The condition is caused by a dominant gene (see genetic disorders) but often arises as a new mutation.
The long bones of the arms and legs are affected mainly.
The cartilage that links each bone to its epiphysis (the growing area at its tip) is converted to bone too early, preventing further limb growth.
Those affected have short limbs, a welldeveloped trunk, and a head of normal size except for a protruding forehead.
Dominant genes A dominant characteristic is an e?ect which is produced whenever a gene or gene defect is present. If a disease is due to a dominant gene, those affected are heterozygous – that is, they only carry a fault in the gene on one of the pair of chromosomes concerned. A?ected people married to normal individuals transmit the gene directly to one-half of the children, although this is a random event just like tossing a coin. HUNTINGTON’S CHOREA is due to the inheritance of a dominant gene, as is neuro?bromatosis (see VON RECKLINGHAUSEN’S DISEASE) and familial adenomatous POLYPOSIS of the COLON. ACHONDROPLASIA is an example of a disorder in which there is a high frequency of a new dominant mutation, for the majority of affected people have normal parents and siblings. However, the chances of the children of a parent with the condition being affected are one in two, as with any other dominant characteristic. Other diseases inherited as dominant characteristics include spherocytosis, haemorrhagic telangiectasia and adult polycystic kidney disease.
Recessive genes If a disease is due to a recessive gene, those affected must have the faulty gene on both copies of the chromosome pair (i.e. be homozygous). The possession of a single recessive gene does not result in overt disease, and the bearer usually carries this potentially unfavourable gene without knowing it. If that person marries another carrier of the same recessive gene, there is a one-in-four chance that their children will receive the gene in a double dose, and so have the disease. If an individual sufferer from a recessive disease marries an apparently normal person who is a heterozygous carrier of the same gene, one-half of the children will be affected and the other half will be carriers of the disease. The commonest of such recessive conditions in Britain is CYSTIC FIBROSIS, which affects about one child in 2,000. Approximately 5 per cent of the population carry a faulty copy of the gene. Most of the inborn errors of metabolism, such as PHENYLKETONURIA, GALACTOSAEMIA and congenital adrenal hyperplasia (see ADRENOGENITAL SYNDROME), are due to recessive genes.
There are characteristics which may be incompletely recessive – that is, neither completely dominant nor completely recessive – and the heterozygotus person, who bears the gene in a single dose, may have a slight defect whilst the homozygotus, with a double dose of the gene, has a severe illness. The sickle-cell trait is a result of the sickle-cell gene in single dose, and sickle-cell ANAEMIA is the consequence of a double dose.
Sex-linked genes If a condition is sex-linked, affected males are homozygous for the mutated gene as they carry it on their single X chromosome. The X chromosome carries many genes, while the Y chromosome bears few genes, if any, other than those determining masculinity. The genes on the X chromosome of the male are thus not matched by corresponding genes on the Y chromosome, so that there is no chance of the Y chromosome neutralising any recessive trait on the X chromosome. A recessive gene can therefore produce disease, since it will not be suppressed by the normal gene of the homologous chromosome. The same recessive gene on the X chromosome of the female will be suppressed by the normal gene on the other X chromosome. Such sex-linked conditions include HAEMOPHILIA, CHRISTMAS DISEASE, DUCHENNE MUSCULAR
DYSTROPHY (see also MUSCLES, DISORDERS OF – Myopathy) and nephrogenic DIABETES INSIPIDUS.
If the mother of an affected child has another male relative affected, she is a heterozygote carrier; half her sons will have the disease and half her daughters will be carriers. The sister of a haemophiliac thus has a 50 per cent chance of being a carrier. An affected male cannot transmit the gene to his son because the X chromosome of the son must come from the mother; all his daughters, however, will be carriers as the X chromosome for the father must be transmitted to all his daughters. Hence sex-linked recessive characteristics cannot be passed from father to son. Sporadic cases may be the result of a new mutation, in which case the mother is not the carrier and is not likely to have further affected children. It is probable that one-third of haemophiliacs arise as a result of fresh mutations, and these patients will be the ?rst in the families to be affected. Sometimes the carrier of a sex-linked recessive gene can be identi?ed. The sex-linked variety of retinitis pigmentosa (see EYE, DISORDERS OF) can often be detected by ophthalmoscopic examination.
A few rare disorders are due to dominant genes carried on the X chromosome. An example of such a condition is familial hypophosphataemia with vitamin-D-resistant RICKETS.
Polygenic inheritance In many inherited conditions, the disease is due to the combined action of several genes; the genetic element is then called multi-factorial or polygenic. In this situation there would be an increased incidence of the disease in the families concerned, but it will not follow the Mendelian (see MENDELISM; GENETIC CODE) ratio. The greater the number of independent genes involved in determining a certain disease, the more complicated will be the pattern of inheritance. Furthermore, many inherited disorders are the result of a combination of genetic and environmental in?uences. DIABETES MELLITUS is the most familiar of such multi-factorial inheritance. The predisposition to develop diabetes is an inherited characteristic, although the gene is not always able to express itself: this is called incomplete penetrance. Whether or not the individual with a genetic predisposition towards the disease actually develops diabetes will also depend on environmental factors. Diabetes is more common in the relatives of diabetic patients, and even more so amongst identical twins. Non-genetic factors which are important in precipitating overt disease are obesity, excessive intake of carbohydrate foods, and pregnancy.
