Chromosomal abnormalities

Introduction to chromosomal abnormalities A chromosome is a basic substance that constitutes a nucleus and is a carrier of a gene. Chromosomal abnormalities are also called chromosomedysgenesis. American Chinese Jiang Youxing (1956) found 46 human chromosomes, and Caspersson et al. (1970) first published human chromosomes. Since the International Chromosome Nomenclature Conference in Paris in 1971, more than 3,000 species of abnormal chromosomes and structural aberrations have been found. More than 100 species of chromosomal syndrome have been identified. Mental retardation and growth retardation are common features of chromosomal disorders. basic knowledge The proportion of illness: 0.03% Susceptible people: no special people Mode of infection: non-infectious Complications: ataxia, autosomal dominant cerebellar ataxia in children

Chromosome abnormality

Physical factors (25%):

The radiation environment in which humans are exposed, including natural and artificial radiation. Natural radiation includes cosmic radiation, radiation from the earth and radiation from radioactive substances in the human body, and artificial radiation includes radiation and occupational exposure.

Chemical factors (15%):

People are exposed to a variety of chemicals in their daily lives, some are natural products, some are synthetic, they enter the human body through diet, breathing or skin contact, causing chromosome aberrations.

Biological factors (10%):

When cells in culture are treated with a virus, they often cause various types of chromosomal aberrations, including breakage, pulverization, and interchange.

Mother age effect (5%):

When the fetus is 6-7 months old, all the oogonia cells have developed into primary oocytes, and enter the nuclear network from the first stage of meiosis. At this time, the chromosomes are loosely stretched again, just like the anterior nucleus. It is maintained until ovulation before puberty. With the increase of motherhood, under the influence of many factors inside and outside the mother, many aging changes may occur in the egg, affecting the interrelationship between the chromosomes in the mature division and the action in the late stage of division, which leads to the non-segregation between chromosomes.

Genetic factors (5%):

Chromosomal abnormalities can often manifest as familial tendencies, suggesting that chromosomal aberrations are genetically related.

Autoimmune disease (5%):

Autoimmune diseases appear to play a role in chromosome segregation, such as a strong correlation between increased thyroid primary autoimmune antibodies and familial chromosomal abnormalities.

Chromosomal abnormality prevention

Chromosome hypoplasia is difficult to treat, and the efficacy is not satisfactory. Prevention is more important. Preventive measures include genetic counseling, chromosome detection, prenatal diagnosis and selective abortion to prevent the birth of children.

Chromosomal abnormalities Complications, ataxia, autosomal dominant cerebellar ataxia

There are many kinds of chromosomal abnormalities, the clinical symptoms and signs are complex and diverse, and the performances outside the nervous system are different. For details, please refer to the clinical manifestations of each disease.

Symptoms of chromosomal abnormalities Common symptoms The incidence of tongue-like dementia double palmar line... Small finger single pleated cortical amnesia Ear position Low double breast spacing widened Upper lip thinning earlobe Small super male Attention deficit

Down's syndrome is also called trisome 21 syndrome and congenital stupidity. This is the most common chromosomal disorder in humans. The neonatal morbidity rate is 1/700 to 1/600, which is mental development. The most common cause of delay is 10% of cases of severe mental retardation.

Seguin (1846) first reported the clinical manifestations of the disease, Langdone Down (1866) made a comprehensive description of the disease, British scholars later called the disease Down syndrome, Lejeune et al (1959) proved that the disease by chromosome 21 The triploid caused and advocated the use of the name of the trisomy 21, which was recognized at the 1970 Denver meeting.

In addition to Down syndrome, other chromosomal dysplasia includes Patau syndrome, trisomy 18, Criduchat syndrome, fragile X syndrome, ring chromosome syndrome, Klinefelter syndrome, Turner syndrome, Colpocephaly syndrome, Williams syndrome, Prader-Willi and Angelman syndrome, Rett syndrome, and the like.

1. The clinical features of Down's syndrome are as follows

(1) Children with Down syndrome have certain pathological features at birth, and the symptoms become obvious with age. The craniofacial appearance is round, low nose, and the maxillary dysplasia can cause the face to be flat and the mouth to be slightly tabular. Tongue hypertrophy has deep cracks, often extending out of the mouth, so it is called tongue-like dementia, the inner suede often covers part of the internal hemorrhoids, the patient's cleft palate can be slightly upward, inclined outward, forming a Mongolian-like face, the ear position is low, showing Oval, small earlobe, visible iris gray-white spots, that is, Brushfield's spots, the door is obvious, closed late.

