neurocutaneous syndrome
Introduction
Introduction to neurocutaneous syndrome In the early stages of human embryonic development, both the nervous system and the skin system originate from a tissue called the ectoderm. Neurocutaneous syndrome is a group of diseases in which the nervous system, skin and ocular tissues are abnormally developed during embryonic development, and can also cause mesoderm and endoderm-derived tissues such as heart, lung, kidney, bone and gastrointestinal. Damage. The clinical features are abnormalities in the morphology and function of multiple systems and multiple organs. There are currently more than 40 reports, such as: neurofibromatosis, tuberous sclerosis, brain-surface hemangiomatosis, xeroderma pigmentosum and pigment disorders. The diagnosis of such diseases mainly depends on clinical manifestations, family history, combined with imaging examination, biopsy or genetic testing. Common neurocutaneous syndrome There are the following types: Neurofibromatosis type 1 (NF1): clinically significant skin cream coffee spots and multiple neurofibromatosis. Neurofibromatosis type 2 (NF2): 100% of the disease has central neurofibromatosis, such as bilateral acoustic neuroma, multiple meningioma, non-neoplastic choroid calcification, multi-segment fusiform schwannomas, Spinal ependymoma and astrocytoma; skin manifestations are rare. Tuberous sclerosis (TS), also known as Bourneville disease. The clinical manifestations are mainly facial sebaceous adenoma, seizures and mental decline. Cerebral-face hemangiomatosis, also known as Sturge-Weber syndrome, is a rare neurocutaneous syndrome characterized by facial and intracranial hemangiomas. It is a special type of cerebrovascular malformation and is also a misconfiguration. A type of tumor. The clinical manifestations of xerodermapigmentosum (XP) are mainly that the skin is highly sensitive to sunlight, especially ultraviolet light, and the skin at the exposed site appears pigmentation, dryness, keratosis, atrophy and carcinogenesis, etc. The incidence of ocular tumors is 1000 times higher than that of normal people; about 20% to 30% of patients may have neurological abnormalities, which are neurodegenerative, which may lead to decreased reflex activity, sensorineural deafness, spastic ataxia, and progressive Cognitive impairment, hand and foot, language barriers, mental retardation, etc. Pigment disorders Incontinentiapigmenti (incontinentiapigmenti), also known as pigment incontinence, has characteristic skin changes that can be associated with eye, bone and central nervous system malformations and abnormalities. basic knowledge The proportion of sickness: 0.04%-0.07% Susceptible people: no special people Mode of infection: non-infectious Complications: epilepsy
Cause
Cause of neurocutaneous syndrome
Neurocutaneous syndrome is a group of diseases with hereditary congenital dysplasia. Nodular sclerosis, neurofibromatosis is autosomal dominant; xeroderma pigmentosum (XP) is a rare autosomal recessive disorder caused by DNA repair gene defects; pigment disorders It is a rare x-chromosome-linked dominant hereditary disease; most brain-surface hemangiomatosis is considered to be associated with abnormal embryonic development. Pathogenesis and pathophysiology In the early stage of embryonic development, the ectoderm cells in the dorsal midline of the embryo gradually thickened to form a neural plate. At the second week of the embryo, both sides of the nerve plate bulged to the dorsal side to form a neural crest, and the middle depression The neural tube is formed, and the neural tube develops into a nerve tissue such as a brain and a spinal cord, and the ectoderm on the surface of the embryo is derivatized into a tissue such as a skin. Neurocutaneous syndrome is caused by genetic mutations that cause early embryonic developmental abnormalities. The main manifestations of postnatal dysplasia are the nervous system and abnormal skin manifestations of the ectoderm, and may also involve mesoderm and endoderm-derived tissues such as heart, lung, kidney, bone and Gastrointestinal damage.
Neurofibromatosis
Divided into type I and type II, the type I pathogenic gene is located on the autosome 17q11.2. This gene is a tumor suppressor gene. The mutation of the gene, especially the deletion of the chromosomal locus, results in the inability to produce neurofibromatosis protein. The neurofibromatosis protein is a Tumor suppressor; type I main pathological features: multiple neurofibromatosis distributed in the spinal nerve, cranial nerve, skin or subcutaneous, the tumor cells are arranged in a close relationship with the nerve sheath, the boundary is unclear, no myelin and The myelinated fibers are doped to form clustered Schwann cells; melanin deposition in the basal cell layer of the epidermis leads to skin pigmentation. The type II pathogenic gene is localized to the autosome 22q11.2, a tumor suppressor gene associated with high-risk schwannomas and meningiomas.
