A myopathy may be an inherited disorder, such as muscular dystrophy; it may also be caused by chemical poisoning, a chronic disorder of the immune system, or a metabolic disorder.
Many modi?cations have been devised of the basic steroid molecule in an attempt to keep useful therapeutic effects and minimise unwanted side-effects. The main corticosteroid hormones currently available are CORTISONE, HYDROCORTISONE, PREDNISONE, PREDNISOLONE, methyl prednisolone, triamcinolone, dexamethasone, betamethasone, paramethasone and de?azacort.
They are used clinically in three quite distinct circumstances. First they constitute replacement therapy where a patient is unable to produce their own steroids – for example, in adrenocortical insu?ciency or hypopituitarism. In this situation the dose is physiological – namely, the equivalent of the normal adrenal output under similar circumstances – and is not associated with any side-effects. Secondly, steroids are used to depress activity of the adrenal cortex in conditions where this is abnormally high or where the adrenal cortex is producing abnormal hormones, as occurs in some hirsute women.
The third application for corticosteroids is in suppressing the manifestations of disease in a wide variety of in?ammatory and allergic conditions, and in reducing antibody production in a number of AUTOIMMUNE DISORDERS. The in?ammatory reaction is normally part of the body’s defence mechanism and is to be encouraged rather than inhibited. However, in the case of those diseases in which the body’s reaction is disproportionate to the o?ending agent, such that it causes unpleasant symptoms or frank illness, the steroid hormones can inhibit this undesirable response. Although the underlying condition is not cured as a result, it may resolve spontaneously. When corticosteroids are used for their anti-in?ammatory properties, the dose is pharmacological; that is, higher – often much higher – than the normal physiological requirement. Indeed, the necessary dose may exceed the normal maximum output of the healthy adrenal gland, which is about 250–300 mg cortisol per day. When doses of this order are used there are inevitable risks and side-effects: a drug-induced CUSHING’S SYNDROME will result.
Corticosteroid treatment of short duration, as in angioneurotic OEDEMA of the larynx or other allergic crises, may at the same time be life-saving and without signi?cant risk (see URTICARIA). Prolonged therapy of such connective-tissue disorders, such as POLYARTERITIS NODOSA with its attendant hazards, is generally accepted because there are no other agents of therapeutic value. Similarly the absence of alternative medical treatment for such conditions as autoimmune haemolytic ANAEMIA establishes steroid therapy as the treatment of choice which few would dispute. The use of steroids in such chronic conditions as RHEUMATOID ARTHRITIS, ASTHMA and DERMATITIS needs careful assessment and monitoring.
Although there is a risk of ill-effects, these should be set against the misery and danger of unrelieved chronic asthma or the incapacity, frustration and psychological trauma of rheumatoid arthritis. Patients should carry cards giving details of their dosage and possible complications.
The incidence and severity of side-effects are related to the dose and duration of treatment. Prolonged daily treatment with 15 mg of prednisolone, or more, will cause hypercortisonism; less than 10 mg prednisolone a day may be tolerated by most patients inde?nitely. Inhaled steroids rarely produce any ill-e?ect apart from a propensity to oral thrush (CANDIDA infection) unless given in excessive doses.
