Disease Description (Causes and Symptoms)
- Cause: It is mostly caused by specific mutations in the LMNA gene (the LMNA gene on chromosome 1). It usually occurs as a de novo mutation and shows an autosomal dominant pattern, but it often occurs without a family history.
- Pathophysiology: LMNA mutations lead to the production of an abnormal lamin A-like protein (progerin), causing nuclear membrane instability, accelerated cellular aging, and premature degeneration of tissues (especially blood vessels, skin, and skeletal muscle). Cardiovascular complications caused by premature atherosclerosis are the main cause of death.
- Main symptoms (age of onset): Progressive growth retardation after 9–24 months of age (short stature, low body weight), hair loss (loss of scalp hair, eyebrows, and eyelashes), subcutaneous fat atrophy, a small face, small jaw, and prominent eyes, joint stiffness and skeletal abnormalities, a high-pitched voice, delayed secondary sexual characteristics, and hearing loss. Atherosclerosis, hypertension, angina, stroke, and other conditions may develop before adolescence, so the average age of death is around adolescence (generally from the mid to late teens).
Treatment Methods
- Standard treatment:
- There is currently no definitive treatment (cure).
- Medication: In patients with progeria, the farnesyltransferase inhibitor lonafarnib has recently shown effects in extending survival and improving cardiovascular and weight-related indicators, so its use may be recommended in some cases (consult a specialist regarding indications, adverse effects, and other matters). Low-dose aspirin is often recommended to prevent thrombosis and cardiovascular events.
- Cardiovascular management: Echocardiography, evaluation of the coronary arteries and aorta, treatment of hypertension and lipid abnormalities (including statins if necessary), and cardiology treatment for angina or myocardial ischemia.
- Symptomatic treatment by symptom: Growth and nutritional support (in consultation with a dietitian), physical therapy and joint mobilization (to prevent joint stiffness), dental, audiological, ophthalmological, and orthopedic management, and moisturizing and protection related to the skin and hair.
- Surgery/procedures: Standard cardiac treatment (interventional procedures or surgery) may be considered in cases of severe cardiovascular complications (such as angina or heart failure), but multidisciplinary judgment tailored to the patient’s condition is required each year.
- Lifestyle management and precautions:
- Regular cardiovascular monitoring (echocardiography, blood pressure, blood lipids, etc.) is essential.
- Prompt evaluation is needed for bleeding or thrombotic risk and in the event of infection.
- Manage body temperature and nutrition, and avoid excessive physical stress.
- When taking medications (especially newer drugs such as lonafarnib), monitor for adverse effects (gastrointestinal symptoms, liver enzyme levels, etc.).
- Complications:
- Major complications include cardiovascular complications (atherosclerosis, myocardial infarction, stroke, and heart failure), joint contractures and skeletal abnormalities, malnutrition and growth retardation, and hearing loss.
Checklist Before an Outpatient Visit (Including Example Questions)
- Items to prepare:
- A list of currently used medications and supplements (including dosage and duration of use)
- Previous test results (a copy of genetic test results may also be included), and recent echocardiography, electrocardiography, blood test, and imaging test results
- Growth chart (height and weight tracking), and records of diet, sleep, and activity
- Records of changes in symptoms (fever, chest pain, shortness of breath, changes in consciousness, changes in hearing or vision, etc.)
- Items to check before the visit:
- New symptoms that have developed recently (chest pain, severe headache, hemiplegia, etc.)
- Vaccination history and allergy history
- Family history (especially similar symptoms or whether an LMNA variant has been confirmed)
- Example questions (for patients and caregivers to check themselves):
- How have the recent food intake and weight changed?
- Are sufficient physical therapy and joint exercises being performed?
General Example Questions to Ask the Doctor
- What is the expected course (prognosis) of this disease?
- What tests are recommended for the current symptoms, and how often should they be performed?
- What are the common adverse effects and precautions of the prescribed medication (or the proposed medication)?
- What should be done to prevent cardiovascular complications?
- How is the schedule for multidisciplinary care (cardiology, orthopedics, nutrition, rehabilitation, etc.) organized?
Examples of Disease-Specific Questions
- Please explain the exact name of the LMNA variant identified in the genetic test results (e.g., c.1824C>T) and what it means for my (or my child’s) prognosis.
- What are the indications, expected effects, possible adverse effects, and monitoring plan for lonafarnib (a farnesyltransferase inhibitor) treatment?