Genetic diseases of the nervous system

Introduction to nervous system genetic diseases The nervous system hereditary disease is caused by the change in the quantity, structure or function of the genetic material of the germ cell or the fertilized egg, and the development of the individual with the neurological deficit is the main clinical manifestation. It is different from congenital heart disease caused by rubella virus infection in the mother, and is also different from familial diseases caused by some of the same environmental factors, such as familial hypothyroidism, the latter are non-hereditary. Nervous system hereditary diseases are genetic diseases characterized by symptoms of the nervous system. basic knowledge The proportion of illness: 0.0005%--0.0008% Susceptible people: no special people Mode of infection: non-infectious Complications:

Nervous system genetic disease etiology

(1) Causes of the disease

There are many kinds of diseases of the nervous system, which are familial and lifelong. The etiology and pathogenesis of many diseases have not yet been elucidated. Due to the rapid development of molecular genetics and the completion of the human genome project in the past 10 years, 3×109 humans have been clarified. The sequence of nucleic acid, along with the genetic localization of the genetic diseases of the nervous system, cloning, gene products and breakthroughs in gene diagnosis and treatment, will certainly promote the development of neurogenetics.

(two) pathogenesis

There are 4 genetic methods:

1 single gene inheritance, including autosomal dominant inheritance, recessive inheritance, X-linked recessive inheritance, dominant inheritance, etc.;

2 multi-gene inheritance;

3 mitochondrial disease caused by mutation of mitochondrial DNA;

4 chromosomal disease, abnormal chromosome number or structure.

Nervous system genetic disease prevention

Because of the difficulty in the treatment of nervous system genetic diseases, the efficacy is not satisfactory, prevention is more important, preventive measures include avoiding close relatives marriage, implementing genetic counseling, carrier genetic testing and prenatal diagnosis and selective abortion to prevent the birth of children.

Nervous system genetic disease complications Complications

As the disease progresses, the symptoms and signs that appear may be a manifestation of a certain neurological genetic disease, which can also be regarded as a complication of the disease.

Symptoms of nervous system genetic diseases Common symptoms Involuntary movement vocal dysfunction bow-shaped foot nodule dysarthria paraplegia facial vascular fibroma hepatolenticular degeneration hepatosplenomegaly myoclonus

1. Nervous system genetic diseases can be divided into four categories according to genetic methods:

(1) Single-gene genetic disease: a disease caused by base substitution, insertion, deletion, repetition or dynamic mutation of a single gene. The genetic pattern includes autosomal dominant, autosomal recessive, X-linked recessive, X-linked dominant And dynamic mutation inheritance, clinically common monogenic genetic diseases include pseudohypertrophic muscular dystrophy, hereditary spinocerebellar ataxia, patellar muscular atrophy and hepatolenticular degeneration, many of which are known Biochemical abnormalities lead to ataxia, such as hepatolenticular degeneration is caused by mutation of ATP7B gene on chromosome 13q14.3-q21.1, the latter encodes beta polypeptide of copper transport ATPase, leading to copper metabolic disorder; phytanic acid storage Accumulation disease (Refsum disease) is caused by a mutation in the phytanic acid-CoA-hydroxylase gene.

(2) Polygenic genetic diseases: diseases caused by the interaction of more than one gene mutation with environmental factors, epilepsy, migraine and cerebral arteriosclerosis are common neurogenic polygenic diseases.

(3) Mitochondrial genetic disease: caused by mutations in mitochondrial DNA, including maternal inheritance, including mitochondrial myopathy, mitochondrial myopathy, mitochondrial encephalopathy, etc. Holt (1988) first discovered mtDNA deletion in mitochondrial patients, confirming that mtDNA mutation is a human disease The important cause of the disease establishes a new concept of mitochondrial inheritance that is different from the traditional Mendelian inheritance.

(4) Chromosome disease: caused by abnormal chromosome number or structure, such as a chromosome 21 in the somatic cells of patients with Down syndrome.

2. Common and characteristic symptoms of nervous system genetic diseases:

(1) Common symptoms and signs: including mental retardation, dementia, behavioral abnormalities, language disorders, seizures, nystagmus, involuntary movements, ataxia, clumsiness, paralysis, increased muscle tone, muscle atrophy and sensation Abnormalities, as well as facial abnormalities, facial features, spina bifida, arched foot, finger toe deformity, abnormal skin and liver and splenomegaly.

