Hutchinson-Gilford Progeria Syndrome, “Progeria” or “HGPS” is a rare, fatal genetic condition characterized by an appearance of accelerated aging in children.
Its name is derived from Greek and means "prematurely old." While there are different forms of Progeria, the classic type is Hutchinson-Gilford Progeria Syndrome, which was named after the doctors who first described it in England: in 1886 by Dr. Jonathan Hutchinson, and in 1897 by Dr. Hastings Gilford.
Other Progeroid syndromes include Werner’s syndrome, also known as “adult progeria” which does not have an onset until the late teen years, with a lifespan into the 40’s and 50’s.
Evidence of Hutchinson-Gilford progeria syndrome (HGPS) begins within the first 2 years of life.
At birth, infants usually appear healthy, although sclerodermatous skin changes have been noted in some patients. Typically, the onset of the disease occurs at age 6-12 months, when skin changes and alopecia are first noted and when the infant fails to gain weight.
The following are other suggestive findings:
Short stature and low weight for height, with prenatal onset of growth failure
Prolonged prothrombin time, elevated platelet counts, and elevated serum phosphorus levels
Emotionally, patients with HGPS share the same feelings as age-matched healthy persons with regard to expressing proper mood and affect.
Patients with HGPS are keenly aware of their different appearance and remain reserved in the company of strangers; in the presence of friends, they display affection and good social interaction. Intelligence is normal.
The characteristic clinical findings of Hutchinson-Gilford progeria syndrome (HGPS) include abnormalities of the skin and hair in conjunction with characteristic facial features and skeletal abnormalities.
The composite appearance of the characteristic facies and parieto-occipital alopecia creates a "plucked-bird" appearance. Evidence of significant growth failure manifests within the first 1-2 years of life and prenatal growth failure is often apparent.
The skeletal anomalies are best characterized as a skeletal dysplasia and are thought to be related to microvascular insufficiency and extracellular matrix abnormalities.
Skin and hair findings are as follows:
Sclerodermatous skin changes involving the trunk and extremities but sparing the face: These are usually present within the first 6-12 months of life, although they may be present at birth. The skin changes manifest as indurated, shiny, inelastic skin.
Prominent scalp veins.
Generalized lipodystrophy with loose, aged-appearing skin: Areas of skin may appear loose, wrinkled, and aged because of the loss of subcutaneous fat, particularly over the hands and feet.
Progressive frecklelike hyperpigmentation in sun-exposed areas.
Hair loss: Scalp hair and eyelashes are progressively lost, resulting in baldness with only a few vellus hairs remaining.
Characteristic facies are as follows:
Protruding ears with absent lobes
Thin lips with centrofacial cyanosis
Frontal and parietal bossing with pseudohydrocephaly
Large anterior fontanelle.
Oral and craniofacial anomalies are as follows:
Midface hypoplasia with micrognathia
Dental anomalies, including hypodontia and delayed dentition
Stiff auricular cartilage, small or absent lobules, shortened ear canals
Musculoskeletal abnormalities are as follows:
Thin limbs with prominent joints
Joint contractures and coxa valga with mild flexion of the knees resulting in a wide gait and "horse-riding" stance
Pyriform (pear-shaped) thorax with short, dystrophic clavicles
Hutchinson-Gilford progeria is caused by a tiny, point mutation in a single gene, known as lamin A (LMNA).
Parents and siblings of children with progeria are virtually never affected by the disease. In accordance with this clinical observation, the genetic mutation appears in nearly all instances to occur in the sperm prior to conception. It is remarkable that nearly all cases are found to arise from the substitution of just one base pair among the approximately 25,000 DNA base pairs that make up the LMNA gene.
The LMNA gene codes for two proteins, lamin A and lamin C, that are known to play a key role in stabilizing the inner membrane of the cell's nucleus. In laboratory tests involving cells taken from progeria patients, researchers have found that the mutation responsible for Hutchinson-Gilford progeria causes the LMNA gene to produce an abnormal form of the lamin A protein
That abnormal protein appears to destabilize the cell's nuclear membrane in a way that may be particularly harmful to tissues routinely subjected to intense physical force, such as the cardiovascular and musculoskeletal systems.
4 Making a Diagnosis
A genetic test for Hutchinson-Gilford progeria syndrome diagnosis is currently available.
In the past, doctors had to base a diagnosis of progeria solely on physical symptoms, such as skin changes and a failure to gain weight, that were not fully apparent until a child's first or second year of life.
This genetic test now enables doctors to diagnose a child at a younger age and initiate treatment early in the disease process.
This genetic test for Hutchinson-Gilford progeria syndrome also serves to reassure parents of affected children that their disorder stems from a sporadic genetic mutation and that therefore it is unlikely that any future offspring would have the condition.
No treatment for progeria has proven effective. Most treatment focuses on reducing complications (such as cardiovascular disease) with coronary artery bypass surgery or low-dose aspirin. Children may also benefit from a high-energy diet.
Growth hormone treatment has been attempted. The use of Morpholinos has also been attempted in order to reduce progerin production. Antisense Morpholino oligonucleotides specifically directed against the mutated exon 11–exon 12 junction in the mutated pre-mRNAs were used.
Potential therapeutic targets for the inhibition of progerin farnesylation
A type of anticancer drug, the farnesyltransferase inhibitors (FTIs), has been proposed, but their use has been mostly limited to animal models. It has been proved that pravastatin and zoledronate are effective drugs when it comes to the blocking of farnesyl group production.
