H. El-Abdin, BDS, FDSRCPS*, A. Ruprecht, DDS, MScD, FRCD(C)**,
C. Halstead, DDS, MSD***
*King Saud University College of Dentistry, P.O. Box 60169, Riyadh 11545, Saudi Arabia
**Oral and Maxillofacial Radiology, The University of Iowa College of Dentistry, Iowa City, Jowa, USA
***University of Virginia Health Sciences Center, Department of Dentistry, Virginia, USA

Tuberous sclerosis is one oi the neurocutaneous syndromes manifested by adenoma sebaceum, epilepsy, and mental retardation and is referred to as the Pringle-Boumeville syndrome. Characteristically, the cutaneous lesion has a butterfly pattern in the nasolabial folds, chin, and forehead. Oral lesions are rare, and mainly consists of fibrous masses. They were reportedly observed after the use of drugs for the treat­ ment of epilepsy and are considered to be iatrogenic. In this study, a 27-year-old male Saudi patient, refer­ red for treatment of an intraoral fibrous lesion, was reported with a case of tuberous sclerosis. This is the first case that has been reported from Saudi Arabia ancf no incidence figures are available.

According to Scully,1 tuberous sclerosis, also known as Bourneviile's disease or epiloia,2 is one of the neurocutaneous syndromes which includes Sturge-Weber Syndrome and Von Recklinghausen's neurofibromatosis. Tuberous sclerosis was first reported by Von Recklinghausen in 1863.3 More cases were reported by Bourneville4 and Pringle5 while Vogt described more fully the stigma which consist of adenoma sebaceum (angiofib- romatous lesion), epilepsy and mental handicap.6 Subsequently, the disease was referred to as the Pringle-Bourneville syndrome.7

The cutaneous lesion, which may consist of telangiectasia or small firm elevated nodules of a red or yellow gray color, are found over the nose (usually in a butterfly pattern), nasolabial folds, chin, and forehead. Oral lesions consisting offibrous   masses   were   not   described   until   the 1940's.8

The disease is rare with a reported incidence between 1:30,000 and 1:500,007 and has not been previously reported in Saudi Arabia. The fol­ lowing is a case report of a Saudi suffering from the disease.

Case Report

A 27-year-old Saudi male, hospitalized for chronic renal failure in the Department of Internal Medicine, King Saud University, was referred for surgical removal of gingival hyperplastic nodules prior to denture construction. The extraoral exami­ nation showed a cooperative, somewhat inatten­ tive, patient with some evidence of mental retarda­ tion and poor memory, which was confirmed by a subsequent neurological examination. He was, otherwise, well-nourished and developed, and not obviously distressed.

The skin over the middle third of the face, the nose, and nasolabial folds, as well as the chin, showed small nodules ranging from the size of a pinhead to about 4 mm in diameter [Fig. 1 ]. Those over the nose were distributed in the typical shape of a butterfly. The nodules were light-brown and slightly elevated giving the chin (although bearded), a rough appearance [Fig. 2]. Examina­ tion of the back and neck of the patient revealed more isolated lesions [Fig. 3]. The hands and feet revealed numerous periungual nodules consistent with fibromata [Fig. 4|.

During intraoral examination, whitish-gray hyperplastic fibroma-like gingival nodules were found predominantly in the anterior segments of both upper and lower edentulous ridges [Fig. 5a]. There were further isolated buccal lesions [Fig. 5b].

There was bone loss in the lower left premolar region on the orthopantomograph. Skull films, as part of the neurological work-up, showed intracra­ nial calcification and increased thickening of the calvaria.

One elongated nodule on the crest of the ridge of the lower left mandible was removed under local anesthetic and submitted for histopathological examination. Sections showed a lobular mass sur­ faced by stratified squamous epithelium showing parakeratosis and marked acanthosis with elon­ gated rete pegs. The underlying connective tissue showed a very sclerotic and acellular collagen. Scattered among the interlacing bundles of colla­ gen were many variably-sized blood vessels with numerous islands of endothelial cells. A diagnosis of tuberous sclerosis (Bourneville-Pringle syn­ drome) was made.

Tuberous sclerosis was first reported in 1863 by Von Recklinghausen who described sclerotic lesion in the brain and myomas in the heart of a newborn child.3 During 1880 Bourneville described sclerotic areas in the brain of another child.4 The child was mentally retarded. It was he who used the term tuberous to describe the lesions because they were potato-like in appearance, shape, and texture. In 1885 Balzer and Menetrier, using the term adenoma sebaceum, reported on facial lesions which consisted of discrete red papules.9 In 1890, Pringle described firm whitish or grayish facial lesions, distributed over the nose and nasolabial folds, similar to those of Balzer and Menetrier.s It was not until 1908, however, that Vogt recognized the relationships of the cerebral disease of Von Recklinghausen and the above facial lesions.6 He delineated the now accepted triad of adenoma sebaceum, epilepsy, and mental retardation for the Pringle-Bourneville syn­ drome.9, 10

Oral manifestations were not reported in the early literature. They appeared in the 1940's when drugs for the treatment of the associated epilepsy were employed. This suggests that many ofthe gin­
gival fibrous changes described as part ofthe syn­ drome may be iatrogenic. 11, 12, 13, 14 As more cases were reported, the complexity of the syndrome became apparent. In 1960, Gorlin and associates provided a good review of tuberous sclerosis in an article dealing with several syndromes of oral man­ ifestations.15 The features described by them included adenoma sebaceum (which is not a true adenoma), epilepsy, and mental deficiency. The latter was attributed to glial nodules of the cerebral cortex, the so-called tuberous sclerosis. Also described as part ofthe syndrome were striated or dystrophic fingernails as well as sublingual and periungual fibromata; the latter being similar to those found in our patient. Other findings included large flesh-colored plaques on the trunk, "shag­reen" (rough leather) patches in the lumbo-sacral area, fibrous nodules on the skin, abnormal pig­ mentation, renal tumors, hepatic and pancreatic hamartomata, retinal tumors (phacomata), rhab-domyomata, large vessel and bony abnormalities, and imperfect genital development.

The oral manifestations described were fib­ romata of the gingiva, tongue, or palate, and sebaceous hyperplasia ofthe palate. Davis11 and his colleagues described the oral lesions as elon­ gated fibrous proliferation of the gingiva and firm nodules of the hard palate similar to those found in our patient.

Incidence figures vary for as high as 1:30,000 and as low as 1:500,000, indicating the rarity ofthe disease. Frequency figures in mental institutions have also varied, although to a smaller degree, with reported frequency of 0.5% in American institu­ tions and 0.6 - 0.7% for European institutions.16 No Middle East figures are available.

Carol17 and Hoff1B and co-workers have reported enamel defects associated with the dis­ ease in one patient and six patients, respectively. Although one might assume that severe diseases with recurrent infections could lead to secondary enamel hypoplasias, the pattern that Hoff and co­ workers had suggested was that the defect was pre-sent throughout amelogenesis.

The prognosis for the patients varies with the sev­ erity and age at the onset of the disease, with increased severity of retardation and earlier onset giving a poorer prognosis.19 Death is usually due to status epilepticus, tumor of the heart, viscera, and brain infection. According to Mackler20 and co­ authors, 30% of the patients die before the age of five years and 75% before the age of 20. In patients with less complete forms of the disease, the life expectancy increases so that some have lived into the eighth decade.21

Early diagnosis may be difficult as the disease may not fully develop until the latter part of the first decade in patients with mental retardation and even later in those patients with normal intellect.