Canad. M. A. J. Nov. 1, 1957, vol.

77

SHORT COMMUNICATIONS: MULTIPLE LIPOMATOsIs 881

SHORT COMMUNICATIONS
FAMILIAL MULTIPLE LIPOMATOSIS*
JOHN A. SHANKS, M.B., Ch.B., Provost, Alta., W. PARANCHYCH, B.Sc.,t Edmonton, Alta., and J. TUBA, Ph.D.,t Edmonton

MULTIPLE subcutaneous fatty tumours occurring in a family have not been extensively studied. Whether this is due to their rarity or to the benign nature of the condition is uncertain, but the opportunity has arisen to investigate a large family so affected, and an attempt has been made to throw more light on the matter.
GENERATION

Iwo unrelated families were investigated. The M family was large, and about a quarter of the members were affected. The W family was small, and only one member was affected. The accompanying family trees show the occurrence of lipomatosis. In all but three cases where tumours were excised, the diagnosis rested on the finding of one or more subcutaneous tumours of any size, which were soft, mobile and not attached to the skin. Any errors are likely to be of the "false negative" variety, since small tumours may escape the attention of the patient (and perhaps elude the examiner).
NATURE OF MULTIPLE LIPoMATOsIs

In the people studied the sexes were equally affected. The age of onset was mostly in the

FlhMILY M

EI

JE7 JJi@
1 23

0*
4

Li
6

10

11

12

13

14

3 4 5

6 7 8

9 10 11 12 13 14 15 16 17

18

19

20 21

22 23 24 25 F 26 27 28 29

600 02

0 0
1
2

13 12 11 10 Lipomata present

14

15

16

17

Male

Information from relative

0 U LI

Female
Lipomata present

w
0
Personally examined or information obtained from
self
Fig. 1

Lipomata absent

Inadequate information regarding lipomata Stillbirth

Lipomata absent

J2'7 Deceased aged 7 years

The main object has been to determine the etiology of multiple subcutaneous lipomata and their association, if any, with a metabolic abnormality.
*From the Provost Medical Centre and the Department of Biochemistry, University of Alberta. tDepartment of Biochemistry, University of Alberta.

third decade, although the youngest was under 10 years. The first tumours appeared as small symptomless lumps under the skin at any of the commonly affected sites. In the worse cases new ones appeared throughout life. Some grew slowly and steadily, while others stopped enlarging at some stage. The tumours ranged from 5 mm. to 7 cm. in diameter and were spherical

882 SHORT COMMUNICATIONS: MULTIPLE LIPoMAToSIS

Novr.1, 1957, vol. 77

Canad. M. A. J.

FAMILY W

GENERATION

WIQ

Several of the second generation have some symptoms of fat intolerance and one has had an attack of cholecystitis. ANALYSIS OF SERUM AND TIsSUE LIPIDS The analyses of serum total cholesterol, free cholesterol, phospholipids and total lipids were carried out on aliquots of purified extract of serum and tissues. Serum was extracted and the extract purified by the method of Sperry.10 Aliquots of the purified extract were then evaporated to dryness under a stream of nitrogen and analyzed. Total cholesterol was determined by dissolving the residue in glacial acetic acid, and the colour was then developed with acetic anhydride-sulfuric acid (Lieberman-Burchard). Free cholesterol was determined by dissolving the residue in acetone-alcohol (1:1), precipitating with digitonin, subsequenitly dissolving the digitonide in glacial acetic acid, and then developing the colour by the Lieberman-Burchard reaction. Analysis of phospholipids consisted of digesting the phospholipids with a perchloric-nitric acid mixture, and then measuring the amount of phosphorus by the method of Fiske and Subbarow.5 Total lipids were determined as

I * O0@@
1

2
Fig. 2

or egg-shaped. The number found at examination varied from one to over 80. The most heavily infested patient had had about 40 tumours removed on two previous occasions, which would bring her total to well over 120, although these were not all present at one time. The affected sites were the forearms, upper abdomen and lower chest, thighs, back, upper arms and lower legs. Only one patient complained of tenderness. In the others, the tumours were symptomless except where they were exposed to trauma or where they overlay a tendon and caused a pulling sensation on movement. The characteristic fluctuant feeling of a lipoma was always present. They were usually quite mobile, and never disappeared spontaneously.

repcrted by Bragdon.2 All determinations were done in duplicate or triplicate, and a standard curve and recoveries were done with each set of analyses. Recoveries ranged between 94 and 107%. Eleven normal sera analyzed by these methods gave normal values. The results of the analyses are presented in the combined table. The total cholesterol was slightly raised in one case (without tumours), and all other results were within nornmal limits given by Keys.7 Several excised tumours were analyzed chemically and found to be almost identical with normal subcutaneous fat, which is mainly triglycerides.
ETIOLOGY

EXAMINATION AND INVESTIGATION All the people personally interviewed were questioned about past history and general health, with special attention to symptoms of gall-bladder disease. A complete physical examination (rectal examination was omitted under the age of 16) including urinalysis was carried out. The past history revealed no significant physical ailments. The general health of most members of family M is good, and the build and general appearance of all members of the second generation are remarkably similar. They are strong and heavily built, gain weight easily, eat heartily and have seborrhceic skins. One unmarried man has spent several months in a mental hospital with a paranoid psychosis. Three other males are single, one of whom is "eccentric". In one family the third generation contains a person with minor epilepsy; in another family there is eczema and in another there is a strong neurotic tendency.

cases, but in two of these it preceded the appearance of lipomata by over three years. Although all members of family M are heavily built and well covered, there has been no association between tumour formation and weight

Phillips9 has described multiple lipomatosis following mental or emotional upset and cites another case." There was a possible source of psychic trauma in three of the present affected

gain.

