Humangenetik 28, 281--284 (1975) © by Springer-Verlag 1975
Dermatoglyphic Analysis as a Diagnostic Tool in Wilson Disease ?* g . Grosse University of Kiel Medical School, Department of Pediatrics, Kiel Received January 27, 1975
Summary. DermaVoglyphic analysis was performed in a family with 3 children with Wilson disease. With our findings we could not confirm the results published in two earlier papers by other authors who noted a positive relation between Wilson disease and an increased number of whorls. The practical significance of the findings is discussed. Zusammen/assung. Es wurden Untersuchungen der ttautleisten in einer Familie durchgefiihrt, in der 3 Kinder an ~ . Wilson erkrankt sind. Mit unseren Befunden konnten wir die Ergebnisse anderer Autoren nieht best~tigen; sic fanden eine positive Beziehung zwisehen M. Wilson und der Anzahl der Wirbel. Die praktische Signifikanz der Befunde wird diskutiert.
Introduction A n increased incidence of whorls on t h e fingertips of p a t i e n t s with Wilson disease was a p p a r e n t l y first described b y Hodges a n d Simon (•962). This finding got some s u p p o r t b y t h e p u b l i c a t i o n of V o r m i t t a g et al. (1973) who in a d d i t i o n f r e q u e n t l y n o t e d t h a t t h e D-line e n d e d in t h e f o u r t h i n t e r d i g i t a l area. These results p r o m p t e d an i n v e s t i g a t i o n of t h e d e r m ~ t o g l y p h i c s of a f a m i l y in which 3 children were d i a g n o s e d to h a v e W i l s o n disease b y t h e a c c e p t e d criteria of low ceruloplasmin a n d serum copper, increased u r i n a r y excretion of copper, a n d b y liver b i o p s y (the l a t t e r o n l y in case I I I , 7 ) as well as K a y s e r - F l e i s c h e r ring, e x c e p t in I I I , 7 .
Results The p e r t i n e n t findings are s u m m a r i z e d in Table 1. The following conclusions can be d r a w n : 1. There is no increase of whorls on t h e finger tips (3 whorls, including t h e double loops, i.e. 3 % as o p p o s e d to 30% e x p e c t e d (Wendt, 1971), if our s a m p l e were unrelated). O n l y one of t h e whorls occurred in a h o m o z y g o t e while none were seen in t h e necessarily h e t e r o z y g o u s p a r e n t s - - s u r e l y n o t a significant increase.
2. N o increased D-line exit in t h e f o u r t h i n t e r d i g i t a l area ( T y p e - - g a m m a : 10~o versus 15.8~o e x p e c t e d ; c o m b i n e d values of males a n d females from Holt, 1968). * Prof. Dr. H.-R. Wiedemann to his 60th birthday.
282
R,. Grosse
1,2
6-8
1 maie
D
~[~
2
9,10
3
12
,~
5
14
6
7
female
G
normal
@
numberofmalesandfemales
@
affected (Wilson'sdisease)
Q
numbProf females
G
deceased
Line undersymbol:personallyseen
Fig. 1. Pedigree of the B-family. Affected children are double first cousins. III,1 was not available for investigation of the dermat0glyphics
Discussion I t appears to be a generally accepted fact that the pattern type a n d - - n o t independently--the total ridge count is a heritable trait influenced by many genes. Therefore a visible and clinically relevant modification can only be expected in the case of gross genetic imbalance, e.g. in chromosomal syndromes (Wendt et al., 1970, 1971) and in eases of mutant genes affecting the form of the fingers, e.g. the F-syndrome, (Crosse et al., 1969) not considering in this connection the influence of teratogenes at the appropriate time. I t is therefore difficult to accept that one mutant gene - - in addition one that in its homozygous state causes an inborn error of metabolism - - should exert a significant effect on the pattern type of the finger tips or the D-line ending. Admittedly Hodges and Simon (1962) as well as Vormittag et al. (1973) call for cautious interpretation of their results, possibly because of the same reasoning, and it was the purpose of this communication to underline their precaution. I t is by no means our aim to demonstrate the opposite with our results, derived from the investigation