Tuberous sclerosis is characterized clinically by facial sebaceous adenomas, seizures, and mental retardation. The disease is autosomal dominant, but disseminated cases are not uncommon. The genes located at 9q34 or 16p13.3 are tumor suppressor genes, named TSC1 and TSC2, respectively; the gene products are hamartin (misshapen tumor) and tuberin (potato globulin), both of which regulate cell growth.
Tuberous sclerosis is an autosomal dominant disorder with variable episomal prevalence. There is a positive family history of the disease in 20-30% of cases. Pathological changes: The typical manifestation in the brain is subventricular nodules, often in the anterior horn of the lateral ventricles, which are microscopically hyperplastic large astrocytes with a tendency to calcify, with varying numbers. The cerebral cortex can also see some hard nodules, grayish in color, with elevated surface of the cerebral gyrus, about 1-2 cm in diameter, with varying numbers, and microscopically the nodules are neuroglial, composed of some giant multinucleated astrocytes. These nodules can thin out the normal cerebral cortex. Similar lesions can also be seen in the central gray matter, brainstem, or cerebellar areas. Depending on the location of the nodules, a variety of neurological symptoms may be manifested clinically.
Clinical manifestations.
1. Skin manifestations Typical skin changes include Epidermolysis Bullosa, facial angiofibroma and sharkskin-like spots. These changes may not be present in every child, but in 90% of patients, the skin is white, oval or other shaped, with clear boundaries with the surrounding skin, and depigmented at birth. They vary in size from 1 cm to several centimeters in length and can be seen on the trunk and extremities, with an asymmetrical distribution, rarely on the face but sometimes on the scalp, where the hair is white. The number of depigmentation spots varies for each person, from a few to more than 10. In normal people, 1-2 patches can sometimes be seen, which has no diagnostic significance. Some patients may also see clusters of small, irregularly shaped, confetti-like patches of pigment loss. Facial hemangioma is a characteristic sign of this disease. It used to be called sebaceous adenoma, but it is not actually a sebaceous gland, but is composed of blood vessels and connective tissue, reddish-brown in color or of the same shade as the skin, elevated on the skin, papular or fused into small groups, with a smooth surface without exudation or secretion. They are scattered on the sides of the nose and on the skin of the nasolabial folds. When the number is large, it may extend to the jaw area and sometimes the forehead. Facial hemangioma is not seen at birth, but gradually increases after 4-10 years of age. This body film has diagnostic value and can be seen in about 70-80% of patients. Fibromas of the finger (toe) nail are located around the finger (toe) nail and under the nail, and resemble a small fleshy nodule. About 15-20% of patients have this presentation. Fibromas are more common in women than in men, but they are less common before puberty, and multiple nail fibromas have diagnostic value for this condition. Some patients have more sharkskin-like spots on both sides of the trunk or back, slightly elevated on the skin, with irregular borders and rough surface. 20%-30% of patients after puberty can see this lesion, and some can see slightly elevated patches of skin on the forehead when they are taken out at birth, which is helpful for diagnosis.
2. Ocular changes Fundus examination often reveals mulberry-shaped astrocytoma or plaque-like malformation tumor each without pigmented areas. The retinal misophthalmos is one of the important signs of the disease. Although large retinal lesions can affect vision, complete vision loss is uncommon. Occasionally, patients lose vision due to a retinal detachment, vitreous hemorrhage, or large lesions that are not visible.
Neurological symptoms The most common ones are epilepsy, mental retardation, and occasionally hemiplegia or other limited neurological abnormalities. 80%-90% of patients have epilepsy, often manifested as infantile spasms in infancy, and in older children as complex partial seizures or other limited seizures, or generalized tonic-clonic seizures or Lemmox-Gastaut syndrome. Mental retardation often coexists with epilepsy, but some patients have only convulsions without mental retardation. The number of neurological nodules varies, and they are often located in the subventricular membrane of the lateral ventricular base, and calcification can be seen in X-ray plain film, but calcification takes time, so it is not common in infants. The tumor can cause high intracranial pressure, behavioral changes and uncontrollable convulsions. The tumor can cause high intracranial pressure, behavioral changes and uncontrollable convulsions. Some of them can also be seen in the area of cerebral cortex defect, which may be related to the obstruction of neuronal migration during neocortex formation.
4.Other systems The disease may involve other parts of the body besides skeletal muscle. 50%-80% of patients have angiomyolipoma of the kidney, which is histologically benign and composed of smooth muscle, adipose tissue and blood vessels, and renal tumors are not as common in children as in adults. 2/3 of patients have rhabdomyosarcoma of the heart, which is caused by cardiac tumors, and pulmonary involvement is seen in only 1% of children with tuberous sclerosis, more in women than in men. males.
Diagnostic criteria.
1.Confirmed diagnosis of the disease breakdown Ken has 1 major indicator listed in the table below; or 2 secondary objectives; or 1 secondary indicator plus 2 tertiary indicators.
2, may be the disease has 1 secondary indicators listed in the table below plus 1 tertiary indicators; or 3 tertiary indicators.
3, suspected for this disease 1 secondary indicator or 2 tertiary indicators.
Main indicators.
1.Facial vascular fibers
2.Multiple finger (toe) nail fibroids
3, cerebral cortex nodules (histologically confirmed)
4, subventricular nodules or giant cell astrocytoma (histologically confirmed)
5, multiple subventricular calcified nodules extending into the ventricles (radiologically confirmed)
6.Multiple retinal astrocytomas
Secondary indicators.
1, cardiac rhabdomyosarcoma (histologically or radiologically confirmed)
2, Other retinal malformation tumors or achromatic plaques
3, Brain nodules (radiologically confirmed)
4, non-calcified subventricular nodules (radiologically confirmed)
5.Sharkskin-like plaques
6.Forehead plaques
7, pulmonary lymphangioleiomyomatosis (histologically confirmed)
8, renal angiomyolipoma (histologically or radiologically confirmed)
9, tuberous sclerosis polycystic kidney (histologically confirmed)
Tertiary indicators.
1.Depigmented spots
2, skin confetti-like pigment loss spots
3, renal cystic-like changes (radiologically confirmed)
4, irregular enamel destruction depressions in milk teeth or permanent teeth
5, rectal polyp malformation tumor (histologically confirmed)
6.Bone cystic change (radiologically confirmed)
7.Lymphangioleiomyoma of the lung (radiologically confirmed)
8, “migratory traces” or gray matter ectopia in the white matter of the brain (radiologically confirmed)
9.Gingival fibroma
10.Angiomyolipoma of organs other than the kidney (histologically confirmed)
11.Infantile spasms
Treatment.
For epilepsy, different antiepileptic drugs can be used according to the patient’s age and seizure type. Carbamazepine can be used for epilepsy that starts with focal freak episodes. Valproic acid is mostly used for generalized seizures. ACTH is only used for infantile spasms. Surgery is not effective because the encephalopathy becomes multiple, but if the tumor is located in an important area causing convulsive seizures, callosal dissection is feasible.