General side-effects may include weight gain, fat distribution of the cushingoid type, ACNE and HIRSUTISM, AMENORRHOEA, striae and increased bruising tendency. The more serious complications which can occur during long-term treatment include HYPERTENSION, oedema, DIABETES MELLITUS, psychosis, infection, DYSPEPSIA and peptic ulceration, gastrointestinal haemorrhage, adrenal suppression, osteoporosis (see BONE, DISORDERS OF), myopathy (see MUSCLES, DISORDERS OF), sodium retention and potassium depletion.... corticosteroids
The disease usually appears within the ?rst three years of life, beginning in the pelvic girdle and lower limbs and later spreading to the shoulder girdle. The calf muscles become bulky (pseudohypertrophy). The weakness gives rise to a characteristic waddling gait and, when rising from the supine position, the child rolls on to his face and then uses his arms to push himself up. Death usually occurs by the middle of the second decade from respiratory infections. Prenatal screening of female carriers using gene probes is increasingly available. (See DYSTROPHY; MUSCLES, DISORDERS OF – Myopathy.)... duchenne muscular dystrophy
Arrhythmias An abnormal rate or rhythm of the heartbeat. The reason is a disturbance in the electrical impulses within the heart. Sometimes a person may have an occasional irregular heartbeat: this is called an ECTOPIC beat (or an extrasystole) and does not necessarily mean that an abnormality exists. There are two main types of arrhythmia: bradycardias, where the rate is slow – fewer than 60 beats a minute and sometimes so slow and unpredictable (heartblock) as to cause blackouts or heart failure; and tachycardia, where the rate is fast – more than 100 beats a minute. A common cause of arrhythmia is coronary artery disease, when vessels carrying blood to the heart are narrowed by fatty deposits (ATHEROMA), thus reducing the blood supply and damaging the heart tissue. This condition often causes myocardial infarction after which arrhythmias are quite common and may need correcting by DEFIBRILLATION (application of a short electric shock to the heart). Some tachycardias result from a defect in the electrical conduction system of the heart that is commonly congenital. Various drugs can be used to treat arrhythmias (see ANTIARRHYTHMIC DRUGS). If attacks constantly recur, the arrhythmia may be corrected by electrical removal of dead or diseased tissue that is the cause of the disorder. Heartblock is most e?ectively treated with an arti?cial CARDIAC PACEMAKER, a battery-activated control unit implanted in the chest.
Cardiomyopathy Any disease of the heart muscle that results in weakening of its contractions. The consequence is a fall in the e?ciency of the circulation of blood through the lungs and remainder of the body structures. The myopathy may be due to infection, disordered metabolism, nutritional excess or de?ciency, toxic agents, autoimmune processes, degeneration, or inheritance. Often, however, the cause is not identi?ed. Cardiomyopathies are less common than other types of heart diseases, and the incidence of di?erent types of myopathy (see below) is not known because patients or doctors are sometimes unaware of the presence of the condition.
The three recognised groups of cardiomyopathies are hypertrophic, dilated and restrictive.
•Hypertrophic myopathy, a familial condition, is characterised by great enlargement of the muscle of the heart ventricles. This reduces the muscle’s e?ciency, the ventricles fail to relax properly and do not ?ll suf?ciently during DIASTOLE.
In the dilated type of cardiomyopathy, both ventricles overdilate, impairing the e?ciency of contraction and causing congestion of the lungs.
In the restrictive variety, proper ?lling of the ventricles does not occur because the muscle walls are less elastic than normal. The result is raised pressure in the two atria (upper cavities) of the heart: these dilate and develop FIBRILLATION. Diagnosis can be di?cult and treatment is symptomatic, with a poor prognosis. In suitable patients, heart TRANSPLANTATION may be considered. Disorders of the heart muscle may also be
caused by poisoning – for example, heavy consumption of alcohol. Symptoms include tiredness, palpitations (quicker and sometimes irregular heartbeat), chest pain, di?culty in breathing, and swelling of the legs and hands due to accumulation of ?uid (OEDEMA). The heart is enlarged (as shown on chest X-ray) and ECHOCARDIOGRAPHY shows thickening of the heart muscle. A BIOPSY of heart muscle will show abnormalities in the cells of the heart muscle.
Where the cause of cardiomyopathy is unknown, as is the case with most patients, treatment is symptomatic using DIURETICS to control heart failure and drugs such as DIGOXIN to return the heart rhythm to normal. Patients should stop drinking alcohol. If, as often happens, the patient’s condition slowly deteriorates, heart transplantation should be considered.