(2) The average length of the child born at birth is slightly shorter than that of the normal newborn. The difference is more obvious with age. The height of the adult patient is rarely higher than that of the normal 10-year-old child. The hand is short and thick, the palm is wide, and there is only one horizontal pattern. It is characterized by horizontal palm pleats (through the hand) and other characteristic skin lines, such as the short and inward flexion of the little finger, showing a single pleat (ie, the fifth finger is two), the muscle tension is reduced, most children 3 to 4 The age is still not walking, infants and young children Moro reaction is slow or unable to lead, eating difficulties, children with significant mental and mental development abnormalities, IQ IQ is 20 to 70, an average of 40 to 50, mostly below the Gaussian curve, 90% of patients When I was 5 years old, I would speak. Most of the performances were quiet, docile, easy to approach, and the life expectancy was 40 years old.

(3) Some patients can see cataract, congenital heart disease or heart disease secondary to cerebral embolism and brain abscess, gastrointestinal abnormalities such as duodenal stenosis, atlantoaxial joint instability, strenuous exercise can lead to spinal cord compression, young and middle-aged The incidence of granulocyte and lymphocytic leukemia is higher than that of ordinary people. Alzheimer's disease is almost common in patients in their 40s, with inattention, low speech, poor spatial orientation, memory and judgment, and seizures.

2. Clinical features of other chromosomal hypoplasia

(1) Trisomy 13 syndrome: Trisomy 13 syndrome is also known as Patau syndrome. The incidence of live births is 1 in 2000, more women than men, and the average age of mothers is 31 years.

Children with small head, forehead bulging, small eyes, iris defect, corneal opacity, olfactory loss, low ear position, cleft lip and palate, capillary hemangioma, multi-finger (toe) deformity, finger bending, heel kyphosis, right The heart, umbilical hernia, hearing loss, hypertonia and severe mental retardation, etc., mostly died in early childhood.

(2) Trisomy 18 syndrome: Trisomy 18 syndrome has a live birth rate of 1 in 4000, which is more common in women. The average maternal age of the patient is 34 years.

The child showed growth retardation, ptosis, eyelid deformity, low ear position, small mouth, small squat, skin spots, indicating that the finger exceeded the middle finger and clenched the fist, and pointed (toe) deformity, cradle foot (rocker-bottom Feet), large and short toes, ventricular septal defect, umbilical hernia or inguinal hernia, short sternum, small pelvis and increased muscle tone, occasional seizures, severe mental retardation, etc., often died in early infants.

(3) Meow Syndrome: Criduchat syndrome is caused by the short arm of chromosome 5.

A few weeks to months after birth, the kittens are crying, severe mental retardation, excessive eye spacing, epicanthal folds, short head deformities, full moon face, anti-congenital cleft palate Distorted, small jaw, decreased muscle tone and strabismus.

(4) Fragile X syndrome: Fragile-X syndrome is a fragile site with abnormal X chromosome, and Martin and Bell (1943) first reported an X-linked hereditary mental retardation. Lubs (1969) found that the family had a vulnerable site at the end of the long arm of the X chromosome, which confirmed that the site had unstable genetic CGG repeats, 43-200 normal human repeats, more than 200 patients, and redundant sequences. The RNA-binding protein gene (FMR1) can be inactivated, affecting protein expression and causing symptoms.

This syndrome is the most common cause of hereditary mental retardation. It is estimated that 1/1500 male infants can be affected. Because women have two X chromosomes, the involvement rate is 50%, to a lesser extent. It is estimated that more than 10% The male hereditary mental retardation has abnormal fragile X chromosomes, sometimes females are involved, but the condition is mild. Rousseau et al. describe a simple and sensitive experimental method using DNA analysis techniques to treat children during pregnancy and after birth. Diagnosis, because the length of the repeated triplet codon is related to the degree of mental retardation, the fragile X chromosome variant is occasionally seen in men with normal intelligence, and the patient's grandson may be sick.

The child presented with a typical triad: mental retardation, special looks (such as long face, large ears, wide forehead, large nose and wide sacral bow) and large testicles, etc., the child's height is normal, the large testicles generally appear in 8 9 years old, 85% of children may have mental retardation, mostly moderate, often manifested as behavioral abnormalities, mostly before puberty, common self-injury behavior, hyperactive and impulsive behavior, and stereotypes and weird movements. ADHD, more words, autistic patients may have a unique clap action, 9% to 45% of children may have seizures, DNA test can confirm the diagnosis.

(5) Cyclic chromosome: The ring chromosome is characterized by mental retardation and various body malformations.

(6) Klinefelter syndrome: Klinefelter's syndrome has a chromosome phenotype of XXY. It is only found in males. The patient is tall and looks like a testis-free appearance. The shoulders are wide, hair and body hair are sparse, and the tone is high. Chemotherapy and small testicles, muscle tension is reduced, usually accompanied by mental retardation, but to a lesser extent, the disease is complicated by mental illness, asthma and endocrine dysfunction, such as high incidence of diabetes.

(7) Turner syndrome: The chromosome of Turner syndrome is XO (45X) type, which is only found in women. The patient is short in stature, has a squat in the neck, has a triangular face, a small chin, a wide nipple pitch, and a finger (toe) bend. Elbow valgus and nail development are incomplete, may be too far from the facial features, internal suture folds, sexual growth retardation and moderate mental retardation.

