Progeria is a rare genetic disorder wherein children age rapidly due to genetic defect. Such a kind of disease was first described in the year 1886 by Jonathan Hutchinson and later by Hastings Gold in the year 1897. This disease is therefore also known as the Hutchinson–Gilford progeria syndrome.
Symptoms of progeria begin to show effect within the first 2 years of life. Children appear to be normal at birth; however certain distinct facial features have been noticed in some. The following are the signs and symptoms of progeria disease  :
- Slow growth
- High pitched voice
- Skin becomes wrinkled and thin
- Loss of hair in areas of scalp, eyebrows and eyelashes
- Head appears to be larger than the face
- Eyes are prominent
- Eyelids do not close properly
In addition to the above mentioned symptoms, individuals with progeria also suffer from several health issues. These include, onset of heart disease, hearing loss, insulin resistance, fragile bones, development of scleroderma, hip dislocation, stiff joints and abnormal tooth formation.
Entire Body System
Side effects included mild diarrhoea, fatigue and nausea. For the main outcome measure of weight: Nine of the 25 children had a 50% or more increase over their estimated annual weight gain before treatment. [nhs.uk]
[…] bias can determine the role of synonymous SNPs in human diseases Christina McCarthy, Alejandra Carrea & Luis Diambra BMC Genomics (2017) Genome-wide association analysis identifies genetic variations in subjects with myalgic encephalomyelitis/chronic fatigue [nature.com]
"Progeria is an ultra-rare, fatal, pediatric disease with no approved treatment. We are very pleased with FDA Breakthrough Therapy designation for lonafarnib in Progeria and progeroid laminopathies as we prepare for NDA filing in 2019." [prnewswire.com]
For this fatal pediatric disease with no known treatments, only single-group clinical trials have been conducted to date because of ethical considerations and are therefore the sole source of data to demonstrate safety and efficacy of any potential new [jamanetwork.com]
premature graying of the hair) Premature baldness Scleropoikiloderma Trophic ulcers of the legs Juvenile cataracts Hypogonadism Tendency to diabetes Calcification of the blood vessels FULL TEXT [annals.org]
English - French progeria 220 millions of speakers Translator English - German Progerie 180 millions of speakers Translator English - Japanese 早老症 130 millions of speakers Translator English - Korean 조로증 85 millions of speakers Translator English - Vietnamese [web.archive.org]
The child also had a gangrenous ulcer over the left foot, a finding not highlighted in the literature. [ncbi.nlm.nih.gov]
Disease manifestations include severe failure to thrive, scleroderma-like skin, global lipodystrophy, alopecia, joint contractures, skeletal dysplasia, global accelerated atherosclerosis leading to heart failure, and debilitating strokes. [eigerbio.com]
dysplasia with abnormalities in bone structure, skeletal strength, and decreased range of joint mobility. [secure.ssa.gov]
Progeria patients die early due to conditions such as atherosclerosis, skeletal dysplasia, and stroke. Progeria and the most progeroid laminopathies are caused due to a mutation in the lamin A/C (LMNA) gene, which encodes for lamin A protein. [pharmaceutical-technology.com]
Hutchinson-gilford progeria is a skeletal dysplasia. J Bone Miner Res. 2011 Jul. 26(7):1670-9. [Medline]. Ding SL, Shen CY. Model of human aging: recent findings on Werner's and Hutchinson-Gilford progeria syndromes. [emedicine.medscape.com]
At 18 months of age, irregular pigmentary changes of the abdomen, early occipital alopecia, superficial scalp veins, glyphic nasal tip, absent ear lobules, coarse hair that stands on end, crowded dentition with delayed tooth development, and dystrophic [ncbi.nlm.nih.gov]
[…] childhood and characterized by growth reduction, failure to thrive, a typical facial appearance (prominent forehead, protuberant eyes, thin nose with a beaked tip, thin lips, micrognathia and protruding ears) and distinct dermatologic features (generalized alopecia [orpha.net]
Absence of Subcutaneous Fat
She died 7 hours after birth and presented with intrauterine growth retardation, premature aging, absence of subcutaneous fat, brachydactyly, absent nipples, hypoplastic external genitalia, and abnormal ear lobes. [ncbi.nlm.nih.gov]
It is clinically characterised by postnatal growth retardation, midface hypoplasia, micrognathia, premature atherosclerosis, absence of subcutaneous fat, alopecia and generalised osteodysplasia. [eurasnet.info]
[…] of subcutaneous fat Absent fat below the skin Lack of fatty tissue below the skin [ more ] 0007485 Autosomal dominant inheritance 0000006 Autosomal recessive inheritance 0000007 Congestive heart failure Cardiac failure Cardiac failures Heart failure [rarediseases.info.nih.gov]
[…] of subcutaneous fat, thin and wrinkled 'sclerodermatous' skin, prominent superficial veins, and nail dystrophy [Figure 1], [Figure 2] and [Figure 3]. [ijo.in]
A new clinical condition linked to a novel mutation in lamins A and C with generalized lipoatrophy, insulin-resistant diabetes, disseminated leukomelanodermic papules, liver steatosis, and cardiomyopathy. [ncbi.nlm.nih.gov]
Face, Head & Neck
The children usually present in late infancy and early childhood with a characteristic phenotype of alopecia; short stature; abnormal skin, teeth, and nails; beaked nose; loss of subcutaneous fat; and failure to thrive. [ncbi.nlm.nih.gov]
