Anatomy of Eccrine Sweat Glands in D1, G1 and 18 Trisomy Syndromes*

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Vol. 50, No. 6

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ANATOMY OF ECCRINE SWEAT GLANDS IN D1, G1 AND 18 TRISOMY SYNDROMES* BENJAMIN H. LANDING, M.D. AND THEADIS H. WELLS, H.T. (ASCP)

Despite their ready availability for diagnostic study, ecerine sweat glands have not been reported to show diagnostic anatomic abnormality in any of the known ehromosomal disorders, nor in a large number of genetic diseases. Previous studies in this department have established the relations of sweat gland duet

ing of the duct, interwoven secretory coils, etc.) were not measured. A study of these will be made in a subsequent investigation. The mean sweat gland duct length (MSGDL) was calculated for

length and secretory coil size to sex, age,

(SGI) was also calculated for each patient

height, weight, weight to the two-thirds power, surface area and calculated total body water of patients throughout childhood (1). These data provide a background for investigation of the anatomy of the ecerine sweat glands in a wide variety of chromosomal and genetic diseases. Data demonstrating that these glands are anatomically normal in fibrocystie diseases (cystic fibrosis of the pancreas) have previously been

each patient; the product of the coil measurements, called the coil area, was calculated for each

gland and the mean (MCA) derived for each patient. The ratio of "mean sweat gland duct length" to "mean coil area", called the sweat gland index

(MSGDL/MCA = SGI). Table I summarizes the data on those patients clinically diagnosed as having one of the three trisomy syndromes, as well as those with ArnoldChiari malformation. Also listed are the cytogenetic findings on those patients who had chromosomal studies (white blood cell); all patients tested were found to be trisomic for the appropriate chromosome except for patient S of the 18 trisomy population, who was found to have an isoehromosome in the E-group. Figure 1 illustrates

published (2). The present study reports the graphically the relation of mean sweat gland duet results of investigation of the anatomy of ec- length to mean coil area for the four groups under crine sweat glands in patients with the clinical pictures of D1 trisomy (trisomy 13—15), 18

trisomy (E trisomy, trisomy 16—18), and ft

study; for comparison, a control population of

157 patients without specific chromosomal disease

(1), and a series of 36 patients with fibrocystie disease are also included in the graph (1). Figure 2 presents the sweat gland indices for the same groups of patients, in relation to the crown-heel lengths of the patients; height was chosen as the parameter to be presented because it shows the

trisomy (trisomy 21, Down syndrome) in comparison to patients with Arnold-Chiari malformation and to a control population. The patients with Arnold-Chiari malformation (myelomenin- closest statistical relation to sweat gland duct gocele, hydrocephalus, cerebellar dysplasia, etc.) length of the body parameters listed above (1). were included as a "control" population with Figure 3 presents the data in another form, comthe patients with 18 and D1 trisomy to maldevelopment of the central nervous system paring control patients with crown-heel length 70 cms or not due to chromosomal abnormality. less, and the C1 trisomy and Arnold-Chiari paMATERIALS AND METHODS

Specimens of anterior abdominal skin were obtained at autopsy, and fixed in 10% neutral formalin for at least 7 days (2). Maceration and micro-

tients to controls with crown-heel length 141 ems or less. Figures 4—7 present representative examples of eccrine sweat glands of the C1 trisomy, 18 trisomy and control groups.

dissection were performed by a previously reported method (3). For each patient, at least ten and not more than

RE5ULT5

Although the validity of the conclusions is

limited by the fact that only 12 of 49 pathirty sweat glands were randomly isolated and tients diagnosed as having one of the three

then placed in a smooth, thin layer of vasoline on the bottom of a Petri dish. The measurements of chromosomal disorders had the diagnosis conduet length and coil dimensions were made with firmed cytogenetically, the accuracy of clinical

a calibrated ocular micrometer in a dissecting diagnosis of the 18 and ft trisomy syndromes, microscope at magnifications of 30X or 90X (Figs.

4 and 5). Glands with aberrant structure (branch- at least, would appear adequate for the pur-

poses of this study. With this reservation, the * From the Departments of Pathology of the data presented demonstrate that patients with Childrens Hospital of Los Angeles and the Uni- G1 trisomy have cccrine sweat glands which versity of Southern California School of Medicine. differ from those of controls by having relaAccepted for publication January 10, 1968. 475

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TABLE I trisomy (Down Syndrome, trisomy 21)

G1

Data on populations with chromosomal abnormality, and on the series with Arnold-Chiari malformation. The specimen from one patient in the G1 trisomy group (,15) was taken in close proximity to a nipple and the glands are thought to be apocrine. Case

Sex

1

M

Age

Length

MSGDL

(Days)

F

2 3 4 5 6 7 8

M

M M M F F

F

11

F

12 13 14

M F M M M

15 16 17 18 19 20

F F F

M

21

(mm.)

