What Is Tuberous Sclerosis?

Tuberous sclerosis (TSC), also known as Bourneville disease, is an autosomal dominant neurodermal syndrome. There are also sporadic cases. The organs of the ectodermal tissue are abnormally developed, and brain, skin, and peripheral nerves can appear. Multiple kidney, kidney and other organs are involved. The clinical features are facial sebaceous adenoma, seizures, and decreased intelligence. The incidence rate is about 1/6000 live babies, and the male to female ratio is 2: 1.

Basic Information

nickname

Bourneville disease

English name

tuberous sclerosis

Visiting department

Neurology

Multiple groups

Onset in childhood, more men than women

Common causes

Autosomal dominant inheritance

Common symptoms

Sebaceous adenomas of the face, seizures, and decreased intelligence

Causes of tuberous sclerosis

The disease is a hereditary disease, inherited by autosomal dominant inheritance. Familial cases account for about one third, that is, the TSC1 or TSC2 gene mutated from one parent; sporadic cases account for about two thirds, that is, birth When the patient carried the newly mutated TSC1 or TSC2 gene, no family members were sick. TSC1 mutations are more common in familial patients, and TSC2 mutations are more common in sporadic patients.

Clinical manifestations of tuberous sclerosis

Depending on the affected area, there may be different manifestations. Typical manifestations are facial sebaceous adenomas, seizures, and decreased intelligence. More than childhood onset, more men than women.

Skin damage

It is characterized by sebaceous adenomas in the triangular area of the nose and nose, with a symmetrical butterfly distribution, which is pale red or reddish-brown. 90% appear before the age of 4 and increase with age, rarely involving the upper lip. 85% of patients have more than 3 1mm leaf-shaped, oval or irregular pigmentation spots after birth, especially observed under ultraviolet light, seen in the limbs and trunk. 20% of shark skin spots in the lumbosacral region can appear after 10 years of age, slightly higher than normal skin, local skin thickening and rough, grayish brown or slightly brown plaques. 13% of patients can show sub-nail bed fibroids, also known as Koenen tumors, which grow from the fingernail (toe) nail groove. Toenail is common, and is more common in adolescence. It can be the only skin lesion in this disease. Among them, more than 3 spots of depigmentation and fibroids under the nail bed are the most characteristic skin lesions of the disease. ^[1-2] Others such as coffee milk spots, skin fibroids, etc. can be seen.

2. Nervous system damage

(1) The main neurological symptoms of epilepsy are 70% to 90% of the incidence. As early as infancy, the seizures can take various forms, starting from infantile spasms to partial focal or complex seizures. A general outbreak. Frequent and persistent epileptic seizures can be followed by epilepsy personality disorder such as violation of stubbornness and stubbornness. If accompanied by depigmentation of the skin, nodular sclerosis can be diagnosed, and later it will be converted into comprehensive, simple partial and complex partial seizures, and the author frequently has personality changes.

(2) The decline of intelligence is more progressive, accompanied by mental symptoms such as emotional instability, naive behavior, impulsiveness, and disorder of thinking. Almost all people with reduced intelligence have seizures. Those with early-onset epilepsy are prone to mental decline and seizures with peak People with abnormal rhythm EEG often have severe mental retardation, and some patients may show autism.

(3) A few may have positive signs of the nervous system. Such as extrapyramidal signs or monoplegia, hemiplegia, paraplegia, hypertenon reflexes, etc., such as subventricular nodules blocking the cerebrospinal fluid circulation pathway or local giant nodules, concurrent tumors can cause increased intracranial pressure. ^[2]

3. Eye symptoms

50% of patients have a retinal glioma, called a lens tumor. Fundus examination showed multiple worm-like or mulberry-like calcified nodules near or near the papillae behind the eyeball, or yellow-and-white ring-shaped damage around the retina ^[2] . In addition, small eyes, exophthalmos, glaucoma, opaque crystals, cataracts, vitreous hemorrhage, pigmented retinitis, retinal hemorrhage, and primary optic nerve atrophy can occur.

4. Kidney disease

Renal vascular smooth muscle lipomas (AML) and renal cysts are the most common, manifested as painless hematuria, proteinuria, hypertension, or abdominal mass. Among TSC deaths, 27.5% of those who die due to kidney disease account for this. The second leading cause of death from illness.

5. Heart disease

Cardiac rhabdomyosarcoma can occur in 47% to 67% of patients. This tumor is usually the largest in neonatal period and shrinks to disappear with increasing age. It can cause heart failure. It is the most important cause of death in infancy of this disease. The prenatal ultrasound is the earliest. A tumor can be found at 22 weeks gestation, suggesting that 50% of TSC is likely.

6. Lung disease

Pulmonary lymphangiomyomatosis (LAM) affects the lungs. It is common in women of childbearing age. It is an overgrowth of connective tissue, smooth muscle and blood vessels to form reticular nodules and multiple small cystic changes. Pulmonary heart disease, such as shortness of breath and cough, can occur Performance of sexual pneumothorax.

7. Bone lesions

Bone sclerosis, cranial sclerosis is the most common, and it also occurs in the digits and toes, caused by trabecular bone hyperplasia; cystic changes, all bones can be involved, X-rays can be found; spina bifida and polydactyly .

8. Other organs

The gastrointestinal tract, thyroid gland, parathyroid gland, uterus, bladder, adrenal gland, breast, thymus, etc. may all be affected. Currently TSC is considered to involve all tissues except skeletal muscle and pineal gland.

Tuberous sclerosis test

Plain skull

Nodular calcification in the brain and giant brain gyrus caused by giant brain gyrus.

