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 [5] [6]:

• 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.

• Disability

  In 2003, NHGRI researchers, together with colleagues at the Progeria Research Foundation, the New York State Institute for Basic Research in Developmental Disabilities, and the University of Michigan, discovered that Hutchinson-Gilford progeria is caused [genome.gov]

  Clinical features include severe growth failure, cachectic appearance, retinopathy, hypertension, renal failure, skin photosensitivity, and intellectual disability. [merckmanuals.com]

  Instead, she became an outspoken advocate for disabled people in Milford, Connecticut. Long before it became customary to do so, "She got that town to become friendly to the disabled," Collins said. "She made it happen." [edition.cnn.com]

• Fatigue

  Most common adverse effects reported were vomiting, nausea, diarrhoea, fatigue, upper respiratory tract infection, decreased appetite and headache. The marketing authorisation for Zokinvy was recommended under exceptional circumstances. [ema.europa.eu]

  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]

  IMPORTANT SAFETY INFORMATION The most common adverse reactions are vomiting (90%), diarrhea (81%), infection (78%), nausea (56%), decreased appetite (53%), fatigue (51%), upper respiratory tract infection (51%), abdominal pain (48%), musculoskeletal pain [prnewswire.com]

  […] 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]

• Pediatric Disease

  "Eiger is advancing only the most promising, targeted therapies for rare diseases," said Lisa Porter, MD, Chief Medical Officer of Metabolic Diseases at Eiger. "Progeria is an ultra-rare, fatal, pediatric disease with no approved treatment. [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]

• Collapse

  A cell from a child with progeria collapses in on itself. (PRF) The drug lonafarnib blocks the enzyme that puts farnesyl onto lamin A protein. [blogs.plos.org]

  A cell from a child with progeria collapses in on itself. Credit: PRF The drug lonafarnib blocks the enzyme that puts farnesyl onto lamin A protein. [medicalxpress.com]

• Juvenile Cataract

  The characteristics of this syndrome are: Shortness of stature, characteristic habitus Canities (i.e., premature graying of the hair) Premature baldness Scleropoikiloderma Trophic ulcers of the legs Juvenile cataracts Hypogonadism Tendency to diabetes [annals.org]

• Failure to Thrive

  Affected children typically look normal at birth and in early infancy, but then grow more slowly than other children grow and do not gain weight at the expected rate (failure to thrive). [secure.ssa.gov]

  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]

  Search Search for a rare disease Hutchinson-Gilford progeria syndrome Disease definition Hutchinson-Gilford progeria syndrome is a rare, fatal, autosomal dominant and premature aging disease, beginning in childhood and characterized by growth reduction, failure [orpha.net]

• Heart Disease

  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. [symptoma.com]

  Characteristics & Signs: 1) Growth failure 2 ) Loss of body fat and hair 3) Aged-looking skin 4) Stiffness of joints 5) Hip dislocation 6) Heart diseases Since children with Progeria experience premature aging they will experience diseases associated [progeria2010researchproject.weebly.com]

  Children typically experience medical issues that are usually associated with older age, such as hair loss, bone changes, hearing loss, joint stiffness, atherosclerosis (hardening of the arteries), and heart disease. [thinkgenetic.com]

  Children with Progeria are genetically predisposed to premature, progressive heart disease. Death occurs almost exclusively due to widespread heart disease, the leading cause of death worldwide. [progeriaresearch.org]

• Osteoporosis

  […] bilateral talus deformities of the feet, bilateral dislocated hips, pes planus, a fractured femur (which healed without complications), aseptic necrosis in the left nuclear head of the femur, bilateral fixed hip flexion deformities, bone dysplasia, osteoporosis [ncbi.nlm.nih.gov]

  SUGGESTED PROGRAMMATIC ASSESSMENT* Suggested MER for Evaluation: • Clinical history and examination documenting characteristic physical findings; • Genetic testing reports for LMNA mutation; • Imaging of the skeleton showing diffuse osteopenia/osteoporosis [secure.ssa.gov]

  […] primary clinical manifestations of progeria include short stature and skin changes, the disease is associated with a variety of imaging manifestations 1,2: erosion of superior aspects of ribs osteolysis of distal clavicle acro-osteolysis Wormian bones osteoporosis [radiopaedia.org]

• Hip Dislocation

  Characteristics & Signs: 1) Growth failure 2 ) Loss of body fat and hair 3) Aged-looking skin 4) Stiffness of joints 5) Hip dislocation 6) Heart diseases Since children with Progeria experience premature aging they will experience diseases associated [progeria2010researchproject.weebly.com]

  Orthopedic manifestations of HGPS are multiple and shoulder dislocation is a rare skeletal trauma in progeria syndrome. Our patient had simultaneous shoulder and hip dislocation associated with a low energy trauma. [ncbi.nlm.nih.gov]

  They also often suffer from symptoms typically seen in much older people: stiffness of joints, hip dislocations and severe, progressive cardiovascular disease. [genome.gov]

  Progeria signs include growth failure, loss of body fat and hair, aged-looking skin, stiffness of joints, hip dislocation, generalized atherosclerosis, cardiovascular (heart) disease and stroke. [progeriaresearch.org]

• Joint Stiffness

  Children typically experience medical issues that are usually associated with older age, such as hair loss, bone changes, hearing loss, joint stiffness, atherosclerosis (hardening of the arteries), and heart disease. [thinkgenetic.com]

  Characteristic features include: Baldness, prominent scalp, veins and eyes, small jaw, delayed tooth formation Thin limbs with prominent joints, short stature, joint stiffness, hip dislocations Thickened, tight and shiny skin over joints. [dermnetnz.org]

  stiffness Stiff joint Stiff joints [ more ] 0001387 Lipoatrophy Loss of fat tissue in localized area 0100578 Micrognathia Little lower jaw Small jaw Small lower jaw [ more ] 0000347 Multiple joint contractures 0002828 Narrow mouth Small mouth 0000160 [rarediseases.info.nih.gov]

