Hereditary gingival fibromatosis

ORAL PATHOLOGY Gneral .

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GINQIVAL FIRROlVLATOSIS

Report of an Affected Family With Associated Splenomegaly and Skeletal and Soft-Tissue Abnormalities Peter F. Laband, D.D.S., DrNedDent., George Habib, M.B., M.R.C.P. (Ed.), and G. S. Humphreys, M.B., San Fernando, Trinidad, B.W.I.

H

EREDITARY ‘gingival fibromatosis is a rather rare condition in which the gingival tissue hypertrophies and the emerging teeth become buried in varying degrees beneath the redundant hypertrophic tissues. This gingival hypertrophy may encroach onto the hard palate. Other names used to describe this condition are elephant&is gingivae, idiopathic hyperplasia of the gums, fibromatosis gingivae, and difu-se fibroma of the gum.s.In the family studies that have been published1-3 the condition has been handed down as an autosomal dominant, and transmission has been through an affected parent. However, sporadic casesare said to OCCUP.~~ 4 The stimulus of the presence of teeth appears to be necessary for this fibrous hypertrophy of the gingivae to occur, since the condition is not seen before the eruption of teeth. Also, surgical excision of redundant tissue only is regularly followed by recurrence of gingival overgrowth,*p 3,5 but hypertrophy ceases to recur when teeth are simultaneously removed, The histopathologic changes regularly found include simple hyperplasia of fibrous tissue of the corium, with little evidence of inflammation, associated with some epithelial hyperplasia.

PRESENT

STUDY

This article reports an East Indian family from central Trinidad in which the mother and five of seven surviving children examined were found to be affected with gingival fibromatosis. The family tree is shown in Fig. 1. Two sisters of the affected parent are not affected. The children’s father, whom we also examined, is not affected. A study of this family supports the generally 339

MOTliEi

m

Fig. I.-

171y Affected tree of family

affected and skeletal

FATHER

-

0

0

Unaffected . . gmglval flbromatosis abnormalities.

with hereditary and soft-tissue

with

SPIenomogaly

Fie. 2.

gingival flbromatosis in ll-year-old boy. Protruding Wigs. 2 and 3.- Hereditary cover teeth and keep lips apart. Note enlarged nose.

flbrous

tissues

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held view that the condition is transmitted as an autosomal dominant. The feature of particular interest in this family is the fact that there are associated abnormalities which appear to be transmitted along with the gene for gingival hypertrophy. Gingival Hypertrophy.-The extent of gingival hypertrophy varied slightly among the affected members of the family, as indicated in Table I. The mother was the least severely affected. In her case only the upper jaw was involved by overgrowth of gingival tissue, the proliferation extending, as in the others, onto the hard palate. In the other affected members of the

Fig. I.-Two

girls of same family, aged 8 and 13 years. Note gaping tissues, enlarged noses and ears.

Fig. Sy-Proflle Fig. 6.-Proflle

lips, protruding

of 13-year-old girl shown in Fig. 4. of B-year-old girl shown in Fig. 4.

gingival

R.. R. ( mother ]

38

F

‘Upper gingira only af- Ears rather large and very soft; reeetlfectcd; molars on both ing mandible ; pes cavus-toes normal ; sides show through ; exright terminal- phalanges of thumbs tension to hard oalatc!. rather short : all nails normal: all worse on right &e ’ met.acarpophalangeal joints hyperextended, and those of thumbs subluxate readily; some degree of subluxation in left shoulder

B. R.

14

M

Both gingivae affected, Thumbnails are spikes; terminal phaextreme; extension onto langes of thumbs short ; toenails are palate spikes; metacarpophalangeal joints of thumb subluxate readily; pcs cavus; hallux valgus; head of humerus subluxates easily out of glenoid; ears thick, fleshy, and “floppy”; nose enlarged

