Werner syndrome
Introduction
Introduction to Werner Syndrome Werner syndrome is also known as adult premature aging, cataract-scleroderma-premature syndrome, a congenital autosomal recessive hereditary disease, with an old-fashioned face, short stature, adolescent white hair, youth cataract, hard limbs Skin-like skin changes, osteoporosis, tissue calcification, diabetes and gonadal dysplasia are the main features. basic knowledge The proportion of illness: 0.0003% Susceptible people: no special people Mode of infection: non-infectious Complications: brain tumors liver cancer fibrosarcoma melanoma liver enlargement
Cause
Cause of Werner Syndrome
(1) Causes of the disease
This disease is an autosomal recessive hereditary disease, which is more common in the offspring of a blood marriage. In particular, the offspring of the cousin are mostly children, and the disease gene is located at 8p12~p11.
(two) pathogenesis
At present, the most remarkable finding is that when the skin fibroblast culture is carried out on this disease, its division and proliferation are particularly slow, and the cell survival time is 1/8 to 1/3 of that of normal human, and the cultured fibroblast enzyme activity There are also various abnormalities. The 6-phosphate glucose dehydrogenase (G-6PD) and hypoxanthine guanine-transferase (HGPRT) increase the heat-labile component and increase the tissue factor activity. The subcutaneous tissue was replaced by connective tissue, which indicated that the newly synthesized connective tissue increased. Biochemical analysis showed an increase in hexosamine and hydroxyproline, and an increase in subcutaneous dermatan sulfate. The fibroblast culture was obtained from the atrophic lesion of the patient's skin. Collagen synthesis is hyperactive, and it has been reported that hyaluronic acid excretion in the urine increases, and the adipose tissue of the patient is reduced, but the fat cells become large, and the number of insulin-specific receptors decreases.
Based on the disease, multiple sexual dysfunction and gonadal dysplasia, it is speculated that it may be related to hypopituitarism. It is found that patients with abnormal blood calcium and skin and subcutaneous tissue have calcium deposits, so it is envisaged that the disease may be related to the parathyroid. Related to hypergonadism, others believe that the function of liver inactivated hydrocortisone is poor, resulting in increased cortisone and anti-protein assimilation, showing growth arrest, tissue atrophy and diabetes, but none of the above assumptions Widely recognized.
The main pathological changes of this disease are: calcific aortic atherosclerosis, often accompanied by peripheral atherosclerosis, skin and subcutaneous soft tissue atrophy, systemic slender body and testicles severely atrophy, the incidence of malignant tumors is high.
According to Fleischner, the epidermal hyperkeratosis of the disease, degeneration of the skin appendage, varying degrees of dermal fibrosis and hyaline degeneration, stenosis, adrenal spheroidal band tend to widen, fibrosis and other tissues can occur throughout the body Connective tissue changes, muscle atrophy due to loss of muscle fiber destruction and fibrosis, is a common histological change of the disease, in addition, there are muscle fiber swelling, horizontal stripes disappear, muscle fiber size and shape irregularities.
Aortic and macrovascular calcification is a common pathological change of this disease. All cases have severe atherosclerosis that is disproportionate to age. Cardiac infarction occurs in the coronary arteries. There are also arterial calcification and transparent arteriosclerosis. The most obvious features of cardiovascular disease are severe calcification of the aorta or mitral valve. In some cases, pituitary chromoblastoma may occur, and some pituitary basophilic adenomas may occur.
Cerebral cortical atrophy due to arteriosclerosis was observed in the brain tissue, but no lipofuscin pigmentation and amyloid corpuscle were observed, and no abnormalities were found in peripheral nerves.
Prevention
Warner syndrome prevention
1. Efforts to reduce the incidence of genetic diseases in the population must take effective preventive measures. For individuals, take common measures including premarital examination, genetic counseling, prenatal examination and early treatment of genetic diseases.
2. Ensure that both men and women live happily after marriage. The important part of the health of future generations is not to close relatives, reduce the incidence of genetic diseases, reduce the frequency of harmful genes, and reduce transmission opportunities.
Complication
Warner syndrome complications Complications brain tumor liver cancer fibrosarcoma melanoma liver enlargement
In addition to easy to develop brain tumors, the incidence of liver cancer, breast tumors, fibrosarcoma, melanoma is also high, individual cases can occur liver, accompanied by dysfunction and anemia.
Symptom
Werner Syndrome Symptoms Common Symptoms Coma Premature Aging, Reflexes Disappearing Abnormally Short Adolescents, White Hair, Eyes, Amenorrhea, Osteoporosis, Attenuated, Beak-like, Sharp-nosed
Sexual onset, male to female ratio is 1:1, although most cases are familial, but there are scattered cases, all cases are normal at birth, to normal development in early childhood, only to school age or puberty growth suddenly stagnated, At the same time, the limbs and the trunk are stagnant at the same time, so they can maintain uniform symmetry, short stature, and the nose bridge is towering, showing a unique beak-like nose (eagle hook nose).
