Progeria - a rare genetic disease, first described by Guilford, which appears premature aging associated with its underdevelopment.Progeria is classified into the nursery, called syndrome Hutchinson (Hutchinson) -Gilforda and adults - Werner syndrome.
This disease is marked strong growth retardation since childhood, changes in the structure of the skin, cachexia, the absence of secondary sexual characteristics and hair, hypoplasia of internal organs and appearance of an old man.This corresponds to the mental state of the patient age, epiphyseal cartilage plate closes early, but the body has a children's proportions.
Progeria refers to an incurable disease and is the cause of serious atherosclerosis that develops as a result of various strokes and heart disease.And as a result this genetic abnormality is fatal, ie,it is fatal.As a rule, the child can live, on average, thirteen years old, although there are cases with a lifespan of over twenty years.
Children Hutchinson-Gilford pro
This disease is extremely rare in the ratio of 1: 4,000,000 births in the Netherlands and 1: 8,000,000 in the United States.Moreover, the disease affects more boys than girls (1.2: 1).
Consider two forms of Hutchinson-Gilford progeria: classical and non-classical.
Currently, described more than a hundred cases of childhood progeria.And basically this disease affects children of the white race.For Hutchinson-Gilford progeria tend polymorphic defeat.Children with this syndrome seem quite normal at birth.But a year or two there is a serious lag in growth.Usually these children differ too short and still lower body weight according to its length.
For children with progeria complete baldness is characterized by not only the scalp, but also the lack of eyelashes, eyebrows, even from an early age.Skin looks weak and wrinkled as a result of the absolute loss of subcutaneous fat, skin cyanosis is present.For head disproportion characteristic craniofacial bones that resemble the face of a bird with a hooked nose, abnormally small lower jaw, bulging eyeballs and protruding ears.It is these features large bald head and a small jaw, give the appearance of an old man kind of child.
Other Progeria clinical manifestations include: incorrect and late teething, thin and high-pitched voice, pear-shaped chest and reduction in size of the clavicle.Limbs are usually thin, and altered elbow and knee joints give the sick child "posture of the rider."
in children before the year marked skleropodobnye seal, congenital or acquired nature, on the buttocks, thighs and abdomen.Children with progeria is characterized by hyperpigmentation of the skin, which only increased over the years, and hypoplasia of nails, in which they become yellow, thin and convex-like hour glasses.However, since the age of five, develop common form of atherosclerosis with a large lesion of the aorta and the arteries, especially the coronary and mesenteric.And much later appear heart murmur and cardiac hypertrophy, left ventricular.Early occurrence of atherosclerosis in children, becomes the cause of the brevity of life.But the main cause of death is considered to be a myocardial infarction.
When progeria are known cases of ischemic stroke.Such children in intellectual development is absolutely no different from healthy children, sometimes even ahead of them.Children with this diagnosis live on average about fourteen years.
With Progeria children's non-classical forms of the mass of the body length behind slightly, over time the hair is stored and lipodystrophy is progressing much more slowly;possible recessive inheritance.
Until now, the exact cause of the Progeria unclear.Presumptive etiology of the disease is a metabolic disturbance in the connective tissue, resulting in proliferation of fibroblasts by cell division and increasing the formation of collagen with reduced synthesis of glycosaminoglycans.Slow formation of fibroblasts is due to disturbances in the intercellular substance.
The causes of child syndrome progeria considered mutations in LMNA, which is responsible for encoding lamin A. This is a protein that makes up one of the layers of the nucleus of the cell membrane.
In many cases, progeria occurs sporadically, and in some families found in siblings, especially in consanguineous marriages, which suggests a possible autosomal recessive type of inheritance.In studies of patients with skin cells have been found in which impair the ability to correct fractures and damage to DNA and play a genetically homogeneous fibroblasts change atrophic epidermis and dermis, contributing to the disappearance of subcutaneous fat.
for adult progeria characteristic autosomal recessive inheritance with the defective gene ATP-dependent helicase or WRN.There is speculation in the chain linking the violations between DNA repair and exchange of connective tissue.
also found that Hutchinson-Gilford progeria have abnormalities in the cells of the carrier, which can not fully get rid of the cross-linking of DNA caused by chemical agents.When diagnosing these cells with the syndrome have found that they are not able to fully pass the fission process.
Olovnikov In 1971, it was suggested on shorter lengths of telomeres in cell formation.And in 1992, it has already been proven in patients with adult progeria syndrome.The analysis, which connects the Hayflick limit, the length of the telomeres and the enzyme telomerase allows you to combine the natural aging process of the formation of the clinical symptoms of child Hutchinson-Gilford progeria.Since this form of Progeria is extremely rare, we can only hypothesize about the type of inheritance, which has similarities with Cockayne syndrome is manifested by individual characteristics of premature aging.