HEREDITY t Family M represents Case 1 referred to the Heredity Counseling Committee. In family M, multiple lipomatosis is transmitted as a dominant characteristic which appears to be highly or fully penetrant, with a typical age of onset. The dominant transmission of the condition is shown by the following observations: (a) Only affected persons can have
tBy Dr. Margaret Thompson, Chairman, Heredity Counseling Committee, University of Alberta.

Canad. M. A. J.

Nov. 1, 1957, vol. 77

SHORT COMMUNICATIONS: MULTIPLE LIPOMATOSIS 883

TABLE I.
No. of lipomata

Individual Age

Sex

Colour of eyes

Blood group

(Values in mg. per 100 ml. serum) Free Total chole- Phosphochole*Fat in- Neutral lipid sterol sterol fat tolerance
127
+ -

Family M GII: 4

60
58 56

F
M

80+ GGB
15
0?

BMNP CDe/CDe Fy(a+) K-

328 329

112 85

181

GIl: GII: GII:

GII:

5 6

GGB GGB GGB

GGB
Blue

229

7 8

55
M

53
M

60
11
F F
M

GII: 12 GII: 14 GIII: 1 GIII: 5 GIII: 9 GIII: 11 GIII: 12 GIII: 13 GIII: 25

GIII: 26

49 44
40

6
1
15 0 0 0

GGB

32
26 17 15
14 24

M M F
M

23
21 16

GIII: 27 GIII: 28
Family W GII: 1

0
0

Dark brown Light brown BMNP CDe/cDE Fy(a-) KGGB Dark brown BMNP CDe/CDe Fy(a-) KDark brown AI BMNP CDe/cde Fy(a+) KDark brown BMNP CDe/cde Fy(a+) KLight brown A2MMP CDe/cde Fy(a+) KLight blue A2MMP CDe/cde Fy(a+) KGGB Dark brown A2MMP CDe/cde Fy(a+) KBrown

BMMP CDe/CDe Fy(a+) KA2BMNP CDe/cde Fy(a+) KBMNP CDe/CDe Fy(a+) KBMNP CDe/cde Fy(a+) KA2MMP CDe/cde Fy(a+) K-

327
320

88
114

208 155
178
140

131

164 +
+

352
245
340

132

124

80
98

188
214 183

307** 233
214

78 60
54

168
199

252

66
55

151

225

98 169

194 166 202 181

345

52
48 52
109

43

17

178

*Fat intolerance was considered to be present if fatty foods could not be eaten without epigastric discomfort, lence, bloating or more severe symptoms. **Normal range for age is 105 - 264.

GGB-Grey-green-blue.

flatu-

affected offspring. No unaffected members of family M have transmitted the condition to their descendants, and there are no "skips". (b) Males and females are equally likely to be affected. The 15 affected in family M include eight males and seven females. (c) Approximately half the offspring of affected persons are themselves affected. Excluding the members of generation IV, all of whom are still too young to exhibit the disease, 33 offspring of affected individuals have survived childhood. Of these, 14 are affected and 19 unaffected, a close approximation to the expected 1:1 ratio. Family W provides no genetical information so far. Because the incidence of multiple lipomatosis in family M is in accord with expectation on the basis of dominant inheritance, with a typical age of onset, it seems unnecessary for this family to postulate any precipitating factor such as emotional shock. Data for testing a possible linkage of the gene for multiple lipomatosis with blood group genes are being accumulated. It was originally hoped that biochemical tests might indicate the presence of a metabolic abnormality in some of the younger members, pos-

sibly showing a pre-lipomatous condition, but tests so far have not shown any such abnormality.
DISCUSSION The conclusions to be drawn from this study are mostly negative. A clear distinction must be made between familial multiple subcutaneous lipomatosis and other lipomatous conditions. Solitary lipomata, often attaining a large size, have been observed in almost every part of the body. Multiple internal lipoma formation has also been described." Small tumours overlying the sacrum and sacro-iliac joints are a not uncommon cause of backache. These have been called episacral lipomata but may be herniated lobules of fat. Subcutaneous lipomata in profusion may develop after psychic trauma.3"9 Multiple subcutaneous lipomatosis has been confused with neurofibromatosis,3 and an attempt to correlate the two conditions has been made," but this does not appear to be the case. When subcutaneous lipomata, often in large numbers, are found in so many members of a family it is hard to escape the conclusion that there is a hereditary factor in the etiology, and this would appear to constitute a distinct disease. Gene mutation may explain its beginning.