of this one family. But our results certainly reduce the hope of Hodges and Simon that dermatoglyphic analysis can be a helpful tool for early detection of homozygotes or even identification of heterozygotes. Even if the statistically significant increase of whorls in patients with Wilson disease (24.55% versus 38% )--as shown by the above authors--could be confirmed in a larger unbiased series, who would be so daring as to diagnose individuals with, for instance, 4 whorls as having Wilson's disease, or on the other hand restrain two persons, each with 3 or 4 whorls on their fingertips, from marriage because they
Dermatoglyphies in Wilson Disease
283
Table 1 Pedigree Right/ I No. left hand
II
III
IV
V
Ending of D-line type
TRC
III,2
I~ L
Ull U12
U10 W9
Ull Ull
U12 U12
U7 U8
beta beta
103
III,3
R L
U12 U12
U13 DL14
U13 U14
U12 U13
U13 U9
beta beta
125
III,4
g L
DL16 U9
LA LA
U3 U6
U11 U8
U4 U4
alpha beta
61
III,5
1% L
U14 U9
1%7 R4
U7 A
U10 U13
Ull U6
alpha gamma
80
1~ L
Ull U9
R2 U4
U6 LA
U16 U17
U17 U14
alpha epsilon
96
III,7
R L
U15 U16
TA U5
U12 U15
Ull U13
U12 U15
alpha delta
II,3
t~ L
U9 U9
U3 R2
U5 U7
U7 U10
U10 U5
delta gamma
II,5
1% L
U13 U6
1%16 1%3
UI0 U13
U16 U13
U13 U9
alpha beta
112
II,11
R L
U15 U15
U6 R5
U9 U9
U10 U11
U5 U4
beta beta
89
R L
U14 U16
R2 R2
UI0 U9
U8 R8
U2 U8
alpha beta
79
III,6
II,13
114 67
U = ulnar loop, R = radial loop, W = whorl (the higher ridge count is indicated), DL = double loop, LA = low arch, TA = tented arch. D-line exit classification according to Holt (1968).
c o u l d be h e t e r o z y g o t e s for W i l s o n ' s disease. T h i s c e r t a i n l y r e q u i r e s t o o m u c h of t h i s m e t h o d ; p a r t i c u l a r l y in t h e i n d i v i d u a l ease d e r m a t o g l y p h i c a n a l y s i s is o f no clinical help. L a b o r a t o r y d a t a are u n a v o i d a b l e . F o r a e x c e l l e n t g e n e r a l d i s c u s s i o n of t h e r e l a t i o n b e t w e e n d e r m a t o g l y p h i c s a n d disease t h e r e a d e r is r e f e r r e d to t h e p u b l i c a t i o n s o f W e n d t et al. (1970, 1971).
Acknowledgement. The valuable criticism of Prof. Dr. G. G. Wendt is greatly appreciated.
References Grosse, F. g., Herrmann, J., Opitz, J. ~ . : The F-syndrome or the F-form of aero-pectoralvertebral dysplasia. Birth Defects Original Article Series g, 3, 48--63 (1969) I-Iodges, 1%. E., Simon, 1%. ft. : Relationship between finger print patterns and Wilson's disease. J. Lab. Clin. Med. 60, 629--640 (1962) Holt, B. : The genetics of dermal ridges. Springfield (Ill.) : C. C. Thomas 1968 Vormittag, W., Weninger, N., FIayen, tI.: Zur Beziehung zwischen Hautleistenverlauf und Morbus Wilson. I-Iumangenetik 18, 337--340 (1973)
284
R. Grosse
Wendt, G. G., Rube, M., Kindermann, I. : Krankheiten und Papitlarleisten der Fingerbeeren. Eine kritische Betraehtung. 2. Kolloquium Hautleisten und Hautfurchen, pp. 291--310. Berlin 1970 Wendt, G. G., Rube, M., Kindermann, I.: Papillarleisten und Krankheiten. Dtsch. med. Wschr. 96, 1056--1062 (1971) Dr. F. R. Grosse Universit~its-Kinderklinik D-2300 Kiel, Fr6belstraBe 15/17 Federal Republic of Germany
Dermatoglyphic Analysis as a Diagnostic Tool in Wilson Disease ?* g . Grosse University of Kiel Medical School, Department of Pediatrics, Kiel Received January 27, 1975
Summary. DermaVoglyphic analysis was performed in a family with 3 children with Wilson disease. With our findings we could not confirm the results published in two earlier papers by other authors who noted a positive relation between Wilson disease and an increased number of whorls. The practical significance of the findings is discussed. Zusammen/assung. Es wurden Untersuchungen der ttautleisten in einer Familie durchgefiihrt, in der 3 Kinder an ~ . Wilson erkrankt sind. Mit unseren Befunden konnten wir die Ergebnisse anderer Autoren nieht best~tigen; sic fanden eine positive Beziehung zwisehen M. Wilson und der Anzahl der Wirbel. Die praktische Signifikanz der Befunde wird diskutiert.
