Nail-patella syndrome

What causes nail-patella syndrome?

Nail-patella syndrome is caused by genetic changes (pathogenic variants or mutations) in the LMX1B gene in about 95% of people with the syndrome. The LMX1 B 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.

Last updated on 05-01-20

How is nail-patella syndrome diagnosed?

Nail-patella syndrome is diagnosed based on the signs and symptoms present (this is called a "clinical diagnosis" and means that laboratory or genetic testing is not necessary for the diagnosis). The diagnosis may be made when a person has a thorough clinical exam and/or imaging studies that identify symptoms such as fingernail or toenail abnormalities (present in 98% of people with the syndrome), small or absent kneecaps, elbow abnormalities, and/or iliac horns (a bone finding common in people with this syndrome but uncommon in people who do not have the syndrome). The diagnosis can be made when a person has at least one (but usually more than one) characteristic symptom. Because about 95% of people with this syndrome have a mutation in the 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.

Last updated on 05-01-20

How is nail-patella syndrome inherited?

Nail-patella syndrome is inherited in an autosomal dominant manner. Like most genes, the LMX1B gene comes in a pair (two copies). One copy of the gene is inherited from each parent. When a syndrome is inherited in an autosomal dominant manner, a person must only have a pathogenic variant in one copy of the gene to have the syndrome.

When a person who has a genetic change in the LMX1B gene has children, for each child there is a:

  • 50% chance to inherit the changed copy of the LMX1B gene, meaning he or she will have nail-patella syndrome
  • 50% chance to inherit the working copy of the LMX1B gene, meaning he or she will not have nail-patella syndrome

About 88% of people with nail-patella syndrome have a genetic change in the LMX1B gene that is inherited from a parent. In some cases, the parent may not have been previously diagnosed with nail-patella syndrome because the symptoms were mild. In about 12% of people with nail-patella syndrome, the genetic change in the LMX1B gene was not inherited from either parent. Instead, the genetic change was new in the person diagnosed with nail-patella syndrome. Genetic changes that are new in a person are called de novo.

Last updated on 05-01-20

What is the long-term outlook for people with nail-patella syndrome?

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.

Last updated on 05-01-20

How might nail-patella syndrome be treated?

After a diagnosis of nail-patella syndrome, a person may be recommended to undergo screening for health problems that are more common in people with the syndrome. This may include having regular blood pressure checks, urine tests to watch for the development of kidney problems, and examinations by a medical eye doctor (ophthalmologist) to check for signs of glaucoma.

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.

Last updated on 05-01-20


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The RareGuru disease database is regularly updated using data generously provided by GARD, the United States Genetic and Rare Disease Information Center.

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