital anomaly, combining polydactyly and syndactyly, in which affected individuals have an extra finger or toe that is connected, via fusing or webbing, to an adjacent digit.[1][2]

Signs and symptoms

Presentations of polysyndactyly vary in location and size of the duplicated digit, and in the extent of webbing between digits.[2][3][4]

The extra digit is most commonly postaxial,[5] on the same side as the pinky or little toe.[3] Preaxial polysyndactyly, in which the duplicated digit is on the side of the thumb or big toe, is less common.[3] Crossed polysyndactyly, in which polysyndactyly is present on the hand and foot, and is preaxial on one and postaxial on the other, is extremely rare and often occurs with other genetic disorders.[6]

Polysyndactyly may be classified by the level of duplication. The extra digit may be small and comprise only soft tissue,[7] but usually includes at least one bone, most commonly the distal and middle phalanges.[4][8] Partial or complete duplication of the proximal phalanx, metacarpal or metatarsal can also occur.[4][7]

Fusing of the extra digit may be incomplete,[4] giving the appearance of the extra digit being partially connected to the (otherwise normal) adjacent digit. However, complete fusion of the extra digit to the adjacent digit, via soft tissue and skin, is more common.[4]

Causes

Polysyndactyly is typically inherited, in an autosomal dominant pattern.[2][6][9] The specific mutations leading to polysyndactyly are varied between among types of the condition and different families. However, many cases are caused by changes to genetic elements affecting the signaling molecule Sonic Hedgehog (SHH). Primarily, mutations are found in the zone of polarizing activity regulatory sequence, or ZRS, that controls the expression of SHH in developing limbs. Many cases of polysyndactyly are the result of duplications of the ZRS[10][11][12] or the nearby pre-ZRS region.[13][14]

Polysyndactyly can be associated with the presence of other genetic disorders. It is a hallmark of Carpenter's syndrome, an autosomal recessive disorder that is also associated with craniosynostosis, obesity, short stature, and other malformations.[15] Patients with other syndromes, including Pallister-Hall syndrome[16] and Greig cephalopolysyndactyly syndrome[17] may also display polysyndactyly of varying severity.

Polysyndactyly has full penetrance but variable expressivity; individuals who possess an allele for polysyndactyly may have a different severity of the condition. This has been seen in case studies where a parent has hexadactyly in their 4th and 5th fingers but their child has hexadactyly in their 1st, 2nd, 3rd and 4th fingers.[18]

Diagnosis

Polysyndactyly can be diagnosed in utero through sonographic and genetic testing, though sonography may be preferred due to the cost and risk associated with genetic testing.[19] Ultrasounds, typically done at the 14th to 16th week of pregnancy, can detect the presence of extra metacarpals, metatarsals, or phalanges.[19][20] Genetic testing of the fetus examines disruptions in the HOXD13 gene at 2q31-q32 and in the GLI3 gene at 7p13. These genomic regions regulate proliferation and differentiation in the limb bud, and can lead to phenotypic anomalies, including polysyndactyly, if mutated. Postnatally, polysyndactyly is diagnosed by observation of an extra digit and X-rays to confirm the presence of an extra metacarpal, metatarsal, or phalanx.[19][21]

Treatment and Prognosis

Polysyndactyly is treated through surgical excision of the extra digit. The choice of which digit to remove affects post-operative outcomes; factors that must be considered when determining which digit to excise include the neurovascular bundles, angle differences, risks for impaired circulation, post-operative appearance, and residual deformities.[5][7]

Treatment is generally aimed at normalizing both function and appearance of the affected extremity[3] and, in the case of polysyndactyly of the foot, shoe fit and comfort.[22] The underlying cause of polysyndactyly determines the overall quality of life for individuals diagnosed with this condition. If there are no comorbid or underlying genetic conditions, surgical removal of the extra digit generally results in a high quality of life. Parents of children with polysyndactyly have reported high physical, social, emotional, and school functioning and good psychosocial health after removal of the extra digit.[23]