2. Head CT or MRI

On plain scan, multiple nodular or low-density lesions on the edge of the subventricular ventricle and the surface of the cerebral cortex can be seen. Part of the nodules can show high-density calcification, which is bilateral multiple. The enhancement is generally enhanced. Nodules that can not be displayed by plain scan can be found. Cortical and cerebellar nodules are diagnostic.

3. EEG

Visible high amplitude irregularities and various epilepsy waves.

4. Cerebrospinal fluid

normal.

5. Abdominal ultrasound

Visible renal leiomyomatoma, renal cysts, polycystic kidney.

6. Echocardiography

Cardiac rhabdomyomas are easy to find in newborns and infants. The tumors become smaller in the first three years, and gradually disappear in adulthood. Therefore, the positive rate of detection in older children and adults is low.

7. ECG

Arrhythmias can be found, pre-excitation syndrome is common.

8. Chest X-ray

Pulmonary hamartoma, pneumothorax and other diseases can be found. ^[1-2]

Nodular Sclerosis Diagnosis

1. confirmed TSC

2 major indications or one major indication plus two minor indications;

2. TSC to be diagnosed

1 primary indication plus 1 secondary indication;

3. Possible TSC

1 major indication or 2 or more minor indications. [3]

4. Main indications

(1) Facial angiofibroma or forehead plaque;

(2) Non-traumatic refers to (toe) nail or peronychial fibroma;

(3) hypopigmentation spots ( 3);

(4) Shark-like rash (connective tissue mole);

(5) Multiple retinal hamartoma nodules;

(6) cortical nodules;

(7) Subventricular tubercle;

(8) Subventricular giant cell astrocytoma;

(9) Single or multiple cardiac rhabdomyomas;

(10) Pulmonary lymphangiomyomatosis;

(11) Renal vascular leiomyoma.

5. Secondary indications

(1) Multiple, randomly distributed enamel depressions;

(2) Hamartoma rectal polyps (histologically confirmed);

(3) Bone cyst (confirmed by radiology);

(4) Radial transitional beam of white matter (confirmed by radiology);

(5) gingival fibroma;

(6) Non-renal hamartoma (confirmed by histology);

(7) retinal pigment deficiency;

(8) Confetti lesions;

(9) Multiple renal cysts (histologically confirmed).

6. Remarks

(1) If the abnormal development of the cerebral cortex and the white matter metamorphic bundle coexist, only one indication can be counted;

(2) If pulmonary lymphangiomyomatosis coexists with renal angioleiomyoma, other TSC indications are required to confirm the diagnosis;

(3) Abnormal development of the white matter and focal cortex is common in TSC patients, but because it often appears alone and is not specific, it is only used as a secondary indication.

Differential diagnosis of tuberous sclerosis

According to its multi-system and multi-organ involvement characteristics, it needs to be distinguished from other diseases involving the skin, nervous system and eyes, such as neurofibromatosis and cerebral facial hemangiomatosis. Hypopigmented plaques can be found in 0.8% of newborns, most of which have no medical significance. Other diseases such as vitiligo, partially pigmented nevus and white spot disease and Vogt-Koyanagi-Harade syndrome can also have hypopigmented plaques, which need to be associated with TSC. Identification. Patients with seizures need to be distinguished from primary or secondary epilepsy. Imaging needs to be distinguished from cerebral cysticercosis. ^[2]

Nodular Sclerosis Treatment

Because TSC1 and TSC2 proteins are involved in regulating mammalian rapamycin target protein (mTOR) kinase activity, the use of rapamycin to treat TSC is considered. Rapamycin is a macrolide antibiotic. It is used in antifungal therapy because it inhibits mTOR activity and participates in regulating cell growth. It is also used as an immunomodulatory drug after organ transplantation.

Anti-epileptic treatment, early control of seizures can help prevent secondary epilepsy and brain damage and cognitive behavioral damage. Individualized medication is recommended for infantile spasms. Studies have shown that aminohexene acid is effective in 73% of TSC infantile spasms TSC-related epilepsy may not work well with many antiepileptic drugs, and some small sample studies show that surgical treatment can achieve satisfactory results.

Renal vascular smooth muscle lipoma, bleeding is easy to occur when the tumor diameter is greater than 3.5cm to 4.0cm, and there are indications for intervention. Renal artery embolization or partial nephrectomy is feasible. Some studies have also proven that mTOR inhibitors are effective against renal angiomyolipoma, but the FDA has not approved this indication.

Pulmonary lymphangiomyomatosis is more common in women of childbearing age, suggesting that estrogen may be involved in stimulating the growth of lung smooth muscle cells. Progesterone therapy and / or oophorectomy can reduce estrogen production, but the treatment effect varies widely between individuals. Studies have shown that mTOR inhibitors are effective against pulmonary lymphangiomyomatosis, and the FDA has not yet approved this indication.

Other symptomatic treatments include dehydration and lowering of cranial pressure, impaired cerebrospinal fluid circulation, feasible surgical treatment, and facial sebaceous adenoma can be treated with cosmetic surgery. ^[1]

Nodular sclerosis prognosis

At present, there is no effective means to cure the disease, nor can it accurately predict the course and severity of the disease. However, after close monitoring and proper treatment, the patient's life can not be affected.

references

1. Edited by Wu Jiang. Neurology. Beijing: People's Medical Publishing House, 2005: 326-327.

2. Edited by Wang Weizhi. Neurology. Beijing: People's Medical Publishing House, 2006: 1367-1368.

3.RoachES, SparaganaSP. Diagnosis of tuberoussclerosis complex: JChildNeurol, 2004: Sep; 19 (9): 643-9.