Skin damage
Hair whitening is the earliest appearance of the disease. It occurs at the age of 10 to 20 years old. It usually starts from the scalp and eyebrows, and has progressive hair loss. The eyebrows and pubic hair also fall off. By the age of 40, all hair can be white or Become bald, face and skin atrophy, showing the face of the elderly, to adolescence, limb skin, subcutaneous tissue and muscle can occur diffuse atrophy of the centripetal, therefore, the skin is tightened, showing an over-extended appearance, and tightly combined with the subcutaneous tissue Together, this change of upper limbs is more than the lower limbs, but the trunk changes are not obvious. Localized keratin hyperplasia is also a common lesion of the disease. It occurs mostly in the palm of the hand, at the bottom of the foot, and sometimes can cause local problems due to the occurrence of sputum (the corns). Pain, in the lateral part of the foot and the Achilles tendon, etc., can form ulcers, and it is not easy to cure. Other skin lesions still have telangiectasia, skin pigmentation atrophy and systemic soft tissue calcification, the latter usually For perivascular calcification.
2. Osteoarticular lesions
Due to skin atrophy, tension, subcutaneous tissue fibrosis and local vascular blood supply disorders, the results may result in limited joint movement, atrophy of the extremities and tonic deformation. In addition, the characteristic abnormality of this disease is systemic osteoporosis. Due to premature stagnation of systemic development, it often occurs that the hands and feet are too small, the limbs are short and accompanied by muscle tissue wasting.
3. Cardiovascular disease
Often systemic, the main features are severe cardiovascular disease, manifested as local symptoms of insufficiency such as coronary heart disease.
4. Endocrine abnormalities
Occasionally, the disease has endocrine dysfunction, such as diabetes retinopathy, diabetes, and can increase vascular disease. Occasionally, diabetic coma can occur. The disease often has sexual dysfunction. Males show sexual organ dysplasia and libido. Low, women manifest as early menstruation, less menstruation, premature amenorrhea, labia majora, vagina, internal genital and breast dysplasia or insufficiency.
5. abnormal nervous system
One-third of patients have mild neurological symptoms, the most important of which is myofascular muscle atrophy involving distal limbs, deep distal tendon reflexes disappearing, some cases may have paresthesia, and about half of patients have mental retardation. Can be associated with infantile mood; a small number of cases may have psychiatric symptoms and seizures, the incidence of non-cancerous tumors is higher, the most common are meningioma and schwannosarcoma.
6. Five facial lesions
Nearly half of the patients had abnormally high-pitched voices. Laryngoscopy revealed atrophy of the vessels on or near the vocal cords, superficial changes in dilatation or bulging, and mucosal hyperemia. This mucosal change caused high-pitched sounds.
Examine
Warner syndrome check
1. Biochemical examination: Blood lipid analysis in most patients showed elevated cholesterol, -lipoprotein and triglyceride, urine creatinine, and elevated amino acids.
2. Immunological examination: T cell reduction and T cell immune function are low, and anti-lymphocyte antibodies can be positive.
3. X-ray examination: osteoporosis of the spine and limbs, in the soft tissues of the limbs, especially around the bony prominence, linear and circular calcification shadows, in the aorta, aortic valve, mitral valve and coronary artery, There is extensive calcification and signs of heart enlargement and congestive heart failure.
4. Chemical analysis of lesion biopsy showed elevated hydroxyproline and glucosamine.
Diagnosis
Diagnosis and diagnosis of Werner syndrome
diagnosis
Cataract is the main feature of this disease, mostly occurring in the 20 to 30 years old, so it is called young cataract, crystal turbidity is star-shaped, often bilateral, more often appear in the posterior pole of the lens.
When the condition is in the chronic stage and the clinical symptoms and signs are more typical, the diagnosis is not difficult, but it may be difficult to diagnose at an early stage. According to the clinical characteristics of premature whitening, special face and characteristic body type, combined with laboratory And X-ray findings for diagnosis, Irwin summarized the clinical manifestations of the disease into the following four groups:
1. Characteristic body type and constitution: 1 short stature in puberty; 2 short torso and slender limbs; 3 with beak-like nose.
2. Premature aging: 1 hair prematurely white; 2 premature baldness; 3 sounds sharp and weak; 4 atherosclerosis; 5 skin atrophy; 6 youth cataract.
3. Scleroderma-like changes: 1 skin and subcutaneous tissue atrophy; 2 local keratosis; 3 skin on the back of the foot is too tight; 4 ankle Achilles tendon, heel and toe ulcer.
4. Other manifestations: 1 diabetes tendency; 2 gonadal dysplasia; 3 osteoporosis; 4 local calcification.
5. Occasional morbidity among siblings: Clinically, diagnoses can be made based on these four characteristics, but it must be noted that 3 of the 3 and 3 of the 2nd and 4 of the 4th are not The necessary diagnostic conditions, in addition, 3 and 4 of the fourth item can also occur in the upper limbs.
Differential diagnosis
Diagnosis should pay attention to the difference between this syndrome and muscular dystrophy. The muscle atrophy is most obvious in the diaphragm. The patient has an "axchet-face". In severe cases, the mandibular and cervical muscles can be severely atrophied. Nervous reaction is the most important identification point of the two. It should also be noted that this syndrome is differentiated from scleroderma, scleroderma and acral sclerosis with palm skin sclerosis. According to these diseases, there is no whitening of the hair, too early. Baldness and the presence and shape of Werner syndrome are relatively easy to identify.
Werner syndrome must be carefully identified with natural aging (Table 1). In addition, it must be associated with Rothmund syndrome, cutaneous cataract with neuromyositis (Andogsky syndrome), and children with hypoplasia. Premature aging (Hutchinson syndrome), hair, nail dystrophy with ectodermal dysplasia (Ellis-van Greveld syndrome), myotonia dystrophy (Steinert syndrome), etc., to distinguish them, the list of identification points is as follows .