N. R.

13

F

Both upper and lower Ears rather large and very soft; receding mandible: large nose : nail absent gingivae affected, upper fr;m second ‘toe & each’ foot,: other worse; hard palate affeeted t.ocnails like spikes surrounded by small pits ; small thumbnails : short terminal phalanges of thumbs and M. P.; joints of the thumbs subluxate readily; very slight hallux valgus ; both halluces have very small nails ; head of humerus abnormally mobile, although subluxation not definite; marked pea cavus

H. R.

12

M

Both upper and lower gingivae affected, upper worse; extension right back into hard palate; most of teeth show through, molars completely so ; high, arched palate

Ears large, fleshy, and soft; large nose; nails very small, but definite nails in pits; na& on s&ond digit very small; other toenails better developed than in siblings; all metatarsophalangeal joints hyperextend; thumbs have short terminal phalanges and small nails; little fingers have very small nails ; M. P. joints hyperextend; shoulders subluxate; abnormal amount of anteroposterror movement at knee joints; marked bilateral pes cavus; marked kyphosis

8. R.

8

F

Whole of both gingivae affected; crowns of teeth show through; extension onto hard palate

Ears large, cartilages soft; large nose; receding: mandible ; toenails nothing more than s ikes surrounded by small oits: no nai.P at all on left second toe &l’only a small bump on right seeond toe; hallux has very small nail; thumbs have short terminal ubalanges and subluxate at metacarpophalangeal joint; nails small; humeral heads subluxate; both knee joints have abnormal degree of anteroposterior mobility ; metatarsarophaltigeal and metacarpophalangeal joints excessively mobile.

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GINGIVAL

TABLE I PATIENT

1 AGE

L. R.

5-6

B. R.

9

1 SEX

F

( DESCRIPTION

B. R.

(CONT'D)

OF GINGIVAE

Both gingivae affected, worse in upper jaw; extension onto hard palate; teeth show through

Family

members not affected

F

10-12 mo.

F

343

FIBROMATOSIS

1

SKELETAL

FINDINGS

Ears soft and fleshy, with soft cartilage; short terminal phalanges of both thumbs; left second toe has no nail ; right second toe is small spike surrounded by a pit; other nails reasonably well formed; toes hyperextend at metatarsophalangeal joints; all central phalangeal joints also hyperextend; humeral heads subluxate, more marked on right by gingival

hypertrophy

Hyperextension of first left metacarpophalangeal joint; humeral heads subluxate, more marked on right Gingivae appear at uresent

normal

Suspicion

of broadening

of nose

family both upper and lower jaws were involved, and in all cases the redundant tissue extended onto the hard palate (Figs. 2 to 6). In three of the children, however, the upper jaw was clearly more extensively involved. Each had a full complement of teeth, and the teeth were buried beneath the redundant tissue to varying extents (Figs. 8 and 9). In some cases the crowns of many teeth projected slightly through the hypertrophied gingivae. In the most severely affected case the teeth were completely buried. Pathologic findings.‘-Tissue was examined from two cases treated by

Fig. 7..-Mother -

and four

tiected children. Note characteristic facies. surgical removal of flbrous gingivae.

I ;Dr. John D. Arneaud,

pathologist.

The boy has unde :rgone

iVIicroscopically, the sections of a portion 0.Tmucosa and underlying submucosa of B. R., 15 years of age, showed t.hc following: The superficial mucosa consisted of a layer of prccornified ~11s. There was dcnsc melanin in the basal layer. The r&e pegs wwc prolonged and dipped down deeply into the submucosa and, in places deep in the submucosa, thcrc wcrc dilated cystlikc structures with keratinized cpithelial cells. The submucosa was also characterized by a loose collagen network in which there were focal collections of inflammatory cells, mainly plasma cells. which were particularly marked in the perivascular zone. Associated Abnormtabities.-Abnormalities which appeared to have been transmitted along with the gene for gingival fibromatosis were seen among the affected members of t,he family. Three types of abnormality were observed: (1) enlargement of the soft tissue of the nose and ears with an associated soft consistency of their respective cart.ilage; (2) splenomegaly; and (3) skeletal abnormalities, namely, absence or reduction in size of toenails and thumbnails with associat.edshortening of the terminal phalanx and an abnormal degree of mohi1it.y of several joints, particularly the first metacarpophalangeal joints and the shoulder joints. The enlargement of soft tissue of ears and nose was, in this family, the most closely associated abnormality, and it was seen in all members affected with gingival fibromatosis. The nose was fleshy in its dist.al portion, with a palpable increase in the amount of tissue of the dermis, and this extended some distance on to the bony portion of the nose. The cartilaginous septum was soft. The ears also tended to be fleshy, the lobes being affected most, and the cartilage of the pinna, too, had an unusually soft consistency. The peculiar enlargement of the nose, the appeara.nce of the ears? and the receding jaw, which was regularly present, gave the affected members a characteristic facics and an unusually strong resemblance to one another (Fig. 6). The degree of soft-tissue enlargement of t.he nose varied slightly in each case, and the appearance of the

