Tuberous Sclerosis John Kanu UVA School of Medicine.

Tuberous SclerosisTuberous Sclerosis

John KanuJohn Kanu

UVA School of MedicineUVA School of Medicine

IntroductionIntroduction What is Tuberous Sclerosis?What is Tuberous Sclerosis? - a genetic disorder that causes benign tumors to form in many different - a genetic disorder that causes benign tumors to form in many different

organs:organs: - brain (developmental delay, seizures) - heart- brain (developmental delay, seizures) - heart - eyes - heart- eyes - heart - kidney - lungs- kidney - lungs - skin- skin

PrevalencePrevalence: true prevalence unknown: true prevalence unknown approximately 50,000 in the U.S.approximately 50,000 in the U.S. Over a million worldwideOver a million worldwide

GeneticsGenetics: One-third are known to be : One-third are known to be inheritedinherited Two-third believed to be Two-third believed to be spontaneous mutationspontaneous mutation TSC-1 & TSC-2 gene responsible: tumor suppressor genesTSC-1 & TSC-2 gene responsible: tumor suppressor genes

Patient’s InfoPatient’s Info

AgeAge: 28 y/o Female: 28 y/o Female

PMHPMH - Obsessive Compulsive Disorder- Obsessive Compulsive Disorder - Depression- Depression

SHSH - Live alone; denied tobacco use, rare alcohol use- Live alone; denied tobacco use, rare alcohol use

Clinical HxClinical Hx

Tuberous SclerosisTuberous Sclerosis - incidentally diagnosed 3 yrs ago- incidentally diagnosed 3 yrs ago - initially p/w new onset abdominal pain - initially p/w new onset abdominal pain

. while living in Atlanta . while living in Atlanta Initial work-up at Emory(which include)Initial work-up at Emory(which include) CT Scan (abdomen)CT Scan (abdomen) - absent ®-kidney- absent ®-kidney - ®-Kidney: multiple lesions c/w - ®-Kidney: multiple lesions c/w angiomyolipomasangiomyolipomas

Clinical HxClinical Hx (cont.) (cont.)

MRI (brain)MRI (brain) - two subependymal nodules- two subependymal nodules

Action taken at the timeAction taken at the time - evaluated by Nephrology & Medical - evaluated by Nephrology & Medical

Genetics at EmoryGenetics at Emory - followed with surveillance ultrasound: by her - followed with surveillance ultrasound: by her

report everything has been stablereport everything has been stable

Clinical HxClinical Hx (cont.) (cont.)

She recently moved to Charlottesville for work She recently moved to Charlottesville for work purposes.purposes.

She desired follow-up at UVAShe desired follow-up at UVA

FHFH Negative for Tuberous SclerosisNegative for Tuberous Sclerosis cousin with Tourette’scousin with Tourette’s Renal failure in dad due to HUS (hemolytic Uremic Renal failure in dad due to HUS (hemolytic Uremic

Syndrome)Syndrome) Uterine and colon cancer in both grandmothersUterine and colon cancer in both grandmothers

UVA imageUVA image – CT (Lung) – CT (Lung)

- innumerable thin-- innumerable thin-walled 1 – 5 mm walled 1 – 5 mm cystscysts in lung parenchymain lung parenchyma

Lung ImageLung Image (cont.) (cont.)

- Findings consistent - Findings consistent with with lymphangio-lymphangio-leiomyomatosisleiomyomatosis

UVA imageUVA image - abdomen - abdomen

- - absentabsent left Kidney left Kidney

- mixed density intra-- mixed density intra-parenchymal renal parenchymal renal lesion w/ fat lesion w/ fat attenuation cystsattenuation cysts

- findings c/w - findings c/w renal renal angiomyolipomaangiomyolipoma

UVA imageUVA image – brain MRI – brain MRI

- single enhancing - single enhancing subependymal nodule subependymal nodule along the body of the along the body of the left lateral ventricleleft lateral ventricle

Brain MRIBrain MRI (cont.) (cont.)

- no hydrocephalus- no hydrocephalus - Findings can be seen - Findings can be seen

in in Tuberous SclerosisTuberous Sclerosis

- No classic-appearing - No classic-appearing cortical tubers were cortical tubers were identifiedidentified

MRI – BrainMRI – Brain (cont. 0 (cont. 0

-heterogenously-enhancing -heterogenously-enhancing lesion adjacent to the frontal lesion adjacent to the frontal horn of (L)-lateral ventricle: horn of (L)-lateral ventricle: most likely primary brain most likely primary brain neoplasm (pilocytic neoplasm (pilocytic astrocytoma)astrocytoma)

However, However, subependymal subependymal giant cell astrocytomasgiant cell astrocytomas occurs in 6 – 16% of pts. occurs in 6 – 16% of pts. Tend to be noncancerousTend to be noncancerous

Patient’s coursePatient’s course

AsymptomaticAsymptomatic from a from a neurological neurological standpointstandpoint

- no spells suggestive of seizures- no spells suggestive of seizures - no cognitive deficit: completing her masters - no cognitive deficit: completing her masters

in Educational Psychologyin Educational Psychology - no headaches, nausea or vomiting- no headaches, nausea or vomiting AsymptomaticAsymptomatic from from Kidney standpointKidney standpoint

Pt.’s PE findingsPt.’s PE findings

HeadHead: : - bumps on her nose c/w adenoma sebacium- bumps on her nose c/w adenoma sebacium ChestChest:: - - LungsLungs: CTA bilaterally (good air movement): CTA bilaterally (good air movement) - lesion over (L)-shoulder anteriorly c/w a - lesion over (L)-shoulder anteriorly c/w a

shagreen’s patchshagreen’s patch AbdomenAbdomen: normal findings: normal findings LELE: ®-calf hypomelanotic macule: ®-calf hypomelanotic macule

DiagnosisDiagnosis Tuberous SclerosisTuberous Sclerosis

Diagnostic critieriaDiagnostic critieria - Facial angiofibromas- Facial angiofibromas - hypomelanotic macules- hypomelanotic macules - Shagreen patch- Shagreen patch - Subependymal nodule- Subependymal nodule - subependymal giant cell astrocytoma- subependymal giant cell astrocytoma - Lymphangiomyomatosis- Lymphangiomyomatosis - Renal angiomyolipoma- Renal angiomyolipoma

PlanPlan CNS SurveillanceCNS Surveillance (imaging) (imaging) - - MRIMRI every two years every two years - sooner in the event of any clinical changes- sooner in the event of any clinical changes - discuss possibility of hydrocephalus & seizure- discuss possibility of hydrocephalus & seizure Pulmonary standpointPulmonary standpoint - follow-up (f/u) at pulmonary clinic (life-time - follow-up (f/u) at pulmonary clinic (life-time

monitor)monitor) Renal standpointRenal standpoint - f/u at nephrology clinic (life-time ultrasound - f/u at nephrology clinic (life-time ultrasound

surveilance)surveilance) Psychiatry:Psychiatry: anti-seizure prophylaxis anti-seizure prophylaxis

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References:References: - Tuberous Sclerosis Alliance- Tuberous Sclerosis Alliance