Congenital heart disease accounts for 1–2 per cent of all cases of organic heart disease. It may be genetically determined and so inherited; present at birth for no obvious reason; or, in rare cases, related to RUBELLA in the mother. The most common forms are holes in the heart (atrial septal defect, ventricular septal defect – see SEPTAL DEFECT), a patent DUCTUS ARTERIOSUS, and COARCTATION OF THE AORTA. Many complex forms also exist and can be diagnosed in the womb by fetal echocardiography which can lead to elective termination of pregnancy. Surgery to correct many of these abnormalities is feasible, even for the most severe abnormalities, but may only be palliative giving rise to major diffculties of management as the children become older. Heart transplantation is now increasingly employed for the uncorrectable lesions.
Coronary artery disease Also known as ischaemic heart disease, this is a common cause of symptoms and death in the adult population. It may present for the ?rst time as sudden death, but more usually causes ANGINA PECTORIS, myocardial infarction (heart attack) or heart failure. It can also lead to a disturbance of heart rhythm. Factors associated with an increased risk of developing coronary artery disease include diabetes, cigarette smoking, high blood pressure, obesity, and a raised concentration of cholesterol in the blood. Older males are most affected.
Coronary thrombosis or acute myocardial infarction is the acute, dramatic manifestation of coronary-artery ischaemic heart disease – one of the major killing diseases of western civilisation. In 1999, ischaemic heart disease was responsible for about 115,000 deaths in England and Wales, compared with 153,000 deaths in 1988. In 1999 more than 55,600 people died of coronary thrombosis. The underlying cause is disease of the coronary arteries which carry the blood supply to the heart muscle (or myocardium). This results in narrowing of the arteries until ?nally they are unable to transport su?cient blood for the myocardium to function e?ciently. One of three things may happen. If the narrowing of the coronary arteries occurs gradually, then the individual concerned will develop either angina pectoris or signs of a failing heart: irregular rhythm, breathlessness, CYANOSIS and oedema.
If the narrowing occurs suddenly or leads to complete blockage (occlusion) of a major branch of one of the coronary arteries, then the victim collapses with acute pain and distress. This is the condition commonly referred to as a coronary thrombosis because it is usually due to the affected artery suddenly becoming completely blocked by THROMBOSIS. More correctly, it should be described as coronary occlusion, because the ?nal occluding factor need not necessarily be thrombosis.
Causes The precise cause is not known, but a wide range of factors play a part in inducing coronary artery disease. Heredity is an important factor. The condition is more common in men than in women; it is also more common in those in sedentary occupations than in those who lead a more physically active life, and more likely to occur in those with high blood pressure than in those with normal blood pressure (see HYPERTENSION). Obesity is a contributory factor. The disease is more common among smokers than non-smokers; it is also often associated with a high level of CHOLESTEROL in the blood, which in turn has been linked with an excessive consumption of animal, as opposed to vegetable, fats. In this connection the important factors seem to be the saturated fatty acids (low-density and very low-density lipoproteins [LDLs and VLDLs] – see CHOLESTEROL) of animal fats which would appear to be more likely to lead to a high level of cholesterol in the blood than the unsaturated fatty acids of vegetable fats. As more research on the subject is carried out, the arguments continue about the relative in?uence of the di?erent factors. (For advice on prevention of the disease, see APPENDIX 2: ADDRESSES: SOURCES OF INFORMATION, ADVICE, SUPPORT AND SELFHELP.)
Symptoms The presenting symptom is the sudden onset, often at rest, of acute, agonising pain in the front of the chest. This rapidly radiates all over the front of the chest and often down over the abdomen. The pain is frequently accompanied by nausea and vomiting, so that suspicion may be aroused of some acute abdominal condition such as biliary colic (see GALLBLADDER, DISEASES OF) or a perforated PEPTIC ULCER. The victim soon goes into SHOCK, with a pale, cold, sweating skin, rapid pulse and dif?culty in breathing. There is usually some rise in temperature.
