Have you ever wondered what a single gene alteration in our body could do? 

Imagine a condition where such a change ages a child’s body at an alarming rate, robbing them of the innocence of youth before they’ve had the chance to truly experience it. 

Yes, this condition exists and is called progeria, or Hutchinson-Gilford progeria syndrome (HGPS). Well, this is the classical progeria that most of you may have heard of, but there are other types of progeria which mostly differ in the time of their onset. One of them is Werner syndrome, or adult progeria, which sets on during early adulthood.

In this article, we’ll discuss majorly about the symptoms and causes of classical progeria, and very briefly about some other similar syndromes.

What is progeria?

Hutchinson-Gilford progeria syndrome is a rare, fatal genetic disorder characterised by traits resembling premature ageing in children. The disease was named after two scientists, Jonathan Hutchinson and Hastings Gilford, who described it in the late 1800s.¹

Progeria affects around 1 in 20 million people globally, but in newborns, it is slightly more common with an incidence of 1 in 4 million births. Unfortunately, children with progeria don’t live very long. They usually pass away between the ages of 6 and 20 years due to complications of the brain or heart, such as atherosclerosis, heart failure, and strokes.²

Atherosclerosis happens when your arteries get blocked, and it's a major cause of death for many adults. However, in children with progeria, it manifests at a very young age, often severely, and ultimately leads to death.²

What are the signs and symptoms of progeria? 

Newborns with progeria appear healthy at birth. But within a year or two, they start to show signs of ageing, such as slow growth and hair loss. Surprisingly though, their intelligence and cognitive abilities remain unaffected. However, rapid ageing does lead to some noticeable symptoms later in life.¹ These may be classified as:

Dermatological defects

These refer to conditions affecting the skin, hair, and nails. Dermatological issues seen in progeria include:³ 

• Thin, dry, and wrinkled skin, with varied pigmentation, resembling scleroderma
• Hair loss advancing from partial to complete baldness (total alopecia)
• Loss of eyelashes and eyebrows
• Deformed or discoloured (dystrophic) nails
• Hardening and tightening of skin with time

Skeletal, growth, and facial defects

These include growth defects, and deformities in the skeleton and the structure of facial bones. Such anomalies seen in children with progeria are:^4,5,6

• Short stature, due to poor growth
• Larger head in proportion to the face (macrocephaly)
• Long and thin beak-shaped nose
• Lean appearance due to loss of body fat under skin (subcutaneous fat)
• Visible scalp veins
• A soft spot on the head, called fontanelle, which normally closes with age, remains open
• Small lower jaw (micrognathia), positioned posteriorly (retrognathia)
• Thin lips with a bluish tinge (circumoral cyanosis)
• Late formation of teeth; irregular and crowded teeth observed
• Abnormal skull development
• Swollen and stiff joints, limiting movement and often causing osteoarthritis
• Hip dislocation, i.e., hip displaced from its correct position
• Narrow sunken pear-shaped chest
• Smaller and weaker bones than normal, e.g., shortened collar bones 

Abnormalities in other organ systems

Symptoms of progeria also include issues with the heart (cardiovascular system), sensory organs (ears and eyes), and hormones (endocrine system), such as:^3,6

• Severe heart disease, due to plaque buildup in arteries
• Not being able to fully close eyes while sleeping (nocturnal lagophthalmos)
• Loss of hearing 
• Ear lobes small or absent
• Clouding of eye lens, called cataract
• Lack of sexual maturation
• Body not responding well to the hormone insulin, called insulin resistance

Children with progeria also tend to speak in a thin, high-pitched voice. Apart from these symptoms, their immune system, liver, kidney, and gastrointestinal (stomach) functions are normal.³

When to consult a doctor?

Progeria is often identified in infants or young children during routine check-ups when they begin displaying signs of premature ageing. The symptoms are quite evident. If you notice any signs or symptoms of progeria in your child, you must immediately book an appointment with their doctor (paediatrician). 