(2) Characteristic symptoms and signs: KF ring such as hepatic nucleus degeneration, erythema of erythema dementia, telangiectasia with ataxia telangiectasia, facial vascular fibrosis of tuberous sclerosis Tumors, etc.

3. The main clinical manifestations of nervous system genetic diseases:

(1) Intelligent decline: also known as mental dysplasia, according to the degree of mental decline can be divided into three levels of idiot, idiot and fool, idiot IQ (IQ) in 0 ~ 30; fools IQ in 30 ~ 50; The IQ is 50 to 70. If the IQ is above 70, it is low energy.

(2) Abnormal behavior: It is one of the common genetic diseases in the nervous system. It is often associated with mental decline, which is characterized by excitement, irritability, irritability, personality changes, etc. A small number of patients may be impulsive and misdiagnosed as mental illness.

(3) Speech disorder: speech impairment in neurogenetic diseases may be caused by aphasia due to hypoplasia of the central nervous system, or by a dysarthria caused by the coordination of vocal organs. The former is incomprehensible and does not know. I dont understand and cant express it. The latters speech is slow and weak, the pronunciation is frustrated, the nasal sound, the spit is vague, etc.

1 difficulty in pronunciation, such as spastic paraplegia and post-blasting dysarthria in cerebral palsy, such as cerebellar ataxia language,

2 Incompetent language, pronounced in the pharyngeal muscle atrophy and the weakness of the muscle dystrophy, is common in torsion spasm of extrapyramidal diseases, myoclonus, and high and low paroxysmal dysphonia during dance movements.

(4) Involuntary movement: a common symptom of a genetic disease involving the extrapyramidal system. It can express tremor characterized by increased muscle tone and reduced movement; dance movement with reduced tension and increased movement; and irregular movement of muscles and muscles with irregular muscle tension , torsion, etc.; and rhythmic muscle contraction of myoclonus, such as myoclonic epilepsy, olive-ponsory-cerebellar degeneration.

(5) convulsions: is one of the common symptoms of hereditary nervous system diseases, convulsions can be focal, systemic, large or small attacks, often coexist with intelligent decline, such as nodular sclerosis, phenylketonuria, etc. .

(6) Certain characteristic postures and other abnormalities: for example, face-shoulder-sputum muscular dystrophy, myotonic dystrophy, special face of mucopolysaccharidosis; skull defect of neurofibromatosis, hereditary mutual aid Disordered extraocular muscle paralysis, corneal nucleus degeneration of the corneal KF ring, hereditary cerebellar ataxia nystagmus; and cataract, lens shift, narrow skull, spina bifida, short limbs, arched foot, gait Etc., all have certain diagnostic value.

Examination of nervous system genetic diseases

1. Chromosome examination: Conventional chromosomal examination includes the number and shape of chromosomes, whether there are haplotypes in the chromosomes, the appearance of triploids, whether the chromosomes are distorted, translocations, inversions, etc.

Chromosomal examination should be performed in the following cases:

1 family members with congenital malformations;

2 women and their husbands with multiple history of abortion;

3 children with Down syndrome, brothers and sisters and parents;

4 patients with neurological disorders with obvious mental decline and abnormal body condition.

2. Biochemical enzyme detection: The diagnosis of many hereditary metabolic diseases depends on the diagnosis of serum, skin fibroblasts, and the lack of certain special enzymes in white blood cells.

3. Cytological examination: Gaucher cells are found in the liver, spleen or bone marrow of some genetic diseases such as Gaucher disease, and "foam cells" can be found in the bone marrow of Niemann-Pick patients.

4. Recombinant nucleic acid technology: The messenger RNA (mRNA) is isolated from the brain tissue or living specimen of the body of a known genetically ill person, and the genetic information is transferred to the DNA by reverse transcriptase, ie, formed on the complementary DNA (cDNA). The DNA probe is then used to detect the nucleic acid isolated in the living specimen by using the nuclear labeled cDNA, which serves as a genetic diagnosis and opens up a new way for the diagnosis of the nervous system genetic disease.

