Arachnodactyly literally means spidery fingers, and describes the long, slender fingers typical of patients with Marfan syndrome (MFS). Many clinicians regard arachnodactyly as pathognomonic of MFS; however, this view is misleading as arachnodactyly is a key element of the marfanoid habitus, which is present in several heritable disorders of connective tissue (HDCTs). Other features of the marfanoid habitus include long hands and feet, increased skin stretch, joint hypermobility and characteristic changes in the physiology of the pectum. Here, we focus on the differential diagnosis of diseases with features of the marfanoid habitus. Ectopia lentis (lens dislocation) and aortic root dilation or dissection are cardinal features of MFS. Distinguishing MFS from other HCDTs has important implications for treatment, as cardiovascular and ocular complications commonly seen in patients with MFS are not seen in all HDCTs. Joint hypermobility syndrome and Ehlers–Danlos syndrome are also HDCTs, neither of which is associated with ectopia lentis or aortic changes. Some of the rarer forms of Ehlers–Danlos syndrome are associated with severe vascular, dental and skin pathologies. This Review serves as a guide for correctly diagnosing members of the HDCT family.
Arachnodactyly is a key feature of the marfanoid habitus and thus a reliable pointer to the presence of a heritable disorder of connective tissue (HDCT)
Joint hypermobility syndrome is the most commonly seen HDCT
The differential diagnosis of arachnodactyly is wide and extends to include many rare genetic syndromes
Incomplete forms of the marfanoid habitus are highly prevalent and can be benign, but should lead to an assessment for the presence of an HDCT
Neither arachnodactyly nor the marfanoid habitus on its own can be regarded as pathognomonic of Marfan syndrome in the absence of either cardiac or ocular involvement
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Steinberg, I. A simple screening test for the Marfan syndrome. Am. J. Roentgenol. Radium Ther. Nucl. Med. 97, 118–124 (1966).
Walker, B. A. & Murdoch, J. L. The wrist sign. A useful physical finding in the Marfan syndrome. Arch. Intern. Med. 126, 276–277 (1970).
Eldridge, R. The metacarpal index. A useful aid in the diagnosis of the Marfan syndrome. Arch. Intern. Med. 113, 248–254 (1964).
McKusick, V. A. The Marfan Syndrome. Heritable Disorders of Connective Tissue, 4th edn 61–223 (C. V. Mosby, St Louis, 1972).
Beighton, P. H., Solomon, L. & Soskolne, C. Articular mobility in an African population. Ann. Rheum. Dis. 32, 413–417 (1973).
Tanner, J. M. & Whitehouse, R. H. The Harpenden skinfold caliper. Am. J. Phys. Anthropol. 13, 743–746 (1955).
Grahame, R. & Beighton, P. Physical properties of the skin in the Ehlers–Danlos syndrome. Ann. Rheum. Dis. 28, 246–251 (1969).
Farmer, A. D., Douthwaite, M. A., Gardiner, S., Aziz, Q. & Grahame, R. A novel in vivo skin extensibility test for joint hypermobility. J. Rheumatol. 37, 1513–1518 (2010).
Loeys, B. L. et al. The revised Ghent nosology for the Marfan syndrome. J. Med. Genet. 47, 476–485 (2010).
Beighton, P., De Paepe, A., Steinmann, B., Tsipouras, P. & Wenstrup, R. J. Ehlers–Danlos syndromes: revised nosology, Villefranche, 1997. Ehlers–Danlos National Foundation (USA) and Ehlers–Danlos Support Group (UK). Am. J. Med. Genet. 77, 31–37 (1998).
Grahame, R., Bird, H. A. & Child, A. The revised (Brighton 1998) criteria for the diagnosis of benign joint hypermobility syndrome (BJHS). J. Rheumatol. 27, 1777–1779 (2000).
Beighton, P., Grahame, R. & Bird, H. A. Hypermobility of Joints, 4th edn (Springer, London, 2011).
