Nail Patella Syndrome

What is Nail Patella Syndrome?

Nail patella syndrome is a rare genetic condition that causes problems with nails, bones, kidneys and eyes. The classic syndrome presentation includes:

• Nail dysplasia
• Patella hypoplasia or aplasia
• Elbow arthrodysplasia
• Iliac horns ^[1]

Image 1 – Visible Abnormality of Nails

Causes

Nail patella syndrome is caused by genetic mutations in the LMX1B gene. It is not known why exactly mutations in this gene appear^[2].

Genetics

LMX1B gene belongs to a group of genes called transcription factors. These genes provide instructions for protein production. Produced proteins bind to specific places in DNA and regulate the activity of other genes. LMX1B gene plays an important role in early embyogenesis. It is involved in development of limbs, nails, kidneys and eyes. Nail patella syndrome develops when the function of this gene is lost.

Nail patella syndrome is inherited in autosomal-dominant pattern. That means only one copy of mutated gene is necessary for the syndrome to manifest. In most cases the mutated gene is inherited from one parent. In some cases the mutation appears spontaneously with no family history^[2].

Symptoms

The severity of symptoms is very variable amongst individuals, but there are some typical characteristics that affect most of the patients as well as symptoms that are rarely encountered:

• Finger and toe nail dysplasia- usually apparent when the child is born or at early infancy. Thumbs are mostly involved, as well as index and middle fingers. Other deformities of nails can include:
  • Split nails
  • Abnormal thickness
  • Small and narrow form
  • Discoloration
  • The crescent shaped, light area in the base of the nail can be malformed or differently shaped
• Knee cap deformity- knee caps can be small, misshaped or underdeveloped or not present at all.
• Other bone deformities.
  • Some patients have underdeveloped parts of calf and thigh bones that cause deformities and limitations in range of movements. With time these deformities can cause osteoarthritis.
  • Bones that shape the elbow joint can be underdeveloped. It can cause deformity and limitations in the movements of the joint.
  • Iliac horns- abnormal projection of superior portion of the hip bone
  • Underdeveloped shoulder blades
  • Curvature of the spine-scoliosis

• Eye abnormalities
  • Glaucoma
  • Hyperpigmentation of iris- it appears dark (also see Pigment dispersion syndrome)
  • Clowerleaf shaped iris
  • Cataracts
  • Microcornea
• Kidney disease
  • Nephrotic syndrome
  • Glomerular kidney disease

Kidney disease can cause anemia, edema, high blood pressure, small amounts of blood in the urine and life threatening complications^[3,4].

Differential Diagnosis

• Alport syndrome
• Genitopatellar syndrome
• Meier-Gorlin syndrome
• Patellar aplasia-hypoplasia
• Small patella syndrome
• RAPADILINO syndrome- radial and patellar aplasia, cleft palate, diarrhea, dislocated joints, limb malformations, long nose, and normal intelligence^[3,4].
• Also see Smith-Magenis syndrome

Diagnosis

Definite diagnosis of nail patella syndrome can be made by genetic DNA testing and finding mutation in the LMX1B gene. There are also tests that have to be done to evaluate organ system involvement.

Laboratory analysis

• DNA testing
• Urine analysis- higher than normal levels of blood and protein in urine can suggest kidney disease
• Glomerular filtration rate has to be observed to assess kidney function

Imaging studies

• X-ray imaging can be sufficient to assess the involvement of bone structures. X-ray can show dysplastic patella, iliac horns as well as other skeletal part involvement
• MRI is used if a surgery is planned, to assess the anatomy of ligaments and muscles
• Dual energy X-ray absorbtiometry- a method that allows to assess bone density in various locations. People with this syndrome usually have decreased bone density in hips that can lead to fractures.

Other tests

• Eye examination and vision tests
• Kidney biopsy in case kidney function is deteriorating

Treatment

There is no cure for nail patella syndrome. Usually the treatment is symptomatic.

Medications

• ACE inhibitors to control blood pressure and proteinuria
• Medications to treat glaucoma
• Although non-steroid anti inflammatory medications are idely used, for patients with nail patella syndrome they should be avoided due to their affect on kidneys. Read about treatment for patello-femoral pain.

Surgery

• Replacement of knee caps
• Knee replacement surgery
• Surgical correction of elbow anomalies
• In some cases scoliosis can be severe and require surgery (also see tethered cord syndrome)
• In some cases kidney transplantation is required

Other treatment

• Physical therapy
• Braces, splints for skeletal deformities
• Social support ^[4,5]

Life expectancy

The prognosis depends of the severity of symptoms. Around 30-50% of patients develop kidney disease that might require kidney transplantation. With appropriate treatment life expectancy is close to average ^[4].

References

1. General information for patients: http://www.npsuk.org/
2. Causes: https://ghr.nlm.nih.gov/condition/nail-patella-syndrome#definition
3. Symptoms: http://www.nhs.uk/conditions/nail-patella-syndrome/Pages/Introduction.aspx
4. Information about disease and its treatment: http://emedicine.medscape.com/article/947391-overview#a4
5. Detailed information about the syndrome: https://rarediseases.org/rare-diseases/nail-patella-syndrome/