What's Hutchinson-Gilford progeria syndrome?
Hutchinson-Gilford progeria syndrome (HGPS) is an ultra-rare disorder of accelerated aging. A specific new (de novo) change in the LMNA gene makes a toxic, shortened form of lamin A called progerin, which distorts the cell nucleus and damages tissues. From infancy children show failure to thrive, hair loss, loss of body fat, tight sclerodermatous skin, prominent scalp veins, a characteristic facial appearance, and joint contractures, while intelligence stays normal. The leading cause of death is early, accelerated atherosclerosis with heart attacks and strokes, usually in the teens. This entry confirms LMNA.
| Also indexed as | OMIM:176670, MONDO:0008310 |
|---|---|
| Features mapped | 19 |
| Treatments mapped | 3 |
| Published sources | 8 |
| Last reviewed | 2026-08-04 |
Signs and symptoms
Severe failure to thrive
Children with Hutchinson-Gilford progeria usually look normal at birth, then stop gaining weight and growing as expected. This profound failure to thrive typically appears during the first year of life.
Aortic valve stenosis
The aortic valve can stiffen and narrow (calcific aortic stenosis), adding to the cardiovascular burden, especially as survival lengthens with treatment.
Stroke
Narrowing of brain arteries can cause strokes at a young age.
Myocardial infarction
Early coronary disease leads to heart attacks (myocardial infarction), often in childhood or the teens.
Atherosclerosis
In Hutchinson-Gilford progeria the arteries stiffen and clog with fatty deposits far earlier than normal. This severe atherosclerosis is the central driver of the condition, and its complications in the heart and brain are the usual cause of death, generally between ages 6 and 20.
Generalized abnormality of skin
The skin is widely affected in Hutchinson-Gilford progeria, with scleroderma-like changes in which patches of skin become hardened and tight. These skin changes appear early and are one of the features that help the condition be recognized.
Lack of skin elasticity
The skin in Hutchinson-Gilford progeria can become abnormally tight, especially over the abdomen and upper thighs, so it loses its normal give. This tightening usually becomes apparent in the first few years of life.
Absence of subcutaneous fat
Children with Hutchinson-Gilford progeria lose the layer of fat just under the skin, which makes veins more visible and contributes to the aged appearance. This loss of subcutaneous fat typically becomes apparent in the first few years of life.
Craniofacial disproportion
The skull and face grow out of proportion to each other in Hutchinson-Gilford progeria, contributing to the condition's distinctive facial appearance.
Dental crowding
The teeth often come in crowded together in Hutchinson-Gilford progeria, one of the characteristic mouth and face features of the condition.
Hypodontia
Some children with Hutchinson-Gilford progeria are missing one or more teeth, a finding seen on dental imaging in this condition.
Ankyloglossia
Some people with Hutchinson-Gilford progeria have ankyloglossia, or tongue-tie, in which the tissue anchoring the tongue to the floor of the mouth is short or tight and limits how the tongue can move.
Reduced bone mineral density
Hutchinson-Gilford progeria involves bone changes that develop early in childhood. The bones can become weaker and altered in structure, contributing to the skeletal problems seen in the condition.
Limitation of joint mobility
Joints in Hutchinson-Gilford progeria can develop contractures, meaning they become fixed and lose part of their normal range of motion. This joint contracture appears early and is one of the features that help the condition be recognized.
Joint stiffness
Joint contractures, where joints tighten and lose their full range of motion, are an early feature of Hutchinson-Gilford progeria and can help point to the diagnosis.
Growth delay
Growth slows dramatically in Hutchinson-Gilford progeria. After appearing normal at birth, children fail to gain weight and grow much more slowly than their peers, so they remain very small for their age while the rest of the body shows signs of accelerated aging.
Precocious atherosclerosis
Children with Hutchinson-Gilford progeria develop severe atherosclerosis, a hardening and narrowing of the arteries that normally occurs only in much older adults. This early, severe artery disease is a central part of the condition.
Osteolysis
Acro-osteolysis, the gradual resorption (dissolving away) of bone at the fingertips and the outer ends of the collarbones, is a characteristic skeletal feature of Hutchinson-Gilford progeria. It contributes to the short, tapering fingers and narrow shoulders seen in the condition.