Farnesyltransferase inhibitors (FTIs) are drugs that inhibit the activity of an enzyme needed in order to make a link between progerin proteins and farnesyl groups. This link generates the permanent attachment of the progerin to the nuclear rim. In progeria, cellular damage can be appreciated because that attachment takes place and the nucleus is not in a normal state. Lonafarnib is an FTI, which means it can avoid this link, so progerin cannot remain attached to the nucleus rim and it now has a more normal state.
Pravastatin, traded as Pravachol or Selektine, is included in the family of statins. As well as zoledronate (also known as Zometa and Reclast, which is a bisphosphonate), its utility in HGPS is the prevention of farnesyl group formation, which progerin needs to provoke the disease. Some animal trials have been realized using FTIs or a combination of pravastatin and zoledronate so as to observe whether they are capable of reversing abnormal nuclei. Unlike FTIs, pravastatin and zoledronate were approved by the U.S. FDA (in 2006 and 2001 respectively), although they are not sold as a treatment for progeria. Pravastatin is used to decrease cholesterol levels and zoledronate to prevent hypercalcaemia.
Rapamycin, also known as Sirolimus, is a macrolide. There are recent studies concerning rapamycin which conclude that it can minimize the phenotypic effects of progeria fibroblasts. Other observed consequences of its use are: abolishment of nuclear blebbing, degradation of progerin in affected cells and reduction of insoluble progerin aggregates formation. All these results do not come from any clinical trial, although it is believed that the treatment might benefit HGPS patients.
A 2012 clinical trial found that the cancer drug Lonafarnib can improve weight gain and other symptoms of progeria.
Currently, there is no known method of prevention for Hutchinson-Gilford progeria syndrome (HGPS). The condition occurs randomly during the development of the sperm or egg.
The condition is generally diagnosed in infants who are 6-24 months old. Early diagnosis of HGPS is important because prompt treatment and regular medical checkups help extend the child's lifespan.
7 Lifestyle and Coping
Lifestyle modifications are necessary in order to cope with progeria.
There are some steps that can be easier for you to practice at home for your child suffering from progeria syndrome. These are:
Dehydration seriously affects the progeria syndrome child. So always be sure that your child is properly hydrated. Always keep observing that your child takes plenty of water, particularly during hot summer days or in illness.
Provide the child with progeria syndrome a small but frequent meals, as nutrition can be the issue of the growth of the children with the disease of progeria syndrome. The frequent small meals help to add calories and are a good lifestyle changes.
Give your child with progeria syndrome occasions of doing physical activity regularly. Consult with the doctor to know which activities are best for your child.
Getting soft or padded shoes for your child is a good lifestyle remedy. The reduction of body fat will also lead to the reduction of fat in the feet. The condition may cause discomfort in progeria syndrome.
Apply sunscreen with SPF 15 generously for a child with progeria syndrome is a good lifestyle remedy. Reapply it every 2 hours or more if your child swims or perspire.
Make sure that child has been immunized till date. Because they are exposed to the risk of infections when they are suffering from progeria syndrome.
Given the opportunity for learning, progeria syndrome does not affect the intellect of the child. So, they can attend regular session of the schools at the right age level.
Coping with Progeria Syndrome
Coping with progeria syndrome is not at all easy for both the parents and the child with progeria syndrome. It is emotionally upsetting when you will know that your child has been detected with progeria syndrome.
Immediately you will know that the child is encountering multiple problems, many challenges, and cut-short life span. For all of you dealing with the problem will only suggest a great obligation to emotional, physical and economic crisis. Having disorders like progeria syndrome, the support group, comprises of family, friends and other health professionals, play a very valuable part. In support group you will find people with progeria syndrome.
Interact with them; it will assist you to hold your sentiment regarding the emotion arising out of the condition of the child. If there is none in your group, then you can contact with the health professionals or clergymen. It will help a lot. You can inquire your doctor about the independent or self-help group in the community.
There are also other good sources of support groups in your area and you may consult with them. These are: public library, health department, telephone directory, and also internet forum. You will not be able to find progeria syndrome -specific group because the disorder is very rare. But, it is possible to find out parents of children suffering from any chronic disorders.
Helping Your Child to Cope with Progeria Syndrome
Helping a child to cope with progeria syndrome is very hard and painful. Your child with progeria syndrome may be under the spell of grief and fear because they know that their life will be cut-short because of the progeria syndrome. Your child, immediately need your support in making explanation of the notion of death taking help from religion and spirituality.
You may need to satisfy your child by answering him/her about the conditions of the family after death.
It is very important that you should talk with your child frankly and truthfully. Try to reassure within the limit of your belief system. You need to know the way of interaction to the child with progeria syndrome. The clergymen or the therapist may help you to prepare the conversation for the valuable guidance.
Your child may directly talk with the therapists for getting comfort and solace for progeria syndrome.
8 Risks and Complications
There are several complications associated with progeria.
Progeria is an irreversible disorder. The rapid onset of premature aging is not preventable, which causes many complications to arise:
Atherosclerosis (severe hardening of arteries) - which causes blood vessels to stiffen and thicken, restricting blood flow
If blood fails to adequately flow to the heart or to the brain, other complications may arise, including: Heart attack, Congestive heart failure, Stroke, Seizures
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