Hutchinson-Gilford Progeria Syndrome: Comprehensive Imaging Guide and Clinical Overview
Overview
Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare genetic disorder characterized by accelerated aging beginning in early childhood. The name derives from its first detailed descriptions by Jonathan Hutchinson in 1886 and Hastings Gilford in 1904. The term “progeria” originates from Greek roots meaning “premature old age.” Clinically, affected children appear normal at birth but rapidly develop features such as growth retardation, distinctive craniofacial dysmorphisms (prominent eyes, thin nose with a beaked tip, small chin, thin lips), alopecia, aged skin, joint contractures, and loss of subcutaneous fat. The inheritance pattern is typically sporadic autosomal dominant caused by de novo mutations in the LMNA gene, which encodes lamin A, a nuclear envelope protein.
Key Imaging Features
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Conventional radiographs often reveal osteopenia with generalized demineralization prominently affecting long bones.
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Characteristically, narrowed and sclerotic long bones with metaphyseal and epiphyseal dysplasia, including acro-osteolysis (resorption of distal phalanges), are seen.
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Cranial imaging shows premature closure or diastasis of cranial sutures along with multiple Wormian bones in the calvaria.
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Chest X-rays demonstrate a small, narrow thoracic cage with clavicular hypoplasia or dysplasia and thin, resorbed ribs prone to fractures.
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The spine often reveals ovoid vertebral bodies, kyphosis, and scoliosis.
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Vascular imaging including MRA can detect early arteriosclerosis with carotid artery stenosis and thickening of cerebral arteries.
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Brain MRI may display ischemic changes, white matter abnormalities, and lacunar infarctions related to cerebrovascular disease caused by accelerated atherosclerosis.
Pathophysiology
Hutchinson-Gilford Progeria Syndrome is caused by a de novo point mutation (commonly c.1824C>T) in the LMNA gene, producing a defective form of lamin A called progerin. This mutant protein disrupts nuclear envelope integrity, leading to cellular senescence and widespread tissue degeneration. In the skeleton, this manifests radiologically as poor bone mineralization, growth defects, and remodeling abnormalities. The vascular pathology entails accelerated arteriosclerosis due to endothelial dysfunction and abnormal vascular smooth muscle cells, resulting in early vessel stenosis visible on vascular imaging. These cellular and tissue-level changes are the biological basis for imaging findings such as osteoporosis, cranial sutural abnormalities, and vascular narrowing.
Differential Diagnosis
Conditions with overlapping clinical and imaging features include:
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Werner syndrome: another progeroid syndrome but with adult onset and minimal skeletal deformities.
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Restrictive dermopathy: shares skin and skeletal features but is lethal in the neonatal period with distinctive histological findings.
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Mandibuloacral dysplasia: caused by different LMNA mutations with overlapping skeletal changes, but often includes metabolic abnormalities.
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Imaging distinction is primarily based on the timing of presentation, severity, and pattern of bone and vascular abnormalities.
Imaging Protocols and Techniques
Optimal evaluation of Hutchinson-Gilford Progeria Syndrome involves a combination of radiologic modalities:
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Plain radiography of the skull, chest, spine, and appendicular skeleton is essential for baseline assessment and monitoring of skeletal abnormalities, including osteopenia, acro-osteolysis, and clavicular/rib deformities.
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Bone densitometry (DXA) may be useful to quantify osteoporosis severity.
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MRI of the brain is recommended to assess ischemic changes, infarcts, and white matter abnormalities secondary to vascular disease.
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Magnetic resonance angiography (MRA) or Doppler ultrasound of cerebral and carotid arteries facilitate detection and monitoring of early arteriosclerosis and stenosis.
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Serial imaging is critical to monitor progression of skeletal dysplasia and vascular complications; radiologists should be attentive to pitfalls such as overlapping signs with other dysplasias and age-related changes.
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