Nail-patella syndrome causes changes in the nails, elbows, kneecaps (patellae), and hip bone. The most common symptom of the syndrome is having missing or underdeveloped fingernails and toenails. Other symptoms may include having small or missing kneecaps, underdeveloped elbows, and an extra small piece of bone on both sides of the hip (called iliac horns). People with nail-patella syndrome are at an increased risk for developing high fluid pressure in the eye (glaucoma) and kidney disease.

Nail-patella syndrome is caused by genetic changes (pathogenic variants or mutations) in the LMX1B gene. The syndrome is inherited in an autosomal dominant manner. Diagnosis is usually suspected when a person has symptoms of the syndrome. The diagnosis can be confirmed by genetic testing. Treatment for nail-patella syndrome may include physical therapy or surgery for joint problems. Other treatments depend on the symptoms present in each person.

Most people who have nail-patella syndrome have kneecaps that are small, absent, or irregularly shaped. This can cause problems such as frequent kneecap dislocation or early-onset arthritis. One kneecap may be affected more than the other. Most people with the syndrome also have problems with one or both of their elbows because different parts of the elbow did not develop correctly. Some people are not able to fully extend their elbows or may have a hard time turning (rotating) the lower part of the arm when their arm is straight. The elbow may dislocate easily.

Changes in the pelvic bones called iliac horns can often be seen on x-ray and are found in 70% of people with nail-patella syndrome. Iliac horns are small pointy growths of bone (bony projections) that are not normally found on people's hip bones. Although these changes do not cause any health problems, iliac horns, if present, can be used to diagnose nail-patella syndrome.

Other less common symptoms may include gastrointestinal problems such as constipation or irritable bowel syndrome. There may be nerve (neurological) problems affecting the hands and feet, such as reduced sensitivity to pain and temperature, numbness, tingling, or burning sensations. The hands and feet may be unusually cold, even in warm weather. Dental problems may include weak, crumbling teeth and thin dental enamel.

People with nail-patella syndrome are at a higher risk to develop increased pressure in the eye (glaucoma). About 30-50% of people with nail-patella syndrome have kidney disease. The most common feature of kidney disease is having high levels of protein in the urine (proteinuria). High blood pressure (hypertension) is also common in people with kidney disease. In about 5% of people with nail-patella syndrome, the kidney disease may progress to kidney failure.

The symptoms associated with nail-patella syndrome can vary widely, even among people in the same family. This concept is called variable expressivity.

LMX1B gene in about 95% of people with the syndrome. The LMX1B gene gives the body instructions to make a protein that is thought to control when other genes are "turned on." These other genes make proteins important for the development of the nails, kneecaps, elbows, kidneys, and eyes. However, the exact function of the LMX1B gene, and the effect of pathogenic variants on its function, are not completely understood.

In rare cases, people who have symptoms of nail-patella syndrome do not have a pathogenic variant in the LMX1B gene. Therefore it is thought that there may be other genes in which pathogenic variants cause nail-patella syndrome.

LMX1B gene, genetic testing that identifies a mutation in this gene can confirm the diagnosis both in people with a clinical diagnosis, and in cases where the clinical diagnosis is uncertain.

Symptoms of nail-patella syndrome affecting the knee and elbow (orthopedic problems) may be treated with physical therapy, braces, splints, or surgeries. Before a person with nail-patella syndrome has surgery for orthopedic problems, an MRI is recommended to make sure the doctors understand the unique anatomy of the joint or body part. Other symptoms of the syndrome, such as glaucoma or high blood pressure (hypertension), can be treated with medications as the medical problem would in people who do not have the syndrome. In some cases, people with nail-patella syndrome may require a kidney transplant. It is recommended that people with the syndrome avoid non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, due to their increased risk of kidney problems.

While many people with nail-patella syndrome do not have serious medical problems, many people have medical complications, including frequent kneecap dislocations, the development of early-onset arthritis, glaucoma, or kidney problems. About 5% of people with nail-patella syndrome develop end-stage kidney disease, meaning that the kidneys stop working and the person may require a kidney transplant. In general, people with the syndrome do well after kidney transplants. Whether or not a person has kidney disease may be the best indicator of the long-term outlook for people with nail-patella syndrome.