(8) Colpocephaly syndrome: Colpocephaly syndrome is a rare brain malformation, many causes, some are due to chromosome III triploid chimerism, often misdiagnosed as multiple types of ventricular dilatation with brain development abnormalities, patients showed Mental retardation, paralysis and seizures, optic nerve hypoplasia leading to visual abnormalities, lateral ventricle occipital angles significantly expanded, cortical gray margin overlap thickening, white matter thinning.

(9) Williams syndrome: Williams syndrome is a small deletion in the region of the 7th chromosome-encoded elastin gene, the neonatal morbidity rate is 1/2 million, first described by Williams, it is not clear whether the brain has characteristic lesions, A 35-year-old patient biopsy has been reported in the literature, and no other brain abnormalities have been found except for Alzheimer's disease.

The patient has mild mental retardation, premature music ability, extraordinary musical ability, and amazing memory for the score. Listen to the symphony and remember it all; some patients can write large paragraphs of description, wording and content correct, but not It will depict simple things, children with developmental delays, unique appearance, such as wide mouth, almond eyes, nostrils upturned, small and pointed ears, called "small goblin-like" appearance; gentle personality, sensitive to auditory stimuli, speech communication ability Later, there may be defects in visual space and exercise capacity, and there may be cardiovascular malformations such as aortic stenosis.

(10) Prader-Willi and Angelman syndrome: The incidence of newborns in Prader-Willi syndrome is 1/2 million, and the prevalence of both sexes is equal. It is caused by the deletion of chromosome 11 q11-q13, and cytogenetic analysis and DNA can be used. A combination of analysis methods was used to detect this chromosomal defect, and 70% of cases were caused by a non-hereditary deletion of the paternal X chromosome.

The child showed a decrease in muscle tone, paralysis of the tendon, short stature, deformed face, obvious genital developmental disorder, and joint flexion at birth. After 1 year, there was obvious mental retardation or hypomentia, due to excessive eating. Obese.

Angelman syndrome is caused by the deletion of chromosome 11 q11-q13. Unlike Prader-Willi syndrome, this disease is caused by maternal monogenic genetic defects. The child presents with severe mental retardation, microcephaly and early epilepsy. Attacks, anti-epileptic drugs are not sensitive, there are rare marionette-like postures and movement disorders, often want to laugh or smile, the old name "happy puppet syndrome."

(11) Rett syndrome: Rett syndrome was first described by Rett (1966). The cause is unknown, and X chromosome is dominantly inherited. Some people speculate that the metabolic mechanism is involved in the disease, and the incidence rate is 1/15,000 to 1/10,000. Seen in women, can survive for many years, males are homozygous, often can not survive.

If it is a female, it develops normally at the time of birth and early in life. At 6 to 15 months, the hand's voluntary movement is lost, the communication ability is lost, the body is retarded, and the head is enlarged. The typical symptoms are hand movement and sputum. Stereotyped exercise, gradual emergence of ataxia and lower limb rigidity, and ultimately loss of walking and language ability, may occur episodes of excessive ventilation and breath holding, normal respiratory rhythm and seizures.

The disease can be misdiagnosed as Kanner's loneliness syndrome. The difference between the two is the loss of exercise ability in the early stage of Rett syndrome, the lack of attention and the disappearance of joint movement of the eyeball.

Chromosome abnormality examination

1. The serological examination of Down syndrome showed a decrease in serotonin, an increase in alkaline phosphatase in leukocytes, an increase in erythrocyte diphosphate glucose, and a 50% increase in superoxide dismutase, but it was not associated with abnormal development and mental retardation.

2. About one-third of children with Down syndrome have elevated serum alpha-fetoprotein content, increased serum chorionic gonadotropin content, and decreased estriol content during pregnancy 4 to 6 months, which may indicate fetal Down syndrome. Pregnant women with positive results should undergo amniocentesis and test the amniocytes or chromosomes of the patients.

Maternal amniocentesis can detect chromosomal abnormalities in amniotic fluid cells, and early screening of children with Down syndrome and other chromosomal hypoplasia.

Chromosome examination can detect the amniocytes or chromosomes of patients by fluorescent in situ hybridization technique. For example, Down syndrome can find chromosome 21 as triploid.

Diagnosis of chromosomal abnormalities

diagnosis

Mainly based on the characteristic symptoms, signs and chromosome examination of the child, the detection of chromosomal abnormalities can be diagnosed.

Differential diagnosis

The clinical manifestations of Down syndrome caused by trisomy 21 and chromosomal translocation are difficult to distinguish, and there is a strong correlation between them. It is related to the age of the mother. The mothers of the 21 trisomy usually have a large reproductive age. However, the incidence of chromosomal translocation is lower in older or younger pregnant women. The Down syndrome subtypes are chimeric, some cell chromosomes are normal, some are abnormal, chimeric patients may have typical manifestations of Down syndrome, and some patients have normal intelligence. .

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