Display Settings:

Format

Send to:

Choose Destination
We are sorry, but NCBI web applications do not support your browser and may not function properly. More information

Hutchinson-Gilford Progeria Syndrome.

Source

GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014.
2003 Dec 12 [updated 2011 Jan 06].

Excerpt

DISEASE CHARACTERISTICS:

Hutchinson-Gilford progeria syndrome (HGPS, progeria) is characterized by clinical features that develop in childhood and resemble some features of accelerated aging. Although signs and symptoms vary in age of onset and severity, they are remarkably consistent overall. Children with HGPS usually appear normal at birth. Profound failure to thrive occurs during the first year. Characteristic facies, with receding mandible, narrow nasal bridge and pointed nasal tip develop. During the first to third year the following usually become apparent: partial alopecia progressing to total alopecia, loss of subcutaneous fat, progressive joint contractures, bone changes, nail dystrophy, and abnormal tightness and/or small soft outpouchings of the skin over the abdomen and upper thighs, and delayed primary tooth eruption. Later findings include low-frequency conductive hearing loss, dental crowding, and partial lack of secondary tooth eruption. Additional findings present in some but not all affected individuals include photophobia, excessive ocular tearing, exposure keratitis, and Raynaud phenomenon. Motor and mental development is normal. Death occurs as a result of complications of severe atherosclerosis, either cardiac disease (myocardial infarction) or cerebrovascular disease (stroke), generally between ages six and 20 years. Average life span is approximately 13 years.

DIAGNOSIS/TESTING:

The diagnosis is based on recognition of common clinical features and detection of either the c.1824C>T (p.Gly608Gly) heterozygous LMNA mutation in the classic form of HGPS or one of three of the heterozygous LMNA mutations c.1822 G>A (p.Gly608Ser), c.1821 G>A (p.Val607Val), or c.1968+1G>A in atypical HGPS. LMNA is the only gene known to be associated with HGPS.

MANAGEMENT:

Treatment of manifestations: A regular diet with frequent small meals is recommended. Treatment for an abnormal lipid profile includes exercise as cardiovascular and neurologic status allow, diet modification, and medication such as statins as warranted. Routine physical and occupational therapy, active stretching and strengthening exercises, and hydrotherapy are recommended. Medication dosages are based on body weight or body surface area, not age. General anesthesia and intubation should be used with caution. Because the stiffened peripheral vasculature may be less tolerant to dehydration, maintaining optimal hydration orally is recommended. Anticongestive therapy is routine for congestive heart failure. Hip dislocation is best managed with physical therapy and body bracing; surgery involving bones should be avoided if possible. Primary tooth extractions may be required to avoid dental crowding. Shoe pads are recommended, as lack of body fat leads to foot discomfort. Use of sunscreen on all exposed areas of skin, including the head, is recommended for outdoor activities. Age-appropriate schooling is usually recommended. Prevention of secondary complications: Low-dose aspirin (2-3 mg/kg body weight) is recommended. Surveillance: annual or semi-annual electrocardiogram (ECG), annual echocardiogram, carotid duplex ultrasound examination, neurologic examination, MRI/MRA of the head and neck, lipid profile, dental examination, audiometry, ophthalmology examination, dual X-ray absorptiometry to measure bone density, hip x-ray to evaluate for avascular necrosis and progressing coxa valga, assessment for joint contractures, and assessment of activities of daily living. Agents/circumstances to avoid: dehydration; large crowds with taller/larger peers because of the risk of injury.

GENETIC COUNSELING:

Almost all individuals with HGPS have the disorder as the result of a de novo autosomal dominant mutation. Because HGPS is typically caused by a de novo mutation, the risk to the sibs of a proband is small. However, because one instance of apparent somatic and germline mosaicism has been reported, the recurrence risk for parents of a child with HGPS may be on the order of one in 500. Because of the (unlikely) possibility of recurrence as a result of germline mosaicism in one of the parents, prenatal testing is possible.

Copyright © 1993-2014, University of Washington, Seattle. All rights reserved.

PMID:
20301300
[PubMed]
Books & DocumentsFree full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Write to the Help Desk