SCHIZOPHRENIA is another example of the combined effects of genetic and environmental in?uences in precipitating disease. The risk of schizophrenia in a child, one of whose parents has the disease, is one in ten, but this ?gure is modi?ed by the early environment of the child.... genetic disorders
Ultrasound is replacing ISOTOPE scanning in many situations, and also RADIOGRAPHY. Ultrasound of the liver can separate medical from surgical JAUNDICE in approximately 97 per cent of patients; it is very accurate in detecting and de?ning cystic lesions of the liver, but is less accurate with solid lesions – and yet will detect 85 per cent of secondary deposits (this is less than COMPUTED TOMOGRAPHY [CT] scanning). It is very accurate in detecting gall-stones (see GALL-BLADDER, DISEASES OF) and more accurate than the oral cholecystogram. It is useful as a screening test for pancreatic disease and can di?erentiate carcinoma of the pancreas from chronic pancreatitis with 85 per cent accuracy.
Ultrasound is the ?rst investigation indicated in patients presenting with renal failure, as it can quickly determine the size and shape of the kidney and whether there is any obstruction to the URETER. It is very sensitive to the presence of dilatation of the renal tract and will detect space-occupying lesions, di?erentiating cysts and tumours. It can detect also obstruction of the ureter due to renal stones by showing dilatations of the collecting system and the presence of the calculus. Adrenal (see ADRENAL GLANDS) tumours can be demonstrated by ultrasound, although it is less accurate than CT scanning.
The procedure is now the ?rst test for suspected aortic ANEURYSM and it can also show the presence of clot and delineate the true and false lumen. It is good at demonstrating subphrenic and subhepatic abscesses (see ABSCESS) and will show most intra-abdominal abscesses; CT scanning is however better for the retroperitoneal region. It has a major application in thyroid nodules as it can di?erentiate cystic from solid lesions and show the multiple lesions characteristic of the nodular GOITRE (see also THYROID GLAND, DISEASES OF). It cannot differentiate between a follicular adenoma and a carcinoma, as both these tumours are solid; nor can it demonstrate normal parathyroid glands. However, it can identify adenomas provided that they are more than 6 mm in diameter. Finally, ultrasound can di?erentiate masses in the SCROTUM into testicular and appendicular, and it can demonstrate impalpable testicular tumours. This is important as 15 per cent of testicular tumours metastasise whilst they are still impalpable.
Ultrasonic waves are one of the constituents in the shock treatment of certain types of gallstones and CALCULI in the urinary tract (see LITHOTRIPSY). They are also being used in the treatment of MENIÈRE’S DISEASE and of bruises and strains. In this ?eld of physiotherapy, ultrasonic therapy is proving of particular value in the treatment of acute injuries of soft tissue. If in such cases it is used immediately after the injury, or as soon as possible thereafter, prompt recovery is facilitated. For this reason it is being widely used in the treatment of sports injuries (see also SPORTS MEDICINE). The sound waves stimulate the healing process in damaged tissue.
Doppler ultrasound is a technique which shows the presence of vascular disease in the carotid and peripheral vessels, as it can detect the reduced blood ?ow through narrowed vessels.
Ultrasound in obstetrics Ultrasound has particular applications in obstetrics. A fetus can be seen with ultrasound from the seventh week of pregnancy, and the fetal heart can be demonstrated at this stage. Multiple pregnancy can also be diagnosed at this time by the demonstration of more than one gestation sac containing a viable fetus. A routine obstetric scan is usually performed between the 16th and 18th week of pregnancy when the fetus is easily demonstrated and most photogenic. The fetus can be measured to assess the gestational age, and the anatomy can also be checked. Intra-uterine growth retardation is much more reliably diagnosed by ultrasound than by clinical assessment. The site of the placenta can also be recorded and multiple pregnancies will be diagnosed at this stage. Fetal movements and even the heartbeat can be seen. A second scan is often done between the 32nd and 34th weeks to assess the position, size and growth rate of the baby. The resolution of equipment now available enables pre-natal diagnosis of a wide range of structural abnormalities to be diagnosed. SPINA BIFIDA, HYDROCEPHALUS and ANENCEPHALY are probably the most important, but other anomalies such as multicystic kidney, achondroplasia and certain congenital cardiac anomalies can also be identi?ed. Fetal gender can be determined from 20 weeks of gestation. Ultrasound is also useful as guidance for AMNIOCENTESIS.
