Pediatric Neurofibromatosis

Introduction to pediatric neurofibromatosis The disease is the most common syndrome in neurocutaneous syndrome, and is a disease in which tissues and organs originating from the ectoderm are abnormally developed. Often expressed as abnormalities in the nerves, skin, and eyes, and sometimes in organs that develop in the mesoderm or endoderm. Due to the different organs and systems involved, clinical manifestations are diverse. At present, there are more than 40 such diseases, but only three are common, namely neurofibromatosis, tuberous sclerosis and cerebral hemangiomatosis (Sturge-Weber syndrome). These diseases are often common. The chromosomal dominant inheritance has a higher, incomplete penetrance. The current etiology of these diseases is still unclear and may be related to some variation in early embryonic development. basic knowledge The proportion of illness: 0.003% Susceptible people: children Mode of infection: non-infectious Complications: eyeballs, fractures

Causes of pediatric neurofibromatosis

(1) Causes of the disease

For autosomal dominant inheritance, the penetrance rate is highly variable. It is known that the disease is genetically located on the chromosome, type I is on chromosome 17 (17q11); type II is on chromosome 22 (22q1113), multiple Neurofibromatosis is a common autosomal dominant genetic disease caused by multiple systemic damage caused by neural crest differentiation and migration abnormalities in the early stage of embryogenesis.

(two) pathogenesis

The disease is highly variable, and all systems and organs can be affected. It is born with chronic progression. Complications occur more than 10 years later. According to clinical manifestations, cell biology and molecular biology, it is divided into type I. Neurofibromatosis type I (NFI) is also known as von Recklinghausen disease and neurofibromatosis type II (NFII), which is a bilateral acoustic neuroma.

1. Type I neurofibromatosis: The main pathological features are tumors that grow along the thick peripheral nerves (ie, multiple neurofibromas and schwannomas distributed in the spinal nerves, cranial nerves, skin or subcutaneous nerves), and tumor sizes vary. Closely associated with the cerebral sheath, with cells of the mesoderm of the pericardium and adventitia, most of the skin or subcutaneous neurofibroma are located in the dermis and invading the subcutaneous tissue, the lesion boundary is unclear, the tumor is not enveloped, and there is mature Neonatal collagen fibers, unmyelinated and myelinated fiber axonal doping, and can be seen in clusters of Schwann cells, the central nervous system can also be seen in tumorigenesis, the most common is optic glioma, in the basal ganglia and Glioma can also occur in the thalamus. In type II, it is an acoustic neuroma and a meningioma. Other tumors can also occur, such as Wilms tumor, neuroblastoma and pheochromocytoma. Generally speaking, regardless of the central or peripheral nerves. The neurofibromatosis is mostly benign, but it can also be malignant, with about 5% converted to neurofibrosarcoma.

2. Type II neurofibromatosis: The pathological changes of acoustic neuroma belong to vestibular schwannomas, NFII often has meningioma, meningioma, astrocytoma and posterior sphincter sphincter tumor, skin tumor with schwannomas Lord, occasional cutaneous neurofibromatosis, rarely plexiform neurofibroma.

Pediatric neurofibromatosis prevention

A characteristic single-strand conformation polymorphism analysis of a modified DNA sequence provides an accurate prenatal examination for fetal DNA, using linkage analysis in family cases (affected and unaffected family members) Prenatal diagnosis can achieve a certain degree of precision and terminate pregnancy if necessary.

Pediatric neurofibromatosis complications Complications

Neurofibroma may block the cerebral blood vessels and cause hemiplegia and mental retardation. Because of the severity and uncertainty of this disease, it is not surprising that there are psychological disorders. Malignant tumors in NFI patients are also worthy of attention. Neurofibroma occasionally differentiates. Neurofibrosarcoma or malignant schwannomas; the incidence of pheochromocytoma, rhabdomyosarcoma, leukemia and Wilms disease is higher than in the general population, however, central nervous system tumors (including optic glioma, brain and spinal cord) in NFI patients The incidence of meningioma, neurofibromatosis, astrocytoma and schwannomas is high, so it is an important cause of morbidity and mortality in patients.

Tumor compression nerve can cause dysfunction, oppression of respiratory tract affects breathing, progressive vision loss or eyeball protrusion, hearing loss, tinnitus, dizziness, accompanied by learning difficulties and behavioral disorders, pathological fractures, sacral pseudoarticular formation, etc. Can be associated with convulsions, language and motor developmental delays.

Symptoms of neurofibromatosis in children Common symptoms Learning difficulties Dizziness Hearing loss Tumor block oppression of the eyeball Congenital bone dysplasia Facial muscle weakness Tinnitus number of coffee milk plaque sacral pseudoarthrosis formation

1. Skin changes: Coffee milk spots are important signs of this disease. They can be found at birth. They are light brown (color of coffee plus milk), vary in size, shape is different, do not bulge on the skin, no scaling No abnormalities, except for the palms, soles and scalp, other parts of the body can be affected. Normal children can sometimes see 1 or 2 coffee milk spots, no diagnostic significance, more than 6 coffee milk spots with a diameter greater than 5mm Diagnostic value, sometimes in the armpits of the armpits or other parts of the trunk, some 1 ~ 3mm diameter freckled light brown spots, called axillary freckles, clusters appear, the number is often more, also has diagnostic significance.

