Nail-patella syndrome is a rare genetic condition that impacts the development of several parts of the body. It is identified at birth or during early childhood due to its distinct physical characteristics. The signs and symptoms can vary significantly in range and severity, as some individuals experience mild signs while others have more pronounced developmental differences.
Symptoms and Physical Manifestations
The most recognized signs of nail-patella syndrome involve a classic group of four abnormalities affecting the nails, knees, elbows, and hip bones. Nail changes, or dysplasia, are a primary feature and can range from underdeveloped or absent nails to those with ridges, pits, or splitting. These changes are most frequently observed on the thumbnails and index fingers, with toenails being affected less often.
Skeletal differences are a defining component of the syndrome, particularly concerning the kneecaps, or patellae. Individuals may have patellae that are small, irregularly shaped, or absent, which can lead to joint instability and recurrent dislocation. The elbows are also commonly affected, with many people experiencing limitations in their range of motion. This can include an inability to fully extend the arm or rotate the forearm due to underdeveloped bones at the elbow joint.
Another characteristic feature is the presence of bilateral iliac horns, which are bony projections on the pelvic bones. These are often not associated with any symptoms and are discovered incidentally on X-ray images. Beyond these core signs, some individuals may develop other health issues. Approximately 30-50% of people with the condition experience kidney problems (nephropathy), and there is an increased likelihood of developing glaucoma, which involves elevated pressure within the eye.
Genetic Basis and Inheritance
Nail-patella syndrome is caused by mutations in the LMX1B gene. This gene provides instructions for making a protein that is important for the early embryonic development of the limbs, kidneys, and eyes. When a mutation occurs in the gene, it disrupts the normal formation of these structures, leading to the characteristic features of the syndrome.
The condition is inherited in an autosomal dominant pattern. This means an individual needs to inherit only one copy of the mutated gene from a parent to be affected. A parent with nail-patella syndrome has a 50% chance of passing the altered gene to each of their children.
While often passed down through families, the syndrome can also occur in individuals with no prior family history. In an estimated 10-20% of cases, nail-patella syndrome results from a new (de novo) mutation in the LMX1B gene. This spontaneous genetic change is not inherited from a parent.
Diagnosis and Monitoring
The diagnostic process for nail-patella syndrome begins with a clinical evaluation. A healthcare provider will conduct a physical examination, looking for the characteristic signs of the condition, such as abnormalities of the nails, knees, and elbows. The individual’s personal and family medical history is also reviewed to identify any known occurrences of the syndrome.
To confirm the skeletal features, imaging tests are often used. X-rays are useful for visualizing bone and joint irregularities, such as underdeveloped patellae, elbow joint issues, and the presence of iliac horns on the pelvic bones. These radiological findings provide strong evidence to support a diagnosis.
For a definitive confirmation, molecular genetic testing is available. This test analyzes a blood sample to identify a mutation in the LMX1B gene, which confirms the diagnosis. Following a diagnosis, ongoing monitoring is a standard part of care. Regular urine tests (urinalysis) are performed to screen for proteinuria (protein in the urine), an early sign of kidney involvement. Routine eye examinations are also recommended to check for glaucoma.
Management and Treatment Approaches
There is no cure for nail-patella syndrome, so treatment is focused on managing specific symptoms and improving an individual’s quality of life. The approach is tailored to the unique set of signs experienced by each person and involves a team of specialists. This team may include an orthopedist for bone and joint issues, a nephrologist for kidney care, and an ophthalmologist for eye health.
For musculoskeletal problems, management strategies include physical therapy to help with movement and joint stability. Bracing may be recommended for unstable joints, and pain can be managed with over-the-counter or prescription medications. In more severe instances of joint dislocation or instability, surgical procedures may be considered to restructure or replace the affected joint.
If kidney disease develops, treatment focuses on slowing its progression. Medications such as angiotensin-converting enzyme (ACE) inhibitors may be prescribed to control blood pressure and reduce protein loss through the urine. In cases where kidney failure occurs, which happens in about 30% of those with kidney involvement, dialysis or a kidney transplant becomes necessary. For individuals who develop glaucoma, medicated eye drops are the standard treatment to lower pressure inside the eye.