In gynaecology, POLYCYSTIC OVARY SYNDROME can readily be detected as well as FIBROID and ovarian cysts. Ultrasound can monitor follicular growth when patients are being treated with infertility drugs. It is also useful in detecting ECTOPIC PREGNANCY. (See also PREGNANCY AND LABOUR.)... ultrasound
Causes include chromosomal abnormalities, genetic defects, drugs taken during pregnancy, exposure to radiation, and infections. In some cases, the cause of a defect is unknown. Defects that are due to chromosomal abnormalities include Down’s syndrome. Some defects, such as achondroplasia and albinism, are usually inherited from 1 or both parents (see gene; genetic disorders). Certain drugs and chemicals (called teratogens) can damage the fetus if the mother takes or is exposed to them during early pregnancy. Teratogenic drugs include thalidomide (now rarely prescribed) and isotretinoin, which is used in the treatment of severe acne. Alcohol can affect the development of the brain and face (see fetal alcohol syndrome).
Irradiation of the embryo in early pregnancy can cause abnormalities. Very small doses of radiation increase the child’s risk of developing leukaemia later in life (see radiation hazards).
Certain illnesses, such as rubella (German measles) and toxoplasmosis, can cause birth defects if they are contracted during pregnancy.
Brain and spinal cord abnormalities, such as spina bifida and hydrocephalus, and congenital heart disorders (see heart disease, congenital) result from interference with the development of particular groups of cells. Other common defects include cleft lip and palate.
Ultrasound scanning and blood tests during pregnancy can identify women at high risk of having a baby with a birth defect. Further tests such as chorionic villus sampling, amniocentesis, or fetoscopy may then be carried out.... birth defects
Genes are organized into chromosomes in the cell nucleus. Genes controlling most characteristics come in pairs, 1 from the father, the other from the mother. Everyone has 22 pairs of chromosomes (called autosomes) bearing these paired genes, in addition to 2 sex chromosomes. Females have 2 X chromosomes; males have an X and a Y chromosome.
Most physical characteristics, many disorders, and some mental abilitiesand aspects of personality are inherited. The inheritance of normal traits and disorders can be divided into those controlled by a single pair of genes on the autosomal chromosomes (unifactorial inheritance, such as eye colour); those controlled by genes on the sex chromosomes (sex-linked inheritance, such as haemophilia); and those controlled by the combination of many genes (multifactorial inheritance, such as height).
Either of the pair of genes controlling a trait may take any of several forms, known as alleles. For example, the genes controlling eye colour exist as 2 main alleles, coding for blue and brown eye colour. The brown allele is dominant over blue in that it “masks” the blue allele, which is called recessive to the brown allele. Only 1 of the pair of genes controlling a trait is passed to a child from each parent. For example, someone with the brown/blue combination for eye colour has a 50 per cent chance of passing on the blue gene, and a 50 per cent chance of passing on the brown gene, to any child. This factor is combined with the gene coming from the other parent, according to dominant or recessive relationships, to determine the child’s eye colour. Certain genetic disorders are also inherited in a unifactorial manner (for example, cystic fibrosis and achondroplasia).
Sex-linked inheritance depends on the 2 sex chromosomes, X and Y. The most obvious example is gender. Male gender is determined by genes on the Y chromosome, which is present only in males. Any faults in a male’s genes on the X chromosome tend to be expressed outwardly because such a fault cannot be masked by the presence of a normal gene on a 2nd X chromosome (as it can in females). Faults in the genes of the X chromosome include those responsible for colour vision deficiency, haemophilia, and other sex-linked inherited disorders, which almost exclusively affect males.
Multifactorial inheritance, along with the effects of environment, may play a part in causing certain disorders, such as diabetes mellitus and neural tube defects.... inheritance
A mutation results from a fault in the replication of when a cell divides. A daughter cell inherits some faulty , and the fault is copied each time the new cell divides, creating a cell population containing the altered.
Some mutations occur by chance. Any agent that makes mutations more likely is called a mutagen.
There are several types of mutation. Point mutations affect only one gene and may lead to the production of defective enzymes or other proteins. In other mutations, chromosomes (or parts of them) are deleted, added, or rearranged. This type may produce greater disruptive effects than point mutations.
If a mutated cell is a somatic (body) cell, it can, at worst, multiply to form a group of abnormal cells. These cells often die out, are destroyed by the body’s immune system, or have only a minor effect. Sometimes, however, they may become a tumour.
A mutation in a germ cell (immature egg or sperm) may be passed on to a child, who then has the mutation in all of his or her cells.
This may cause an obvious birth defect or an abnormality in body chemistry.
The mutation may also be passed on to the child’s descendants.
Genetic disorders (such as haemophilia and achondroplasia) stem from point mutations that occurred in the germ cell of a parent, grandparent, or more distant ancestor.
Chromosomal abnormalities (such as Down’s syndrome) are generally due to mutations in the formation of parental eggs or sperm.... mutation
An affected child’s growth rate is monitored by regular measurement of height.
X-rays and blood tests may help identify an underlying cause, which will then be treated.
Growth hormone is given for hormone deficiency, and also to treat short stature due to disorders such as Turner’s syndrome.
(See also growth, childhood.)... short stature
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