Abstract Details

Title The Diagnostic Accuracy of Clinical Manifestations in Identifying People with Tuberous Sclerosis Complex

Topic General Neurology

Presentation(s) S13 - General Neurology 1 (11:39 AM-11:51 AM)

Poster/Presentation
Number 003

Background Up to 10-15% of PwTSC do not carry an identifiable pathological genetic variant and are diagnosed clinically. In such situations, family members cannot be screened using genetic testing.

Objective To establish the diagnostic accuracy of tuberous sclerosis complex (TSC) clinical features to better guide the screening process for the families of people with TSC (PwTSC).

Design/Methods We used the TSC Natural History Database, a longitudinal database of PwTSC from 22 North American centers. We used a definite genetic TSC diagnosis as our gold standard. We estimated the sensitivity (95% confidence interval [CI]) of TSC-related skin, structural brain, renal, and cardiac manifestations, as well as combinations of these manifestations. Using a series of sensitivity analyses to test alternate assumptions, we estimated positive and negative predictive values (PPV and NPV).

Results Among 1,300 PwTSC, 50.3% were female, and the mean age at diagnosis was 3.7 years. The sensitivity of any skin or structural brain manifestation was 98.7% (95% CI: 98.0%, 99.2%). The PPV and NPV were 83.2 (95% CI: 81.6%, 84.6%) and 98.4% (95% CI: 97.8%, 98.8%), respectively, while assuming 50% prevalence and 80% specificity. Including cardiac manifestations marginally increased the sensitivity, PPV, and NPV to 99.5% (95% CI: 98.9%, 99.7%), 83.3% (95% CI: 81.8%, 84.7%), and 99.4% (95% CI: 99.0%, 99.6%), respectively. Other combinations of TSC manifestations had lower or similar diagnostic accuracy.

Conclusions Screening for brain and skin manifestations in family members of genetic-negative PwTSC is sufficient, with excellent sensitivity and NPV. Further cardiac screening may be indicated in select cases.

Authors/Disclosures
Jimmy Li, MD (University of Sherbrooke) PRESENTER	Dr. Li has received research support from Fonds de recherche du Québec - Santé.
zaki E. el haffaf, MD	Prof. el haffaf has nothing to disclose.
Jean-Baptiste Lattouf, MD	Mr. Lattouf has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ipsen. Mr. Lattouf has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Mr. Lattouf has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Mr. Lattouf has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merk. Mr. Lattouf has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ipsen. Mr. Lattouf has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BMS. Mr. Lattouf has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Ipsen.
Philippe Major, MD (CHU Ste-Justine PO SA178275-D)	Dr. Major has nothing to disclose.
Mark R. Keezer, MD, PhD (Centre Hospitalier Universite de Montreal)	The institution of Dr. Keezer has received research support from TD Bank. The institution of Dr. Keezer has received research support from Savoy Foundation. The institution of Dr. Keezer has received research support from Canadian Institutes of Health Research. The institution of Dr. Keezer has received research support from Fonds de Recherche Québec Santé. The institution of Dr. Keezer has received research support from Canadian Institutes of Health Research. The institution of Dr. Keezer has received research support from Precision Child Health Partnership Catalyst Program.

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