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Arachnodactyly
[edit]Arachnodactyly ("spider fingers") or achromachia is a condition in which the fingers and toes are abnormally long, slender and curved inwards in comparison to the palm of the hand and arch of the foot.[1] These appearances can be normal in some individuals, but potentially may be related to disease in others. [1]
Signs and symptoms
[edit]
Arachnodactyly can be a result of normal variation or it can be a symptom of an underlying disease. It is an important component of Marfanoid habitus, which is found in several different disorders (see Related disorders).[2] Previously, a test would be done by measuring and evaluating metacarpal lengths, but this test is no longer in use as two new tests (Steinberg and Walker-Murdoch) have rendered it useless.[2] The Steinberg Test is one of the methods used to identify arachnodactyly. It involves folding one's thumb across the palm and closing the fist over it. If the thumb extends farther than the hypothenar eminence, then the test is positive.[2] Another method is the Walker-Murdoch test, where one attempts to wrap their wrist with their thumb and little finger. If the thumb and finger overlap by at least a fingernail length, the test is positive for arachnodactyly.[2]
Genetics
[edit]Fibrillin microfibrils and bone formation
[edit]Arachnodactyly is caused primarily by a mutation in the fibrillin-1 (FBN1) gene, but may also be connected to the mutation in fibrillin-2 (FBN2). These genes serve to encode for connective tissue glycoproteins of the same names. The fibrillin-1 and -2 proteins are integral to 10-nm-diameter microfibrils. [3] Mutations in the fibrillin genes can result in opposing phenotypes such as arachnodactyly versus brachydactyly or tall stature versus short stature.[4] Fibrillin assemblies are important complexes in the regulation of bone anabolism and catabolism. The individual proteins are responsible for regulating the TGFβ and BMP signalling pathways[5] through involvement with latent transforming growth factor β binding proteins (LTBPs). Fibrillin-1 regulates the amount of TGFβ available in the cell by binding to LTBPs.[6] TGFβ is involved in cartilage formation[7] and both pathways are important for digit formation. In mice, a loss of fibrillin-2 proteins has resulted in fused digits as the loss prevents the destruction of targeted mesenchymal cell death.[5] Meanwhile, a reduction of fibrillin-1 proteins results in aberrant activation of TGFβ signalling.[4]
Diagnosis and management
[edit]Possible future treatments
[edit]Some studies have been done on therapy via TGFβ neutralization using a drug called losartan.[4] They found that it can help to maintain normal bone mass in mice with Marfan's syndrome, but that it also had a harmful effect on the mouse's heart development.[5] Nevertheless, this treatment could possibly be used to decrease the amount of bone fractures in patients. Recent clinical trials on marfanoid children have found no statistically significant adverse affects to losartan, suggesting that it may in fact be an effective treatment for patients with Marfan's syndrome or related arachnodactyly based disorders.[4]
Related disorders
[edit]- Marfan's syndrome: characterized by increased height, arachnodactyly and hypermobility of the joints along with heart and eye abnormalities. It is caused by a FBN1 mutation. [8]
- Beals-Hecht syndrome (Congenital contractural arachnodactyly): characterized by arachnodactyly and ear deformities resulting from a mutation in FBN2.[9][10]
- Dolichostenomelia: a similar condition to arachnodactyly, where the entire body is abnormally long and slender.[1]
- Ehlers-Danlos syndrome: characterized by fragile and extensible skin and joint hypermobility.[11]
- Loeys-Dietz syndrome: characterized by vascular abnormalities, cleft palate and an increased risk for aneurysms.[12]
- Homocystinuria: characterized by skeletal and ocular abnormalities and usually does not surface until early childhood.[13]
- Shprintzen-Goldberg syndrome: characterized by arachnodactyly and skeletal defects, as well as brain and cardiovascular abnormalities.[14]
- Van Den Ende-Gupta syndrome: an extremely rare condition defined by craniofacial features, arachnodactyly, camptodactyly and skeletal abnormalities.[2]
- Stickler syndrome: characterized by ocular and facial abnormalities.[15]
References
[edit]- ^ a b "Arachnodactyly". Medline Plus. Retrieved 10 October 2015.
- ^ a b c d e Grahame, Rodney; Hakim, Alan J. (2013-06-01). "Arachnodactyly--a key to diagnosing heritable disorders of connective tissue". Nature Reviews. Rheumatology. 9 (6): 358–364. doi:10.1038/nrrheum.2013.24. ISSN 1759-4804. PMID 23478494.
- ^ Vasudevan, D M (2013). Textbook of Biochemistry for Medical Students. JP Medical Ltd. p. 722. Retrieved 15 October 2015.