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345

FIBROMATOSIS

ears varied even more. In the youngest child, a lo-month-old girl who did not now show any gingival abnormality, there was a slight suspicion that an increase in the soft tissue of the nose was commencing. SplenomegaZy.-Splenomegaly was observed in t.he mother and in three of five affected children. The degree of splenomegaly and its relationship to the liver-function tests are shown in Table II. In one affected girl, in whom the spleen could not be felt, liver-function tests showed some abnormality. In one case liver-function tests were not made. Presumably, the splenomegaly is the result of hepatolienal fibrosis. There is some evidence that the extent of the splenomegaly may be related to age (see history of mother). The youngest patient did not have a palpable spleen, and the recorded size of the spleen appeared to increase with age. The largest spleens were felt in the mother and the eldest child. The liver was palpable, though not grossly enlarged, in four cases. The skeletal abnormalities seen among the affected members arc listed in Table I. Pes cavus was seen in the mother and three of the children. Varying

PATIENT

R. R. (mother)

I

AGE

I SEX

38

F

I

SPLENOMEGALY

Spleen, 4 fingerbreadths Liver edge IIgb,

63%

WBC, 3,000 Platelets, 103,000

LIVER-FUNCTION

I

TESTS

Total protein, 6.1 (albumin, 2.7 Cm.) No measurable bilirubin Thymol turbidity, 2 units Zinc sulfate turbidity, 9 units Thymol flocculation, nil Colloidal gold, 4 plus

B. R.’

14

M

Spleen, handbreadths Liver, 2 fingerbreadths Hgb, 82% WBC, 4,000 Platelets, 79,00O/cm.

Total protin, 7.4 Gm. % (albumin, Total bilirubin, 0.6 mg. % Thymol turbidity! 3 units Zinc sulfate turbidity, 6 units Thymol flocculation, negative Colloidal gold, 2 plus

N. R.*

13

F

Spleen, negative Liver, 2 fingerbreadths Hgb, 82% WBC, 6,000 Platelets, 64,00O/cm.

Total protein, 6.1 Gm. (albumin, Thymol turbidity, 4 units Thymol flocculation, nil Zinc sulfate turbidity, 4 units Colloidal gold, 1 plus No measurable bilirubin

IL lL*

12

M

Spleen tipped Platelets, 118,00O/cm.

Not done No abnormalities

13. R.*

9

F

Platelets,

5. R.’

8

F

Spleen, 2 to 3 fingerbreadths Liver, 1 to 2 fingerbreadths sb 9;~oo Plateieti,

L. R.

5

*Dec. 20. 1961.

F

109,00O/cm.

86,00O/em.

No hepatosplenomegaly Hgb 27% WBC 9,000 Platelets, 67,00O/cm.

Total protein, Thymol

3.1)

6.3 Gm. % (albumin,

turbidity,

2 units

Zinc sulfate turbidity, 5 units Thymol flocculation, nil Colloidal gold, 2 plus No measurable bilirubin Thymol turbidity! 1 unit Zinc sulfate turbidity, 3 units Thymol flocculation, nil Colloidal gold, negative

4.9)

3.5)

(S.S., (i.M. 84 O.P. March. 1964

346

Fig.