40

0.7

41

8

9 60 62 53 12

F F

9 10

(cms.)

6 8

MCA

Range

Range

SGI

(sq. mm.)

.01

.01—02

1.5

0.6—0.9 1.1—1.8

.02

.01—.07

70 75

43.5

1.4

1.2—1.5

.03

.01—05

47

44 46

1.0 1.0 1.2

0.9—1.4 0.8—1.1

.02 .07 .03

.01—03 .06—08 .01—08

50 14

40

.05

.01—08

38

.02 .03 .03 .02 .05 .05 .07

.02—.03 .02—.04

47

47 49 49

1.0 1.4

50

60

1.3 1.1 1.3 1.3 2.3

345 628 660 780 770 2125 3458

66 78

1.2 1.5

79 83

1.8

86

51

54 54 56.5

103

123

1.0—1.4 1.4—2.2 0.8—1.2 1.2—1.8 1.0—1.6 0.9—1.2 1.0—1.5 1.0-1.5 1.9—2.8

1.9

66 128 112 90 107 212

Cygenetic

.01—05 .01—04 .03—08 .02—08 .01—11 .04—.08 .02—.08 .01—.04 .03—.08

1.7 1.9 2.6

0.8—1.4 1.0—2.1 1.6—2.3 1.2—1.7 1.5—2.1 1.4—2.4 2.1—3.1

.05 .03 .03 .06 .03 .06 .07

1\/SGIL

Range

(sq.mm.)

1.5

.01-.04 .03—15 .01—15

Confirmed Confirmed

50

43 55 26 26 33

24 50 60 25 57 27 37

Confirmed Confirmed

—

Patients

Means

21

Mean of total

17

Mean of patients not

1.4

1.4

.46

.04 .04

.018 .017

.02—07

.44 1.2—1.7

.02—.07

43 44

15.95 16.12

.61

.04

.028

.03—07

37

10.86

1.2—1.8

confirmed

Mean of patients confirmed 1.4

4

SGI

Range

1.1—1.8

D1 trisomy (trisomy 13—15) Case

Sex

Age

Length

MSDGL

(Days)

(mm.)

42

1.1

0.8—1.2

.05

.02—06

22

42.5

0.7

0.6—1.0

.02

.01—05

40

7

46 46

0.9 1.3 0.7 1.3 1.0 0.9 0.7 0.7

0.8-1.3

.02 .07 .03 .05 .04 .04 .03 .03

.01—03

0.9—1.4 0.6—0.8 1.1—1.6 0.7—1.3 0.8—1.1 0.6—0.8 0.5—0.9

45 19 23 26 29 23 35 23

Range

(sq.mm.)

Range

2

F

3 4

F

5

M M M M

135

M

24 77

Patients

21

3 8 2

F

47 49

50 50 51

52

Means

9

Mean of total Mean of patients not

1

Mean of patients confirmed

10

SGI

(ems.)

F

6 7 8 9 10

Range

1 9

1

M

MCA

Range

(sq. mm.)

MSGDL

0.9 0.9

.24 .22

0.6—1.1 0.7—1.7

.04 .03

.04—.12

.01—03 .02—.06 .01—.04

.02—06 .01—.04 .01—.04

.014 .012

0.9—1.4

.07

29

.01—05

30

.04—12

Confirmed

SGI

.02—.07

confirmed

1.3

Cytogenetic

8.69 8.49 19

477

ECCRINE GLANDS IN TRISOMY SYNDROMES

TABLE I—Continugd 18 trisomy (E trisomy) Case

Sex

F F F

1

2 3 4

M F M

5 6 7

F F F F F

8 9 10 11 12 13 14 15 16 17 18

F F F F F

M F

Age

Length

MSGDL

(Days)

(ems.)

(mm.)

42 43

1.1 0.9

1.0—1.4 0.8—1.1

.04 .03

44 44 45 46 47 47 47 47 48 49 49 50

1.4 0.9 1.0 0.7 1.0 1.0 1.0 1.4 1.1

1.2-1.7 0.8—1.1

.06 .04

0.8—1 .2

.03 .02

50

0.8

51

1.0 1.3

3 11

60 15 26

2 21

60

424

2 97 35 18 60 57 32 76 910

54 68

11

7

0.6—0.9 0.9—1.1 0.9-1.2 0.9-1.2 1.2—1.5 1.0—1.3 1.2—1.7 1.0—1.2 0.9—1.3 0.75—.95 0.8—1.1 1.0-1.5 0.9-1.3

1.4 1.1 1.1

1.1

1.1 Mean of total 1.1 Mean of patients not confirmed Mean of patients confirmed 1.0

18

SGI

.02—05 .02—05 .03—09

28 30

.02—07

23 33

Cytogenetic

(sq. mm.)

