Nail Patella Syndrome - Causes, Symptoms, Diagnosis, and Treatment

Introduction:

Nail patella syndrome is characterized by the presence of changes in the nails, knees, elbows, and pelvis. The phenotypic and hereditary nature of the syndrome was first described by Dr. E. M. Little. It affects one or more areas of the body, causing multiple manifestations, and the severity of the disease varies among individuals. Studies show that around 30 % to 50 % of patients affected with this syndrome have shown renal manifestations, and 15 % of cases progressed to renal failure. It can be diagnosed by the proper history, radiological findings, and genetic testing. The prognosis of the condition is good, with appropriate treatment. It is important to regularly monitor the patient to prevent serious complications.

What Is Nail Patella Syndrome?

Nail patella syndrome is a rare genetic disorder that is characterized by changes in the nails, elbows, knees, and pelvis. Other terminologies to describe this condition include Fong disease, hereditary onycho osteodysplasia (HOOD syndrome), Iliac horn syndrome, Turner-Kieser syndrome, and Osterreicher syndrome.

What Is the Etiology of Nail Patella Syndrome?

Nail-patella syndrome is acquired as a result of an autosomal dominant pattern of inheritance. Studies report that the mutation in the LMX1B (LIM homeobox transcription factor 1-beta) gene located on chromosome 9q34 is the etiology of nail-patella syndrome.

What Is Autosomal Dominant Inheritance Pattern?

Autosomal dominant inheritance pattern occurs when only a single copy of a mutated gene is present in any one of the parents or as a result of a new mutation in the affected individual. The chance of transmitting the disease from one generation to another in each pregnancy is 50 %.

What Is the Epidemiology of Nail Patella Syndrome?

It is reported to be a rare disorder with an incidence of 1 in 50,000 people. It is estimated that around 86 % of affected patients inherited the syndrome from their parents with the mutated gene. In 12 % of cases, it arises as a result of new genetic mutations. The children of the affected parents have a 50 % chance of inheriting the disease.

What Is the Pathogenesis of Nail Patella Syndrome?

LMXB1 gene is called the transcription factor as it provides instruction for the production of certain proteins that binds with the specific region of DNA and control other gene activity. It plays an important role in fetal organ development, such as the eyes, limbs, kidneys, etc. The mutation in the LMXB1 gene would result in aberrant production of the proteins, or it may affect the protein binding of the DNA, thereby resulting in nail-patella syndrome.

What Are the Symptoms of Nail Patella Syndrome?

The symptoms of nail-patella syndrome include:

1. Nail Abnormalities - Around 96 % to 98 % of cases show abnormalities in nails, which include:

• Hypoplastic nails (underdeveloped nails).

• Anonychia (absent nails).

• Discolored nails.

• Pitted nails.

• Ridged and split nails.

• Thumb nails are most commonly affected by this condition.

2. Knee Abnormalities - About 74 % of cases with this syndrome show knee abnormalities,

• Abnormal patella.

• Unstable knee bone.

• Small or irregularly shaped patella.

• Absent patella.

• Frequent dislocation of the patella bone.

3. Elbow Abnormalities - Around 70 % of cases show elbow involvement; it includes:

• Elbows show limitations in actions such as pronation, extension, and supination.

• Cubitus valgus (elbows may be angled outward).

• Antecubital pterygium (elbows may show abnormal webbing, thereby affecting normal functions).

4. Iliac Horns - Around 70 % to 76 % of cases show iliac horns. The presence of iliac horns is seen in most cases with nail-patella syndrome. Iliac horns are characterized by the horn-like outgrowths of the iliac bones in the pelvis region, which can be felt through the skin and are usually asymptomatic.

5. Eye Abnormalities - It is found that patients with nail-patella syndrome have an increased risk of developing glaucoma (pressure in the eyes). Lester’s sign is the pigmentary changes in the iris that consists of a zone of darker pigmentation resembling a clover leaf or flower.

6. Kidney Abnormalities - Around 30 % to 35 % of cases with nail-patella syndrome show kidney abnormalities. It manifests as proteinuria (protein in the urine) followed by hematuria (blood in the urine), which progresses to renal failure. Renal problems are exaggerated during pregnancy.

Other Symptoms:

Other symptoms in patients with nail-patella syndrome include:

• Numbness or tingling sensation in the hands due to poor blood circulation.

• Osteoporosis (brittle and fragile bones).

• Dental hypoplasia (improperly formed enamel).

• Arthrogryposis (a term that denotes the group of diseases affecting the joints).

• Constipation.

• Hypothyroidism (decreased thyroid hormone production).

• ADHD (attention deficit hyperactivity disorder) is a neurodevelopmental disorder.

How Is Nail Patella Syndrome Diagnosed?

1. History - A thorough medical and family history would provide a major clue in diagnosing the disease. Family history helps to understand the genetic link in families, and medical history would help in understanding the symptoms of the disease.

2. Clinical Examination - Clinical examination of the patient would reveal the features such as poorly developed nails and knees. Other features such as eye abnormalities, renal dysfunction, and iliac horns.

3. Radiological Findings - The radiological findings are as follows:

• Dislocated hypoplastic patella bones.

• Absent patella.

• Radial head dysplasia.

• Presence of iliac horns.

• The prominence of the medial epicondyle.

4. Gene Target Testing - Gene target deletion or duplication analysis helps to check for the mutation in the LMXB1 gene and would help confirm the condition's diagnosis.

How Is Nail Patella Syndrome Managed?

There is no exact cure for the condition; the treatment is aimed at managing the symptoms and improving survival.

• Analgesics - Are given to relieve pain in patients with nail-patella syndrome.

• Splinting - Can be done to fix the displaced bones.

• Surgery - Can be carried out to fix skeletal problems.

• Physiotherapy - This would help in improving elbow functions.

• Angiotensin-Converting Enzyme (ACE) Inhibitors - This would help reduce blood pressure and prevent the advent of proteinuria and the progression of renal failure.

• Dialysis or Renal Transplantation - Is suggested in patients with renal failure.

• Other Measures - The treatment for other associated symptoms and conditions with the syndrome, such as glaucoma, constipation, dental anomalies, and epilepsy, must be addressed with the appropriate drugs.

What Are the Complications of Nail Patella Syndrome?

The complications include:

• Hypertension.

• Glaucoma.

• Renal failure.

• Preeclampsia (high blood pressure during pregnancy).

How to Prevent the Complications of Nail Patella Syndrome?

The complications can be prevented or reduced by the following measures:

• Regular monitoring of blood pressure.

• Urinalysis (to check for kidney function).

• Glaucoma screening.

• DEXA (dual-energy X-ray absorptiometry) scan (to check for the density of the bones).

• Dental examination (once every six months to prevent dental complications).

Conclusion:

Nail patella syndrome is a rare hereditary condition with an autosomal dominant inheritance. Earlier diagnosis of the condition and addressing the issues promptly would help in improving the prognosis of the syndrome. The most serious complications of the syndrome, such as glaucoma and renal dysfunction, can be prevented by regular monitoring and screening.