Treatment is immediate relief of the pain by injections of diamorphine. Thrombolytic drugs should be given as soon as possible (‘rapid door to needle time’) and ARRHYTHMIA corrected. OXYGEN is essential and oral ASPIRIN is valuable. Treatment within the ?rst hour makes a great di?erence to recovery. Subsequent treatment includes the continued administration of drugs to relieve the pain; the administration of ANTIARRHYTHMIC DRUGS that may be necessary to deal with the heart failure that commonly develops, and the irregular action of the heart that quite often develops; and the continued administration of oxygen. Patients are usually admitted to coronary care units, where they receive constant supervision. Such units maintain an emergency, skilled, round-the-clock sta? of doctors and nurses, as well as all the necessary resuscitation facilities that may be required.
The outcome varies considerably. The ?rst (golden) hour is when the patient is at greatest risk of death: if he or she is treated, then there is a 50 per cent reduction in mortality compared with waiting until hospital admission. As each day passes the prognosis improves with a ?rst coronary thrombosis, provided that the patient does not have a high blood pressure and is not overweight. Following recovery, there should be a gradual return to work, care being taken to avoid any increase in weight, unnecessary stress and strain, and to observe moderation in all things. Smoking must stop. In uncomplicated cases patients get up and about as soon as possible, most being in hospital for a week to ten days and back at work in three months or sooner.
Valvular heart disease primarily affects the mitral and aortic valves which can become narrowed (stenosis) or leaking (incompetence). Pulmonary valve problems are usually congenital (stenosis) and the tricuspid valve is sometimes involved when rheumatic heart disease primarily affects the mitral or aortic valves. RHEUMATIC FEVER, usually in childhood, remains a common cause of chronic valvular heart disease causing stenosis, incompetence or both of the aortic and mitral valves, but each valve has other separate causes for malfunction.
Aortic valve disease is more common with increasing age. When the valve is narrowed, the heart hypertrophies and may later fail. Symptoms of angina or breathlessness are common and dizziness or blackouts (syncope) also occur. Replacing the valve is a very e?ective treatment, even with advancing age. Aortic stenosis may be caused by degeneration (senile calci?c), by the inheritance of two valvular leaflets instead of the usual three (bicuspid valve), or by rheumatic fever. Aortic incompetence again leads to hypertrophy, but dilatation is more common as blood leaks back into the ventricle. Breathlessness is the more common complaint. The causes are the same as stenosis but also include in?ammatory conditions such as SYPHILIS or ANKYLOSING SPONDYLITIS and other disorders of connective tissue. The valve may also leak if the aorta dilates, stretching the valve ring as with HYPERTENSION, aortic ANEURYSM and MARFAN’S SYNDROME – an inherited disorder of connective tissue that causes heart defects. Infection (endocarditis) can worsen acutely or chronically destroy the valve and sometimes lead to abnormal outgrowths on the valve (vegetations) which may break free and cause devastating damage such as a stroke or blocked circulation to the bowel or leg.
Mitral valve disease leading to stenosis is rheumatic in origin. Mitral incompetence may be rheumatic but in the absence of stenosis can be due to ISCHAEMIA, INFARCTION, in?ammation, infection and a congenital weakness (prolapse). The valve may also leak if stretched by a dilating ventricle (functional incompetence). Infection (endocarditis) may affect the valve in a similar way to aortic disease. Mitral symptoms are predominantly breathlessness which may lead to wheezing or waking at night breathless and needing to sit up or stand for relief. They are made worse when the heart rhythm changes (atrial ?brillation) which is frequent as the disease becomes more severe. This leads to a loss of e?ciency of up to 25 per cent and a predisposition to clot formation as blood stagnates rather than leaves the heart e?ciently. Mitral incompetence may remain mild and be of no trouble for many years, but infection must be guarded against (endocarditis prophylaxis).
