Tuberous sclerosis

Introduction to tuberous sclerosis Tuberous sclerosis (also known as nodular sclerosis, Bourneville disease). The disease can be classified as neurocutaneous syndrome (also known as cantharichomal hamartoma), which is caused by abnormal development of organs in the ectoderm. The lesions involve the nervous system, the skin and the eyes, and may also involve the mesoderm. Embryonic organs such as heart, lung, bone, kidney and gastrointestinal. Clinical features are facial sebaceous adenomas, seizures, and decreased intelligence. basic knowledge The proportion of illness: 0.005% Susceptible people: no special people Mode of infection: non-infectious Complications: renal failure, heart failure, epilepsy, respiratory failure

Cause of tuberous sclerosis

(1) Causes of the disease

Tuberous sclerosis is an autosomal dominant inheritance, but it is also a common sporadic case. The gene is located at 9q34 or 16p13.3, which is a tumor suppressor gene, named TSC1 and TSC2, respectively; the gene products are Hamartin and Tuberin (potato globulin), which regulates cell growth.

(two) pathogenesis

TSC1 and TSC2 each cause half of the tuberous sclerosis, but the genetic phenotypes of the two are identical. The TSC1 gene is located at 9q34.3 and contains 23 exons, of which the first and second exon are non-existent. In the coding region, the 3rd to 23rd exons are coding regions, which are transcribed from the 222th nucleotide, and the gene product is a miscellaneous TSC2 gene located at 16P13.3, with 41 exons and genes. The product is nodulin. At present, TSC1 and TSC2 are tumor suppressor genes. The mutations include base deletion, insertion, missense replication or repeated mutations. However, no hotspots have been found yet, and genotypes have not been found. The relationship between phenotypes is also unclear.

Glial hyperplastic sclerosis nodules occur extensively in the cerebral cortex, white matter, basal ganglia and subependymal, often with calcium deposition, ectopic disease and vascular proliferation.

The pathological changes in the brain are many hard nodules in the cerebral cortex, ectopic cell clusters in the white matter, small nodules in the ventricle wall, and the number of cortical nodules ranging from 1 to 40, with the frontal lobe being the most However, it can also occur in the thalamus, basal ganglia, cerebellum, brainstem and spinal cord. The nodules vary in size, and some may exceed 3 cm in diameter, and the giant brain is deformed.

Histological examination of the nodules consists of very dense fine colloidal fibers containing morphologically abnormal glial cells and normal or atypical neurons. Calcium deposits or cystic changes in the nodules, normal cortical structures Frequent disorder, small nodules under the ventricle of the ventricle protrude into the room, showing a shiny white, hard texture, forming a so-called "candle tear" sign, sometimes blocking the cerebrospinal fluid circulation pathway and causing hydrocephalus, ectopic nuclei in the white matter The mass is also composed of glial cells and deformed ganglion cells, which have fewer nerve fibers and are mainly distributed between the ventricular wall and the cerebral cortex.

Brain lesions generally have no malignant changes. The sebaceous adenoma of the skin is composed of hyperproliferative sebaceous glands, connective tissue and dilated capillaries.

The disease can often be associated with retinoic glioma, heart and kidney tumors or deformities, and tumors of the thyroid, thymus, breast, stomach, intestine, liver, spleen, pancreas, adrenal gland, ovary, bladder and uterus are also found.

Tuberous sclerosis prevention

Genetic counseling, prevention measures include avoidance of close relatives, carrier genetic testing and prenatal diagnosis and selective abortion to prevent the birth of children.

Nodular sclerosis complications Complications, renal failure, heart failure, epilepsy, respiratory failure

This disease often invades multiple organs and tissues. Any organ or tissue can be affected. The clinical manifestations are complicated and diverse due to different lesions. There may be complications such as renal failure, heart failure, status epilepticus and respiratory failure.