Introduction A n increased incidence of whorls on t h e fingertips of p a t i e n t s with Wilson disease was a p p a r e n t l y first described b y Hodges a n d Simon (•962). This finding got some s u p p o r t b y t h e p u b l i c a t i o n of V o r m i t t a g et al. (1973) who in a d d i t i o n f r e q u e n t l y n o t e d t h a t t h e D-line e n d e d in t h e f o u r t h i n t e r d i g i t a l area. These results p r o m p t e d an i n v e s t i g a t i o n of t h e d e r m ~ t o g l y p h i c s of a f a m i l y in which 3 children were d i a g n o s e d to h a v e W i l s o n disease b y t h e a c c e p t e d criteria of low ceruloplasmin a n d serum copper, increased u r i n a r y excretion of copper, a n d b y liver b i o p s y (the l a t t e r o n l y in case I I I , 7 ) as well as K a y s e r - F l e i s c h e r ring, e x c e p t in I I I , 7 .
Results The p e r t i n e n t findings are s u m m a r i z e d in Table 1. The following conclusions can be d r a w n : 1. There is no increase of whorls on t h e finger tips (3 whorls, including t h e double loops, i.e. 3 % as o p p o s e d to 30% e x p e c t e d (Wendt, 1971), if our s a m p l e were unrelated). O n l y one of t h e whorls occurred in a h o m o z y g o t e while none were seen in t h e necessarily h e t e r o z y g o u s p a r e n t s - - s u r e l y n o t a significant increase.
2. N o increased D-line exit in t h e f o u r t h i n t e r d i g i t a l area ( T y p e - - g a m m a : 10~o versus 15.8~o e x p e c t e d ; c o m b i n e d values of males a n d females from Holt, 1968). * Prof. Dr. H.-R. Wiedemann to his 60th birthday.
282
R,. Grosse
1,2
6-8
1 maie
D
~[~
2
9,10
3
12
,~
5
14
6
7
female
G
normal
@
numberofmalesandfemales
@
affected (Wilson'sdisease)
Q
numbProf females
G
deceased
Line undersymbol:personallyseen
Fig. 1. Pedigree of the B-family. Affected children are double first cousins. III,1 was not available for investigation of the dermat0glyphics
Discussion I t appears to be a generally accepted fact that the pattern type a n d - - n o t independently--the total ridge count is a heritable trait influenced by many genes. Therefore a visible and clinically relevant modification can only be expected in the case of gross genetic imbalance, e.g. in chromosomal syndromes (Wendt et al., 1970, 1971) and in eases of mutant genes affecting the form of the fingers, e.g. the F-syndrome, (Crosse et al., 1969) not considering in this connection the influence of teratogenes at the appropriate time. I t is therefore difficult to accept that one mutant gene - - in addition one that in its homozygous state causes an inborn error of metabolism - - should exert a significant effect on the pattern type of the finger tips or the D-line ending. Admittedly Hodges and Simon (1962) as well as Vormittag et al. (1973) call for cautious interpretation of their results, possibly because of the same reasoning, and it was the purpose of this communication to underline their precaution. I t is by no means our aim to demonstrate the opposite with our results, derived from the investigation of this one family. But our