Endocarditis is an infection of the heart which may acutely destroy a valve or may lead to chronic destruction. Bacteria settle usually on a mild lesion. Antibiotics taken at vulnerable times can prevent this (antibiotic prophylaxis) – for example, before tooth extraction. If established, lengthy intravenous antibiotic therapy is needed and surgery is often necessary. The mortality is 30 per cent but may be higher if the infection settles on a replaced valve (prosthetic endocarditis). Complications include heart failure, shock, embolisation (generation of small clots in the blood), and cerebral (mental) confusion.
PERICARDITIS is an in?ammation of the sac covering the outside of the heart. The sac becomes roughened and pain occurs as the heart and sac rub together. This is heard by stethoscope as a scratching noise (pericardial rub). Fever is often present and a virus the main cause. It may also occur with rheumatic fever, kidney failure, TUBERCULOSIS or from an adjacent lung problem such as PNEUMONIA or cancer. The in?ammation may cause ?uid to accumulate between the sac and the heart (e?usion) which may compress the heart causing a fall in blood pressure, a weak pulse and circulatory failure (tamponade). This can be relieved by aspirating the ?uid. The treatment is then directed at the underlying cause.... heart, diseases of
Cramp Painful spasm of a muscle usually caused by excessive and prolonged contraction of the muscle ?bres. Cramps are common, especially among sportsmen and women, normally lasting a short time. The condition usually occurs during or immediately following exercise as a result of a build-up of LACTIC ACID and other chemical by-products in the muscles
– caused by the muscular e?orts. Cramps may occur more frequently, especially at night, in people with poor circulation, when the blood is unable to remove the lactic acid from the muscles quickly enough.
Repetitive movements such as writing (writer’s cramp) or operating a keyboard can cause cramp. Resting muscles may suffer cramp if a person sits or lies in an awkward position which limits local blood supply to them. Profuse sweating as a result of fever or hot weather can also cause cramp in resting muscle, because the victim has lost sodium salts in the sweat; this disturbs the biochemical balance in muscle tissue.
Treatment is to massage and stretch the affected muscle – for example, cramp in the calf muscle may be relieved by pulling the toes on the affected leg towards the knee. Persistent night cramps sometimes respond to treatment with a drug containing CALCIUM or QUININE. If cramp persists for an hour or more, the person should seek medical advice, as there may be a serious cause such as a blood clot impeding the blood supply to the area affected.
Dystrophy See myopathy below.
In?ammation (myositis) of various types may occur. As the result of injury, an ABSCESS may develop, although wounds affecting muscle generally heal well. A growth due to SYPHILIS, known as a gumma, sometimes forms a hard, almost painless swelling in a muscle. Rheumatism is a vague term traditionally used to de?ne intermittent and often migratory discomfort, sti?ness or pain in muscles and joints with no obvious cause. The most common form of myositis is the result of immunological damage as a result of autoimmune disease. Because it affects many muscles it is called POLYMYOSITIS.
Myasthenia (see MYASTHENIA GRAVIS) is muscle weakness due to a defect of neuromuscular conduction.
Myopathy is a term applied to an acquired or developmental defect in certain muscles. It is not a neurological disease, and should be distinguished from neuropathic conditions (see NEUROPATHY) such as MOTOR NEURONE DISEASE (MND), which tend to affect the distal limb muscles. The main subdivisions are genetically determined, congenital, metabolic, drug-induced, and myopathy (often in?ammatory) secondary to a distant carcinoma. Progressive muscular dystrophy is characterised by symmetrical wasting and weakness, the muscle ?bres being largely replaced by fatty and ?brous tissue, with no sensory loss. Inheritance may take several forms, thus affecting the sex and age of victims.
The commonest type is DUCHENNE MUSCULAR DYSTROPHY, which is inherited as a sex-linked disorder. It nearly always occurs in boys.
