hereditary lymphedema I

Hereditary lymphedema type I, also known as Milroy disease, is a rare genetic disorder that affects the lymphatic system. It is characterized by chronic swelling (lymphedema) in the lower extremities, typically starting at birth or during early childhood.

Key Features:

• Congenital onset: Swelling usually starts at birth or within the first few years of life.
• Lower extremity involvement: Lymphedema primarily affects the legs and feet.
• Genetic inheritance: Hereditary lymphedema type I is inherited in an autosomal dominant pattern, meaning a single copy of the mutated gene is enough to cause the condition.

Other relevant information:

• The condition can also be associated with other symptoms such as skin changes, hair growth on the legs, and mild intellectual disability.
• Hereditary lymphedema type I is caused by mutations in the FLT4 gene, which plays a crucial role in the development of the lymphatic system.
• The condition is relatively rare, affecting approximately 1 in 100,000 people worldwide.

References:

• [8] describes Milroy disease as a condition that affects the normal function of the lymphatic system.
• [9] states that hereditary lymphedema generally shows an autosomal dominant pattern of inheritance with reduced penetrance, variable expression, and variable age at onset.

Based on the provided context, here are the signs and symptoms of hereditary lymphedema:

Common Symptoms

• Swelling (edema) in affected parts of the body [1]
• Swelling may develop slowly, and you may not notice unusual swelling in lymphedema's early stages [2]
• A feeling of heaviness or tightness in the affected limbs [3]
• Restricted range of motion [3]
• Recurring episodes of swelling [3]

Additional Features

• Upslanting toenails [4]
• Deep creases in the toes [4]
• Wart-like growths (papillomas) [4]
• Prominent leg veins [4]
• Antenatal hydrops or cystic hygroma [5]
• Short stature [5]
• Mild learning difficulties [5]
• Congenital heart disease (commonly coarctation of the aorta) [5]

Other Symptoms

• Swelling in the foot, ankle, calf, and/or thigh [7]
• Swelling in the hand or arm [7]
• A sensation of tightness or heaviness in the limbs [7]
• Swelling often begins in the feet and ankles and progresses up the legs to the knees [8]

Please note that these symptoms may vary from person to person, and not everyone with hereditary lymphedema will experience all of them. If you suspect you or a family member has this condition, it's essential to consult a medical professional for proper diagnosis and treatment.

References: [1] - Context result 1 [2] - Context result 2 [3] - Context result 3 [4] - Context result 4 [5] - Context result 5 [7] - Context result 7 [8] - Context result 8

Based on the provided context, here are some diagnostic tests for hereditary lymphedema:

• Lymphoscintigraphy: This test uses a small amount of radioactive material to visualize the lymphatic system and diagnose lymphedema. [1]
• MRI scan: A magnetic resonance imaging (MRI) scan can produce 3D, high-resolution images of the involved tissue, helping to diagnose lymphedema. [2]
• CT scan: A computed tomography (CT) scan uses X-rays to create detailed images of the body, which can help diagnose lymphedema. [2]
• Genetic testing: Genetic tests can detect genetic variants associated with hereditary lymphedema, such as primary lymphedema. [3][5]

It's worth noting that a combination of clinical assessment and imaging studies is often used to diagnose lymphedema. Additionally, genetic diagnosis can confirm the clinical diagnosis and establish the subtype of the lymphatic malformation syndrome. [7]

Based on the available information, it appears that there are limited effective drug therapies for the management of primary (hereditary) lymphedema.

• Currently, there is no cure for primary lymphedema, and treatment options focus on managing symptoms and preventing complications [4].
• The use of drugs targeting the PI3K/AKT/mTOR pathway has been explored as a potential therapeutic approach, but more research is needed to determine their effectiveness [2].
• Tetracycline antibiotics have been used off-label to treat patients with chronic filarial secondary lymphedema, and may also be beneficial for primary lymphedema, although this requires further investigation [3].

It's worth noting that clinical trials are ongoing to explore new treatments for lymphedema. For example, a clinical trial (ULTRA) is investigating the use of bestatin (ubenimex) as a potential treatment for lymphedema, which started in May 2016 [1]. Additionally, research has shown that ketoprofen may improve skin damage in patients with lymphedema, but more studies are needed to confirm its effectiveness [6].

In terms of specific drug treatments, there is limited information available. However, it's essential to consult a healthcare provider for personalized advice on managing primary lymphedema.

References: [1] May 10, 2017 — Based on the research, bestatin (also known as ubenimex), is being tested in a clinical trial that started in May 2016 — known as ULTRA — as a ... [2] by GE Jones · 2017 · Cited by 26 — There are currently no effective drug therapies available for the management of primary lymphoedema. However, the use of drugs targeting the PI3K/AKT/mTOR ... [3] by S Brown · Cited by 3807 — Tetracycline antibiotics (e.g., doxycycline) have been used to treat patients with chronic filarial secondary lymphedema and decrease limb and ... [4] There is no cure for primary lymphedema. However, an effective compression regimen, active lifestyle and maintenance of normal body weight will limit ... [6] Oct 18, 2018 — Two early-stage clinical trials led by Stanford researchers have shown that ketoprofen can improve skin damage in patients with lymphedema. [9] Treatments may include physical therapy or other treatment to keep lymphatic fluid moving and reduce swelling and pain. Your healthcare provider may also ...

Based on the provided context, it appears that differential diagnosis for hereditary lymphedema involves considering various conditions that can mimic or be associated with lymphedema.

Common genetic conditions associated with lymphoedema

According to search result [10], common genetic conditions associated with lymphoedema include Turner syndrome and Noonan syndrome. However, there are numerous other genetic conditions that can be classified under this category.

• Turner syndrome: This condition is characterized by the presence of only one X chromosome in females, leading to various physical and developmental abnormalities. Lymphedema is a known complication of Turner syndrome [10].
• Noonan syndrome: This rare genetic disorder affects both males and females, causing heart defects, short stature, and other physical characteristics. Lymphedema has been reported in individuals with Noonan syndrome [10].

Other vascular anomalies and overgrowth conditions

Search result [13] highlights that differential diagnosis of primary lymphedema includes other vascular anomalies and overgrowth conditions. These can include:

• Milroy disease: This is a rare genetic disorder affecting the lymphatic system, leading to chronic swelling (lymphedema) in affected limbs [15].
• Lipedema: A disease characterized by abnormal growth of adipose tissue, which can cause swelling in nearly every part of the body [12].

Diagnostic considerations

When diagnosing hereditary lymphedema, it is essential to consider other conditions that may present with similar symptoms. These include:

• Deep vein thrombosis
• Hypoalbuminemia
• Renal failure
• Lipedema (as mentioned earlier)

Accordingly, a comprehensive differential diagnosis for hereditary lymphedema should take into account these various conditions and their potential association with lymphoedema.

References: [10] GE Jones · 2017 · Cited by 26 [13] CL Sudduth · 2022 · Cited by 14 [15] Apr 1, 2013