Alopecia
Hair loss is one of the most recognizable signs of Hutchinson-Gilford progeria. It usually begins as patchy thinning in the first years of life and progresses to complete loss of scalp hair, eyebrows, and eyelashes.
How it is diagnosed
Hutchinson-Gilford progeria syndrome
Diagnosed using: LMNA genetic testing.
“The diagnosis of Hutchinson-Gilford progeria syndrome (HGPS) is based on recognition of common clinical features and the detection of the recurrent p.Gly608Gly mutation in exon 11 of the LMNA gene, which is present in almost all individuals with HGPS.”
Hutchinson-Gilford progeria syndrome
Diagnosed using: radiological tests.
“Diagnosis involves a clinical evaluation, along with genetic and radiological tests, for skeletal and cardiovascular abnormalities.”
Treatment and management
What the research describes, not a recommendation. Treatment decisions belong with your clinician.
This covers treatments that appear in the published research mapped here. Investigational and experimental therapies are not included, so their absence is a boundary of this map, not a sign they do not exist.
lonafarnib
Lonafarnib is an FDA-approved farnesyltransferase inhibitor and the only approved medicine for Hutchinson-Gilford progeria. It offers modest benefit by reducing how much progerin builds up and modestly improving survival; it does not cure the condition.
Used to help with: Hutchinson-Gilford progeria syndrome.
“…the farnesyltransferase inhibitor lonafarnib extends the lifespan by limiting progerin…”
supportive and cardiovascular management
Because the disease affects many systems, symptomatic and multidisciplinary care, especially close cardiovascular monitoring and management, remains the mainstay alongside lonafarnib.
Used to help with: Hutchinson-Gilford progeria syndrome.
“Symptomatic management remains the mainstay of…”
transcatheter aortic valve replacement
Transcatheter aortic valve replacement is a procedure that replaces a narrowed, calcified aortic heart valve without open-chest surgery, threading the new valve in through a blood vessel. In Hutchinson-Gilford progeria it is being explored for high-risk patients with severe aortic valve disease; it does not treat the underlying condition.
Used to help with: Hutchinson-Gilford progeria syndrome.
“Cardiovascular interventions such as transcatheter aortic valve replacement and ascending aortic constriction are being explored for high-risk patients.”
What changes how it shows up
Carrying the genetic change is not the whole story. The factors below are described in the research mapped here as changing whether, or how strongly, the condition appears. They modulate how the genotype is expressed; they do not, on their own, cause or cure it.
LMNA progerin mutation
Hutchinson-Gilford progeria is caused by a new (de novo) single-letter change in the LMNA gene. This change produces progerin, an abnormal form of the lamin A protein, which damages the cell nucleus and drives the systemic premature aging seen in the condition.
Described as modulating: Hutchinson-Gilford progeria syndrome.
“Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare genetic disorder caused by a de novo point mutation in the LMNA gene, resulting in progerin, an abnormal form of lamin A.”
skeletal dysplasia rather than osteoporosis
The bone problem in Hutchinson-Gilford progeria is best understood as a unique skeletal dysplasia, meaning the bones grow with abnormal shape and structure, rather than as osteoporosis or as bone loss from poor nutrition. On a standard DXA scan the areal bone density looks low, but this largely corrects once the result is adjusted for how small these children are, volumetric bone density is closer to normal, and fracture rates are not increased. The characteristic findings are structural: abnormal bone geometry and strength, with radiographic changes such as bone resorption rather than the thinning seen in age-related osteoporosis.
Described as modulating: Hutchinson-Gilford progeria syndrome.
“Taken together, these findings suggest that the phenotype of HGPS represents a unique skeletal dysplasia.”
How to read the evidence labels
Where this comes from
This guide is built from 8 published source(s). Every claim above links back to one of them. Click any source ID to read the original on PubMed.
Take it further
Printed, source-linked documents built from this condition's graph — ready to bring to an appointment or attach to a coverage request. Every claim carries its published source, the same as this guide.