Symptoms There are three chief types of myopathy. The commonest, known as pseudohypertrophic muscular dystrophy, affects particularly the upper part of the lower limbs of children. The muscles of the buttocks, thighs and calves seem excessively well developed, but nevertheless the child is clumsy, weak on his legs, and has di?culty in picking himself up when he falls. In another form of the disease, which begins a little later, as a rule at about the age of 14, the muscles of the upper arm are ?rst affected, and those of the spine and lower limbs become weak later on. In a third type, which begins at about this age, the muscles of the face, along with certain of the shoulder and upper arm muscles, show the ?rst signs of wasting. All the forms have this in common: that the affected muscles grow weaker until their power to contract is quite lost. In the ?rst form, the patients seldom reach the age of 20, falling victims to some disease which, to ordinary people, would not be serious. In the other forms the wasting, after progressing to a certain extent, often remains stationary for the rest of life. Myopathy may also be acquired when it is the result of disease such as thyrotoxicosis (see under THYROID GLAND, DISEASES OF), osteomalacia (see under BONE, DISORDERS OF) and CUSHING’S DISEASE, and the myopathy resolves when the primary disease is treated.
Treatment Some myopathies may be the result of in?ammation or arise from an endocrine or metabolic abnormality. Treatment of these is the treatment of the cause, with supportive physiotherapy and any necessary physical aids while the patient is recovering. Treatment for the hereditary myopathies is supportive since, at present, there is no cure – although developments in gene research raise the possibility of future treatment. Physiotherapy, physical aids, counselling and support groups may all be helpful in caring for these patients.
The education and management of these children raise many diffculties. Much help in dealing with these problems can be obtained from Muscular Dystrophy Campaign.
Myositis ossi?cans, or deposition of bone in muscles, may be congenital or acquired. The congenital form, which is rare, ?rst manifests itself as painful swellings in the muscles. These gradually harden and extend until the child is encased in a rigid sheet. There is no e?ective treatment and the outcome is fatal.
The acquired form is a result of a direct blow on muscle, most commonly on the front of the thigh. The condition should be suspected whenever there is severe pain and swelling following a direct blow over muscle. The diagnosis is con?rmed by hardening of the swelling. Treatment consists of short-wave DIATHERMY with gentle active movements. Recovery is usually complete.
Pain, quite apart from any in?ammation or injury, may be experienced on exertion. This type of pain, known as MYALGIA, tends to occur in un?t individuals and is relieved by rest and physiotherapy.
Parasites sometimes lodge in the muscles, the most common being Trichinella spiralis, producing the disease known as TRICHINOSIS (trichiniasis).
Rupture of a muscle may occur, without any external wound, as the result of a spasmodic e?ort. It may tear the muscle right across – as sometimes happens to the feeble plantaris muscle in running and leaping – or part of the muscle may be driven through its ?brous envelope, forming a HERNIA of the muscle. The severe pain experienced in many cases of LUMBAGO is due to tearing of one of the muscles in the back. These conditions are usually relieved by rest and massage. Partial muscle tears, such as occur in sport, require more energetic treatment: in the early stages this consists of the application of an ice or cold-water pack, ?rm compression, elevation of the affected limb, rest for a day or so and then gradual mobilisation (see SPORTS MEDICINE).
Tumours occur occasionally, the most common being ?broid, fatty, and sarcomatous growths.
Wasting of muscles sometimes occurs as a symptom of disease in other organs: for example, damage to the nervous system, as in poliomyelitis or in the disease known as progressive muscular atrophy. (See PARALYSIS.)... muscles, disorders of
Patients often have a poor sleep pattern, waking exhausted. Unexplained headache, urinary frequency and abdominal symptoms are common, but no cause has been found. Patients generally score highly on measures of anxiety and DEPRESSION. Fibromyalgia is not an ideal description; idiopathic di?use-pain syndrome and non-restorative sleep disorder are increasingly preferred terms.
