What are the other Names for this Condition? (Also known as/Synonyms)

• Fong Disease
• Osteo-Onychodysplasia
• Turner-Kieser Syndrome

What is Nail-Patella Syndrome? (Definition/Background Information)

• Nail-Patella Syndrome (NPS) is an inherited condition characterized by abnormalities of the nails, knees, elbows, and pelvis
• Some affected people may also experience problems in other areas of the body such as the kidneys and eyes
• The severity of the condition and the associated signs and symptoms can vary significantly from person to person, even among members of the same family
• Nail-Patella Syndrome is caused by changes (mutations) in the LMX1B gene and is inherited in an autosomal dominant manner
• The treatment of Nail-Patella Syndrome is supportive and based on the signs and symptoms present in each person

(Source: Nail-Patella Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Nail-Patella Syndrome? (Age and Sex Distribution)

• Nail-Patella Syndrome is a rare inherited disorder occurring at an estimated frequency of 1:50,000
• The onset of symptoms may occur in the neonatal, infant, or childhood phase
• Both genders may be affected
• The condition may affect individuals worldwide

What are the Risk Factors for Nail-Patella Syndrome? (Predisposing Factors)

• A positive family history may be an important risk factor, since Nail-Patella Syndrome is an inherited condition
• Currently, no other risk factors have been clearly identified for NPS

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Nail-Patella Syndrome? (Etiology)

In most cases, Nail-Patella Syndrome is caused by mutation(s) in the LMX1B gene.

• This gene is believed to make a protein that regulates other genes by “switching them on” during development 
• The condition is inherited in an autosomal dominant manner, with variable expressivity

Autosomal dominant inheritance: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

In autosomal dominant inheritance with variable expressivity, individuals with the same genetic condition show a wide range signs and symptoms. While some may be asymptomatic or exhibit only mild signs and symptoms, others may experience life-threatening complications from the disease. It is believed that factors other than gene mutation(s), such as lifestyle and environment contribute the development of the disease.

What are the Signs and Symptoms of Nail-Patella Syndrome?

The signs and symptoms of Nail-Patella Syndrome may include:

• Absence of pectoralis minor muscle 
• Absent distal interphalangeal creases 
• Anonychia
• Antecubital pterygium 
• Biceps aplasia
• Cleft palate 
• Cleft upper lip
• Clinodactyly of the 5th finger 
• Disproportionate prominence of the femoral medial condyle
• Elongated radius 
• Glenoid fossa hypoplasia 
• Glomerulonephritis 
• Hypoplasia of first ribs
• Hypoplastic radial head 
• Keratoconus
• Lester's sign 
• Limited elbow extension
• Lumbar hyperlordosis 
• Microcornea 
• Microphakia
• Pectus excavatum
• Pes planus
• Ptosis
• Quadriceps aplasia
• Scoliosis 
• Sensorineural hearing impairment 
• Short stature
• Spina bifida 
• Talipes equinovarus
• Triceps aplasia

Based on the frequency of symptoms observed, the following information may be noted:

Very frequently present symptoms in 80-99% of the cases:

• Abnormality of the fingernails
• Aplasia/Hypoplasia of the patella
• Concave nail
• Cubitus valgus 
• Exostoses
• Hypoplastic toenails
• Iliac horns 
• Joint hyperflexibility 
• Joint stiffness
• Patellar dislocation
• Ridged nail
• Skeletal dysplasia 
• Thickening of the lateral border of the scapula

Frequently present symptoms in 30-79% of the cases:

• Joint swelling 
• Nephrotic syndrome 
• Osteoarthritis
• Patellar aplasia
• Proteinuria

Occasionally present symptoms in 5-29% of the cases:

• Cataract
• Glaucoma 
• Glomerulopathy
• Hearing impairment
• Hematuria
• Hypertension 
• Nephropathy 
• Renal insufficiency
• Vasculitis

(Source: Nail-Patella Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Nail-Patella Syndrome Diagnosed?

Nail-Patella Syndrome is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies, such as pelvic X-ray to check for iliac horns
• Biopsy studies, if necessary
• Molecular genetic testing to check for or confirm causative gene mutation(s)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Nail-Patella Syndrome?

The complications of Nail-Patella Syndrome may include:

• Low self-esteem
• Severe pain due to arthritis
• Kidney malfunction 
• Chronic kidney failure leading to end-stage kidney disease

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Nail-Patella Syndrome Treated?

There is no cure for Nail-Patella Syndrome, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops. The treatment methods may include:

• Medications for high blood pressure and glaucoma
• Braces and splints for abnormalities concerning the bones
• Surgeries to correct bone abnormalities
• Physical therapy
• Dialysis for chronic kidney malfunction
• Kidney transplantation for end-stage renal disease

How can Nail-Patella Syndrome be Prevented?

Currently, Nail-Patella Syndrome may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Nail-Patella Syndrome? (Outcomes/Resolutions)

• The prognosis of Nail-Patella Syndrome is dependent upon the severity of the signs and symptoms and associated complications, if any
• In general, the prognosis may be assessed on a case-by-case basis
• In about 5% of the cases, end-stage renal disease is reported to occur, necessitating kidney transplantation

Additional and Relevant Useful Information for Nail-Patella Syndrome:

Nail-Patella Syndrome may be known by the following additional synonyms:

• Arthro-Onychodysplasia
• Onychoosteodysplasia

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/