Progeria

Alternate names

Hutchinson Gilford progeria syndrome; Hutchinson Gilford syndrome; HGPS

Definition

Progeria leads to extreme premature aging and affects many different body systems. The symptoms begin within a year of life with poor growth and weight gain. Children with progeria have a characteristic facial appearance with a large head, small mouth and chin, narrow nose and large eyes.

Epidemiology

It has been estimated that about 1 in 4,000,000 babies are born with progeria and about 1 in 20 million people in the world have this condition.

Cause

• Mutations in the LMNA gene cause Hutchinson-Gilford progeria syndrome.
• The LMNA gene provides instructions for making a protein called lamin A.
• This protein plays an important role in determining the shape of the nucleus within cells.
• It is an essential scaffolding (supporting) component of the nuclear envelope, which is the membrane that surrounds the nucleus.

Gene mutations

• Mutations that cause Hutchinson-Gilford progeria syndrome result in the production of an abnormal version of the lamin A protein.
• The altered protein makes the nuclear envelope unstable and progressively damages the nucleus, making cells more likely to die prematurely.
• Researchers are working to determine how these changes lead to the characteristic features of Hutchinson-Gilford progeria syndrome.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

Hutchinson-Gilford progeria syndrome is considered an autosomal dominant condition, which means one copy of the altered gene in each cell is sufficient to cause the disorder. The condition results from new mutations in the LMNA gene, and almost always occurs in people with no history of the disorder in their family.

Signs and symptoms

Signs and symptoms may include:

• Poor growth (failure to thrive)
• Large head size relative to face
• Loss of fat under the skin
• Delayed eruption of teeth and other dental abnormalities
• Baldness (alopecia)
• Stiff joints
• Thin, weak bones (osteoporosis)
• Progressive heart disease
• Normal intelligence
• In the first years of life, growth delay, loss of fat, skin changes, and baldness may occur.
• Children with progeria have many symptoms of aging typically seen in older adults.
• These can include joint stiffness, loss of teeth, osteoporosis, hearing loss, and heart disease. Most people with this condition die in their teens from a heart attack or stroke.

Diagnosis

Hutchinson-Gilford progeria syndrome (HGPS) should be suspected in individuals with severe growth failure, areas of sclerodermatous skin, partial alopecia that progresses to total alopecia by age two years, generalized lipodystrophy, retrognathia, x-ray findings including distal clavicular and terminal phalangeal resorption as well as coxa valga, and delayed/incomplete primary tooth eruption, all in the setting of normal intellectual development.[1].

Growth deficiency

• Short stature (<3rd percentile)
• Poor weight gain (<3rd percentile), weight distinctly low for height
• Diminished subcutaneous body fat globally

Facial features

• Head disproportionately large for face
• Long narrow nose
• Thin vermilion of the upper and lower lips
• Retrognathia and micrognathia
• Ectodermal

Dental. Delayed eruption and delayed loss of primary teeth, partial secondary tooth eruption, dental crowding

Skin. Taut, variably pigmented, sclerodermatous, skin outpouchings over lower abdomen and/or proximal thighs

Hair. Total alopecia, sometimes with very sparse downy immature hair remaining; loss of eyebrows

Dystrophic nails

Musculoskeletal

• Coxa valga with wide-based, shuffling gait, sometimes accompanied by avascular necrosis of the femoral head
• Osteolysis of the distal phalanges
• Short clavicles with distal resorption
• Pear-shaped thorax

Other

• Thin, high-pitched voice
• Low-frequency conductive hearing loss
• Nocturnal lagophthalmos (the inability to fully close the eyes while sleeping)

The diagnosis of classic genotype HGPS is established in a proband with the above Suggestive Findings and a heterozygous c.1824C>T pathogenic variant in LMNA identified on molecular genetic testing.

Treatment

• A regular diet with frequent small meals is recommended.
• Primary tooth extractions after the secondary tooth has erupted and/or fully descended may be required to avoid dental crowding. [2].
• Use of sunscreen on all exposed areas of skin, including the head, is recommended for outdoor activities.
• Hip dislocation is best managed with physical therapy and body bracing; reconstructive hip surgery is possible, but comorbidities of surgery in this high-risk population should be considered.
• Shoe pads are recommended, as lack of body fat leads to foot discomfort.
• Routine physical and occupational therapy, active stretching and strengthening exercises, and hydrotherapy are recommended.
• Maintain optimal hydration, while encouraging physical activity, to minimize stroke risk.
• Anticoagulation as needed for cardiovascular and neurovascular complications.
• Medication dosages are based on body weight or body surface area, not age.
• Nitroglycerin can be beneficial for angina; anticongestive therapy is routine for the treatment of congestive heart failure.
• General anesthesia and intubation should be performed with extreme caution, ideally with fiberoptic intubation, if possible.
• Exposure keratopathy can be treated with ocular lubrication.
• Hearing aids can be used when clinically necessary.
• Age-appropriate schooling with adaptations for physical needs is usually recommended.

NIH genetic and rare disease info

• NIH info on Progeria

Progeria is a rare disease.

Progeria Resources
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