- ^ a b c d Sengle, Gerhard; Sakai, Lynn Y. (2015-09-01). "The fibrillin microfibril scaffold: A niche for growth factors and mechanosensation?". Matrix Biology: Journal of the International Society for Matrix Biology. 47: 3–12. doi:10.1016/j.matbio.2015.05.002. ISSN 1569-1802. PMID 25957947.
- ^ a b c Smaldone, Silvia; Ramirez, Francesco (2015-09-25). "Fibrillin microfibrils in bone physiology". Matrix Biology: Journal of the International Society for Matrix Biology. doi:10.1016/j.matbio.2015.09.004. ISSN 1569-1802. PMID 26408953.
- ^ Davis, Margaret R.; Summers, Kim M. (2012-12-01). "Structure and function of the mammalian fibrillin gene family: implications for human connective tissue diseases". Molecular Genetics and Metabolism. 107 (4): 635–647. doi:10.1016/j.ymgme.2012.07.023. ISSN 1096-7206. PMID 22921888.
- ^ Díaz-Hernández, Martha Elena; Rios-Flores, Alberto Jesús; Abarca-Buis, René Fernando; Bustamante, Marcia; Chimal-Monroy, Jesús (2014-04-29). "Molecular Control of Interdigital Cell Death and Cell Differentiation by Retinoic Acid during Digit Development". Journal of Developmental Biology. 2 (2): 138–157. doi:10.3390/jdb2020138.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ Velvin, Gry; Bathen, Trine; Rand-Hendriksen, Svend; Geirdal, Amy Østertun (2015-11-26). "Systematic review of chronic pain in persons with Marfan syndrome". Clinical Genetics. doi:10.1111/cge.12699. ISSN 1399-0004. PMID 26607862.
- ^ Tunçbilek, Ergül; Alanay, Yasemin (2006-06-01). "Congenital contractural arachnodactyly (Beals syndrome)". Orphanet Journal of Rare Diseases. 1: 20. doi:10.1186/1750-1172-1-20. ISSN 1750-1172. PMC 1524931. PMID 16740166.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ Godfrey, Maurice (1993-01-01). Pagon, Roberta A.; Adam, Margaret P.; Ardinger, Holly H.; Wallace, Stephanie E.; Amemiya, Anne; Bean, Lora JH; Bird, Thomas D.; Fong, Chin-To; Mefford, Heather C. (eds.). Congenital Contractural Arachnodactyly. Seattle (WA): University of Washington, Seattle. PMID 20301560.
- ^ Anderson, Linda K. (2015-07-01). "CE: Nursing Management of Patients with Ehlers-Danlos Syndrome". The American Journal of Nursing. 115 (7): 38–46, quiz 47-48. doi:10.1097/01.NAJ.0000467274.82951.57. ISSN 1538-7488. PMID 26067654.
- ^ MacCarrick, Gretchen; Black, James H.; Bowdin, Sarah; El-Hamamsy, Ismail; Frischmeyer-Guerrerio, Pamela A.; Guerrerio, Anthony L.; Sponseller, Paul D.; Loeys, Bart; Dietz, Harry C. (2014-08-01). "Loeys-Dietz syndrome: a primer for diagnosis and management". Genetics in Medicine: Official Journal of the American College of Medical Genetics. 16 (8): 576–587. doi:10.1038/gim.2014.11. ISSN 1530-0366. PMC 4131122. PMID 24577266.
- ^ Walter, John H.; Jahnke, Nikki; Remmington, Tracey (2015-01-01). "Newborn screening for homocystinuria". The Cochrane Database of Systematic Reviews. 10: CD008840. doi:10.1002/14651858.CD008840.pub4. ISSN 1469-493X. PMID 26423208.
- ^ Greally, Marie T. (1993-01-01). Pagon, Roberta A.; Adam, Margaret P.; Ardinger, Holly H.; Wallace, Stephanie E.; Amemiya, Anne; Bean, Lora JH; Bird, Thomas D.; Fong, Chin-To; Mefford, Heather C. (eds.). Shprintzen-Goldberg Syndrome. Seattle (WA): University of Washington, Seattle. PMID 20301454.
- ^ Robin, Nathaniel H.; Moran, Rocio T.; Ala-Kokko, Leena (1993-01-01). Pagon, Roberta A.; Adam, Margaret P.; Ardinger, Holly H.; Wallace, Stephanie E.; Amemiya, Anne; Bean, Lora JH; Bird, Thomas D.; Fong, Chin-To; Mefford, Heather C. (eds.). Stickler Syndrome. Seattle (WA): University of Washington, Seattle. PMID 20301479.