results certainly reduce the hope of Hodges and Simon that dermatoglyphic analysis can be a helpful tool for early detection of homozygotes or even identification of heterozygotes. Even if the statistically significant increase of whorls in patients with Wilson disease (24.55% versus 38% )--as shown by the above authors--could be confirmed in a larger unbiased series, who would be so daring as to diagnose individuals with, for instance, 4 whorls as having Wilson's disease, or on the other hand restrain two persons, each with 3 or 4 whorls on their fingertips, from marriage because they
Dermatoglyphies in Wilson Disease
283
Table 1 Pedigree Right/ I No. left hand
II
III
IV
V
Ending of D-line type
TRC
III,2
I~ L
Ull U12
U10 W9
Ull Ull
U12 U12
U7 U8
beta beta
103
III,3
R L
U12 U12
U13 DL14
U13 U14
U12 U13
U13 U9
beta beta
125
III,4
g L
DL16 U9
LA LA
U3 U6
U11 U8
U4 U4
alpha beta
61
III,5
1% L
U14 U9
1%7 R4
U7 A
U10 U13
Ull U6
alpha gamma
80
1~ L
Ull U9
R2 U4
U6 LA
U16 U17
U17 U14
alpha epsilon
96
III,7
R L
U15 U16
TA U5
U12 U15
Ull U13
U12 U15
alpha delta
II,3
t~ L
U9 U9
U3 R2
U5 U7
U7 U10
U10 U5
delta gamma
II,5
1% L
U13 U6
1%16 1%3
UI0 U13
U16 U13
U13 U9
alpha beta
112
II,11
R L
U15 U15
U6 R5
U9 U9
U10 U11
U5 U4
beta beta
89
R L
U14 U16
R2 R2
UI0 U9
U8 R8
U2 U8
alpha beta
79
III,6
II,13
114 67
U = ulnar loop, R = radial loop, W = whorl (the higher ridge count is indicated), DL = double loop, LA = low arch, TA = tented arch. D-line exit classification according to Holt (1968).
c o u l d be h e t e r o z y g o t e s for W i l s o n ' s disease. T h i s c e r t a i n l y r e q u i r e s t o o m u c h of t h i s m e t h o d ; p a r t i c u l a r l y in t h e i n d i v i d u a l ease d e r m a t o g l y p h i c a n a l y s i s is o f no clinical help. L a b o r a t o r y d a t a are u n a v o i d a b l e . F o r a e x c e l l e n t g e n e r a l d i s c u s s i o n of t h e r e l a t i o n b e t w e e n d e r m a t o g l y p h i c s a n d disease t h e r e a d e r is r e f e r r e d to t h e p u b l i c a t i o n s o f W e n d t et al. (1970, 1971).
Acknowledgement. The valuable criticism of Prof. Dr. G. G. Wendt is greatly appreciated.
References Grosse, F. g., Herrmann, J., Opitz, J. ~ . : The F-syndrome or the F-form of aero-pectoralvertebral dysplasia. Birth Defects Original Article Series g, 3, 48--63 (1969) I-Iodges, 1%. E., Simon, 1%. ft. : Relationship between finger print patterns and Wilson's disease. J. Lab. Clin. Med. 60, 629--640 (1962) Holt, B. : The genetics of dermal ridges. Springfield (Ill.) : C. C. Thomas 1968 Vormittag, W., Weninger, N., FIayen, tI.: Zur Beziehung zwischen Hautleistenverlauf und Morbus Wilson. I-Iumangenetik 18, 337--340 (1973)
284
R. Grosse
Wendt, G. G., Rube, M., Kindermann, I. : Krankheiten und Papitlarleisten der Fingerbeeren. Eine kritische Betraehtung. 2. Kolloquium Hautleisten und Hautfurchen, pp. 291--310. Berlin 1970 Wendt, G. G., Rube, M., Kindermann, I.: Papillarleisten und Krankheiten. Dtsch. med. Wschr. 96, 1056--1062 (1971) Dr. F. R. Grosse Universit~its-Kinderklinik D-2300 Kiel, Fr6belstraBe 15/17 Federal Republic of Germany