Tuberous sclerosis
The tuberous sclerosis gene is located at 9q34 or 16p13.3 and is a tumor suppressor gene, named TSC1 and TSC2 respectively; the TSC1 gene encodes a hamartoma protein (Hamartin), and the TSC2 gene encodes a potato globulin (tuberin). They regulate cell proliferation by inhibiting the proliferation and differentiation of cells by inhibiting the mTOR signaling pathway. The characteristic pathological changes of tuberous sclerosis are multiple nodules scattered in the brain, distributed in the gray matter and white matter of the cerebral hemisphere, with the most frontal lobe, but also in the thalamus, basal ganglia, cerebellum, brainstem and spinal cord, white matter. There are ectopic cell clusters, the size of the nodules is different, and the histological examination nodules are composed of very dense fine colloidal fibers, which contain morphologically abnormal glial cells and normal or atypical neurons, which may be present in the nodules. Calcium salt deposition or cystic changes, normal cortical structure often occurs; small nodules under the ventricular ventricle protrude into the room, showing a shiny white, hard texture, forming a so-called "candle tear" sign, sometimes blocking cerebrospinal fluid circulation Pathway causes hydrocephalus; skin sebaceous adenoma is composed of hyperproliferative sebaceous glands, connective tissue and dilated capillaries; this disease may be associated with retinoic glioma, heart and kidney tumors or deformities. Tumors with organs such as the thyroid, thymus, breast, gastrointestinal, liver, spleen, pancreas, adrenal gland, ovary, bladder or uterus have also been found.
Brain-face hemangiomatosis
The pathogenesis is still unclear, but most scholars believe that it is related to abnormal embryonic development. Studies have found that pathological brain and facial hemangioma is a drainage vein caused by abnormal development of the early embryo and middle and outer ectoderm. This type of abnormal vein is easy to cause cerebral blood flow and blood stasis; due to cerebral ischemia Abnormalities of brain calcification and brain atrophy; pathological changes of brain-face vascular disease include pial hemangioma, venous endothelial cell hyperplasia, meningeal thickening of the lesion, atrophy of the cerebral cortex, reduction of neurons and nerve fibers, gliosis and Calcium deposits; skin changes to congenital weakness of the capillary wall.
Coloring dry skin disease
Nucleic acid excision repair (NER) is the main pathway for DNA repair in mammalian cells, and it is also the main mechanism for preventing UV carcinogenesis. There are seven different complement types (XPA to XPG) and one set of variants (XPV) in the hereditary dry skin disease, seven of which are associated with different protein defects in the nucleotide excision repair pathway. Due to defects in the nucleotide excision repair gene (XPA-XPG), the nucleic acid excision repair pathway is not functioning properly, and the cells are susceptible to UV-induced damage or distortion, causing complex pathological changes in the skin of the exposed light, such as freckles, epidermis. Hyperplasia, basal cell carcinoma, squamous cell carcinoma, malignant melanoma; variant xeroderma pigmentosum has normal nucleotide excision repair and is caused by a mutation in a gene encoding DNA polymerase. Pathological changes: early skin pathology is non-specific, may have hyperkeratosis, chronic inflammatory cell infiltration of dermis, irregular increase of melanin in basal cell layer, increase of melanocytes; pigmentation in metaphase, basal cell layer and dermis Melanin, part of the epidermal atrophy, dermal telangiectasia and precancerous lesions; late stage cancer, showing the changes in the organization of various tumors.
