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A clinical and genetic study of tuberous sclerosis



Graduation date: 1972Tuberous sclerosis is a serious heritable human disorder\ud that involves many organ systems. It was first recognized as a\ud disease entity over a century ago. Its mode of transmission in\ud familial cases has been fairly well established to be that of a single\ud gene locus autosomal dominant trait. However, the majority of\ud cases reported in the medical literature have been found to be of\ud de novo mutational origin. The finding of a high proportion of these\ud sporadic cases was confirmed in the present study and is consistent\ud with the markedly lowered fertility of affected individuals.\ud The population of the Oregon State Fairview Hospital and\ud Training Center, the state institution for the mentally retarded, was\ud investigated relative to the incidence of patients with tuberous sclerosis\ud and the clinical, radiological and genetic aspects of the ten\ud propositi were evaluated. Two parents of the ten index cases were\ud found to be affected with the disease thereby bringing the: total of\ud ascertained cases to 12. This number of affected residents represents\ud an incidence in Oregon of about 1 per 175,000 and this estimate\ud is probably lower than the actual frequency of tuberous sclerosis in the\ud state. Yet, this incidence is approximately comparable to that\ud reported in several published reviews of tuberous sclerosis in other\ud countries.\ud Physical and radiographic examinations were accomplished for\ud the index cases. All available relatives (77 percent of living relatives)\ud of the propositi were examined and photographed. Skull x-rays of the\ud two affected parents revealed intracranial calcifications typical of the\ud disorder.\ud A majority of the ten propositi exhibited dermatological legions\ud such as a typical facial rash, fibromata of the fingers and toes,\ud "sharkskin-like" plaques, depigmented areas and cafe-au-lait spots.\ud All affected individuals were found to display x-ray abnormalities\ud with intracranial calcifications being the most frequently found radiographic\ud lesion.\ud Implications derived from this study regarding genetic counseling\ud of affected persons and their families are discussed with emphasis\ud on the importance of a thorough genetic history, complete medical\ud examination of the patient and of close relatives; and, where indicated,\ud selected x-rays of the affected person and relatives considered to be\ud possible carriers of the trait. The wide spectrum of expressivity for this condition must be borne in mind when carrying out a genetic\ud analysis.\ud With the present limited knowledge regarding the causation of\ud "spontaneous point mutations" and the lack of effective measures to\ud prevent such de novo genetic aberrations, it is not feasible to diminish\ud the frequency of sporadic cases of tuberous sclerosis. On the\ud other hand, correct diagnosis and appropriate genetic counseling\ud should allow a significant decrease in the transmission of this trait\ud to the progeny of affected persons and should permit reassurance of\ud relatives of sporadic cases regarding the risk of recurrence in these\ud families. However, the usual precautions pertaining to the designation\ud of any affected individual as a sporadic rather than a familial\ud case must be followed and this admonition is particularly relevant\ud to a heritable disorder with marked variability of expressivity as is\ud the case for tuberous sclerosis

Year: 1972
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