Progeria

Progeria aging

Overview of Progeria

The statistics of the Global Genes have shown that nearly 350 million people worldwide suffer from some severe and rare diseases. These diseases are mainly genetic and are mostly present at birth. The reports of the joint initiatives of the World Health Organization (WHO) and the March of Dimes (MOD) established that congenital defects of different forms accounted for nearly 7% of the neonatal mortalities across the globe. Progeria is one such rare genetic disorder which has a prevalence of about 1 in 4-8 million new births (source: factsheets of Progeria Research Foundation).

It is one of the rarest diseases in the world that causes accelerated aging in small children. Medical teams all over the world are working towards developing some effective treatment for this disease. Efforts are being directed more towards the genetic treatments which can be started right from the gestation period, in order to facilitate the birth of a healthy child.

 

What is Progeria?

progeria dnaProgeria is a rare genetic disease, found in very few neonates all over the world that is characterized by abnormal premature aging and associated cardiovascular disorders. The disease derives its name from the Greek word “pro” that means early and “geros” meaning old age. The occurrence of the disease was jointly discovered by Hutchinson and Gilford in the year 1897. Hence the disease is also known as Hutchinson Gilford Progeria Syndrome (HGPS).

Progeria mainly arises due to genetic mutations, which is partly determined by the age of conception of the mother. The children affected with Progeria do not usually live for more than 14-15 years. Although the incidence rate of the disease is very low, at present nearly 200-250 children throughout the world have Progeria at any one time.

 

What causes Progeria?

Progeria mainly arises from genetic factors. Till date, several genetic theories have been put forward to explain the exact cause of Progeria. Scientists have discovered an existing link between the rate of aging and the length of the telomere. The repetitive sequence TTAGGG which cap the individual chromosomes (atelomere) reduce in length after each replication. On reaching a critical length, the telomere becomes senescent and cannot undergo further division. This abnormal and untimely shortening of telomeres is the main contributor of Progeria.

Research results have proved that nearly 90% of the Progeria patients have a mutation in the position 1824 of the LMNA gene. An unstable form of a particular protein called Lamin A is generated due to the unexplained replacement of the cytosine with thymine in the aforementioned location.

Through some other research works it has been established that in the Hutchinson Gilford Progeria Syndrome, a major mutation occurs at the site where the enzyme normally performs the cleavage of the prelamin A to form the Lamin A protein. In such cases, the prelamin A accumulates on the nuclear membrane, leading to nuclear blebbing (bulge formation). This phenomenon contributes to the premature aging symptoms of Progeria.

 

What are the visible symptoms of Progeria?

Progeria agingProgeric children are easily identified through a few conspicuous syndromes. All these symptoms are associated with the phenomenon of aging. These listed below in different categories-

Growth symptoms

  • Reduced or stopped growth
  • Short stature
  • Weight disproportionate with height
  • Abnormally large and tilted head

Body fat

  • Abnormally reduced subcutaneous fat
  • Prominent and protruded veins on the scalp

Teeth

Skeletal system

  • Occurrence of distal phalangeal osteolysis
  • Delayed closure and stability of the anterior fontanelle
  • Malformed pear-shaped thorax
  • Micrognathia
  • Clavicle dystrophy
  • Abnormal stance
  • Coxavalga
  • Extremely tightened joint ligaments
  • Very thin and weak limbs

Skin

  • Extremely dry, wrinkled skin (toad skin)
  • Occurrence of brownish pigmentations in different regions
  • Occurrence of sclerodermatous skin over the proximal thighs and the lower abdomen
  • Irregular bumps on the skin (due to lipodystrophy)
  • Dystrophic nails
  • Alopecia (absence of hair and eyebrows)

Other symptoms

  • Bulging out eyes
  • Lagophthalmos
  • Shuffling and a wide-based gait
  • Pinched nose
  • Formation of an abnormally curved nasal tip
  • Projecting ears, with no earlobes

 

What are the different types of Progeria?