  Children with progeria age too quickly, developing symptoms common in much older people, such as joint stiffness and heart disease. [fiercebiotech.com]

  These include, onset of heart disease, hearing loss, insulin resistance, fragile bones, development of scleroderma, hip dislocation, stiff joints and abnormal tooth formation. [symptoma.com]

• Alopecia

  ICD-9: 259.8 PROGRESSION Children with HGPS usually appear normal at birth with signs of the disease occurring at age 6 – 12 months, with skin changes, alopecia, and failure to thrive. [secure.ssa.gov]

  Hutchinson-Gilford progeria syndrome also causes hair loss (alopecia), aged-looking skin, joint abnormalities, and a loss of fat under the skin (subcutaneous fat). [checkorphan.org]

  Congenital absence of hair and mammary glands with atrophic condition of the skin and its appendages in a boy whose mother had been almost wholly bald from alopecia areata from the age of six. [whonamedit.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]

• 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]

• Beaked Nose

  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]

• Stroke

  The cause of death is very often related to the heart or a stroke. [mountsinai.org]

  The cause of death is usually related to the heart or a stroke. [nicklauschildrens.org]

  Both large and small vessel disease are present, and strokes are often clinically silent. [ncbi.nlm.nih.gov]

  Some children receive treatment includes growth hormone, medication to prevent heart attacks and stroke, and physical and occupational therapy. [medcraveonline.com]

• Seizure

  Frequency of clinical strokes, headaches, and seizures was reduced from pretrial rates. [ncbi.nlm.nih.gov]

  Depending on your child’s symptoms, the doctor may recommend the use of statins to lower cholesterol, anticoagulants to prevent blood clots, and medications to help reduce blood pressure, headaches, and seizures. [centromedicoabc.com]

  The prevalence of stroke, transient ischemic attack (TIA) and seizures was reduced, as well as the frequency of headaches was lower than the rates before the trial. [pharmaceutical-technology.com]

  Imaging studies (such as magnetic resonance imaging, or MRI): These can be used to watch for strokes, or to check on headaches or seizures, both of which are common in these children. [my.clevelandclinic.org]

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 [7].

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 [8].

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 [9] [10].

The prognosis of the condition is very poor as there is no cure for this disease. The development of cardiac problems and stroke is the major cause of death in children with progeria disease. Therefore, administration of medications may slow down the onset of heart disease and other conditions [4].

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 [2]. 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 [3].

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 [1].

Definition

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 [11].

Cause

Genetic mutation in a single gene is known to trigger the development of progeria syndrome.

Symptoms

Symptoms of progeria syndrome include development of scleroderma, enlarged head, kidney failure, poor eyesight, wrinkled skin, hair loss and cardiac diseases.

Diagnosis

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.

Treatment

Porgeria cannot be treated. But, the symptoms can be managed with medications and supportive therapies.

1. Ding SL, Shen CY. Model of human aging: recent findings on Werner's and Hutchinson-Gilford progeria syndromes. ClinInterv Aging. 2008;3(3):431-44.
2. Scaffidi P, Misteli T. Lamin A-dependent nuclear defects in human aging. Science. May 19 2006;312(5776):1059-63.
3. Dechat T, Pfleghaar K, Sengupta K, et al. Nuclear lamins: major factors in the structural organization and function of the nucleus and chromatin. Genes Dev. Apr 1 2008;22(7):832-53.
4. Merideth MA, Gordon LB, Clauss S, Sachdev V, Smith AC, Perry MB, et al. Phenotype and course of Hutchinson-Gilford progeria syndrome. N Engl J Med. Feb 7 2008;358(6):592-604.
5. Olive M, Harten I, Mitchell R, Beers JK, Djabali K, Cao K, et al. Cardiovascular pathology in Hutchinson-Gilford progeria: correlation with the vascular pathology of aging. Arterioscler Thromb Vasc Biol. Nov 2010;30(11):2301-9.
6. Guardiani E, Zalewski C, Brewer C, Merideth M, Introne W, Smith AC, et al. Otologic and audiologic manifestations of Hutchinson-Gilford progeria syndrome. Laryngoscope. Oct 2011;121(10):2250-5.
7. Sevenants L, Wouters C, De Sandre-Giovannoli A, et al. Tight skin and limited joint movements as early presentation of Hutchinson-Gilford progeria in a 7-week-old infant. Eur J Pediatr. May 2005;164(5):283-6.
8. Cleveland RH, Gordon LB, Kleinman ME, Miller DT, Gordon CM, Snyder BD, et al.A prospective study of radiographic manifestations in Hutchinson-Gilford progeria syndrome. PediatrRadiol. Sep 2012;42(9):1089-98.
9. Sadeghi-Nejad A, Demmer L. Growth hormone therapy in progeria. J PediatrEndocrinolMetab. May 2007;20(5):633-7.
10. Zaremba-Czogalla M, Dubinska-Magiera M, Rzepecki R. Laminopathies: the molecular background of the disease and the prospects for its treatment. Cell MolBiolLett. Mar 2011;16(1):114-48.
11. Kieran MW, Gordon L, Kleinman M. New approaches to progeria. Pediatrics. Oct 2007;120(4):834-41.
12. Zaremba-Czogalla M, Dubinska-Magiera M, Rzepecki R. Laminopathies: the molecular background of the disease and the prospects for its treatment. Cell Mol Biol Lett. Mar 2011;16(1):114-48.