Dolichonychia in Women with Marfan syndrome.

Objectives: Dolichonychia refers to nails that are elongated and slender. This nail morphology has been described in single case reports of patients with Ehlers-Danlos syndrome, hypohidrotic ectodermal dysplasia, and Marfan syndrome.

Methods: The length and width of fingernails were measured in patients with Marfan syndrome and in individuals without the syndrome. A fingernail index was calculated for each person. A nonparametric sign test was used to compare the mean fingernail index of patients with Marfan syndrome and control subjects.

Results: The fingernail index ranged from 0.92 to 1.52 in patients with Marfan syndrome and from 0.77 to 1.30 in control individuals. The median fingernail index in women with Marfan syndrome (1.455) was significantly greater than the median fingernail index in women control subjects (1.080) (P = 0.035). Dolichonychia, defined as a fingernail index greater than or equal to 1.30, was present in six of eight (75%) of women with Marfan syndrome as compared with only one of 40 (2.5%) of women control subjects.

Conclusions: Dolichonychia is a physical finding present in some patients with Marfan syndrome. The detection of long narrow fingernails in women should suggest the possibility of Marfan syndrome.

Key Words: dolichonychia, Marfan syndrome, fingernail, women

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Marfan syndrome is an inherited disorder of connective tissue that predominantly involves the cardiovascular, ocular, and skeletal systems. (1-4) The estimated prevalence of Marfan syndrome ranges from one to three individuals per 10,000 population. (5-7) The disorder has an autosomal dominant pattern of inheritance and variable phenotypic expression; however, between 15 and 25% of patients do not have a family history, and represent new mutations. (6-8) Marfan syndrome is caused by mutations in the fibrillin-1 gene (FBN1), which encodes an extracellular matrix protein. (5-10)

Dolicho- is derived from the Greek dolichos, which means "long" or "narrow." Dolichonychia refers to nails that are elongated and slender. Alkiewicz and Pfister (11) used the term in 1976 when they described the appearance of fingernails from a patient with Ehlers-Danlos syndrome; they included a photograph of the patient's fingernails and commented that the quotient between the length and width of the fingernails was 1.9. The possibility of observing dolichonychia in patients with eunuchoidism, hypopituitarism or Marfan syndrome was postulated by Baran and Dawber in 1984. (12) In 1991, Baran et al (13) published an illustration of dolichonychia from a patient with hypohidrotic ectodermal dysplasia. Two years later, we reported an adult woman with Marfan syndrome who had dolichonychia. (14) Prompted by our initial observation, we decided to evaluate additional patients with Marfan syndrome for the presence of dolichonychia.

Materials and Methods

A total of 14 patients with Marfan syndrome who met the Ghent diagnostic criteria, (1) and 60 individuals without a personal or family history of Marfan syndrome or other connective tissue abnormality were recruited for this study, which was approved by our institutional review board. For all individuals, the following information was recorded: age, birth date, sex, presence or absence of either back deformity or chest deformity or both, whether there was a family history of Marfan syndrome and whether there was a personal history of either ocular abnormalities or cardiovascular abnormalities or both. Arm span, height, and finger bone length and width were measured. The thumb sign (positive when the thumb protrudes beyond the confines of the clenched fist) and the wrist sign (positive when the thumb and fifth finger overlap when the opposite wrist is grasped proximal to the styloid process of the radius) were also evaluated.

The length and width of each nail from all of the digits on both hands was measured. The length of a nail was taken to be the greatest distance from the proximal nail fold to the hyponychium as determined clinically by the distal pink color of the nail plate; the width was in turn measured at the midpoint of the measured length. The fingernail index for each individual was calculated by summing the quotients of the length to the width of each fingernail and dividing by eight. A nonparametric sign test was used to compare the mean fingernail index of patients with Marfan syndrome and control subjects.

Results

There were six men and eight women with Marfan syndrome included in the study. The men ranged in age from 13 to 43 years (median = 28 yrs). The women ranged from 7 to 29 years (median = 23 yrs); we have previously described the clinical features of one of these women. (14) All of the patients with Marfan syndrome had cardiovascular, ocular, and skeletal features of the syndrome.

The control group included 20 men and 40 women. The men ranged in age from 21 to 59 years (median = 30 yrs). The women ranged from 17 to 59 years (median = 35 yrs). None of the control subjects had either a personal or family history of Marfan syndrome or other connective-tissue abnormality. Also, neither cardiovascular, ocular, nor skeletal features of Marfan syndrome were present in any of the control subjects.