Clinical ?ndings are generally unremarkable; most important is the presence of multiple hyperalgesic tender sites (e.g. low cervical spine, low lumbar spine, suboccipital muscle, mid upper trapezius, tennis-elbow sites, upper outer quadrants of buttocks, medial fat pad of knees). In ?bromyalgia, hyperalgesia (excessive discomfort) is widespread and symmetrical, but absent at sites normally non-tender. Claims by patients to be tender all over are more likely to be due to fabrication or psychiatric disturbance. OSTEOARTHRITIS and periarticular syndrome are much more common and should be excluded, together with other conditions, such as hypothyroidism (see THYROID GLAND, DISEASES OF), SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) and in?ammatory myopathy (see MUSCLES, DISORDERS OF), which may present with similar symptoms.
Cause There is no investigational evidence of in?ammatory, metabolic or structural abnormality, and the problem seems functional rather than pathological. SEROTONIN de?ciency has a signi?cant role in ?bromyalgia syndrome.
Management Controlled trials have con?rmed the usefulness of low-dose AMITRIPTYLINE or DOTHIEPIN together with a graded exercise programme to increase aerobic ?tness. How this works is still unclear; its e?cacy may be due to its normalising effects on the sleep centre or ‘pain gating’ (reduction of pain sensation) at the spinal-cord level. Prognosis is often poor. Nevertheless, suitable advice and training can help most patients to learn to cope better with their condition and avoid unnecessary investigations and drug treatments.... fibromyalgia syndrome
Paralysis due to brain disease The most common form is unilateral palsy, or HEMIPLEGIA, generally arising from cerebral HAEMORRHAGE, THROMBOSIS or EMBOLISM affecting the opposite side of the BRAIN. If all four limbs and trunk are affected, the paralysis is called quadraplegia; if both legs and part of the trunk are affected, it is called paraplegia. Paralysis may also be divided into ?accid (?oppy limbs) or spastic (rigid).
In hemiplegia the cause may be an abscess, haemorrhage, thrombosis or TUMOUR in the brain. CEREBRAL PALSY or ENCEPHALITIS are other possible causes. Sometimes damage occurs in the parts of the nervous system responsible for the ?ne control of muscle movements: the cerebellum and basal ganglion are such areas, and lack of DOPAMINE in the latter causes PARKINSONISM.
Damage or injury Damage to or pressure on the SPINAL CORD may paralyse muscles supplied by nerves below the site of damage. A fractured spine or pressure from a tumour may have this e?ect. Disorders affecting the cord which can cause paralysis include osteoarthritis of the cervical vertebrae (see BONE, DISORDERS OF), MULTIPLE SCLEROSIS (MS), MYELITIS, POLIOMYELITIS and MENINGITIS. Vitamin B12 de?ciency (see APPENDIX 5: VITAMINS) may also cause deterioration in the spinal cord (see also SPINE AND SPINAL CORD, DISEASES AND INJURIES OF).
Neuropathies are a group of disorders, some inherited, that damage the peripheral nerves, thus affecting their ability to conduct electrical impulses. This, in turn, causes muscle weakness or paralysis. Among the causes of neuropathies are cancers, DIABETES MELLITUS, liver disease, and the toxic consequences of some drugs or metals – lead being one example.
Disorders of the muscles themselves – for example, muscular dystrophy (see MUSCLES, DISORDERS OF – Myopathy) – can disturb their normal working and so cause partial or complete paralysis of the part(s) affected.
Treatment The aim of treatment should be to remedy the underlying cause – for example, surgical removal of a displaced intervertebral
disc or treating diabetes mellitus. Sometimes the cause cannot be recti?ed but, whether treatable or not, physiotherapy is essential to prevent joints from seizing up and to try to maintain some tone in muscles that may be only partly affected. With temporary paralysis, such as can occur after a STROKE, physiotherapy can retrain the sufferers to use their muscles and joints to ensure mobility during and after recovery. Patients with permanent hemiplegia, paraplegia or quadraplegia need highly skilled nursing care, rehabilitative support and resources, and expert help to allow them, if possible, to live at home.... paralysis
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
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