References

  1. ↑ Lica L (2020). "Polydactyly and Syndactyly". In Longe JL (ed.). Gale Encyclopedia of Medicine (6th ed.). Gale.
  2. 1 2 3 Holmes LB (October 2011). "Limb Malformations". Common Malformations. Oxford University Press. pp. 146–205. doi:10.1093/med/9780195136029.003.0015. ISBN 978-0-19-513602-9.
  3. 1 2 3 4 Stevenson RE (2015). Human Malformations and Related Anomalies. Judith G. Hall, David B. Everman. Cary: Oxford University Press. ISBN 978-0-19-938604-8. OCLC 936298415.
  4. 1 2 3 4 5 Chen W, Chen L, Huang W, Tian X (March 2021). "Aesthetic and Anatomic Reconstruction of Polysyndactyly of the Fifth Toe Fused With the Fourth Toe". Annals of Plastic Surgery. 86 (3): 323–328. doi:10.1097/SAP.0000000000002437. PMID 32568755. S2CID 219982668.
  5. 1 2 Ko KR, Shim JS, Kang J, Park J (May 2021). "Surgical Outcomes and Predictive Factors of Medial Toe Excision for Polysyndactyly of the Fifth Toe". Foot & Ankle International. 42 (5): 562–569. doi:10.1177/1071100720971289. PMID 33198478. S2CID 226990510.
  6. 1 2 Dewan P, Agarwal N, Dewan P, Batta V (May 2010). "Familial crossed polysyndactyly in four generations of an Indian family". World Journal of Pediatrics. 6 (2): 177–180. doi:10.1007/s12519-010-0020-7. PMID 20127219. S2CID 11914996.
  7. 1 2 3 Woo SJ, Kim BJ, Kwon ST (January 2021). "Case-control study of the treatment of postaxial polysyndactyly of the foot: Comparison of surgical results after removal of the fifth or sixth toe". Archives of Plastic Surgery. 48 (1): 91–97. doi:10.5999/aps.2020.01620. PMC 7861990. PMID 33503751.
  8. ↑ Bae K, Kang MS, Kim TH, Park SS (May 2021). "Classification of Middle Phalangeal Postaxial Polysyndactyly Based on Intraoperative Arthrography Is Useful for Surgical Decision-making in Children Younger Than 2 Years". Journal of Pediatric Orthopedics. 41 (7): 437–443. doi:10.1097/BPO.0000000000001858. PMID 33999568. S2CID 234768434.
  9. ↑ Saygin D, Tabib T, Bittar HE, Valenzi E, Sembrat J, Chan SY, et al. (March 1985). "Transcriptional profiling of lung cell populations in idiopathic pulmonary arterial hypertension". Pulmonary Circulation. 10 (1): 73–92. doi:10.1111/j.1741-4520.1985.tb00636.x. PMC 7052475. PMID 32166015.
  10. ↑ Xu J, Wu J, Teng X, Cai L, Yuan H, Chen X, et al. (September 2020). "Large duplication in LMBR1 gene in a large Chinese pedigree with triphalangeal thumb polysyndactyly syndrome". American Journal of Medical Genetics. Part A. 182 (9): 2117–2123. doi:10.1002/ajmg.a.61757. PMID 32662247. S2CID 220518629.
  11. ↑ Lohan S, Spielmann M, Doelken SC, Flöttmann R, Muhammad F, Baig SM, et al. (October 2014). "Microduplications encompassing the Sonic hedgehog limb enhancer ZRS are associated with Haas-type polysyndactyly and Laurin-Sandrow syndrome". Clinical Genetics. 86 (4): 318–325. doi:10.1111/cge.12352. hdl:11858/00-001M-0000-0025-B3BA-6. PMID 24456159. S2CID 27700015.
  12. ↑ Dai L, Guo H, Meng H, Zhang K, Hu H, Yao H, Bai Y (November 2013). "Confirmation of genetic homogeneity of syndactyly type IV and triphalangeal thumb-polysyndactyly syndrome in a Chinese family and review of the literature". European Journal of Pediatrics. 172 (11): 1467–1473. doi:10.1007/s00431-013-2071-y. PMID 23793141. S2CID 40376029.
