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Hutchinson Gilford Progeria Syndrome - Causes, Symptoms and Treatment

written by: niknak•edited by: DaniellaNicole•updated: 5/26/2010

Hutchinson Gilford progeria syndrome (HGPS) is a rare disease of accelerated aging. HGPS patients fascinate clinicians and the public alike, due to their dramatic appearance and tragically shortened lives. However, research has progressed rapidly and a cure for progeria is now considered possible.

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    What Causes Progeria ? - Progeria Genetics and Pathogenesis

    HGPS is caused by mutations in the Lamin A (LMNA) gene, leading to deletion of amino acids within the protein prelamin A. This protein is a component of the nuclear membrane, providing structural scaffolding for the cell nucleus.

    A consequence of the abnormal nuclear membrane is increased DNA damage and reduced cell division. The same mechanisms seen in cells during the normal ageing process.

    Classical Hutchinson Gilford progeria syndrome follows an autosomal dominant pattern of expression i.e. only one copy of the mutant gene is required to cause the disease. Almost all cases result from a de novo (new) mutations in the egg, sperm or developing foetus. Therefore HGPS does not run in families and the risk of having affected siblings is considered low.

    HGPS is extremely rare with an incidence of around 1 in 6 million newborns, with equal occurrence in girls and boys.

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    Progeria Diagnosis

    The clinical diagnosis of HGPS is based on recognition of common clinical features (see below) and molecular detection of mutations in the LMNA gene. Mean age of diagnosis is 2 years old.

    Based on statistical estimates the Progeria Research Foundation believe there are undiagnosed children with the condition and have launched a campaign named 'Find the Other 150'.

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    Progeria Symptoms

    Children with Hutchinson Gilford progeria syndrome look healthy at birth but show accelerated aging from around 18 months. The range and severity of symptoms in HGPS is variable, but include:

    • short stature
    • low body weight
    • early loss of hair and subcutaneous fat
    • decreased joint mobility and osteoporosis
    • aged facial features and skin.
    • cardiovascular disease e.g stroke. The majority of patients die of cardiac disease
    • Average life expectancy is around 13, ranging from 3-21 years old.
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    Treatments for Progeria – Management and Care of the Progeria Patient

    Management of HGPS patients may include:

    • Maintaining a regular diet where possible: dietary supplements may be useful.
    • Cognitive development is unaffected, therefore age-appropriate schooling is recommended.
    • Cardiac therapy: e.g treatment of angina or congestive heart failure.
    • Hip dislocation can be managed with physical therapy and body bracing. Surgery should be avoided if possible and anesthetics used cautiously.
    • Routine physical and occupational therapy: e.g. active stretching, strengthening exercises and hydrotherapy.
    • Regular electrocardiogram (ECG), lipid profiles, dental examination and hip x-rays.
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    HGPS Research – Rapid advances, Future Hopes and Wider Implications

    A significant breakthrough in HGPS research was the characterisation of the genetic mutation in 2003 and since then the field has advanced rapidly.

    Recent studies using cell cultures and mouse models of HGPS have shown that the pathology can be reduced by treatment with farnesyltransferase inhibitors (FTI) which block protein prenylation.

    Some researchers believe that this rare condition can aid our understanding of cellular pathways that are involved in the development of common age-related pathology such as cardiovascular disease and cancer.

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    FTI Trial – a Possible Cure for Progeria ?

    Trials of FTI (lonafarnib) in children with advanced HGPS are ongoing, but results are not yet available. In mouse experiments, FTI treatment was able to prevent HGPS symptoms developing. However trials in human patients aim to reverse established disease, which could be more elusive goal.

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    Support Groups and Associations

    Progeria Research Foundation - fund HGPS research, promote understanding of progeria worldwide and provide support to families affected by the condition.

    Progeria Family Circle for Europe - aim to promote a strong european progeria community. They organise family reunions in Europe and give individual aid to HGPS children and their families.

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    References

    Laminopathies and the long strange trip from basic cell biology to therapy. H.Worman, L.Fong, A.Muchir & S.Young. Journal of Clinical Investigation. 2009, Vol 119, P1825-36.

    Hutchinson-Gilford Progeria Syndrome. W.Brown, L.Gordon & F.Collins. Gene Reviews University of Washington, Seattle; Aug 2006.

    Progeria Research Foundation Website: http://www.progeriaresearch.org/