1v,1

Means

Patients

Range

MCA

Range

Range

.

02—.04

.01—04 .03—06 .01—06

.04 .02 .04 .05 .05

.03—.06

.06 .06 .05

23 Confirmed Confirmed

35 25 50 25

.04—OS .02—09 .03—09 .03—09

28

.O3—.08

22 20 25 19 28

.04 .04

.01—06 .01—06

.07 .04

.04-.10

(sq.mm.)

Range

.03—07

Confirmed

25

Confirmed

23 18

Confirmed Confirmed

Confirmed SGI

0.9—1.3 1.0—1.3

.04 .05

.014 .015

.02—.07

.03—07

27 26

8.41

.23 .11

0.9—1.2

.04

.012

.02—07

28

3.42

.20

4.36

Arnold-dhiari Malformation Case

1

2 3 4 5 6

7

8 9 10 11

Patients 11

Age

Length

MSGDL

(Days)

(ems.)

(mm.)

2

44

F F

25

F

Sex

M

M M

SGI

.03 .04 .02

.02—05 .01—08

12

44 46

.01-04

33 33 50

8

48

1.2

1.0—1.4

.05

.04—07

27

74

54

1.0

0.9—1.2

.04

.02—08

25

34

54

1.2

1.0—1.5

.04

.02-.05

30

120 212

58

1.2

0.9—1.5

.04

.02—.06

30

65 75

1.1—1.6 0.9—1.5

.04 .04

.02—.06

730

1.4 1.2

.01—05

35 30

2675 4745

116

1.5 1.8

1.3—1.8 1.6—2.1

.08 .09

.05—15 .05—13

19 20

iVSGDL

Range

(sq. mm.)

Range

Means

Mean of total

141

1.3

Cytenetic

(sq. mm.)

0.8—1.1 1.1—1.5 0.9—1.0

M M

Range

1.0 1.3 1.0

F F F

MCA

Range

.25 1.0—1.5

tively long excretory ducts in relation to the

.05

.020

.02—07

SGI 30

10.14

secretory coils (small sweat gland index). Patients with D1 trisomy do not apparently difindex). Similarly, patients with 18 trisomy fer from the control population, although the have glands which differ from normal by hav- number of cytogenetically confirmed patients in ing short ducts in relation to the size of the this group is too small for reliable conclusions. size of their secretory coils (a large sweat gland

478

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TABLE II Statistical summary of the four populations x5, trisomy G1 vs. Arnold-Chiari malformaof Table I compared to the control population. tion = 6.11 (SGI of trisomy 21 large). The chi square values given are not based on Yates' correction.

SGI above 45

1. Patients with crown-heel length 55 cms. or less.

Trisomy G1 Trisomy D1 Controls

10

2 8 23

trisomy G1 large).

(SGI of

trisomy G1 large). x2, Arnold-Chiari malformation vs. normals = not significant at any level.

2 19 6.67

2. Patients with crown-heel length 70 ems. or less. SGI above 30

SGI 30 or less

3 43 6

15 23 2

x2, trisomy 18 vs. controls =

13.4

(SGI of

trisomy 18 small).

x2, trisomy 18 vs. Arnold-Chiari malforma-

tion =

8.36 (SOT of trisomy 18 small). value, trisomy 18 vs. controls = 2.26 (p < .05). SGI above 35

formation

56 17

SGI 35 or less

x2, trisomy D1 vs. controls = not significant at any level. x2, trisomy D1 vs. Arnold-Chiari malformation = not significant at any level. tvalue, trisomy D1 vs. controls = 1.32 (p > .05).

Trisomy G1 Arnold-Chiari mal-

8

7 10

SGI above 35

x2, trisomy G1 vs. controls = trisomy 21 large).

Trisomy 18 Controls Arnold-Chiari

Trisomy G1 Controls Trisomy 18

SGI 45 or less

SGI 35 or less

10

5

1

7

1

x2, trisomy G1 vs. controls = x2, trisomy G1 vs. trisomy 18 =

7.24

(SGI of

7.51 (SGT of

3. Patients with crown-heel length 145 ems, or less.

Trisomy G1 Arnold-Chiari mal-

formation Controls

SGI above 35

SGI 35 or less

14 1

7 10

38

98

x2, trisomy G1 vs. controls = trisomy G1 large).

12.3

(SGI of

x2, trisomy G1 vs. Arnold-Chiari malformation 9.58 (SGI of trisomy G1 large). x2, Arnold-Chiari malformation vs. controls = not significant at any level. tvalue, trisomyGivs. controls = 3.91 (p < .01). value, Arnold-Chiari malformation vs. con-

trols =

0.25 (no significance).