  13. ↑ Potuijt JW, Baas M, Sukenik-Halevy R, Douben H, Nguyen P, Venter DJ, et al. (November 2018). "A point mutation in the pre-ZRS disrupts sonic hedgehog expression in the limb bud and results in triphalangeal thumb-polysyndactyly syndrome". Genetics in Medicine. 20 (11): 1405–1413. doi:10.1038/gim.2018.18. PMID 29543231.
  14. ↑ Potuijt JW, Sowinska-Seidler A, Bukowska-Olech E, Nguyen P, Jankowski A, Magielsen F, et al. (September 2022). "The pZRS non-coding regulatory mutation resulting in triphalangeal thumb-polysyndactyly syndrome changes the pattern of local interactions". Molecular Genetics and Genomics. 297 (5): 1343–1352. doi:10.1007/s00438-022-01921-2. PMID 35821352. S2CID 250492417.
  15. ↑ Temtamy SA (1 July 1966). "Carpenter's syndrome: Acrocephalopolysyndactyly. An autosomal recessive syndrome". The Journal of Pediatrics. 69 (1): 111–120. doi:10.1016/S0022-3476(66)80368-2. PMID 5935752.
  16. ↑ Consales A, Ardemani G, Cinnante CM, Catalano MR, Giavoli C, Villa R, et al. (March 2022). "Neuroimaging appearance of hypothalamic hamartomas in monozygotic twins with Pallister-Hall syndrome: case report and review of the literature". BMC Neurology. 22 (1): 118. doi:10.1186/s12883-022-02618-0. PMC 8943937. PMID 35331151.
  17. ↑ Biesecker LG (April 2008). "The Greig cephalopolysyndactyly syndrome". Orphanet Journal of Rare Diseases. 3 (1): 10. doi:10.1186/1750-1172-3-10. PMC 2397380. PMID 18435847.
  18. ↑ Fried K, Mundel G (June 1974). "Polysyndactyly and Marfan's syndrome". Journal of Medical Genetics. 11 (2): 141–144. doi:10.1136/jmg.11.2.141. PMC 1013109. PMID 4366482.
  19. 1 2 3 Zhang SJ, Lin HB, Jiang QX, He SZ, Lyu GR (August 2021). "Prenatal diagnosis of triphalangeal thumb-polysyndactyly syndrome by ultrasonography combined with genetic testing: A case report". World Journal of Clinical Cases. 9 (23): 6832–6838. doi:10.12998/wjcc.v9.i23.6832. PMC 8362503. PMID 34447832.
  20. ↑ Zimmer EZ, Bronshtein M (September 2000). "Fetal polydactyly diagnosis during early pregnancy: clinical applications". American Journal of Obstetrics and Gynecology. 183 (3): 755–758. doi:10.1067/mob.2000.106974. PMID 10992205.
  21. ↑ Rédei GP, ed. (2008). "Polysyndactyly". Encyclopedia of Genetics, Genomics, Proteomics and Informatics. Dordrecht: Springer Netherlands. p. 1535. doi:10.1007/978-1-4020-6754-9_13251. ISBN 978-1-4020-6754-9. S2CID 239943368.
  22. ↑ Burger E, 't Hart J, Hovius S, Van Nieuwenhoven C (September 2022). "Quality of life in children with preaxial polydactyly of the foot in comparison to adults, postaxial polydactyly and healthy controls". Journal of Pediatric Orthopedics. Part B. 31 (1): 27–33. doi:10.1097/BPB.0000000000001004. PMID 36125884. S2CID 252382615.
  23. ↑ Gao Q, Wang S, Ren J, Wen X (November 2020). "Measuring parent proxy-reported quality of life of 11 rare diseases in children in Zhejiang, China". Health and Quality of Life Outcomes. 18 (1): 372. doi:10.1186/s12955-020-01572-0. PMC 7682005. PMID 33225969.
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