Luke's Tuberous Sclerosis Page
Diagnosing TSC |
| TSC OR NOT TSC?:NON-EXPRESSION AND UNDIAGNOSING TSC Manuel R. Comez, M.D.,Rochester, MN, 55905, USA (17june 1996) A genetic test is available for TSC that tests the blood to determine if the mutation of TSC is prevelant. The first test is performed on an individual that has TSC and then family members genetic coding is compared to the TSC family member genetic coding to see if the same mutation is present. In the half century between 1914 and 1964 Mayo clinic (MC) physicians recognized the tuberous sclerosis complex (ThC) in 71 patients among nearly 2 million who underwent a clinical examination. This is equivalent to one case of TSC for every28000 new patient registrations and an annual ratio of 1.42 new ThC patients. in the subsequent 30 years, (1965-1995), the number of newly diagnosed ThC cases exceeded 400 and were among approximately 3 million new patient registrations. There was some se1ectivity as many patients attended MC after the diagnosis of TSC had been made elsewhere. Be that as it may, in the second half of our century there is one newly diagnosed case for every 7500 patient registrations, an average of more than 13 ThC patients annually. This greater than nine-fold increment of cases was due in part to better methods of assessment and, of course, to advances made in imaging technology. Several possible errors could have been introduced prior to making our calculations. and two chief questions beg an answer. A review of MC records of patients referred with the diagnosis of TSC and their relatives provided data that many at least in part answer these two questions. 1) How many individuals in this cohort had a TsC mutation but expressed no phenotype or its expression was too subtle to be recognized? In the last 30 years, we have recognized at MC only two individuals, a set of twin sisters who, according to our current knowledge, and published diagnostic criteria do not have a ThC phenotye (They' lack signs of ThC directly visible or indirectly displayed by imaging). These two affected but asignomatic sisters are monozygotic twins and each is the mother of one non-affected and one TSC-affected child. Consequently each mother must have passed the ThC mutation to their affected child since the possibility of a new mutation appearing independently in the two first cousins is indeed remote. If so, the twin sisters are not expressing their TSC genotype. 2) Are there clinical or imaging signs that could have led to a false diagnosis of TsC? In the last 30 years there have been no less than 34 patients referred to MC with a definitive or a presumptive diagnosis of TSC which we could not confirm by repeating the clinical exam and imaging studies. The previous tests that suggested the diagnosis of TSC when available were reinterpreted. We found that the commonest cause of the false diagnosis of ThC (14 patients) was to accept hypomelanotic skin macules as a confirmatory sign of TSC. Half of these patients had typical hypomelanotic ash leaf-shaped skin macules while the other half had atypical white spots. The second most common source of error (6 patients) was to interpret small areas of increased attenuation(including bona fide calcifications in a head CT scan) as calcified subependymal nodes of TSC. in two of these patients the proper diagnosis was neurofibromatosis 2, and in one each cynsticercosis, toxoplasmosis, metastatic carcinoma, and multiple hemorrhagic venous angiomas. The third most common cause of error (4 cases) was interpretation of a single retinal lesion as atypical astrocytic hamartoma. The fourth most common cause (3cases)was accepting a single raised and "bumpy"' skin lesion as ashagreen plaque and as diagnostic of ThC. The biopsy proved these lesions were a smooth muscle fiber hamartoma, a lipoma or a connective tissue hamartoma. None of the patients with false ThC had detectable tubers or hamartomas typical of TSC. This home page is intended to be a family resource for families affected by Tuberous Sclerosis. It does not intend to constitute medical advise. Viewers are warned not to take any action with regard to medical treatment relying on the information provided on this page without first consulting the patient's physician.
Deanna Runyan-Wall E-mail address: deannadawn@lukets.org Last updated: April 5, 2008 Created: December 5, 1996 |
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A SPECIAL NEEDS MOM BLOG JOYFUL & JUGGLING
WATCH LUKE'S FOOTBALL TOUCHDOWN ON INSIDE EDITION
LUKE'S Tuberous Sclerosis LIFE STORY
A MOTHER'S JOURNAL of Accepting Tuberous Sclerosis
PRACTICAL FAMILY RESOURCES |
