An interesting case of tuberous sclerosis

Tuberous Sclerosis

 

HISTORY 

2 years old female child  of non consanguinous marriage

—Convulsions  since 6 months of age

—-about 1 episode /month

—-right focal

—-each episode lasting for 20 minutes

—-associated with fever

—- was treated as a case of atypical febrile seizures  by a private practitioner with T.sodium valproate which was discontinued for 3 days

—No other relevant history

BIRTH  HISTORY:

Full term normal vaginal delivery at a hospital

Cried immediately after birth

DEVELOPMENTAL HISTORY:

Developmentally normal

FAMILY HISTORY:

Non consanguinous marriage

Father had seizures till 5 years of age

Elder brother had right focal seizures till 2 years of age and has myoclonic seizures for past 6 months

General examination

—Vitals were stable

—Hypopigmented macules- 3 in number were seen in the back

—A shagreen patch was seen in the left thigh

—Weight :10 kg/12 kg

—Height:80 cm/89 cm

—Head circumference:46 cm/48 cm

Shagreen patch-      facial angiofibroma

father

—CNS EXAMINATION:

—Higher functions :normal

—Cranial nerves:normal

—Motor system:

bulk-normal in all 4 limbs

power-5/5 in all 4 limbs

tone:normal

reflexes-readily elicitable

gait-normal

sensory system-normal

no cerebellar signs

spine and cranium -normal

Cardiovascular system:

first and second heart sounds were heard

no murmur

Respiratory system:

normal vesicular breath sounds were heard

Abdomen:

no organomegaly

Investigations:

Routine  investigations-normal

EEG:poorly formed theta intermixed with delta.bilateral sharp waves with slow wave discharges seen

CT BRAIN:multiple periventricular nodules s/o TORCH infection

—Suggestive of tuberous sclerosis

—Advised ECG,chest x-ray,echo,USG abdomen

—ECG-within normal limits

—Chest x ray –normal

—Echo-normal

—USG abdomen-no evidence of renal pathology

—Ophthalmologist opinion:

-no evidence of mulberry tumor

—IQ testing-Normal

—TORCH screening-negative

TREATMENT:

T.Sodium valproate

TUBEROUS SCLEROSIS

(Bourneville disease,cerebral sclerosis,Epiloa,Tuberous sclerosis complex)

vAutosomal dominant disorder with an inherited frequency of 1/6,000

vExtremely heterogenous disease with a wide clinical spectrum varying from severe MR and incapacitating seizures to normal intelligence and lack of seizures in the same family.

v2 foci-both are tumor suppressors

v1)TSC1(on chromosome 9-hamartin)

v2)TSC2(on chromosome 16-tuberin)

vHeart,kidneys,eyes,lungs and bones

PATHOLOGY

Characteristic gross abnormality in brain is multiple gliotic nodules(tubers)

Over convolutions of cerebral hemispheres and subependymal region

Calcification may occur in the tubers as early as 5 months of life

Tubers in foramen of monro may obstruct  CSF flow

Tubers occasionally differentiate into malignant astrocytoma

CLINICAL FEATURES

ØSeizures are the most common symptom

ØMay manifest as infantile spasms or partial seizures

ØMay later have generalised seizures

ØMay be difficult to control

ØMental function varies greatly

ØOutcome of mental function is generally considered poor

ØOne third of  the patients may have normal intelligence

 

SKIN MANIFESTATIONS

—Adenoma sebaceum

-red or pink papules over nose,cheeks and chin

-1-4 years of age

—  hypopigmented spots over trunk and limbs

-commonly apparent at birth

-3 types:polygonal

ash leaf shaped(most characteristic)

and confetti shaped Shagreen patch-leathery plaque with orange peel consistency

-over lumbosacral or gluteal  region

-develop between 2-5 years of age

Subungual or periungual fibromas:

In 20% , May appear first during adolescence

—HEART:

—50% have rhabdomyomas of heart

—Numerous or solitary at the apex of

heart

—Tend to resolve spontaneously

KIDNEYS:

—In 50-80%

—Manifests as renal cysts or angiomyolipomas

incresed risk of renal cell carcinoma

LUNGS:

Angiomyolipomas may produce cystic or fibrous changes leading to spontaneous pneumothorax

Eyes:

A nodular mulberry tumor can be seen on optic nerve head

MAJOR CRITERIA:

1)facial angiofibromas

2)non traumatic ungual or periungual fibromas

3)hypomelanotic macules

4)shagreen patch

5)Retinal nodular hamartomas

6)cortical tuber

7) subependymal nodules

8)subependymal giant cell cell astrocytoma

9)cardiac rhabdomyoma

10)lymphangiomyomatosis

11)renal angiomyolipoma

vNeuroimaging studies are important in confirming diagnosis

vCT demonstrates calcified nodules in subependymal region

vMRI shows nodular subependymal lesions that are not yet calcified

vNo relation between periventricular calcification and severity whereas greater number of cortical lesions detected by MRI in severely affected patients

TREATMENT

No cure is possible

Treatment is symptomatic

1)drugs to control seizures

2)surgical removal of growth

3)treatment of skin leisions using LASER

TREATMENT OF EPILEPSY:

Vigabatrin is effective in infantile spasms

Topiramate,lamotrigine and levotiracetam are other drugs used

Other modalities available-vagus nerve stimulation,ketogenic diet and resective surgery(focal seizures with good EEG-MRI correlation)