Pigment disorder
Incontinentia pigmenti, also known as pigment incontinence, is a rare x-linked dominant dominant disease. The gene is located on the x-chromosome xpll or Xq28. It has been suggested that the sporadic gene is located in Xpll, with more familial cases. Located at Xq28. The rearrangement of the x chromosome gene results in the inactivation of the IKKr/NEMO gene. The characteristic pathological changes of the skin are divided into three stages: (1) erythema stage: the epidermis is in a sponge state, and the blister under the cornea is visible. There are a lot of acidic cells in the blister, and the dermis has an inflammatory infiltration around the banded blood vessels. (2) period of verrucous hyperplasia: thickening of the spinous layer, irregular papillary hyperplasia, hyperkeratotic or keratinized cells, and the interspinous cells are arranged in a spiral shape. (3) abnormal pigment phase: there are many phagocytes and vascular hyperemia in the upper part of the dermis, which may be caused by the phagocytosis of melanocytic macrophages under the basement membrane, and the underlying hypopigmentation, cell vacuoles Chemical and degeneration, but in some cases, a large number of pigments are seen in the basal cells; fundus examination sees optic atrophy, retinal hemorrhage, pigmentation and other lesions.
Prevention
Neurocutaneous syndrome prevention
The cause is unclear and there are no systematic preventive measures. Prenatal diagnosis can reduce the incidence of disease.
Complication
Neurocutaneous syndrome complications Complications
Different types of neurocutaneous syndrome have different prognosis. The skin lesions of pigmented disorder may have a tendency to gradually decrease, and the pigment may be regressed, but the accompanying alopecia and lesions of the teeth, eyes and central nervous system often do not improve with the skin; symptomatic epilepsy is given, and antiepileptic drugs are given. You can get control and reduce seizures. Type II neurofibromatosis has poor surgical outcome and is prone to recurrence. Lateral facial paralysis and hearing loss may occur.
Symptom
Symptoms of neurocutaneous syndrome Common symptoms A large number of coffee milk spotted tinnitus coffee spot radiation pain hearing loss pigmentation collaterality disorder dizziness memory disorder tumor block compression
Neurofibromatosis
Neurofibromatosis Type I clinical manifestations: (1) milk coffee spots: almost all patients have skin pigmentation spots, light brown, dark brown or brown. Freckle-like pigmentation occurs in the armpits. Physiological changes such as development, pregnancy, menopause, and mental stimulation can make it worse. Sometimes the rash appears later, and it begins to develop and develops slowly during development. (2) multiple neurofibromatosis: patients often complain of a painless subcutaneous mass throughout the body, and gradually increase and expand. Significant progress in puberty and pregnancy. More no clinical symptoms. A small number of manifestations of radioactive or burning pain, tumor compression optic nerve caused by decreased vision. (3) Neurological symptoms: Most patients have no complaints, and only a few patients have mental decline, memory impairment, seizures, limb weakness, numbness and so on. (4) Bone damage: A small number of patients develop skeletal abnormalities at birth, or abnormalities caused by compression of bone during tumor growth. (5) Visceral damage: Neurofibromas growing in the chest, mediastinum, abdominal cavity or pelvic cavity can cause visceral symptoms, which can cause gastrointestinal bleeding or obstruction, and can also cause endocrine abnormalities.
Neurofibromatosis type II skin is rare, with 100% of central nervous system lesions. Bilateral acoustic neuroma with multiple meningiomas, non-neoplastic choroid plexus calcification, bilateral multi-segmental spindle schwannoma or astrocytoma. Symptoms of the nervous system vary depending on the location of the neurofibromatosis, clinical symptoms appear, tinnitus, hearing loss, dizziness, walking swing, ataxia, and even intracranial pressure such as headache, nausea, vomiting, and unclear vision Increase performance.
Tuberous sclerosis
Skin lesions are most characteristic, with approximately 90% of patients having sebaceous adenomas. Usually found in the age of 2 to 5 years old, it is distributed in the mouth and nose triangle area, and it is symmetrical and scattered in pale red or light brown hard waxy papules. It can be faded according to the size of the needle. The size of the needle can be as large as the broad bean. The rash increases and merges into a piece after puberty, and the color is deepened. A small number of visible pigmentation spots, shark skin spots or toe nail fibroids. Secondly, neurological symptoms can occur with seizures, mental retardation, and can also manifest as personality and behavioral abnormalities, emotional disorders and mental disorders. Other manifestations of this disease often combined with other organs of the tumor, such as kidney tumors, rhabdomyosarcoma and so on. Retinal lens tumor is also one of the characteristic manifestations of this disease, and may also have ocular manifestations such as cataract, vitreous hemorrhage, retinitis pigmentosa, retinal hemorrhage and primary optic atrophy.
