Progeria ( dr. Greek προσ- - over, γέρων - old man) is one of the rarest genetic defects . With progeria, changes in the skin and internal organs occur, which are caused by premature aging of the body. Classify children's progeria (Gatchinson’s syndrome (Hutchinson) - Guildford ) and adult progeria ( Werner’s syndrome ).
| Progeria | |
|---|---|
 Progeria patients often have a characteristic appearance: short stature, relatively large head, and a reduced facial part of the skull | |
| ICD-10 | E 34.8 |
| ICD-10-KM | |
| ICD-9 | 259.8 |
| ICD-9-KM | |
| Omim | 176670 |
| Diseasesdb | 10704 |
| Medlineplus | |
| eMedicine | derm / 731 |
| Mesh | D011371 |
The British doctor Jonathan Hutchinson in 1886 for the first time described a case of premature aging in a six-year-old boy, which was manifested by atrophy of the skin and its appendages [1] [2] . Later, his compatriot and colleague Hastings Guilford , having studied the clinical and morphological features of this pathology, introduced the term “progeria”. [2] A progeria of adults was described by the German physician Karl Wilhelm Otto Werner , who, while still a medical student, observed this syndrome in four siblings at the age of about 30 years and documented these observations in his dissertation in 1904.
There are no more than 350 cases of progeria recorded in the world, including 11-year-old Adalia Rose, 17-year-old Haley Okins, 16-year-old Ashanti Eliott-Smith, and 18-year-old Ontlametse Phalatse from Hebron near Johannesburg , which is the only sick progeria representative of the black race. Leon Bota , who suffered from progeria and died on June 5, 2011, is a DJ and hip-hop artist who conducted a video blog on YouTube [3] , as well as American motivational speaker Sam Burns , who died on January 10, 2014 at the age of 17 years.
In children
The cause of childhood progeria is a mutation in the LMNA gene encoding lamin A. Lamines are the proteins from which a special layer of the membrane of the cell nucleus is built . In most cases, progeria occurs sporadically, in several families it is registered in siblings , including from consanguineous marriages, which indicates the possibility of an autosomal recessive type of inheritance. In the skin cells of patients, violations of DNA repair and cloning of fibroblasts , as well as atrophic changes in the epidermis and dermis, the disappearance of subcutaneous tissue were found .
Although childhood progeria can be congenital, in most patients, clinical signs usually appear in the 2-3rd year of life. The growth of the child is sharply slowed down, atrophic changes in the dermis, subcutaneous tissue, especially on the face and limbs, are noted. The skin becomes thinner, becomes dry, wrinkled, on the body there may be scleroderma-like foci, areas of hyperpigmentation. Veins shine through thinned skin. Appearance of the patient: a large head, frontal tubercles protrude above a small pointed ("bird") face with a coracoid nose, the lower jaw is underdeveloped. Muscle atrophy, dystrophic processes in the teeth, hair and nails are also observed; changes in the osteoarticular apparatus, myocardium, genital hypoplasia , impaired fat metabolism, clouding of the lens, atherosclerosis are noted.
The average life expectancy in childhood progeria is 13 years. Most sources indicate the age of death from 7 to 27 years, while cases of reaching adulthood are very rare. Only two cases of patients who survived a 27-year milestone are known - the Japanese, described by Ogihara and others in 1986 and lived 45 years [4] and Tiffany Vedekind who is 41 years old and is considered the oldest of all patients who were diagnosed with Benjamin Button syndrome ".
In adults
Adult progeria has an autosomal recessive inheritance type. The defective gene is WRN (ATP-dependent helicase gene). It is assumed that the process is associated with a violation of DNA repair, exchange of connective tissue.
The histological picture: flattening of the epidermis, homogenization and sclerosis of connective tissue, atrophy of the subcutaneous tissue with its replacement by connective tissue fibers. Clinically, the disease manifests itself during puberty. Slow growth, symptoms of hypogonadism are noted. Usually, in the third decade of life, the patient's hair turns gray and falls out, cataract develops, the skin gradually thinns and subcutaneous tissue on the face and limbs atrophies, as a result of which the arms and especially the legs become thin. Foci of scleroderma - like compaction, dyschromia appear, most pronounced in the distal extremities and on the face, which, along with a thin, coracoid nose, narrowed mouth opening, gives it a maskiness. In places exposed to pressure, hyperkeratosis , chronic poorly healing trophic ulcers develop. Osteoporosis , metastatic calcification of soft tissues, less commonly osteomyelitis , are detected. Often there is diabetes mellitus , the signs of which, like the symptoms of early generalized atherosclerosis, are usually detected in patients aged 30-40 years; malignant neoplasms are possible (for example, skin cancer , sarcoma , adenocarcinoma ).
Diagnosis is based on clinical presentation. The differential diagnosis is carried out with congenital poikiloderma , scleroderma. Symptomatic treatment is mainly aimed at the prevention of atherosclerotic complications, the elimination of diabetes mellitus, trophic ulcers. It is performed by a therapist, endocrinologist or other specialist, depending on the prevailing clinical symptoms. The prognosis for recovery is unfavorable; most patients die from atherosclerotic complications and malignant neoplasms. Prevention is not developed.
Aging
It has been established that a severe form of human progeria (Hutchinson-Guildford syndrome) is associated with molecular changes characteristic of normal aging , among them genomic instability , a decrease in telomere length and a violation of stem cell homeostasis . These data, together with genetic studies of life expectancy, have led to the hypothesis that, with progeria syndromes, a number of pathological changes are accelerated, which, as a rule, control the usual aging process [5] .
Notes
- ↑ Monarch Disease Ontology release 2018-06-29sonu - 2018-06-29 - 2018.
- ↑ Mirsalim Ilyasovich Abdullaev, Shirin Abbaskhanovna Abidova. Hatchinson-Guildford Progeria Syndrome (HGPS) // Young Scientist. - 2018. - Issue. 205 . - S. 7–11 . - ISSN 2072-0297 .
- ↑ Multimedia Slideshow: Transcend and Transgress - Mail & Guardian
- ↑ Hutchinson-Gilford progeria syndrome in a 45-year-old man . US National Library of Medicine National Institutes of Health. Date of treatment January 7, 2010.
- ↑ Progeria syndromes and ageing: what is the connection? Christopher R. Burtner and Brian K. Kennedy // Nature Reviews Molecular cell Biology volume 11 - 2010 - p. 567-578 doi: 10.1038 / nrm2944
Literature
- Fedorova E.V. On Congenital Progeria. - 1980. - T. 4. - P. 66. - (Pediatrics).