There are also statements about accessories Hutchinson-Gilford progeria mutation, autosomal dominant, which arose de novo, ie,without inheritance.She became an indirect confirmation of the syndrome, which is based on the measurement of telomeres includes carriers of the disease, their parents and donors.
Progeria clinical picture of the children's different characteristic premature atherosclerosis, myocardial fibrosis, disorders of cerebral circulation, and increase lipoprotein cholesterol levels, prothrombin time assays, early heart attacks, skeletal abnormalities.In this case, there are marked disparities face and skull, jaw and dental hypoplasia, hip displacement.Long bones in normal cortical structure and progression of peripheral demineralization exposed to recurrent pathological fractures.
mobility of the joints characterized by tight, especially knee with possible contractures of the hip, ankle, elbow and wrist joints.X-ray examination revealed demineralization around joints osteoporosis, varus and valgus deformity of the lower limbs.It is also very often develop swelling and thickening of the collagen fibers.
Werner syndrome or adult progeria shown from 14 to 18 years of age and is characterized by a lag in growth, graying universal parallel progression of alopecia.
Normally, progeria syndrome develops after twenty years and is characterized by an early hair loss, thinning of the skin on the face and extremities, pallor characteristic.Under the skin stretched too visible superficial blood vessels, and subcutaneous fat and muscles located underneath completely atrophied, so of course look disproportionate fine.
Then the skin over bone protrusions gradually becomes thicker and ulcerate.After thirty years in patients with progeria develop cataracts in both eyes, the voice becomes weak, high and hoarse, significantly affects the skin.This is manifested in the form of changes sklerotsermopodobnyh limbs and the face, dry skin, sores on the feet, corns on the feet and telangiectasia.Such patients are usually low growth, with lunoobraznym face, beak-shaped nose, like a bird, narrowed mouth opening and sharply protruding chin, a full body and thin limbs.
progeria patients disrupts the function of sweat and sebaceous glands.On the ledges of bone is formed hyperkeratosis, hyperpigmentation seen overall, changes the shape of the nail plate.And after various injuries to the legs and feet sores appear.In addition to atrophy and thinning, patients show significant changes in the muscles and bones, calcification, generalized osteoporosis, osteoarthritis with erosions.Such patients are restricted in the movements of the fingers and flexion contracture.For patients with progeria characterized by deformation of the bones as rheumatoid arthritis, pain in the extremities, flat feet, and osteomyelitis.
During surveys rentenografii revealed bone osteoporosis, heterotopic calcification of the skin and subcutaneous tissue, ligaments and tendons.Also, the cataract progresses slowly, developing atherosclerosis, which violates the cardiovascular system.In most patients, reduced intelligence.
After forty years to progeria diabetes mellitus, parathyroid glands dysfunction and other diseases of nearly 10% of patients develop tumor pathology as osteogenic sarcoma, astrocytoma, thyroid adenocarcinoma, breast cancer and skin.
lethal outcome is usually the result of cardiovascular pathologies and cancers.
Histological analysis progeria syndrome establish atrophy of skin appendages, which are stored ekkrinnye cancer;The dermis has thus thickening gialiniziruyutsya collagen fibers, and nerve fibers are destroyed.
patients completely atrophied muscles, there is no subcutaneous fat.
disease is diagnosed based on clinical symptoms of progeria.If in doubt in the diagnosis, the ability of fibroblasts to proliferate in culture (reduced rate for Werner's syndrome).To take into account the differential diagnosis of progeria syndrome Hutchinson-Gilford, Rotmunda-Thomson, and systemic sclerosis.
So far, there is no specific treatment for progeria, it has not yet developed.Basically, therapy is symptomatic to the prevention of complications of atherosclerosis and in the healing of venous ulcers, diabetes.
appointed to the anabolic effect of growth hormone, which in some patients increases the body weight and length.The entire treatment process is carried out a number of specialists, such as an endocrinologist, internist, cardiologist, oncologist, and others, depending on the prevailing symptoms.
But in 2006, US researchers noted progression in the treatment of progeria as an incurable disease.They have broken into the culture of fibroblasts farnesyl transferase inhibitor that has previously been tested on cancer patients.And this process of aging cells restored normal form.This drug has been well transferred, so now there is hope that in the future it will be possible in its application, to prevent cheaters even in childhood.
Lonafarniba Efficiency (farnesyl transferase inhibitor) is to increase the amount of fat under the skin, body weight, bone mineralization, which ultimately reduce fractures.
But, nevertheless, is a disease characterized by a poor prognosis.On average, patients with progeria die before the age of thirteen, dying from hemorrhages and heart attacks.