Cerebral hemangiomatosis
Also known as brain trigeminal angiomatosis or Sturge-Weber syndrome, is a rare neurocutaneous syndrome characterized by facial and intracranial hemangiomatosis, a special type of cerebrovascular malformation, also wrong A type of constitutional disease. Facial facial angiomatosis is mostly one side, occasionally bilateral, often distributed along the trigeminal nerve 1, 2 branches, can also affect the third branch or not according to the trigeminal nerve distribution, appear in the neck, trunk or limbs; 75- 90% have seizures; the degree of mental decline varies; there may also be contralateral hemiplegia, partial atrophy and ipsilateral glaucoma.
Coloring dry skin disease
Extremely light-sensitive, acute sunburn after mild sun exposure, accompanied by blisters and persistent erythema, bullous lesions are not easily healed, shallow ulcers or scarring may occur; at exposed sites such as face, lips, conjunctiva, neck And the characteristic freckle-like sputum in the calf appears as a pale brown plaque with a needle size of 1 mm or more, which can be fused into irregular pigmentation spots, which persists for a long time, often with telangiectasia or small hemangioma; Both lesions can sometimes affect the mucous membranes and non-exposed areas of the skin, and soon appear small round or irregularly shaped white atrophy spots. Patients with skin often have sacral keratosis, which can resolve or cause cancer on their own; tumors are prone to occur in UV-exposed areas, and multiple primary skin tumors are common, mostly basal cell carcinoma, squamous cell carcinoma, and malignant melanoma. The incidence of visceral malignant tumors in patients with dry skin disease is also about 10 to 20 times higher than that of normal people, including brain, lung, digestive tract, kidney and hematopoietic system. Eye damage often manifests as photophobia, keratitis and corneal opacity. The nervous system is neurodegenerative, which can lead to decreased reflex activity, sensorineural deafness, spastic ataxia, progressive cognitive impairment, hand and foot movement, speech disorder, mental retardation, etc. The most serious neurological symptom is DeSanctis. -Cacchione syndrome, clinical manifestations of microcephaly, progressive mental retardation, poor growth and development, can also occur deafness, dance hand and foot hyperactivity, ataxia, limb palsy.
Pigment disorder
The main manifestation is skin abnormality, which can be found after birth. The skin changes can be divided into four stages: the first stage: some sick children can see herpes in different sizes on the limbs or trunk, which can appear repeatedly for several weeks to several months. It is easily misdiagnosed as impetigo, but no bacteria can be found in the herpes rupture solution. The second stage: the skin that originally appeared in the herpes area became hard and thick. There was no pigmentation in the above two stages of skin, and some patients did not have the above two stages. The third stage: visible skin has a yellow-brown or gray-black pigmentation, the graphics are strange, can be spiral, line, mesh or sheet, some like marble, mainly distributed in the limbs and trunk. Stage 4: After a few years, the patient's skin pigmentation can completely subside or become lighter. Secondly, often accompanied by nail dysplasia, hair loss, cataract, optic atrophy, delayed teeth or teeth insufficiency; about 30% of children with neurological symptoms, can appear microcephaly, mental retardation and infantile spasm.
Examine
Examination of neurocutaneous syndrome
Laboratory inspection
ESR, alkaline phosphatase, immunoglobulin, blood electrolyte, alpha-fetoprotein, cerebrospinal fluid and other tests can be selected.
Imaging performance
1, abnormal calcification around the lateral ventricle, nodules and cortical nodules, if the nodule is strengthened after injection of contrast agent, suggesting tumorous changes.
2, subependymal giant cell astrocytoma, often located near the interventricular space.
3, hydrocephalus.
4. Many organ systems throughout the body have hamartoma growth.
First, CT performance
Type 1NF1: Large head, non-neoplastic isolated calcification of the choroid plexus or calcification along the entire choroid plexus. The sphenoid wing is underdeveloped, and the temporal lobe is merged into the eye. The pulsating convex eye can be combined with meningioma, schwannomas and glioma.
2NF2 type: vestibular cochlear neuroma, some patients are not associated with cochlear vestibular neuroma, and dural bulging can enlarge the inner ear canal. May be associated with III-VII cerebral schwannomas, single or multiple meningioma, multiple spinal schwannomas.