The fingernail index ranged from 0.77 to 1.30 (median = 1.06) in the control subjects. The median fingernail index in women control subjects was greater than the median fingernail index in men control subjects (Table 1). However, since the fingernail index in the control subjects did not show a bell-shaped distribution, nonparametric methods were used to compare the median fingernail index in the control subjects to that in patients with Marfan syndrome.

[FIGURE 1 OMITTED]

The fingernail index in individuals with Marfan syndrome ranged from 0.92 to 1.52 in men and from 0.96 to 1.59 in women (Table 1). The median fingernail index in male patients (1.020) was not significantly different from the median fingernail index in male control subjects (1.030) (P = 0.813). However, the median fingernail index in women with Marfan syndrome (1.455) was significantly greater (P = 0.035) than the median fingernail index in women control subjects (1.080).

Dolichonychia was defined as a fingernail index greater than or equal to 1.30 (Fig. 1); the upper limit for more than 98% (59 of 60) of control subjects is defined by this number. In the group of control subjects, none of the men and only one of the 40 women (2.5%) had dolichonychia. However, in patients with Marfan syndrome, dolichonychia was present in 75% of the women (Fig. 2) and 17% of the men. The man with dolichonychia had a fingernail index of 1.52.

[FIGURE 2 OMITTED]

Arachnodactyly (Fig. 3a) was deemed present, according to the Ghent criteria, (1) when a patient had a positive thumb sign (Fig. 3b) and a positive wrist sign (Fig. 3c). Arachnodactyly was observed in six of the women (75%) and four of the men (67%) with Marfan's syndrome; dolichonychia was present in five (83%) of these women and one (25%) of these men. In contrast, dolichonychia was present in only one woman and none of the men with Marfan syndrome who did not have arachnodactyly.

Discussion

Dolichonychia is a nail finding that is rarely described in the literature. Previously, elongated, slender fingernails have only been reported in single patients with either Ehlers-Danlos syndrome, (11) hypohidrotic ectodermal dysplasia, (13) or Marfan syndrome. (14) We have evaluated men and women without any personal or family history of connective tissue disease as control subjects to determine the average of the quotients between the length and width of their fingernails. We have also calculated the fingernail index of patients with Marfan syndrome to determine the presence or absence of dolichonychia.

Our study confirms that the normal fingernail index is 1.0 [+ or -] 0.1 as originally described by Alkiewicz and Pfister. (11) In our study, the median fingernail index in the control group was 1.03 in the men and 1.08 in the women. Our study also showed that the median fingernail index in women with Marfan syndrome was significantly greater (P = 0.035) than the median fingernail index in female control subjects.

A fingernail index greater than or equal to 1.30 was defined as dolichonychia. This number was used because it defined the upper limit of more than 98% of control subjets. Dolichonychia was observed in seven of the 12 patients with Marfan syndrome and one woman in the group of 60 control subjects. Specifically, dolichonychia was present in only 17% (one of six) of the men with Marfan syndrome. However, 75% (six of eight) of the women with Marfan syndrome had dolichonychia as compared with only 2.5% (one of 40) of the female control subjects.

Arachnodactyly is one of the major skeletal manifestations of Marfan syndrome. (1,7,8) Overgrowth of the digital tubular bones results in long, thin, spiderlike fingers. (7) The thumb sign and the wrist sign are morphologic features that can be used to clinically assess for arachnodactyly. (2-4,15) In our study, the majority of patients with Marfan syndrome who had dolichonychia also had arachnodactyly: 83% of women (five of six) and 100% of men (one of one). However, one woman with Marfan syndrome and arachnodactyly did not have dolichonychia and vice versa; also, 3 men with Marfan syndrome and arachnodactyly did not have dolichonychia. Therefore, although the presence of elongated, narrow fingernails in patients with Marfan syndrome is not always associated with arachnodactyly, we observed that dolichonychia in patients with Marfan syndrome usually reflects an overgrowth of their finger bones.

[FIGURE 3 OMITTED]

Conclusion

Dolichonychia is a physical finding present in some patients with Marfan syndrome. The detection of long narrow fingernails in a woman should suggest the possibility of Marfan syndrome. In patients with Marfan syndrome, elongated slender fingernails often represent a morphologic feature of arachnodactyly. The presence of dolichonychia in a patient with Marfan syndrome can be referred to as a positive "nail sign."

