What is NPS?

Nail Patella Syndrome is a rare genetic disorder involving the bones, joints and connective tissue. Patients may have problems due to limitation of joint mobility, dislocation or both, especially at the elbow and knee where osteoarthritis may eventually occur. Renal impairment is present in approximately 30-50% of cases. Recent evidence suggests that open angle Glaucoma is also part of Nail Patella Syndrome.


How is NPS diagnosed?

Diagnosis of NPS is most often made by a Clinical Geneticist - a physician trained to recognise, diagnose and treat rare disorders like NPS that are due to gene mutations. Many orthopaedists and nephrologists may also be familiar with NPS. There is no routine laboratory test for NPS. A geneticist may choose to send a blood sample for DNA analysis to confirm the diagnosis. Patients cannot contact testing labs directly. Almost all teaching hospitals will have a clinical genetics practice where you can make an appointment. You can also use this link to find the closest genetic counselor: http://www.nsgc.org/zip_search/index.cfm


How is NPS Transmitted?

NPS is transmitted as a simple autosomal dominant trait. The gene altered in people with NPS is called LMX1B and is located on chromosome 9q34.


What is the incidence of NPS?

NPS is estimated to occur in 1 in 50,000 newborns.


Will I pass NPS on to my baby?

Once NPS is in the family, the risk of transmitting the disorder from parent to offspring is 50% for each pregnancy, regardless of the sex of the child.


Can I have NPS without a family history?

Yes, in cases where there seems to be no previous family history of NPS, it is thought to be caused by a spontaneous gene mutation.


Are there any other names for NPS?

Other names for NPS include: Iliac Horn Syndrome, Hereditary Onycho Osteo Dysplasia (HOOD), Fongs Disease, and Turner Kieser Syndrome.


Which abnormality is most frequently associated with NPS?

The most noticeable skeletal defect associated with NPS is absent or underdeveloped fingernails (and sometimes toenails). Abnormalities occur in 98% of cases. The thumbnails are usually the most severely affected. Nails may be absent, brittle, cracked or split, ridged, discolored, and often concave.


My nails do not appear to be affected. Can I still have NPS?

In cases where the nails don't appear to be affected, closer examination of the lunulae (the light parts of the nails near the cuticle), reveals a pointed (triangular) shape as opposed to a rounded cresent "half moon" shape. The presence of triangular lunulae is strongly suggestive of NPS.


How are knees affected in NPS patients?

Absence or hypoplasia of the kneecaps (patella) and deformities of the knee joint may give the knee a square appearance. The joint may be unstable due to malformations in the bones, muscles and ligaments. Dislocation of the knee joint may occur. Knee abnormalities are present in approximately 92% of cases.


How are elbows affected in NPS patients?

Elbow abnormalities occur in approximately 90% of cases. The joints and bones in the forearm are often deformed, causing incomplete extension due to dislocation of the elbow joints, resulting in reduced mobility and restriction of wrist rotation. Hypoplastic capitellum and small head of radius may occur with contractures (skin and tissue tightened across joints), This may give the elbow a webbed appearance.


What are illiac horns?

The pelvic bones of NPS patients usually have illiac horns. They are internal "crests" or "spurs" in the midposterior illium. This defect is as yet unknown in any other species or in other diseases of man. It appears to be an expression of the gene mutation. Hip joints may also be deformed causing dislocations.


What is the course of NPS?

Symptoms vary from person to person and for one person through time. The long term course is extremely variable. One person may present mild symptoms, while another person may become wheelchair bound or require a kidney transplant. The severity of NPS can vary as much within a family as between unrelated people. There is no known correlation between specific LMX1B mutations and symptoms of NPS.


What kidney problems are associated with NPS?

Renal (kidney) impairment in NPS occurs in approximately 30-50% of cases. Renal problems in childhood are rare, but do occur. Renal failure is apparently rare prior to the fourth decade. Proteinuria with or without hematuria is the most common early indication of a renal problem. Studies and microscopic observations show hyaline thickening of the glomerular basement membrane presenting a "moth-eaten" appearance.


How can I detect kidney impairment if it occurs?

Routine urine tests should be conducted on at least an annual basis. Ask your physician to monitor blood and protein levels in the urine. Home testing kits are now available in some pharmacies. If protein is detected in the urine, see your physician. If renal impairment is detected, you will probably be referred to a Nephrologist (kidney specialist). Occasionally a kidney biopsy is necessary to detect the degree of kidney impairment.


What treatments/interventions are available for NPS patients when renal impairment is detected?

Some physicians may prescribe medications. In more severe cases, dialysis or kidney transplantation may be needed. Research indicates that kidney disease does not reoccur once the patient undergoes kidney transplantation.


Is "Club foot" associated with NPS?

Yes, Talipes (club or twisted feet) are seen as a frequent feature in NPS. An Orthopedic surgeon should be consulted. Surgery and/or casting are common methods of intervention in the treatment of "Club foot"


Can NPS affect my vision?

Recent evidence suggests that open angle glaucoma is also part of NPS. Open angle Glaucoma is a condition caused by progressive blockage of the outflow of fluid from the front chamber of the eyes which can result in elevated intraocular pressure leading to narrowing of the visual field (tunnel vision) and eventually blindness if left untreated. Other ocular abnormalities occasionally associated with NPS include Keratoconus, Microcornea, Microphakia, cataracts and Ptosis.


How can I prevent vision impairment?

Early detection and treatment of Glaucoma are the only way to prevent vision impairment and blindness. Have your eyes examined by an Ophthalmologist on a regular basis.


What other anomalies are sometimes associated with NPS?

NPS can also affect the nervous system. Many people with NPS have reduced sensitivity to pain and temperature in their fingers and toes. Symptoms of Attention Deficit Hyperactivity Disorder (ADHD) and depression are more common amongst people with NPS than in the general population. These symptoms can be treated in NPS patients in the same way as in the general population. Irritable bowel syndrome may also be more common amongst NPS patients.


What is the focus of current research on Nail Patella Syndrome?

There are currently no major NPS research projects known to NPSW.


How can I participate in a research study?


Iain Mcintosh,PhD



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