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Hutchinson-Gilford Progeria Syndrome.

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GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015.
2003 Dec 12 [updated 2015 Jan 8].

Excerpt

CLINICAL CHARACTERISTICS:

Hutchinson-Gilford progeria syndrome encompasses a spectrum of clinical features that typically 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 Hutchinson-Gilford progeria syndrome (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 14.6 years.

DIAGNOSIS/TESTING:

The diagnosis is based on recognition of common clinical features and detection of heterozygous LMNA mutations either within exon 11 (termed classic HGPS) or at the intronic border of exon 11 (termed atypical HGPS). Molecular genetic testing of LMNA, the only gene in which mutations are known to cause HGPS, is available on a clinical basis.

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 performed with extreme caution, ideally with fiberoptic intubation, if possible. Anticongestive therapy is routine for the treatment of congestive heart failure. Exposure keratopathy caused primarily by nocturnal lagophthalmos can be treated with ocular lubrication. Hearing aids can be used, when clinically necessary. 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 for prevention of cardiovascular and stroke complications. Because the stiffened peripheral vasculature may be less tolerant to dehydration, maintaining optimal hydration orally 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 and/or peripheral cutaneous computed tomography 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. Physical activity should be self-limited.

GENETIC COUNSELING:

Almost all individuals with HGPS have the disorder as the result of de novo autosomal dominant mutation. Because HGPS is typically caused by de novo mutation, the risk to the sibs of a proband is small. However, one instance of apparent somatic and germline mosaicism in a parent has been reported; thus, 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 © 1993-2015, University of Washington, Seattle. All rights reserved.

PMID:
20301300
[PubMed]
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