479

ECCRINE GLANDS IN TRISOMY SYNDROMES

E 3J E

z

I 1Ui

2.5

-J

•

,p

2.0

1

-J

'A

S. icE

1.5

Ui

S

A

1 AX

Ui

ax

A

a *0 .Si Ax •

A

iW ho

o TRISOMY 13-15 x TRISOMY 16-18 s ARNOLD-CHIARI o FIBROCYSTIC DISEASE

A

.08

.04

.00

£ DOWN'S SYNDROME

A

*

a.

A

.20

.16

.12

MEAN COIL AREA IN mm2

IFie. 1. Relation of mean sweat gland duct length to mean coil area for patients with G1 trisomy, D1 trisomy, 18 trisomy, and Arnold-Chiari malformation. Black dots indicate control patients, and circles indicate patients with fibrocystic disease. The dotted triangle indicates the patient with Down syndrome whose skin specimen probably contained apocrine rather than eccrine glands. DOWN's SYNDROME £ O TRISOMY 13-15

80 70

. a.

X

TRISOMY 16-18

ARNOLD-CHIARI

o

60 •

z Z (ii

50

£

.AAa..

°x Aa

•

40

x.d°.•0 .0 A

aA•'.

0 Ui I—

A

X•X

20

FIBROCYSTIC DISEASE

•XA

°r

AO?A

. oCx.

•

.x• A

•

S

•,•

8 Ax

•

£

.1

0

30 40 50 60 70 80 90 100

110

20 130

140

150

160

170

180

HEIGHT IN cm.

Fie. 2. Relation of sweat gland index (MSGDL/MCA), to crown-heel length for the

same populations as Fig. 1.

Patients with Arnold-Chiari complex or fibro- show maldevelopment of the central nervous cystic disease also do not differ from the control system, and that patients with Arnold-Chiari population. The facts that all three populations malformation have normal sweat gland anatconsidered to have chromosomal abnormality omy, indicate that the abnormal sweat glands

480

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75

S

70

S.

. .

S.

.

65

.

.

60 55 50

*,.

*

..

45 >1

z z

40

• .: : ••

35

*

-J 0 30 w

. ....

*

25

° 20

*

_____ • . . .x.

S

.*•

•**

*

15

I0

5 0 18

TRISOMY

DI TRISOMY

CONTROL

(70 cm.

Ci TRISOMY

AC

CONTROL

( 141 cm.

* Confirmed • Not Confirmed tl Arriold-Chiari Mo/formation FiG. 3. Comparison of sweat gland indices of the abnormal populations of Fig. 1 to control populations of differing size. The circled star in the G1 trisomy column indicates the

patient whose specimen is thought to contain apocrine glands.

of the patients considered to have G1 trisomy and 18 trisomy are not due simply to cerebral maldevelopment, but reflect in some more specific way the abnormal gene balance produced by the chromosomal abnormality. Whether the anatomic abnormality of the eccrine glands of patients with G1 and 18 trisomy is reflected in abnormal chemical composition of their sweat, and whether either the anatomic findings or any possible biochemical counterparts have practical diagnostic value, remain to be determined.

ment of microdissected eccrine sweat glands from series of patients clinically diagnosed as having the D1, 18 and G1 trisomy syndromes (trisomy 13—15, trisomy 16—18, and the Down

syndrome). The findings were compared to those of a series of patients with Arnold-Chiari malformation, a developmental disorder of the central nervous system, and to a control populaton. With the reservation that only 12 of 49 patients clinically diagnosed as having one of

the three chromosomal disorders were confirmed cytogenetically, patients with G1 trisomy

were found to have eccrine sweat glands with long excretory ducts relative to the size of the The duct length, secretory coil size, and the secretory coils, and patients with 18 trisomy ratio of the two, were determined by measure- the reverse relation. The patients diagnosed as SUMMAnY

I

.—

. S.

—

.

0i

—

a

4

I

:±H4

Fie. 4. Representative eeerine sweat gland from

a patient with ft trisomy (7). The gland is

mounted on a hemoeytorneter, and stained with Mallory's iron hematoxyhn. (X100). The arrows indicate the length of the duet segment measured. FIG. 5. Coil of ecerine gland from the same patient as fig. 4. The arrows indicate the dimensions of the seeretery coil measured. Preparation as in

Fie. 6. Representative eeerine sweat gland from

a patient with 18 trisomy (8). Preparation as in Fig.4. (X100). FIG. 7. Representative eeerine sweat gland from

a control patient with crown-heel length of 50 ems. Preparation as in Fig. 4. (X100).

Fig. 4. (X100). 481

482

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having D1 trisomy, and those with the Ar-

glands. The Physiology oJ Growth & Body

nold-Chiari malformation had anatomically normal eecrine sweat glands.

Composition. Eds., Cheek, D., at al., In press. 2. Bartman, J. and Landing, B. H.: Morphology of the sweat apparatus in cystic fibrosis. Am. J.

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THE JOURNAL OF INVESTIGATIVE DERMATOLOGY

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