Abstract Details

Title Inversion of Circadian Rhythm in a Patient with Complete Deletion of TSC2

Topic Sleep

Presentation(s) P05 - (-)

Poster/Presentation
Number 019

Objective

Background BACKGROUND: Tuberous sclerosis (TSC) is caused by a wide spectrum of mutations within the TSC1 and TSC2 genes, mostly point mutations and small deletions/duplications. Large deletion/duplication mutations are much less frequent and mostly identified in the TSC2 gene. Disrupted sleep architecture has been reported in TSC, mainly due to sleep-related epileptic events.

Design/Methods DESIGN/METHODS: Study of the phenotype and genotype of a patient with a clinical diagnosis of TSC. TSC1/TSC2 DNA sequencing and deletion test were performed, followed by oligonucleotide microarray.

Results RESULTS: A 32-year-old man had focal seizure onset at 1 year of age. TSC was diagnosed at 5 years. He attended regular school until 17 years with learning difficulties. An intraventricular tumor was found and remained stable for several years. At 22 years, he developed cognitive deterioration and ataxia, CT scan showed an increased volume of the intraventricular lesion. A right frontal subependymal giant cell astrocytoma (SEGA) was resected. At 26 years, angiomyolipomas of the liver, multiple small angiolipomas and several cysts of both kidneys were diagnosed. Two years later, seizures increased and he was reoperated for right residual intraventricular SEGA. At 32 years he was operated for two malignant kidney masses. He could only sleep between 6-7 am and 6-7 pm. Under treatment with melatonin, he could sleep between 10-11 pm and 10-11 am. DNA studies revealed deletion of all exons of the TSC2 gene. Microarray analysis detected a single copy loss of 194.3 Kb at chromosome 16p13.3, overlapping the TSC2 locus and extending in the 5' direction, containing at least 10 other genes.

Conclusions CONCLUSIONS: The variant detected here is associated with a severe TSC phenotype. The complete inversion of circadian rhythm observed in this patient could be the result of disruption of the mTOR pathway.

Authors/Disclosures
Dina R. Amrom, MD (McGill University) PRESENTER	No disclosure on file
Frederick Andermann, MD, FRCPC, F�鶹��ýӳ��	No disclosure on file
Benjamin G. Zifkin, MD	No disclosure on file
Eva Andermann, MD, PhD (Montreal Neurological Inst)	No disclosure on file
Alastair Compston, PhD, FRCP	No disclosure on file

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