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.

• Pain

  Severely restricted blood flow in the heart muscle leads to symptoms such as chest pain. Causes Progeria is a rare condition. It is remarkable because its symptoms strongly resemble normal human aging, but it occurs in young children. [mountsinai.org]

  We report the case of a 13-year-old male treated for pericoronitis and oral pain relating to delayed eruption of first permanent molars. [ncbi.nlm.nih.gov]

  Degenerative changes of the hip socket may result in a hip deformity in which there is an abnormal increase in the angle of the thigh bone (coxa valga), hip pain and hip dislocation. [rarediseases.org]

  "She no longer dey in pain and now dancing away to all di music wey she love. I really wish say dis no be our reality but unfortunately na im. "We want say thank you to everyone wey bin love and support her. [bbc.com]

• Weakness

  Characteristic features include: A striking difference between a person's appearance and his/her real age Greying hair and/or balding, wrinkling and ageing of the face, sunken cheeks, small jaw Small stature (usually less than 1.6m tall), muscle weakness [dermnetnz.org]

  Researchers are working to determine how these changes affect muscle cells and lead to muscle weakness and atrophy in people with L-CMD. [ghr.nlm.nih.gov]

  Mild proximal weakness, contractures, and rigidity of the spine were the primary findings. [doi.org]

  They are prone to developing osteoporosis, a disease where bones become weak and are more likely to break. "All in all, I don't waste energy feeling bad for myself," Berns said. "I surround myself with people that I want to be with. [cnn.com]

• Congestive Heart Failure

  Patients live a median of 13.4 years and die of heart attacks or congestive heart failure. HGPS is caused by the mutation in nuclear lamin A/C (LMNA) gene. It is a very rare condition; it affects one in 4 million newborns worldwide. [eurasnet.info]

  Most children with progeria die of complications related to atherosclerosis, including: Problems with blood vessels that supply the heart (cardiovascular problems), resulting in heart attack and congestive heart failure Problems with blood vessels that [mayoclinic.org]

  Furthermore the development of sleep-related respiratory disorders such as obstructive sleep apnea (OSA) and central sleep apnea or Cheyne-Stokes respiration (CSA-CSR) associated with congestive heart failure (CHF) occur with increasing prevalence in [ncbi.nlm.nih.gov]

  Heart attack. Congestive heart failure. [centromedicoabc.com]

  heart failure Cardiac failure Cardiac failures Heart failure [ more ] 0001635 Generalized osteoporosis 0040160 Growth delay Delayed growth Growth deficiency Growth failure Growth retardation Poor growth Retarded growth [ more ] 0001510 Malar flattening [rarediseases.info.nih.gov]

• 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]

• Macrocephaly

  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]

  Symptoms Symptoms include: Growth failure during the first year of life Narrow, shrunken or wrinkled face Baldness Loss of eyebrows and eyelashes Short stature Large head for size of face ( macrocephaly ) Open soft spot (fontanelle) Small jaw ( micrognathia [mountsinai.org]

  Symptoms Growth failure during the first year of life Narrow, shrunken or wrinkled face Baldness Loss of eyebrows and eyelashes Short stature Large head for size of face (macrocephaly) Open soft spot (fontanelle) Small jaw (micrognathia) Dry, scaly, thin [nicklauschildrens.org]

  Symptoms Symptoms include: Growth failure during the first year of life Narrow, shrunken or wrinkled face Baldness Loss of eyebrows and eyelashes Short stature Large head for size of face (macrocephaly) Open soft spot (fontanelle) Small jaw (micrognathia [ufhealth.org]

• Hip Pain

  Degenerative changes of the hip socket may result in a hip deformity in which there is an abnormal increase in the angle of the thigh bone (coxa valga), hip pain and hip dislocation. [rarediseases.org]

• 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]

  Although cranial hair loss will begin around 10 months of age, HGPS patients will gradually lose body hair and eyebrows until progressing to almost complete alopecia. [news-medical.net]

  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]

• Eruptions

  Orthodontic procedure commencement should be early enough to manage the delayed development and eruption of teeth. Patients taking oral biphosphonates should be advised of this potential complication. [ncbi.nlm.nih.gov]

  […] of teeth Delayed eruption Delayed teeth eruption Delayed tooth eruption Eruption, delayed Late eruption of teeth Late tooth eruption [ more ] 0000684 Failure to thrive Faltering weight Weight faltering [ more ] 0001508 High pitched voice 0001620 Hyperinsulinemia [rarediseases.info.nih.gov]

  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]

• 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]

• Skin Disease

  diseases See the DermNet NZ bookstore . [dermnetnz.org]

  When Bella first raised concerns about Phalatse with doctors, they thought she had a skin disease and tried to treat it with creams. The doctors decided to sign a contract with the Progeria Research Foundation in the United States. [news24.com]

• Flushing

  Patient 2 had staring spells, diaphoresis, and flushing; a previous electroencephalogram suggested diffuse encephalopathy. Pseudotumor cerebri was diagnosed in this child at the NIH at 21 months of age. [doi.org]

• 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]

• Kidney Failure

  Later, the condition causes\n Wrinkled skin Atherosclerosis Kidney failure loss of eyesight Cardiovascular problems. A hardening and tightening of the skin called Scleroderma on trunk and extremities of the body, is prevalent. [play.google.com]

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

  Later, Progeria causes wrinkled skin, atherosclerosis, kidney failure, loss of eyesight, and cardiovascular problems. Scleroderma, a hardening and tightening of the skin on trunk and extremities of the body, is prevalent. [teamcarlyq.com]

  Health issues associated with progeria have much in common with illnesses often suffered by the elderly, including loss of eyesight, kidney failure and heart problems. [dailymail.co.uk]

• Dizziness

  Basso’s slight frame embodies a dizzying span of human experience. He is a young man who appears old, an adult sometimes patronized like a child. He is a scientist and a devout Catholic, a clinical trials patient and a researcher. [nytimes.com]

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.

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