Symptoms of tuberous sclerosis Common symptoms Papular red or purple, slightly... Gum hyperplasia epilepsy and epileptic seizures mental disorders intelligently reduce retinal hemorrhage white birthmark pathological calcification leafy depigmentation

Because this disease often invades multiple organs and tissues, and almost any organ or tissue can be involved, the clinical manifestations are complicated and diverse due to different lesions, but seizures, facial sebaceous adenomas and mental disorders are the most common. The patient may have only one of the three symptoms, and is also completely asymptomatic and found during pathological examination.

Skin symptoms

Skin lesions are the most common and often the main diagnostic basis. About 90% of patients have sebaceous adenomas, usually found at 2 to 5 years old, distributed in the cheeks and lower jaw, forehead, eyelids, nose are visible, symmetrically distributed, It is a light red or reddish-brown hard waxy papule, which can be faded. The size can be from needle tip to broad bean. Sebaceous adenoma is occasionally present at birth. It is more pronounced due to rapid growth during puberty, and 85% of patients can see pigmentation loss. Spot, leaf-shaped, oval or irregular white spot, trunk and upper and lower limbs can appear, more obvious under ultraviolet light, 20% of patients can see green granulated skin spots, more common in the waist and lower back The skin is locally thickened and rough, slightly higher than the skin, is taupe, ranging from a few millimeters to 5 to 6 cm in diameter. The underarm fibroids occur in adolescence, growing from the sulcus, sometimes only the disease. Skin damage, in addition, milk coffee pigmentation spots, skin fibroids, etc. can be seen.

2. Nervous system symptoms

Seizures and mental retardation are characteristics of this disease. Seizures can occur in the early stages of the disease, skin damage or intracranial calcification. Epilepsy can be manifested in any form of seizures, which may initially manifest as infantile spasms and later For generalized or partial seizures, some patients may have only seizures and no other clinical manifestations. 60% to 70% of patients have different degrees of mental retardation, often appearing at 2 to 3 years old, or even earlier. Almost all people with intellectual disabilities have seizures. About 70% of people with normal intelligence have seizures. Those with early epilepsy are more likely to have mental decline. Very few patients show only mental decline without seizures, and also manifest as personality and behavior. Abnormalities, emotional disorders and mental disorders, even with limb paralysis, ataxia, involuntary movements and other symptoms, a small number of patients with hydronephrosis and intracranial hypertension due to obstruction of the cerebrospinal fluid circulation pathway.

3. Other performance

The disease is often combined with tumors of other organs, such as bone tumors, cystic fibrosis, rhabdomyomas, oral fibroids or papilloma; retinal lens tumor is also one of the characteristic manifestations of this disease, usually located in the eyeball The rear pole is yellowish white or grayish yellow with a slight flash, round or elliptical shape, the surface is slightly raised and irregular, the edge is gear-shaped, the size is half to two times the size of the disc, and it increases with age. Trends, lens tumors usually do not cause symptoms, only occasionally lead to blindness, others can be seen with small eyeballs, protruding eyes, glaucoma, crystal opacity, cataract, vitreous hemorrhage, retinitis pigmentosa, retinal hemorrhage and primary optic atrophy Performance, in addition to optic disc edema and secondary optic atrophy due to increased intracranial pressure.

Examination of tuberous sclerosis

1. Cerebrospinal fluid examination is normal.

2. Proteinuria and microscopic hematuria suggest kidney damage.

3. X-ray film can be found in 50% to 70% of patients with intracranial calcification of the skull in the top region.

4. CT examination can find multiple nodules in the brain.

5. EEG examination often has a peak rhythm disorder.

Diagnosis and diagnosis of tuberous sclerosis

According to the family history of autosomal dominant inheritance, typical sebaceous adenoma, more than 3 pigmentation spots, seizures including infantile spasm, intelligent decline can be used for clinical diagnosis, skull X-ray film, can be found in 50% to 70% of patients Intracranial calcification in the apical area, which is caused by deposition of calcium salts in the subependymal nodules. It usually does not exist at birth and gradually appears in childhood. For example, CT findings show intracranial calcification and subependymal Nodules can be diagnosed. If accompanied by kidney or other visceral tumors, EEG examination often has a peak rhythm disorder, which is also helpful for diagnosis.

Attention should be paid to the identification of neurofibromatosis, which also affects the skin, nervous system and retina.

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