5. Prenatal diagnosis: gender can be determined by using pregnant women's amniotic fluid cells or chorionic cells for chromosome examination. If X-linked latent inheritance is rickety in boys, it can provide guidance for terminating pregnancy and provide clues for further examination. When the sex is determined, it can be used for further biochemical enzyme activity or DNA probe detection. For example, Duchenne muscular dystrophy almost occurs in males. When the chromosome is examined, there is a 1/2 chance of onset, so CPK (creatine phosphate) is required. For the determination of kinases and PK (phosphokinase), DNA probes can be used for prenatal diagnosis if the results are still suspicious.

Electrophysiology, imaging X-ray, CT, MRI and pathological examination are of great significance for diagnosis and differential diagnosis.

Diagnosis and differentiation of nervous system genetic diseases

diagnosis

The diagnosis of nervous system genetic diseases depends first on medical history, symptoms, signs and routine auxiliary examinations. Pedigree analysis is an important basis for the diagnosis of genetic diseases, but it is not an absolute basis. As long as there are typical clinical symptoms of genetic diseases, signs, even if there is no family history. Can still make a diagnosis, do a detailed neurological examination to make a diagnosis of the involvement of the nervous system, while paying attention to body examination, to help the diagnosis of hereditary diseases, genetic special diagnostic methods, such as pedigree analysis, chromosome examination, DNA and Gene product analysis and the like can provide important evidence for diagnosis and become the key to diagnosis.

The clinical diagnostic steps are:

1. Collect clinical data: including age of onset, gender, unique symptoms and signs, such as KF ring, fundus cherry erythema and skin milk coffee spots (neurofibromatosis).

2. Genealogical analysis: Determine whether it is a genetic disease, and distinguish it into a single gene, multi-gene and mitochondrial genetic disease, and presume whether it is a dynamic mutation disease based on the presence or absence of hereditary prevalence.

3. Routine auxiliary examination: including biochemistry, electrophysiology, imaging and pathology, which is meaningful for diagnosis and differential diagnosis. Some tests have definite diagnostic value for specific neurological diseases, such as serum of dystrophic muscular dystrophy. Increased creatine kinase, decreased serum copper and ceruloplasmin (CP) levels in hepatolenticular degeneration, increased urinary copper excretion, EEG and EMG features of hereditary myoclonic epilepsy, tuberous sclerosis, Spinal cerebellar ataxia and head MRI examination of the cerebral atrophy of the pons, and nerve biopsy of the sacral muscular atrophy.

4. Detection of genetic material and gene products: including chromosome number and structure, DNA analysis and gene product detection, etc., can diagnose and predict diseases at the level of gene expression. Commonly used detection methods are:

(1) Chromosome examination: check for abnormal chromosome number and structural aberrations, such as more or less than 23 pairs of chromosomes, resulting in deletion, inversion, duplication and translocation after chromosome breakage, mainly to examine children and parents of Down syndrome Patients with mental retardation and abnormal body condition, women who have had multiple abortions and their husbands, have had parents of congenital malformations.

(2) Gene diagnosis: mainly used for single-gene genetic diseases, such as detection of pseudo-hypertrophic muscular dystrophy, familial amyotrophic lateral sclerosis and other gene mutations and linkage analysis, mainly using Southern hybridization, polymerase chain reaction (PCR) Method and restriction fragment length polymorphism analysis (RFLP), etc., can directly detect DNA deletions, duplications and point mutations, and whether or not they have pathogenic genes. The subjects to be diagnosed include symptomatic patients, patients before symptoms, and hidden. Sex genetic disease carriers and high-risk fetuses (prenatal diagnosis).

(3) Detection of gene products: mainly using immunological techniques for protein analysis of genetic diseases of known gene products, such as muscle biopsy in patients with pseudohypertrophic dystrophy, and determination of dystrophin content in myocyte membrane by immunoassay Because genetic defects are caused by abnormal protein products, they can be diagnosed without relying on genetic diagnosis.

Differential diagnosis

1. Determine whether it is a genetic disease and distinguish it into a single gene, multiple genes and mitochondrial genetic diseases.

2. Detection of genetic material and gene products.

The material in this site is intended to be of general informational use and is not intended to constitute medical advice, probable diagnosis, or recommended treatments.