Progeria does not exactly have subtypes. But the different types of progeroid symptoms that arise from gene mutations are discussed below-

  • Hutchinson Gilford Progeria Syndrome: It is caused by the mutations in the LMNA3-5 The child exhibits retarded growth right from a year after birth. The other prominent symptoms are- skin atrophy, osteolysis, alopecia and cardiovascular disorders.
  • Werner’s syndrome: The WRN12 gene mutation is responsible for this disease. In this case, the symptoms start manifesting themselves during the teenage. These children suffer from atherosclerosis, cataract, skin atrophy and osteoporosis.
  • Tay’s syndrome: It occurs due to the mutations in the ERCC2 or ERCC3 gene. This is characterized by congenital ichthyosis, erythroderma, and brittle hair.
  • Cockayne’s syndrome: Mutations in the ERCC6 and the ERCC819 gene leads to this disease. The main symptoms are- atypical photosensitivity, poor development of the nervous system, impaired cognitive skills, auditory disorders and retarded growth. 

Diagnosis of Progeria

Progeria can be accurately detected through the following diagnostic tests-

  • Urinary hyaluronic acid testing: Progeria patients exhibit an abnormally high concentration of hyaluronic acid in the urine and low levels of the essential antioxidant enzymes in the blood.
  • Prenatal testing: Progeria can be detected in the prenatal stage itself by analyzing the DNA extracted from the fetal cells.

 

Is there any treatment for progeria?

There is no treatment for the disease as yet.  The focus is mainly on the symptomatic relief. Since a child suffering from progeria may face cardiac issues, medications (low-dose aspirin) may be administered in order to reduce the risk of heart problems. Surgical interventions such as angioplasty and bypass surgery might be required in order to delay the progression of the disease.

Medications for lowering the blood cholesterol levels (statins), blood pressure levels are given. Medications might be given for easing headaches and seizures. Since the child has a short stature, growth hormone may be administered in order to help the child gain height and weight. The problem of arthritis leading to painful and stiff joints can be eased by occupational therapy and physiotherapy. Additional measures of cushioned shoes, comfortable chairs etc. can comfort the child a bit. The affected child is prone to dental problems. Seeking advice from a pediatric dentist can help in enabling the child to lead a normal life by taking a balanced diet.

Progeria is a very rare disease caused by a gene mutation. Method of prevention of the disease is still unknown.

 

Facts

  • This condition is also known as Hutchinson-Gilford Progeria Syndrome.
  • It is an extremely rare disease affecting only 1 out of 8 million births. Currently, there are only 80 known cases of progeria globally.
  • In one year, a progeria patient typically ages as much as a normal person does in 10 years. During a lifespan of 12-14 years, they age an equivalent of 100+ years.

Facts

  • Surprisingly, this condition doesn’t affect the individual’s intellectual or motor skills.
  • There are genetic tests available for detecting this condition.
  • The most common reason for death amongst progeria patients is a stroke, caused by hardening of arteries (arteriosclerosis).

Facts

  • Out of every 8 million people, only 1 person gets this disease.
  • It is a 100% fatal disease.
  • Until the 1990s, research on progeria could not be even initiated due to the rarity of the disease.
  • See a doctor when the baby starts showing the characteristic signs of premature aging.
  • Regularly check the vital parameters and the blood pressure. Since progeria affects the blood vessels, it might lead to a heart attack or a brain stroke.
  • Get a genetic test done to confirm the diagnosis of progeria and rule out other diseases having similar manifestations. A gene test for the LMNA gene is done to confirm the diagnosis.

Related Conditions

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Dos and Don'ts

Dos
  • See a doctor when the baby starts showing the characteristic signs of premature aging.
  • Regularly check the vital parameters and the blood pressure. Since progeria affects the blood vessels, it might lead to a heart attack or a brain stroke.
  • Get a genetic test done to confirm the diagnosis of progeria and rule out other diseases having similar manifestations. A gene test for the LMNA gene is done to confirm the diagnosis.
Don'ts
  • Push the child or persuade the child for physical activities like a normal child. A child suffering from progeria usually has arthritis and cardiac issues which makes it very difficult to be on par with normal children.
  • Hesitate to seek help from doctors, friends and support groups. Progeria is a very rare disease, the path of the disease is unpredictable and the doctor can help your child deal with it.

 

 

 

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