What Is Hutchinson-Gilford Progeria Syndrome?

Aging is a natural part of life, but some health conditions rapidly speed up the process. One of those conditions is called Hutchinson-Gilford progeria syndrome (HGPS). This rare genetic disorder causes a dramatic appearance of aging that starts in childhood.

HGPS, also known as progeria, is a fatal genetic condition that causes children to develop symptoms that look like premature aging. HGPS very rare, affecting one in four million people worldwide. In 2023, 212 children in 51 countries had been identified as having HGPS or related health conditions called progeroid laminopathies.

HGPS made headlines in January 2022 after YouTube star Adalia Rose died of the condition at 15 years old. Williams regularly posted about her health condition and life on YouTube, where she built up nearly three million followers.

Hutchinson-Gilford Progeria Syndrome Symptoms

People with HGPS usually have a normal appearance as infants but start to show symptoms between 9 and 24 months. During that time, their growth slows down.

"Early on, in the first couple of years of life, you might get a hint that someone has Hutchinson-Gilford progeria syndrome with a kid that isn't growing as much and has a distinctive look," Caleb Bupp, MD, a medical geneticist and assistant professor at Michigan State University, told Health.

Besides a below-average height and weight, other HGPS symptoms include:

• A narrowed face, small lower jaw, thin lips, and beaked nose
• A head that is disproportionately large for the face
• Prominent eyes and incomplete closure of the eyelids
• Hair loss, including eyelashes and eyebrows
• Thinning, spotty, wrinkled skin
• Visible veins
• A high-pitched voice
  

What Causes Hutchinson-Gilford Progeria Syndrome?

A mutation in a single gene, called lamin A (LMNA), causes HGPS. LMNA makes a protein necessary for holding the nucleus in each cell together. A mutant form of the LMNA protein, or progerin, makes cells unstable and speeds up aging.

Rarely do parents have a family history of HGPS. Parents are unlikely to pass this gene down to children, Susan Dulkerian, MD, chair of the department of pediatrics and medical director of newborn services in the Family Childbirth and Children's Center in Maryland, told Health. 

Instead, a "new mutation of the gene that was not present in either parent" causes HGPS, said Dr. Dulkerian.

You cannot prevent HGPS since a random genetic mutation causes the condition. There is also very rarely a family history of the disease that would lead you to suspect the syndrome or prompt genetic testing.

How Is Hutchinson-Gilford Progeria Syndrome Diagnosed?

Some healthcare providers can spot the physical signs of HGPS. Still, most people would not recognize the rare features, Milen Velinov, MD, PhD, an associate professor at the Rutgers Robert Wood Johnson Medical School.

Once healthcare providers suspect a child might have HGPS, they can refer them for comprehensive genetic testing. Other health conditions can cause premature aging, but healthcare providers can use genetic testing to diagnose HGPS.

"Now that we know the gene that causes it, we can definitively diagnose someone with Hutchinson-Gilford by finding the change in the LMNA gene," said Dr. Bupp.

Treatments for Hutchinson-Gilford Progeria Syndrome

There is no cure for HGPS. Instead, healthcare providers focus on treating symptoms and providing physical therapy. Healthcare providers help manage heart disease, said Dr. Dulkerian. Most children with HGPS die from heart failure, heart attack, or stroke.

Children might also take Zokinvy (lonafarnib), which helps prevent the buildup of defective progerin or progerin-like proteins. The Food and Drug Administration approved Zokinvy to treat HGPS in November 2020.

Side effects of Zokinvy may include:

• Fatigue
• Loss of appetite
• Nausea
• Vomiting
• Diarrhea

In a clinical trial, 62 people who took Zokinvy had increased lifespans by an average of three months through the first three years of treatment. Their lifespans increased by 2.5 years after taking Zokinvy for 11 years.

"[HGPS] is a condition that is pretty challenging. We know that the lifespan is capped at 20 years. That is heartbreaking," said Dr. Bupp. "When you have the possibility of finding a treatment for it, it's incredibly exciting."

Other HGPS treatments focus on managing each person's unique symptoms and complications. Healthcare providers may advise one or more of the following as part of an individualized treatment plan:

• Low-dose aspirin to help prevent heart attacks and stroke
• Medications to lower cholesterol and blood pressure and prevent blood clots
• Physical and occupational therapy to help with joint stiffness and hip problems
• Nutritious, high-calorie foods and supplements to maintain weight

Despite treatments for HGPS, the lifespan of people with the disease may still be short. Symptoms involve several systems, Robert Hegele, MD, a professor of medicine at the University of Western Ontario, told Health.

Comorbid Conditions

People with HGPS may have a high risk of developing health conditions like:

• Severe progressive heart disease
• Skin hardening and tightening
• Delayed or abnormal tooth formation
• Muscle mass loss
• Fat loss
• Skeletal abnormalities
• Fragile bones
• Stiff joints
• Hip dislocation
• Type 2 diabetes

Living With Hutchinson-Gilford Progeria Syndrome

HGPS does not affect a child's intellectual development or motor skills like sitting, standing, and walking. Though, HGPS is a fatal disease. Treatment focuses on managing symptoms, prolonging life, and maintaining the quality of life.

All people with HGPS die of heart disease typical of much older adults. The average lifespan is 14.5 years. Leon Botha, a DJ and artist from South Africa, was one of the oldest people with HGPS. Botha died in 2011, one day after his 26th birthday.

Since discovering the affected gene in 2003, scientists have made great strides in developing new treatments like Zokinvy. As of April 2023, more trials are underway to see if Zokinvy can work with other drugs to extend lifespan.

People with HGPS might consider joining a medical trial. The U.S. government maintains a site listing trials looking for participants at clinicaltrials.gov.

A Quick Review

HGPS is a fatal rare genetic disorder that speeds up aging, starting in childhood. Often, HGPS causes a disproportionately-shaped head, prominent eyes, hair loss, and other symptoms. All people with HGPS develop heart disease. Though, medicines can treat heart disease symptoms and extend lifespan.