884 SHORT COMMUNICATIONS: SAFFLOWER OIL AND CHOLESTEROLIEMIA

Canad. M. A. J. Nov. 1, 1957, vol. 77

Multiple subcutaneous lipomatosis occurring in an individual without apparent cause may be a separate disease entity or it may be a manifestation of the familial form where the family is too small to show other affected members. The normal blood biochemical findings provide no evidence for a metabolic abnormality in the field investigated, and chemical analysis as suggested by Kurzweg and Spencer8 has not been helpful. The first generation of family MI was of middle European origin-the father Polish and the mother German. Family W was of English origin. In the three cases where tumours were excised the pathologist reported typical lipomas. It may be possible to reopen this investigation in the future and obtain additional data.
SUMMARY Two families afflicted with multiple subcutaneous lipomata have been studied to determine the etiologv and nature of this condition. The clinical features are described. Normal levels of serum lipids were found and the tumours consisted of neutral fat identical with normal subcutaneous fat. The genetic aspects of the condition are discussed and it is concluded that multiple subcutaneous lipomatosis is transmitted as a dominant characteristic.
We are grateful to the Medical Research Fund, Department of Medicine, University of Alberta, for a generous grant towards the expenses of this investigation. We would also like to thank all the members of the two families who co-operated so cheerfully in the accumulation of these data.
REFERENCES
1. ADAIR, F. E., PACK, G. T. AND FARRIOR, J. H.: Am. J. Cancer, 16: 1104, 1932. 2. BRAGDON, J. H.: J. Biol. Chem., 190: 513, 1951. 3. BURMAN, M.: Bull. Hosp. Joint Dis., 11: 192, 1950. 4. CANTAROW, A. AND TRITMPER, M.: Clinical biochemistry, 5th ed., W. B. Saunders Company, Philadelphia, 1955. 5. FISKE, C. H. AND SUBBAROW, Y.: J. Biol. Chem., 66: 375, 1925. 6. HEILMANN, P. AND SONNECK, H. J.: Hautarzt, 4: 33,

INFLUENCE OF A SAFFLOWER OIL EMULSION ON SERUM CHOLESTEROL LEVEL

HARDING LERICHE, B.Sc., M.D., M.P.H., Willowdale, Ont.

As BARR' points out, the evidence is strong that there is a correlation between atherosclerosis and variations in chemical composition of plasma. Such association or correlation of two variables does not, of course, necessarily imply causation of the one by the other. In a recent paper, Oliver and Boyd13 discuss hormonal factors in atherosclerosis. This endocrine imbalance may promote coronary atherosclerosis by increasing plasma cholesterol, accelerating clotting, inhibiting fibrinolysis and causing alteration in vascular walls. Whereas these factors no doubt are important in individuals, one cannot visualize their importance in accounting for the difference in coronary disease between white North Ameri. cans and Guatemalans, or white South Africans and the Bantu. In such a mass phenomenon more generai differences in the environment should be considered. From epideiniologic evidence, Keys9 found an association between dietary fat intake, serum cholesterol level and coronary artery disease. This is a most important observation.10
Serum cholesterol levels are low and rise only slightly with age in the South African Bantu, conipared with white subjects. The more seriou.s complications of atherosclerosis are about one-tenth as common as amongst comparable whites, as is shown by the autopsy studies of Higginson and Pepler.7 The Bantu have a diet with low fat, low protein and high carbohydrate.15 Coronary thrombosis is rare among the Bantu, as are also appendicitis, gallstones and peptic ulcer. Studying Yemenite Jews in Israel, Toor et al.14 found that serumn cholesterol values, total lipids, and daily dietary fat intakes are lower in recent immigrants, compared

1953. 7. KEYS, A. et al.: J. Clin. Invest., 29: 1347, 8. KuRZWECG, F. T. AND SPENCER, R.: Am. J.1950. Surg., 82: 762, 1951. (Note: These authors review the literature and an extensive bibliography is provided.) 9. PHILLIPS, W.: Lancet, 1: 281, 1957. 10. SPERRY, W. M. AND BRAND, F. C.: J. Biol. Chen., 213: 69, 1955. 11. TEDESCHI, C. G.: Quoted by Burman, M.: Bull. Hosp. Joint Dis., 11: 192, 1950.

CORRIGENDUM In the article "Comparison of the Effects of Promazine and Chlorpromazine in Mental Syndromes" by H. Azima and H. Durost, published in the issue of October 1 (77: 671, 1957) there is an error in Table IV, page 674. The figures under the column headed "Collapse" should be transposed (i.e., 1%' of patients exhibited circulatory collapse on promazine and 10% on

chlorpromazine) .

with immigrants who came to Israel more than 20 years ago. At the present time, for comparable age groups, mortality from arteriosclerotic heart disease is about four times greater amongst the early immigrants, who have lived in Israel for more than 20 years, than amongst the recent arrivals. In a most interesting long-term study on the population of Framingham, Massachusetts, Dawber5 showed that deaths from arteriosclerotic heart disease ale associated markedly with hypertension and hypercholesterolemia, the latter two states either in combination or singly. It would appear that patients with high blood pressure and a