10.

Fig.

11.

Pig.

12.

Fig. lO.spike !S. Fig. 1 l.Fig. 12.hallu IX, bi ilater

:,ther

t OCXlS rils

xmail rmina

Is are spik .I pha’ lamx

8we es. Of

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Fig. 13. Fig. 14. Flg. 13.-Hands of 14-year-old boy. Note subluxation of metacarpophalangeal joints both thumbs. Thumbnails are spikes. Fig. 14.-Hands of 13-year-old girl. Thumbnails are small; the left one is deformed.

Fig. 15.-Roentgenogram

of hand of 14-year-old

boy shows short terminal

phalanx

of

of thumb.

degrees of abnormal joint mobility were observed affecting chiefly the first metacarpophalangeal joint and the shoulder joints. In affected members the head of the humerus could be slid easily out of the glenoid fossa. However, abnormal hyperextension of joints is a fairly common finding among East Indians, occurring apparently as a racial characteristic, although degrees of mobility as gross as those seen in this family are rather unusual. In this family the most striking skeletal abnormality with a fairly clear relationship to the occurrence of gingival hypertrophy was the failure of the

348 toenails to develop normally. In all casesthe second digit was the most sevcrcly involved, and sometimes no nail at all. was visible on that tot. On the other digits (except t.he hallux) the most frequent finding was the presence of a small rudimentary nail in the form of a spike set in a shallow pit. In the hands, nail abnormalities were confined to the thumb. Here, the nail, through usually well formed, was clearly smaller than normal. In the ease of the eldest child, hovvcvcr, thumbnails were present only as small spikes. These nail abnormalities appear to be related to a.n abnormally short terminal phalanx (Figs. 10 to 1.5). A curious feature here is that all nails of the mother were quite normal. Unaffected Children.-There are two unaffect.cd in the family. One girl, said to be 9 years old, shows no sign of gingival fibromatosis and is without doubt free from that genetic trait. However, this girl does show an abnormal degree of mobility of bot,h shoulders and of t.he met.acarpophalangeal joint of the left thumb. The other unaffected child, a lo-monbh-old girl, has no teeth and therefore cannot yet be pronounced free from the abnormality. In this infant there is a slight suggestion of thickening of the soft tissue of the nose, and it. is possible that she may later develop the syndrome. DISCUSSION

The present article records another family in which gingival fibromatosis was apparently transmitted by means of an autosomal dominant gene. In this family the extent of gingival hypertrophy was less in the affected parent than in t.he affected children. There was a tendency for the maxilla to be more severely involved than the mandible, a point which has been reported before.2 The pa1at.ewas severely involved in all the affected members. We have no reliable information as to the time of appearance of the gingival abnormality in any of these children. ‘In the cases reported in the literature, however, it appears that the condition is usually observed to commence at the time of eruption of the permanent tcebh, although it appears that gingival overgrowth has been known to commence with the primary dentition.‘? *pS The youngest patient in this family has some permanent teeth and is believed t.o be 5 to 6 years of age. Unfortunat.ely, in no member of t.hc family is the age accurately known. It is clear that some of the associated abnormalities seen in this family were linked wit.h the gene for gingival fibromatosis. Among the abnormalities studied, an increase in the amount of soft tissue of t.he nose and ears was the one most clearly linked with the presence of redundant gingiva. These changes gave the affect.ed members of the family a very characteristic facies. Although nail changes in some degree were seen in all the affected children, the mother’s nails wcrc normal. However, these nail abnormalities clearly had some genetic basis. This is suggested by the striking tendency in all casesfor the second pedal digit t.o be the most severely affected and by the regular involvement of the thumbnails with sparing of the other digits of the hands. It is reasonable to assume, however, tha.t a different gene is responsible for these changes. The other skeletal abnormalities-excessive joint mobility and pes cavusare of more doubtful st.atus. The former is a common finding among non-