The doctor will examine your child’s body, assess their ability to hear and see, and monitor how they’re growing compared to other kids the same age. Should the doctor have any concerns, they may suggest a blood test to confirm the diagnosis.

What causes progeria?

Progeria is caused by a change (mutation) in a gene called LMNA. This gene normally makes a protein called Lamin A in our body, which keeps the centre of the cell, nucleus, intact. But when a mutation occurs in the LMNA gene, it produces a faulty protein (mutated Lamin A) called progerin, instead. 

Progerin buildup in cells disrupts the covering of the nucleus (nuclear membrane), making the cell unstable and shortening its life span. This cell instability causes early cell death which inturn leads to premature ageing.⁷

The change in the LMNA gene is an autosomal dominant mutation, which means that only one copy of the mutated gene from either parent is enough to cause the disorder. However, progeria is almost never passed down in families. Almost all cases of the disease occur due to a new (sporadic) mutation that happens by chance during early cell division in the child.⁸

Only a few cases of progeria have been seen where both siblings have the condition, suggesting an autosomal recessive pattern. This means both parents carry one copy of the mutated gene for progeria but don't have the condition themselves.⁸

Are there any risk factors for progeria?

• Progeria affects people from all genders, races, and locations equally. Since the disorder is caused due to an extremely rare mutation, there are no surely known risk factors linked with it⁹ 
• However, if someone has had a child with progeria, there’s a 2-3% higher chance of having another child with the disorder. This happens because of a phenomenon called mosaicism, which means that some cells of a parent will have the mutation, while others will not. If this mutation is in the parent’s reproductive (germ) cells, i.e., sperm or egg cells, it will most likely pass to the child⁹
• Most cases of HGPS caused by new LMNA mutations originate from the father, especially if they’re older. Therefore, the father's age is seen as a possible risk factor for progeria¹⁰

Other similar syndromes

There are several other rare syndromes characterised by signs of early ageing as seen in HGPS. These are called progeroid syndromes. The two most commonly known progeroid syndromes, apart from HGPS are:

Weidemann-Rautenstrauch syndrome

This condition is also called neonatal progeroid syndrome and it’s inherited in an autosomal recessive pattern. It starts in the womb itself and the signs of ageing become apparent right from birth. The newborn has an aged appearance, also called “old man look”.¹¹ 

Werner syndrome

Also called adult progeria, Werner syndrome develops during the early teenage years. It is characterised by ageing symptoms, more commonly seen in old age, such as cataracts and early greying of hair. Werner syndrome is also inherited in an autosomal recessive pattern.¹

Some other less known progeroid syndromes include trichothiodystrophy, Cockayne syndrome, Rothmund-Thomson syndrome, Bloom syndrome, ataxia-telangiectasia, and xeroderma pigmentosum. All these disorders lead to shortened life spans and are caused by mutations in genes that help in repairing our genetic material, DNA.¹

Summary

Progeria is a rare but deadly disease without any cure. Discovering that you or your child has it can be very stressful. But there are treatment options available to slow down the progression of the disease. Your doctor will support and guide you through this journey. Moreover, joining support groups may provide you comfort and strength. Connecting with others, asking questions, and sharing similar experiences will remind you that you’re not alone in this.

FAQs

Can my child with progeria attend school?

Yes, your child can attend school like many other children with progeria do. However, they might need some adjustments to feel comfortable and fully participate in activities. It’s important for you to regularly interact with school staff, including nurses, therapists, and teachers so that everyone can share strategies and advice on how to best support your child.

 You should also make sure that the school has proper emergency care facilities in case your child needs them, for example, if they get short of breath or have sudden chest pain because of too much activity.

Is there a way I can treat progeria?

While there's no cure for progeria, researchers are progressing in finding drugs to help manage its symptoms. Lonafarnib, an FDA-approved drug, has been shown to extend the lives of children with progeria by about 2.5 years and improve weight gain, bone structure, and heart function. Surgery to open blocked blood vessels or replace damaged heart valves can also help patients in the later stages of the disease. Additionally, physical therapy may help your child improve mobility, and balance, and reduce pain in hips and feet.