Science may have found a cure for most evils, but it has found no remedy
for the worst of them all--the apathy of human beings.
--Helen Keller

Table 1. Fingernail index in the control subjects and the Marfan
syndrome patients

               Men                Women
                   Marfan                 Marfan
        Control    syndrome   Control     syndrome
        subjects   patients   subjects    patients

Range   0.77-1.20  0.92-1.52  0.91-1.30   0.96-1.59
Median  1.030      1.020      1.080       1.455

Accepted October 23, 2003.

Copyright [c] 2004 by The Southern Medical Association

0038-4348/04/9704-0354

References

1. De Paepe A, Devereux RB, Dietz HC, et al. Revised diagnostic criteria for the Marfan syndrome. Am J Med Genet 1996;62:417-426.

2. Milewicz DM, Cohen PR: The Marfan syndrome, in Dahl MV (ed): Current Opinions in Dermatology. Philadelphia, Rapid Science Publishers, 1966, vol 3, pp 145-149.

3. Cohen PR, Schneiderman P. 12-20: Marfan syndrome, in Demis DJ, Thiers BH, Smith EB, et al (eds): Clinical Dermatology. Philadelphia, J.B. Lippincott Co., 1992, rev 19, pp 1-13.

4. Cohen PR, Schneiderman P. Clinical manifestations of the Marfan syndrome. Int J Dermatol 1989;28:291-299.

5. Milewicz DM. Molecular genetics of Marfan syndrome and Ehlers-Danlos type IV. Curr Opin Cardiol 1998;13:198-204.

6. Milewicz DM. Identification of defects in the fibrillin gene and protein in individuals with the Marfan syndrome and related disorders. Tex Heart Inst J 1994;21:22-29.

7. Pyeritz RE. The Marfan syndrome. Annu Rev Med 2000;51:481-510.

8. Giampietro PF, Raggio C, Davis JG. Marfan syndrome: orthopedic and genetic review. Curr Opin Pediatr 2002;14:35-41.

9. Milewicz DM, Urban Z, Boyd C. Genetic disorders of the elastic fiber system. Matrix Biol 2000;19:471-480.

10. Milewicz DM, Pyeritz RE, Crawford ES, et al. Marfan syndrome: defective synthesis, secretion, and extracellular matrix formation of fibrillin by cultured dermal fibroblasts. J Clin Invest 1992;89:79-86.

11. von Alkiewicz J, Pfister R. Pathomorphologie des Nagels (Semiotik des Nagelorgans), in Atlas der Nagelkrankheiten: Pathohistologie, Klinik und Differentialdiagnose. Stuttgart, Germany, F.K. Schattauer, 1976, pp 17-68.

12. Baran R, Dawber RPR. Physical signs, in Baran R, Dawber RPR (eds): Diseases of the Nails and Their Management. Oxford, Blackwell Scientific Publications, 1984, pp 25-80.

13. Baran R, Barth J, Dawber R. Nail configuration abnormalities, in Nail Disorders: Common Presenting Signs, Differential Diagnosis, and Treatment. New York, Churchill Livingstone, 1991, pp 1-44.

14. Cohen PR, Milewicz DM. Dolichonychia in a patient with the Marfan syndrome. J Dermatol 1993;20:779-782.

15. Dean JC. Management of Marfan syndrome. Heart 2002;88:97-103.

RELATED ARTICLE: Key Points

* Dolichonychia refers to nails that are long and narrow.

* Dolichonychia was present in 75% of women with Marfan syndrome as compared to 2.5% of women control subjects.

* The detection of long narrow fingernails in a women should suggest the possibility of Marfan syndrome.

* The presence of dolichonychia in a patient with Marfan syndrome can be referred to as a positive "nail sign."

Philip R. Cohen, MD, and Dianna McGookey Milewicz, MD, PHD

From the University of Houston Health Center and the Departments of Dermatology and Internal Medicine (Section of Medical Genetics), University of Texas-Houston Medical School, Houston, TX.

This study (HCS-MS-92-028) received the approval of the Committee for the Protection of Human Subjects at the University of Texas-Houston Medical School.

Reprint requests to Philip R. Cohen, MD, 805 Anderson Street, Bellaire, TX 77401-2806. Email: [e-mail]