tuberus sclerosis

Case PresentationDr.Yassin

History

• 22 months old girl .

• K/C of tuberous sclerosis, cardiac rhabdomyoma, seizure disorder.

• Admitted with uncontrolled seizure.

Perinatal history

• nearterm , product of C-section, twin B, apgar score 8 and 8 at 1st and 5th .

• Discharge with mother in good condition.

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

Medication

• Keppra 350 mg 12hourly. 67mg/kg/day

• Phenobarbitone 65 mg daily. 6mg/kg/day

• Viagabatrin 250 mg 12 hourly (just started)

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.

Family history

• Consangious marriage.

• Twin A also tuberous sclerosis.

• Family history of brain tumor.

• No family history of seizure disoder.

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.

On exam

• CNS: normal power, tone ,reflexes,and cranial nerves.

• Unsteady gait.

• CVS: s1+s2+0

• RS: chest clear.

• GIT: abdomen soft no organomegally.

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.

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  .

Short talk on

Tuberous sclerosis

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.

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.

Clinical Manifestations

• Definitive TS is diagnosed when at least 2 major

• or 1 major plus 2 minor features are present .

MAJOR FEATURES OF TUBEROUS SCLEROSIS COMPLEX

• 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

MINOR FEATURES OF TUBEROUS SCLEROSIS COMPLEX

• 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

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

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

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.

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.

Skin Lesions• Facial angiofibromas develop in late

childhood .

• they appear as tiny red nodules over the nose and cheeks .

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

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

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.

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)

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.

Follow up

• brain MRI every 1-3 yr.

• renal imaging (ultrasound, CT, or MRI) every 1-3 yr.

• neurodevelopmental monitoring.

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

THANK YOU