Hutchinson-Gilford progeria
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A 5-year-old has severe growth failure, alopecia, and aged appearance with thin skin and prominent veins. Cardiac workup reveals severe atherosclerosis.
AD (de novo); LMNA (lamin A)
- Specific variant: c.1824C>T (p.Gly608Gly) - activates cryptic splice site → progerin
- Premature aging phenotype (onset ~1-2 years)
- Severe growth failure, alopecia, loss of subcutaneous fat
- "Aged" appearance: thin skin, prominent veins, pinched nose
- Accelerated atherosclerosis
- Death typically by teens (cardiovascular disease)
- Clinical recognition of the progeroid phenotype in early childhood
- Confirm with targeted LMNA testing for the recurrent de novo c.1824C>T (p.Gly608Gly) variant; sequencing if negative
- Baseline cardiovascular and cerebrovascular evaluation (echocardiography, vascular imaging) given accelerated atherosclerosis
- Lonafarnib (farnesyltransferase inhibitor) reduces progerin toxicity and prolongs survival
- Cardiovascular surveillance and risk reduction (low-dose aspirin, statin, antiplatelet therapy) for stroke/myocardial infarction
- Multidisciplinary supportive care: nutrition, physical therapy, skin and joint care, dental and orthopedic monitoring
- Genetic counseling: nearly all cases are de novo; recurrence risk is low but parental gonadal mosaicism is possible
"The iLLuMiNAti are an old, secret society": The LMNA gene is hidden in "iLLMNAti", and the Illuminati are an old, secret society, linking to premature aging and the de novo (secretive) nature of the variant. Lamins are intermediate fiLAMENt proteins.