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European races, and the latter is also commonly seen in otherwise normal persons of all races. The occurrence of splenomegaly is interesting. Splenomegaly is relatively common here in adults, both aa an incidental finding on routine examination and in association with hepatic cirrhosis. However, its presence would seem in this instance to be an example of a true familial disorder. The abnormal liverfunction tests suggest that in this family splenomegaly is due to hepatolienal fibrosis. However, juvenile cirrhosis is very uncommon here and its occurrence in four of seven children in one family must be unprecedented. The tendency noted for the size of the spleen to increase with age suggests that in the family under study hepat.ic fibrosis commenced at an early age and is running a slowly progressive course. All members with splenomegaly are apparently enjoying good health, and all are well nourished. The only member of the family in whom gingival fibromatosis can be definitely excluded shows no splenomegaly. It is a temptation to suggest that these persons have a tendency toward overgrowth of fibrous tissue in the liver on the same genetic basis as the liability to gingival fibromatosis and increase in the soft tissue of the nose and ears. This is not the only possible explanation, however, and it could well be an example of an independent familial disorder. SUMMARY

We have described an East Indian family from Central Trinidad in whom the mother and five of seven living children are affected with gingival fibromatosis. Certain associated abnormalities are also present. Of these abnormalities, thickening of the soft tissue of the nose and ears appears to have a strong association with the gingival abnormality. The status of splenomegaly and certain associated skeletal abnormalities is less certain. The histopathologic appearances of excised gingival tissue are similar to those described previously. About one year after the foregoing observation had been made, the mother of this family was admitted to the hospital with abdominal distention, an enlarged liver, splenomegaly, etc. We thought it advisable to report her case history here, as it seems to confirm our conclusion that fibrosis of the spleen and liver in this family begins at an early age and progresses with the years. CASE

REPORT

Mrs. R. R., a 38-year-old East Indian woman, married and the mother of seven children, was admitted to the hospital on Nov. 17, 1961, with a 2 week history of abdominal distention and pain in the left flank. No further details could be obtained, as the patient’s intelligence level w&9 low. Esamination Findings.-The patient was a well-nourished woman, and she was not in pain. The patient had an undershot chin and prominent superciliary ridges, with accentuated pigmentation of the forehead and around the mouth. The gingivae were hypertrophied. Both lung fields were clear. The pulse wti regular, at 78 per minute. Blood pressure was 110/80. There was no clinical enlargement of the heart, and there was no evidence of heart failure. In the abdomen there was a 2 plus meteorism, and possibly fluid in the peritoneal cavity.