De Paepe, A., Devereux, R. B., Dietz, H. C., Hennekam, R. C. & Pyeritz, R. E. Revised diagnostic criteria for the Marfan syndrome. Am. J. Med. Genet. 62, 417–426 (1996).
Tinkle, B. T. et al. The lack of clinical distinction between the hypermobility type of Ehlers–Danlos syndrome and the joint hypermobility syndrome (a.k.a. hypermobility syndrome). Am. J. Med. Genet. A 149A, 2368–2370 (2009).
Ross, J. & Grahame, R. Joint hypermobility syndrome. BMJ 342, c7167 (2011).
Hakim, A. J. & Grahame, R. Non-musculoskeletal symptoms in joint hypermobility syndrome: indirect evidence for autonomic dysfunction. Rheumatology (Oxford) 43, 1194–1195 (2004).
Zarate-Lopez, N. et al. Unexplained gastrointestinal symptoms and joint hypermobility: is connective tissue the missing link? Neurogastroenterol. Motil. 22, 252–262 (2010).
Bulbena, A. et al. Anxiety disorders in the joint hypermobility syndrome. Psychiatry Res. 46, 59–68 (1993).
Malfait, F., Hakim, A. J., De Paepe, A. & Grahame, R. The genetics of joint hypermobility syndrome. Rheumatology (Oxford) 45, 502–507 (2006).
Homocystinuria due to cystathionine β-synthase deficiency. Online Mendelian Inheritance in Man [online], (2012).
Familial ectopia lentis. National Marfan Foundation [online], (2012).
Loeys, B. L. et al. Aneurysm syndromes caused by mutations in the TGF-β receptor. N. Engl. J. Med. 355, 788–789 (2006).
Van Hemelrijk, C. Renard, M. & Loeys, B. The Loeys–Dietz syndrome: an update for the clinician. Curr. Opin. Cardiol. 25, 546–551 (2010).
Loeys, B. L. & Dietz, H. C. Loeys–Dietz syndrome. In: GeneReviews (eds Pagon, R. A. et al.) [online], (2012).
MASS phenotype. National Marfan Foundation [online], (2012).
Glesby, M. J. & Pyeritz, R. E. Association of mitral valve prolapse and systemic abnormalities of connective tissue. A phenotypic continuum. JAMA 262, 523–528 (1989).
Familial mitral valve prolapse. Online Mendelian Inheritance in Man [online], (2012).
Greally, M. T. et al. Shprintzen–Goldberg syndrome: a clinical analysis. Am. J. Med. Genet. 76, 202–12 (1998).
Van den Ende–Gupta syndrome. Online Mendelian Inheritance in Man [online], (2012).
Putnam, E. A., Zhang, H., Ramirez, F. & Milewicz, D. M. Fibrillin-2 (FBN2) mutations result in the Marfan-like disorder, congenital contractural arachnodactyly. Nat. Genet. 11, 456–458 (1995).
Callewaert, B. L. et al. Comprehensive clinical and molecular assessment of 32 probands with congenital contractural arachnodactyly: report of 14 novel mutations and review of the literature. Hum. Mutat. 30, 334–341 (2009).
Van Buggenhout, G. & Fryns, J. P. Lujan–Fryns syndrome (mental retardation, X-linked, marfanoid habitus). Orphanet J. Rare Dis. 1, 26 (2006).
Rose, P. S. et al. Stickler syndrome: clinical characteristics and diagnostic criteria. Am. J. Med. Gen. A 138, 199–207 (2005).
Stickler, G. B., Hughes, W. & Houchin, P. Clinical features of hereditary arthro-ophthalmopathy (Stickler syndrome): a survey. Genet. Med. 3, 192–196 (2001).
The authors would like to thank their patients whose photographs have been used in this article.
The authors declare no competing financial interests.
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Grahame, R., Hakim, A. Arachnodactyly—a key to diagnosing heritable disorders of connective tissue. Nat Rev Rheumatol 9, 358–364 (2013). https://doi.org/10.1038/nrrheum.2013.24
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