Figure 1: (a) Progeriod facies with frontal bossing, beaked nose. (b) mottled pigmentation around the neck. [idoj.in]
Symptoms and signs of progeria develop within 2 yr and include Growth failure (eg, short stature, delayed tooth eruption) Craniofacial abnormalities (eg, craniofacial disproportion, micrognathia, beaked nose, macrocephaly, large fontanelle) Physical changes [msdmanuals.com]
Large Anterior Fontanels
The characteristic facies show protruding ears, beaked nose, thin lips with centrofacial cyanosis, prominent eyes, frontal and parietal bossing with pseudohydrocephaly, midface hypoplasia with micrognathia and large anterior fontanel. [ncbi.nlm.nih.gov]
A preliminary physical examination of the signs and symptoms confirms progeria. In addition, genetic testing is also carried out to further verify the diagnosis. Genetic testing for the lamin A protein is done which confirms the disease.
Urine analysis of patients with progeria syndrome show elevated levels of hyaluronic acid. Imaging studies of the phalanges, skull, long bones and thorax reveal characteristic findings such as attenuated cortical bone, development of osteopenia, distal bone resoprtion and hip dysplasia .
Other tests which include EEG and echocardiogram to monitor the cardiac activity should be done. Skin biopsy is also done which reveals onset of scleroderma. All these tests confirm the diagnosis of progeria.
So far, no breakthrough has been made for treating progeria. Progeria has no cure. However, various methods have been developed to manage the secondary conditions that accompany the disease.
Medication such as low dose aspirin is administered to slow down the progression of the heart disease. In addition, depending on the child’s condition other class of medications would also be given such as statins, if the blood cholesterol level is high. Growth hormones can also be administered to improve the height and weight of the child .
Therapies to help strengthen the muscles and bones of the child would be carried out. These include physical and occupational therapies which would help relieve the joint stiffness and avoid development of hip problems as the child ages.
Teeth extraction is specifically done to allow proper growth of the permanent teeth. In children with progeria, before the primary teeth fall off, the permanent teeth begin to grow causing improper placement and growth of teeth. In order to avoid such a condition, the primary teeth are extracted to allow the permanent ones to grow properly and in place.
Constant research is being carried out to understand the disease condition so that newer methods can be developed to successful treat the condition  .
Genetic mutation of a single gene has been identified to be the cause behind development of progeria. This gene in which mutation occurs is known as the LMNA gene coding for lamin A . It is responsible for production of protein which is required for holding cells together. Genetic mutation causes the cells to become unstable which makes the process of aging occur faster.
Progeria is a rare occurrence affecting 1 per 8 million live births. The data on incidence of this disease for specific countries is not available.
Under normal conditions, the lamin A gene produces a structural protein which has a farnesyl group attached to it. This group is necessary for the attachment of the protein to the cell nucleus. Once the protein gets successfully attached to the nucleus the farnesyl group is removed. In individuals with progeria, the farnesyl group does not get removed and as a result the protein is permanently attached to the nucleus resulting in abnormal cell formation. Such sequence of events gives rise to the condition progeria .
Progeria disease cannot be prevented. Researchers are yet to confirm whether genetic testing during pregnancy can detect such a condition. More research needs to be done to carefully understand the disease condition and design ways of preventing it.
In this rare genetic condition, children appear to be normal when they are born. However, rapid signs of ageing begin to appear within first 2 years. Children born with this genetic condition do not live longer than 13 years. Heart diseases or stroke are the common causes of death in such children. Progeria cannot be cured; however some newer treatment methods have been developed which can control the symptoms and improve quality of life .
Progeria is a rare genetic disorder that causes early aging in affected children. Children begin to show signs and symptoms of the disease by 6 – 12 months of age. There is no cure for this disease, but few treatment regimes can help manage the secondary conditions. Progeria syndrome is also known as the Hutchinson–Gilford progeria syndrome after the scientists who described it .
Genetic mutation in a single gene is known to trigger the development of progeria syndrome.
Diagnosis of progeria is made by examination of the signs and symptoms of the disease. In addition, genetic testing is also done to confirm the findings. Radiologic examinations would also be required to assess the changes occurring inside the body.
Porgeria cannot be treated. But, the symptoms can be managed with medications and supportive therapies.
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