1. Case Presentation
Dr.Yassin

2. History
• 22 months old girl .
• K/C of tuberous sclerosis, cardiac
rhabdomyoma, seizure disorder.
• Admitted with uncontrolled seizure.

3. Perinatal history
• nearterm , product of C-section, twin B,
apgar score 8 and 8 at 1st and 5th .
• Discharge with mother in good condition.

4. Past History
• Past history: patient presented initially at age of
6 months with Hx of multifocal myoclonus
(flexion spasm) mainly in the upper extremities,
unresponsiveness, lasting for 1 min followed by
post-ictal sleep.
• Diagnosed to have TSC .started on tegrtol and
phenobarbitone. At age of one year tegretol was
replaced with keppra.
• Then became generalized, with staring lastinf for
few seconds no post ictal 5-7 times aday

5. Medication
• Keppra 350 mg 12hourly. 67mg/kg/day
• Phenobarbitone 65 mg daily. 6mg/kg/day
• Viagabatrin 250 mg 12 hourly (just started)

6. Developmental History
• Says mama and dada.
• No concern on vision and hearing.
• Crawal, walking holding forniture unsteady
gait.
• Wave byebye.
• Respond to her name.
• Not following simple order.

7. Family history
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Consangious marriage.
Twin A also tuberous sclerosis.
Family history of brain tumor.
No family history of seizure disoder.

8. On exam
• Looks well , not dysmorphic
• Wt:10.4kg <5th
Ht:89 cm.50th
• HC: 45.5 cm 5-10th
• 4 hypo pigmented lesion on left inner and
outer thigh and trunk ranging from 5 mm
to 2 cm.

9. On exam
• CNS: normal power, tone ,reflexes,and
cranial nerves.
• Unsteady gait.
• CVS: s1+s2+0
• RS: chest clear.
• GIT: abdomen soft no organomegally.

10. Investigation (in the past)
• ECHO: small rhabdomyoma.
• Renal US: WNL.
• EEG: slowing 2-3 hz slow waves
complexes at biparital reigon.
• Brain CT: multiple faint hypodense in left
parietal area.

11. Investigation
• Renal US: WNL.
• Brain MRI:multiple
subependymal hemartomas and
subcortical tubers associated with
broad gyri.
Three of the subependymal hemartoms
• Findings are suggestive of tuberous
sclerosis .

12. Short talk on
Tuberous
sclerosis

13. Tuberous sclerosis complex (TSC)
• One of the neurocautenous syndroms.
• multisystemic disease affects many organ
systems other than the skin and brain,
including the heart, kidney, eyes, lungs,
and bone.
• a prevalence of 1/6,000 newborns.

14. Genitics
• inherited as an autosomal dominant .
• Spontaneous mutations occur in 2/3 of the
cases.
• Molecular genetic studies have identified 2 foci
for TSC: the TSC1 gene is located on
chromosome 9q34, and the TSC2 gene is on
chromosome 16p13.
• The TSC1 gene encodes a protein called
hamartin. The TSC2 gene encodes the protein
tuberin.

15. Clinical Manifestations
• Definitive TS is diagnosed when at least 2
major
• or 1 major plus 2 minor features are
present .

16. MAJOR FEATURES OF TUBEROUS
SCLEROSIS COMPLEX
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Cortical tuber
Subependymal nodule
Subependymal giant cell astrocytoma
Facial angiofibroma or forehead plaque
Ungual or periungual fibroma (nontraumatic)
Hypomelanotic macules (>3)
Shagreen patch
Multiple retinal hamartomas
Cardiac rhabdomyoma
Renal angiomyolipoma
Pulmonary lymphangioleiomyomatosis

17. MINOR FEATURES OF TUBEROUS
SCLEROSIS COMPLEX
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Cerebral white matter migration lines
Multiple dental pits
Gingival fibromas
Bone cysts
Retinal achromatic patch
Confetti skin lesions
Nonrenal hamartomas
Multiple renal cysts
Hamartomatous rectal polyps

18. Eye lesion
• Retinal lesions consist of 2 types:
• 1- hamartomas (elevated mulberry lesions
or plaquelike lesions).
• 2- white depigmented patches (similar to
the hypopigmented skin lesions).
• In KKSH :report two infants with tuberous
sclerosis who initially were considered to
have retinoblastoma

19. CNS lesions
• The characteristic brain lesion is a cortical tuber ..
• Subependymal nodules are lesions found along the wall
of the lateral ventricles where they undergo calcification
and project into the ventricular cavity, producing a
candle-dripping appearance.
• these benign lesions can grow into subependymal giant
cell astrocytomas (SEGAs).
• These tumors can grow and block the circulation of
cerebrospinal fluid (CSF) around the brain and cause
hydrocephalus

20. •
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other neurologic manifestations
cognitive impairment.
autism spectrum disorders.
Epilepsy .
infantile spasms and a hypsarrhythmic
electroencephalogram.
• seizures may be difficult to control and, at a later
age, they may develop into myoclonic epilepsy
•
• Drug of choice for infantile spasms associated
with TSC: is vigabatrin.
• Topiramate, lamotrigine , valproate, and
(ACTH)/steroids are also useful.

21. Skin Lesions
• (ash leaf) :More than 90% of cases show the
typical hypomelanotic macules an on the trunk
and extremities.
• a Wood ultraviolet lamp used for better view.

22. Skin Lesions
• Facial angiofibromas develop in late
childhood .
• they appear as tiny red nodules over the
nose and cheeks .

23. Skin Lesions
• A shagreen patch is also characteristic of
TSC and consists of a roughened, raised
lesion with an orange-peel consistency
located primarily in the lumbosacral region

24. Skin Lesions
• Subangual fibroma: During adolescence
or later, small fibromas or nodules of skin
may form around fingernails or toenails in
15-20% of the TSC patients

25. Cardiac lesion
• Approximately 50% of children with TSC
have cardiac rhabdomyomas.
• although they can cause congestive heart
failure and arrhythmias, they tend to
slowly resolve spontaneously.

26. Kideny lesion
• angiomyolipomas
• The kidneys in 75-80% of patients >10 yr
of age have angiomyolipomas that are
usually benign tumors.
• Single or multiple renal cysts .
• End-stage renal disease .
• Fanconi Syndrome (2 case report in KSA)

27. treatment
• Epilepsy: anti-epeleptic.
• focal cortical resection, corpus callosotomy, or
vagus nerve stimulation.
• Infantile spasm: vigabatrin.
• Rhabdomyomas: supportive.
• Angiomyolipomas: nothing. unless lesion
becomes larger than 4 cm . transcatheter tumor
embolization.
• Subependymal nodules: nothing
• (SEGAs) : need surgical intervention??.
• everolimus can be used if surgery failed.

28. Follow up
• brain MRI every 1-3 yr.
• renal imaging (ultrasound, CT, or MRI)
every 1-3 yr.
• neurodevelopmental monitoring.

29. Take home message
• Diagnosis of TSC relies on a high index of
suspicion when assessing a child with
infantile spasms or myoclonic epilepsy.
• As many as 50% of people with TSC have
normal intelligence no more triad
• Don’t forget to exam the eye after
vigabatrin

30. THANK YOU