What Is Progeria?

Progeria or Hutchinson-Gilford progeria syndrome (HGPS), is a rare genetic condition characterized by a rapidly aging appearance in children. Newborns and infants born with this condition typically look healthy and normal, but may physically display characteristic facial features, such as prominent eyes, protruding ears, thin nose with a beaked tip, small chin, and thin lips within their first two years of life.

They also tend to grow more slowly and gain less weight than other children (failure to thrive). This genetic condition is also called as:

• Hutchinson-Gilford syndrome
• Progeria of childhood
• Premature aging syndrome
• HGPS

Features of Progeria

This condition is reported to occur in approximately 1 in 4 million births in the world, and equally affects both sexes of all races. Other features of progeria include:

• Growth failure (usually during the first year of life)
• Macrocephaly (big head)
• Micrognathia (undersized jaw)
• Absent or delayed teeth formation
• Alopecia (hair loss)
• Aged-looking skin
• Dry, scaly, or thin skin
• Loss of body fat
• Joint abnormalities
• Similar characteristic appearance regardless of ethnic background

Children with progeria tend to develop arteriosclerosis or the severe hardening of the arteries, which increases their risk of having a stroke or heart attack at a young age. These life-threatening complications can also get worse over time. However, progeria does not affect a child’s intellectual development and motor skills, such as standing, sitting, and walking. 

What Causes Progeria?

Hutchinson-Gilford progeria syndrome is caused by LMNA gene mutations. The LMNA gene produces a protein called lamin A, which plays a significant role in keeping the cell’s nucleus together. This protein supports the nuclear envelope, which surrounds the nucleus.

Mutations occur when an abnormal version of lamin A is produced. This abnormal protein progressively damages the nucleus since it makes the nuclear envelope unstable. As a result, more cells tend to prematurely die, enabling the process of premature aging. 

Pattern of Inheritance

Progeria is an autosomal dominant condition, which means that only one copy of the mutant gene is enough to cause the disorder. This genetic condition results from new LMNA gene mutations and can occur in people without a family history of the disorder. 

Hutchinson-Gilford progeria syndrome is not usually passed down from parent to child. The gene mutation in this condition is extremely rare. 

Parents who have never had a child with HGPS may have a 1 in 20 million chance of having one. However, for parents who already had a child with HGPS, their risk of having another child with the condition increases at 2-3 percent. The reason is due to the phenomenon called mosaicism, in which one parent possesses a small proportion of genetic mutation for progeria in their cells, but does not have progeria. Genetic testing can help detect LMNA gene mutations that cause progeria. 

Diagnosis

Diagnosing progeria involves a thorough clinical evaluation of characteristic physical features, patient history, and genetic testing.

Genetic testing enables physicians to diagnose children with the condition at an early age as well as provide early treatment in the disease process. In rare cases, progeria may be recognized at birth when certain suspicious findings are noted, such as scleroderma-like skin (over the newborn’s buttocks, lower abdomen, or thighs), sculptured nose, and midfacial cyanosis. 

Certain imaging tests, such as X-ray studies, may also be performed to check for skeletal abnormalities that are potentially associated with progeria. Evaluations also include specialized cardiac tests and other clinical examinations to check for associated cardiovascular problems and provide appropriate treatment or management of the disease.

Treatment 

In 2012, results of a clinical drug trial for children with HGPS has shown that a type of farnesyltransferase inhibitor (FTI) called lonafarnib, which was developed for cancer treatment, has shown effectiveness for progeria. Each child who participated in the clinical trial showed an improvement in one or more of the following aspects:

• Weight
• Bone structure
• Hearing
• Increased blood vessel flexibility

However, lonafarnib is only available through clinical drug trials and is not FDA-approved for the treatment of progeria. For this reason, HGPS treatment usually depends on the patient’s specific symptoms.

Although there is no specific treatment for progeria, certain medications, such as statins and aspirin, may be given to help prevent a stroke or heart attack.

Management of the disorder may also require a team of specialists, which include:

• Pediatricians
• Pediatric cardiologists
• Orthopedists
• Physical therapists
• Other healthcare professionals

Related Disorders

• Hallermann-Streiff Syndrome: This rare genetic disorder is characterized by craniofacial (skull and facial) malformations along with sparse hair, dental defects, eye abnormalities, atrophy or degenerative skin changes in nasal and scalp areas, and short stature. 

• Acrogeria: Also known as Gottron’s syndrome, is an extremely rare genetic condition that is characterized by premature aging. Its characteristic features include having abnormally small hands and feet along with having thin, delicate skin. Children with this genetic syndrome usually look older than their actual age. Their hands and feet also stay abnormally small into adulthood. 

• Wiedemann-Rautenstrauch Syndrome (WRS): Also known as neonatal progeroid syndrome, is another rare genetic condition that is characterized by an old man appearance at birth, both prenatal and postnatal growth delays, and subcutaneous lipoatrophy (absence or deficiency of a layer of fat under the skin). People with WRS tend to have a decreased life expectancy. 

• De Barsy Syndrome: Inherited as an autosomal recessive genetic trait, this rare disorder is characterized by athetosis (involuntary movements of the arms and legs), degeneration of the skin’s elastic tissues, loss of muscle tone, prominent ears, and cloudy corneas. The loss of skin elasticity usually leads to an old wrinkly appearance of the skin. Infants born with this disorder may look similar to newborns who have HGPS.

• Progeroid Syndrome with features of Ehlers-Danlos Syndrome: This rare genetic condition is characterized by a progeroid appearance. Its other features include fragile skin, multiple birthmarks, scanty eyelashes, sparse eyebrows, and easy bruising. The skin may also show a wrinkled or aged appearance. 

Outlook

People with progeria have an increased risk of developing other life-threatening health problems, such as stroke and cardiovascular disorders.

The average lifespan of people with progeria is 14 years, but some may survive up to their early 20s. The cause of early death is usually associated with heart disease and stroke.

References

Hutchinson-Gilford progeria syndrome. (November 2018) https://ghr.nlm.nih.gov/condition/hutchinson-gilford-progeria-syndrome

Progeria 101/FAQ. (n.d.) https://www.progeriaresearch.org/progeria-101faq/

The PRF Diagnostic Testing Program (n.d.) https://www.progeriaresearch.org/the-prf-diagnostic-testing-program/

Learning About Progeria. (December 2013) https://www.genome.gov/11007255/learning-about-progeria/

Hutchinson-Gilford Progeria. (n.d.) https://rarediseases.org/rare-diseases/hutchinson-gilford-progeria/