Nail-patella syndrome

Alternate names

NPS 1; Onychoosteodysplasia; Turner-Kieser syndrome; Fong disease; Osteo-Onychodysplasia; Arthro-Onychodysplasia

Definition

Nail-patella syndrome causes changes in the nails, elbows, kneecaps (patellae), and hip bone. The features of nail-patella syndrome vary in severity between affected individuals, even among members of the same family.

Epidemiology

The prevalence of nail-patella syndrome is estimated to be 1 in 50,000 individuals.

Cause

Mutations in the LMX1B gene cause nail-patella syndrome. The LMX1B gene provides instructions for producing a protein that attaches (binds) to specific regions of DNA and regulates the activity of other genes. On the basis of this role, the LMX1B protein is called a transcription factor. The LMX1B protein appears to be particularly important during early embryonic development of the limbs, kidneys, and eyes. Mutations in the LMX1B gene lead to the production of an abnormally short, nonfunctional protein or affect the protein's ability to bind to DNA. It is unclear how mutations in the LMX1B gene lead to the signs and symptoms of nail-patella syndrome.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

Nail-patella syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the mutation from one affected parent. Other cases may result from new mutations in the LMX1B gene. These cases occur in people with no history of the disorder in their family.

Signs and symptoms

The symptoms of nail-patella syndrome most commonly affect the way the nails, kneecaps (patellae), elbows, and hip bone form. Almost all people with nail-patella syndrome have nails that are missing, underdeveloped, discolored, split, or ridged. The fingernails are more likely to be affected than the toenails. The thumbnails tend to be the most severely affected.

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.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Abnormal fingernail morphology(Abnormal fingernails)
• Aplasia/Hypoplasia of the patella(Absent/small kneecap)
• Concave nail(Spoon-shaped nails)
• Cubitus valgus(Outward turned elbows)
• Exostoses(Formation of new noncancerous bone on top of existing bone)
• Hypoplastic toenails(Underdeveloped toenails)
• Iliac horns
• Joint hyperflexibility(Joints move beyond expected range of motion)
• Joint stiffness(Stiff joint)
• Patellar dislocation(Dislocated kneecap)
• Ridged nail(Grooved nails)
• Skeletal dysplasia
• Thickening of the lateral border of the scapula(Thickening of the lateral border of the shoulder blade)

30%-79% of people have these symptoms

• Joint swelling
• Nephrotic syndrome
• Osteoarthritis(Degenerative joint disease)
• Proteinuria(High urine protein levels)

5%-29% of people have these symptoms

• Cataract(Clouding of the lens of the eye)
• Glaucoma
• Glomerulopathy
• Hearing impairment(Deafness)
• Hematuria(Blood in urine)
• Hypertension
• Nephropathy
• Renal insufficiency(Renal failure)
• Vasculitis(Inflammation of blood vessel)

1%-4% of people have these symptoms

• Absent distal interphalangeal creases
• Antecubital pterygium
• Back pain
• Limited elbow extension(Decreased elbow extension)
• Lumbar hyperlordosis(Excessive inward curvature of lower spine)
• Patellar aplasia(Absent kneecap)
• Patellar hypoplasia(Small kneecap)
• Pes planus(Flat feet)
• Talipes equinovarus(Club feet)

Diagnosis

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.

Treatment

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.

Prognosis

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.

NIH genetic and rare disease info

• NIH info on Nail-patella syndrome

Nail-patella syndrome is a rare disease.

Nail-patella syndrome Resources
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