The liver was enlarged and just palpal~ln in the t,pigaatrium. Thnc was a 4 plus splnlonqaly. extending all the way down the left flank almost to thcl iliac (,rCst. No other significant findings were not.ed. ‘l’hnr! was no lympha~lc~~~~patl~~. Laho?~~tory Tnresti~aSion.u.-T11o hemoglol~in was 64 per cent. Thcl red blood count. millimeter, with showed a slight hypoehromia. The! white blood count was 2,000 per cd+ 82 per cent neutrophils and 18 per cpnt lymphocgtos. The platelet rount was 103,000 prr cubic! millimeter. Serum prot.rins totaled 8.2 grams per r.cnt (2.9 Gm. $& albumin and 5.3 Gm. R. globulin). Bone marrow studies revealed normoblastir erythropoiesis; normal lcukopoiesis; and megakaryocytes increased slightly in number and suggestive of thrombocytoponia. Progress.-On Dee. 7, 1961, a pancytoprnia was noted, with hemoglobin of 54 per cent, a white blood count of 2,500 per cubic millimet.er, and a platelet count of 60,000. Liver-function tests disclosed the following: Bilirubin, 1.3 mg. per cent (all dircrt) Thymol turbidit,y, 2 unit.s Zinc sulfate turbidity, 8 units Thymol flocculation, 1 plus Colloidal gold reaction, 3 plus Repeated 10 day course# of prcdnisolonr, 10 mg. twice daily, and vitamin K, capsules, 10 mg. daily, mere tried with lit.tle or no platelet rosponse. On Dec. 21, 1961, the platelet count was 43,000 per cubic millimeter. On Dee. 23, 1961, there was a sudden hemiparesis of the entire left side, more marked in the left ‘upper extremity. There was 2 plus fluid in the peritoneal cavity. The sensory changes were marked in Ohe face only. Passive exercises were instituted immediately. On Dec. 26, 1961, the naurologic signs cleared up as suddenly as they had appeared, the arm movements returning earlier than tho leg movements. The platelet count went up to 80,000. By Jan. 11, 1962, the central nervous system was back to normal. It was decided that very little was to be gained from empirical treatment with steroids and/or vitamin K. The diagnosis was paneytopenia due to splenomegaly (hypcrsplenism). It was further decided that a splenectomy, although risky, was the only answer. Mood picture on Jan. 25, 1962, was as follows: The final preoperative Hemoglobin, 65 pt’r ecmt White blood count., 2.000/c.mm. Platelets, 85,000/c.mm. Prothrombin time, 19 seconds (normal, 14 seconds) Operalion.-On #Jan. 31, 1962, a left subcostal incision was made. No peritoneal fluid was found. The omentum was found wrapped around the outer aspect of a firm (rubbery), granular spleen, which was enlarged right down into the left iliac fossa; three spleniculi, each the size of a bean, were also encountered in the splenic hilus. The splenic vein was found enlarged to 5 mm. in diamet,cr, but there was no evidence of portal hypertension. The liver was slightly larger than normal and finely granular. A dissection splenectomy was performed without incident; the patient received 1 pint of blood (Group A, Rh positive) during the operation and another pint during the immediate postoperative period. A liver biopsy was also performed. Fwthw Progresss.-The postoperative course was surprisingly smooth, and the patient was placed on oral feeding on the afternoon of the day of the operation. Postoperative platelet counts were as follows: 125,000/c.mm. on Feb. 2, 1962 165,000/c.mm. on March 2,1962 270,000/c.mm. on April 6, 1962 220,000/c.mm. on May 2, 1962 On Feb. 20, 1962, the patient, in good condition, was discharged from the hospit.al.

Histopathologic Spken: beculae,

Findinga.-

An 810 gram cut surface revealed a meaty appearance, prominent fibrous and occasional siderotic nodules. The capsule and trabeculae were thickened.

traThe

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Mapighian corpuscles were widely separated. Sinusoids were prominent; some were congested, and their walls showed an increase of fibrous tissue. The features were those of chronic congestive splenomegaly. L&over biopsy: There was some increase of fibrous tissue in the portal tracts, but the liver cells and architecture were well preserved. There was no evidence of cirrhosis. . We would like to thank Arthur H. Mike, B.A., M.B., C.H.B., B.A., and John 8. Das, F.R.C.S. (Eng.) , F.R.C.S. (Ed.), for their valuable help and cooperation. REFERENCES

1. Savara, B. S., Suher, T., Everett, F. G., and Burns, A. cf.: Hereditary Gingival Fibrosis, J. Periodont. 26: 12-21, 1954. of the Gums, D. Practitioner 7: 2. Rushton, M.: Hereditary or Idiopathic Hyperpksia 136-146, 1957. 3. Zackin, S. J., and Weiaberger, D.: Hereditary Gingival Fibromatosis, Oral Surg., Oral Med. L Oral Path. 14: 826336, 1961. 4. Buchner, H. J.: Difuse Fibroma of the Gums; Report of Two Cases, J. Am. Dent. A. 24: 2003-2007, 1957. 5. Rapp, R., Nikiioruk, G., Donohue, D. W., and Williams, C. II. M.: Idiopathic Hyperplasia of Gingivae Associated With Macrocheilia and Ankyloglossia, J. Periodont. 26: 51-55, 1955. 6. Englert, R., and Levin, I.: Diffuse Osteofibromatosis; a Symptom Complex, Oral Burg., Oral Med. & Oral Path. 7: 837~841,1954. 7. Thoma, K. H.: Oral Pathology, ed. 4, St. Louis, 1954, The C. V. Mosby Company. 40, POIXTE

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