The neurofibroma of the skin is often not obvious in infants and young children. It increases after puberty and is characterized by nodular bulges, sometimes pedicles, consistent with the skin color or dark red, ranging from a few millimeters to several centimeters, and the number varies. More common in the trunk, less limbs and head, such as tumor compression nerves can cause pain or dysfunction, plexiform neurofibroma often spread to the face, can also be seen in childhood, often destroy the face, neck or mediastinal plexiform nerve fibers Tumors can compress the respiratory tract and affect breathing.

2. Eye abnormalities: Pigmented iris hamartoma (Lisch small body) is often seen in the iris area. It can not be found in general physical examination. It should be observed under the slit lamp. It appears as a protruding brown plaque with clear edges and no special symptoms. It is common after 6 years old and has diagnostic significance.

3. Nervous system: Neurofibromatosis is a hamartoma-like structure in pathology. It is a benign tumor. The nerve fibers in various parts of the body can be involved. Due to the nature of the tumor, different clinical manifestations of the site are also diverse. The stromal tumor can be seen in 15% of patients, showing progressive vision loss, optic atrophy, local pain or ocular protrusion, unilateral or bilateral, acoustic neuroma often occurs after the age of 10, manifested as hearing loss, tinnitus, dizziness and Facial muscle weakness, meningioma, astrocytoma and ependymoma, spinal cord and nerve roots can also be seen in the brain. This disease can be associated with learning difficulties and behavioral disorders, but the mental retardation and seizures are not obvious. More common.

4. Other systems: Skeletal bone often manifests as congenital bone dysplasia, thinning of cortical bone, calcification, etc., often showing sphenoid dysplasia, pathological fracture, pseudo-articular formation of the humerus.

1. Type I neurofibromatosis has the following two or more:

(1) 6 or more coffee milk spots, the diameter before puberty is greater than 5mm, 15mm after puberty.

(2) Axillary freckles.

(3) optic glioma.

(4) More than 2 neurofibromas or 1 plexiform neurofibromatosis.

(5) There is a type I neurofibroma in the first-degree relatives.

(6) Two or more Lisch bodies.

(7) bone lesions.

2. Type II neurofibromatosis

(1) bilateral acoustic neuroma (required MRI, CT or histology confirmed).

(2) One side of the acoustic neuroma, and the first-degree relatives have type II neurofibromatosis.

(3) There is type II neurofibromatosis in the first-degree relatives, and the patient himself has any of the following two diseases: neurofibromatosis, brain (spinal) membrane tumor, schwannomas, glioma.

Examination of pediatric neurofibromatosis

A direct gene diagnostic technique, protein truncation assay, has been applied to identify many mutants of the NF I gene in combination with gene linkage and mutation analysis, making genetic diagnosis and prenatal diagnosis of NF I possible. The NFI gene is located on chromosome 17q11.2. With the improvement of mutation detection technology, gene amplification and allele-specific oligonucleotide hybridization, restriction-length fragment polymorphism linkage analysis, protein truncation analysis, error The combination of chemical fragmentation and denaturing gradient gel electrophoresis can improve the accuracy and reliability of NFI prenatal diagnosis and pre-symptomatic diagnosis. Most patients with NFII are the result of mutation.

Pathological biopsy of skin and subcutaneous nodules or nerve trunk mass can be performed if necessary.

1. Basic examination: Clinical considerations should be based on the following basic examinations, such as electrical audiometry, brainstem evoked potentials, visual evoked potentials, EEG, psychological tests (including predictive learning ability), etc., can be found in brainstem auditory Various abnormalities such as evoked potentials.

2. X-ray photograph: X-ray film in the skull shows bilateral internal auditory canal destruction; bone X-ray examination helps to detect skeletal malformation, and the diseased bone X-ray film can see large, multiple cystic structures, visible transparent District, the cortex is thinned.

3. Vertebral angiography: Helps to detect central nervous system tumors.

4. MRI imaging: MRI imaging of the skull shows bilateral acoustic neuroma, showing abnormal signals in the globus pallidus, thalamus and internal capsules, which may mean the presence of low-grade gliomas or hamartomas, and CT scans. Can not detect, these can be learning difficulties, inattention and language barriers, MRI shows leukoplakia plaque-like abnormal signals, TW1 low signal, TW2 high signal, unknown nature, temporarily called unexplained luminescent substances Asymptomatic patients should be examined repeatedly every year for neurological evaluation, including blood pressure, auditory and visual screening, to explore the complications of neurofibromatosis.

5. Brain or optic nerve CT scan: CT can detect central nervous system tumors, but about 85% of patients have no abnormal brain CT, giants with normal ventricle size are common, and cerebral edema secondary to aqueduct stenosis is rare.

Diagnosis and diagnosis of neurofibromatosis in children

The disease should be differentiated from Watson syndrome, bone fiber dysplasia syndrome, and local soft tissue hemangioma.

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