Second, MR performance:
1 bilateral acoustic neuroma, most of which are heavy on one side;
2 pairs of cranial nerves, peripheral nerve neurofibroma;
3 combined with meningioma or glioma;
4 often accompanied by skeletal deformities, such as spina bifida, skull defects.
Diagnosis
Diagnosis and diagnosis of neurocutaneous syndrome
Diagnosis and differential diagnosis
Neurofibromatosis
In 1987, the National Institutes of Health developed the diagnostic criteria for type I neurofibromatosis: (1) 6 or more milk coffee spots, the maximum diameter before puberty is 5 mm or more, 15 mm or more after puberty; (2) 2 or more Any type of neurofibromatosis or 1 plexiform neurofibromatosis; (3) axillary or inguinal brown freckles; (4) optic glioma; (5) 2 or more Lisch nodules, ie iris hamartoma; Obvious skeletal lesions: such as sphenoid dysplasia, long tubular cortical bone, with pseudoarticular formation; (7) patients with first-degree relatives with type I neurofibromatosis. Patients with two or more of these criteria who can diagnose type I neurofibromatosis.
Diagnostic criteria for type II neurofibromatosis in 2002: Patients with one of the following criteria: (1) bilateral vestibular schwannomas; (2) unilateral vestibular schwannomas, but with a family history (in first-degree relatives) (type II neurofibromatosis patients); (3) unilateral vestibular schwannoma plus meningioma, Schwann cell tumor, glioma, neurofibromatosis and posterior subcapsular lens opacity in any two tumors; (4 Multiple radiation meningioma plus unilateral vestibular schwannomas, Schwann cell tumors, gliomas, neurofibromas, and posterior subcapsular lens opacity.
Tuberous sclerosis
The revised diagnostic criteria made in 1998 were based primarily on clinical presentation and imaging findings. The main features are 11: facial angiofibroma, non-traumatic toe nail fibroids, hypopigmentation plaques (more than 3), multiple retinal hamartoma nodules, shark skin plaques, cortical nodules, ependymal Lower nodules, subependymal astrocytoma, cardiac rhabdomyomas, lymphangiolecular leiomyoma, and renal angiomyolipoma; secondary features are 9: polycystic kidney, milk coffee spots, rectal hamartoma polyps , bone cysts, gingival fibroids, white matter radial transition lines, fundus pigmentation plaques, non-renal hamartomas, and multiple enamel depressions; if there are 2 main features or 1 main feature plus 2 secondary The characteristics were diagnosed as tuberous sclerosis; one major feature plus one secondary feature may diagnose tuberous sclerosis; one major feature or two or more secondary features for the diagnosis of suspected tuberous sclerosis .
Cerebral hemangiomatosis
Diagnosis is based on a typical facial skin hemangioma, plus more than one other symptom, such as epilepsy, glaucoma or exophthalmos. Auxiliary examination: the skull X-ray can show the characteristic double-track calcification consistent with the cerebral gyrus; before the calcification of the soft meningeal hemangioma, the MRI examination has a unique advantage in the flow along the cerebral gyrus and sulcus. Empty shadow, accompanied by brain atrophy; CT is the best examination of hand rupture after calcification of soft meningeal hemangioma, showing mass-like mixed density shadow, unclear edge, cerebral cortical brain calcification, enhanced scanning pial membrane line-like strengthen.
Coloring dry skin disease
In clinical diagnosis, it is mainly based on the typical clinical manifestations of skin, eye and nervous system. Detailed family history, especially the history of close relatives marriage can assist in the diagnosis of this disease. Live cell function tests can be used to determine if a patient's DNA repair function is abnormal, helping to determine the diagnosis. The diagnosis of this disease is simple and rapid, and it is the gold standard for the diagnosis and classification of this disease. The diseases to be identified include freckles, acral aging, and porphyria.
Pigment disorder
Diagnosis is based on typical skin lesions and their developmental processes, combined with clinical features such as elevated eosinophils in peripheral blood, further confirmed by skin tissue biopsy. The diseases to be identified include neonatal erythema, bullous epidermolysis, herpes simplex infection, histiocytosis, herpes zoster, congenital varicella, neonatal impetigo, congenital syphilis, and etomoside melanin , plexiform neurofibroma, linear epidermal sputum, segmental coffee milk plaque, etc.
