What Is It, Causes, Signs, Symptoms, and More
Author:Maria Emfietzoglou, MD
Editors:Alyssa Haag,Stefan Stoisavljevic, MD,Kelsey LaFayette, DNP, RN, FNP-C
Illustrator:Jessica Reynolds, MS
Copyeditor:Stacy Johnson, LMSW
What is nail-patella syndrome?
Nail-patella syndrome (NPS), also known as hereditary onycho-osteodysplasia or Fong disease, is a rare genetic syndrome characterized by unusual changes in one’s nails, kneecaps (patellae), elbows, and iliac bones. Individuals with NPS have an increased risk for glaucoma, kidney disease, and nerve abnormalities. There is currently no cure for NPS; therefore, treatment focuses on managing symptoms.
What causes nail-patella syndrome?
NPS is caused by genetic mutations in the LMX1B gene that encodes for the LMX1B protein. The LMX1B protein is a transcription factor (i.e., a protein that regulates the expression of specific genes) that plays a vital role in the early embryonic development of the limbs, kidneys, and eyes. Mutations of the LMX1B gene can lead to a loss of transcription factor function. These mutations can be either inherited with an autosomal dominant pattern, which means inheriting one copy of the mutated gene can lead to disease development; or de novo when the mutation occurs sporadically. NPS mutations are highly penetrant, meaning that almost every individual with these mutations will have some symptoms of the condition.
What are the signs and symptoms of nail-patella syndrome?
Signs and symptoms of NPS are usually apparent at birth or present during early childhood. Although the clinical manifestations can vary in range and severity, NPS patients typically appear very lean, with decreased muscle mass in the upper arms and legs. They usually find it challenging to gain weight, specifically muscle mass.
Individuals with NPS usually present with abnormalities in the nails, elbows, knees, and hip bones. The most common sign is the absence or underdevelopment of fingers and toenails. Most often, the thumbnails and fifth toenails are affected. Typically, the nails are small, narrow, split, depressed, or discolored. However, they can also appear ridged, pitted, separated longitudinally, or thin.
Patients may also have skeletal abnormalities, including the elbows and patellae. The arm bones (i.e., capitellum and radial head) that meet at the elbow may be malformed or underdeveloped, while there may also be excess skin webbing near the antecubital area. Due to these changes, the range of motion in the elbow may be limited; therefore, an affected individual might not be able to fully extend their forearm or supinate and pronate the forearm at the elbow joint. The patellae may also be malformed, underdeveloped, or completely absent. Further, like the bones that create the elbow joint, the bones in the knee joint (i.e., fibula and femur) may be malformed and underdeveloped, which can lead to subluxation of the patellae and bow-leg deformity.
Another characteristic sign of NPS is having iliac horns, which are small horn-like outgrowths that develop on the bones of the pelvis.
When it comes to the eyes, individuals with NPS can present with the Lester sign when there is dark pigmentation around the iris resembling a flower or clover leaf. Individuals with NPS may also develop increased pressure in their eyes, called open-angle glaucoma. If left untreated, glaucoma can lead to narrowing visual fields and significant vision loss.Finally, some individuals with NPS can present with kidney disease, leading to renal failure. Kidney involvement typically involves microhematuria and proteinuria but can progress to nephrotic syndrome (i.e., anemia, edema, elevated creatinine) and renal failure requiring dialysis or transplantation.
How is nail-patella syndrome diagnosed?
Diagnosis of NPS starts with assessing the individual’s clinical presentation and family history of the disease. Then, imaging tests, including x-rays, CT, and MRI scans, may be performed to identify bone and joint abnormalities. Eye tonometry testing can assess for increased intraocular pressure and identify the presence of glaucoma. Laboratory tests, including urine tests, may also be ordered to assess kidney function. Nonetheless, confirmation of NPS occurs solely through genetic testing. Couples, including an affected parent wishing to have an offspring, can seek genetic counseling as there is a 50% chance of having the condition due to the autosomal dominant inheritance.
How is nail-patella syndrome treated?
As there is no cure for NPS, treatment focuses on managing symptoms. For musculoskeletal abnormalities, treatment can include analgesics, such as nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen, if the kidneys are involved; physiotherapy; splinting; bracing; and surgery. For those with kidney disease, management may include medications (e.g., angiotensin-converting enzyme inhibitors), dialysis, and in more severe cases, renal transplantation. As for the eyes, glaucoma treatment focuses on reducing intraocular pressure and may involve using eye drops containing a combination of beta-blockers (e.g., timolol) and carbonic anhydrase inhibitors (e.g., dorzolamide, acetazolamide), or surgery (e.g., trabeculectomy).
Due to the wide range of signs, symptoms, and presentations, individuals with NPS should be routinely monitored for new or worsening signs and symptoms. Children with the condition should be screened routinely for the development of scoliosis for early detection and treatment. All individuals should follow closely with an ophthalmologist to monitor for glaucoma, cataracts, or a visual impairment, in addition to close monitoring of kidney function for nephropathy.
What are the most important facts to know about nail-patella syndrome?
Nail-patella syndrome (NPS) is a rare disease characterized by nail dysplasia, skeletal abnormalities involving the knees, elbows, and hips, and an increased risk for glaucoma and kidney failure. NPS is caused by a mutation in the LMX1B gene. In most cases, the syndrome is inherited in an autosomal dominant pattern, but the mutation may also develop sporadically without having an affected parent. Diagnosis is suspected based on clinical presentation and family history but is confirmed with genetic testing. As there is no cure, treatment focuses on managing symptoms.
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Resources for research and reference
Genetic and rare diseases information center. Nail-patella syndrome. Retrieved 07/07/2022 from https://rarediseases.info.nih.gov/diseases/7160/nail-patella-syndrome
NHS. Nail patella syndrome. Retrieved 07/07/2022 from https://www.nhs.uk/conditions/nail-patella-syndrome/
Lovelace, Parker D., and Lauren A. May. “Nail Patella Syndrome.” StatPearls, StatPearls Publishing, 2022. PubMed, http://www.ncbi.nlm.nih.gov/books/NBK559190/.
Medscape. Nail-patella syndrome. Retrieved 07/07/2022 from https://emedicine.medscape.com/article/1106294-overview
MedlinePlus. Nail-patella syndrome. Retrieved 02/07/2022 from https://medlineplus.gov/genetics/condition/nail-patella-syndrome/#synonyms
NORD (National Organization for Rare Disorders). Nail-patella syndrome. Retrieved 07/07/2022 from https://rarediseases.org/rare-diseases/nail-patella-syndrome/Sweeney, Elizabeth, et al. “Nail-Patella Syndrome.” GeneReviews®, edited by Margaret P. Adam et al., University of Washington, Seattle, 1993. PubMed, http://www.ncbi.nlm.nih.gov/books/NBK1132/.