AUTHOR AND EDITOR INFORMATION

Section 1 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Background

Nail-patella syndrome (NPS), also known as hereditary osteo-onychodysplasia (HOOD), is an uncommon genetically determined disease that involves organs of both ectodermal and mesodermal origin. Chatelain described NPS in 1820, and Little first documented its hereditary nature in 1897.

Pathophysiology

NPS is inherited as an autosomal dominant trait with a high degree of penetrance but variable expression. Mutations in the gene encoding transcription factor LMX1B, mapped on the long arm of chromosome 9 (9q34), are responsible for the clinical phenotype of NPS. Numerous studies have demonstrated that the NPS locus is linked to that of the ABO blood group and the enzyme adenylate kinase. The NPS locus has been linked to the locus of the alpha1 chain of type 5 collagen.

The diagnostic tetrad includes fingernail dysplasia, absent or hypoplastic patellae, the presence of posterior conical iliac horns, and deformation or luxation (ie, hypoplasia) of the radial heads. Kidney disease and glaucoma are now recognized as part of the syndrome. The most serious complication associated with NPS is nephropathy.

A postulated cause of the progressive renal disease is secondary immune damage to the altered glomerular basement membrane. Curtis et al described a series of patients with NPS who had immune complex nephropathy and altered collagen, and they remarked that the patients with NPS were indistinguishable from patients with Goodpasture disease.

Numerous other skeletal and eye anomalies are also described in patients with NPS.

Frequency

International

The prevalence is estimated to be 1 case in 50,000 live births.

Mortality/Morbidity

The incidence of nephropathy in NPS is reported to be approximately 40% among patients with various degrees of dysfunction. Of these patients, 10% die of renal insufficiency.

Race

No clear racial predominance is recognized.

Sex

Both sexes are equally affected.

Age

No preferential age at onset has been reported; individuals of any age can be affected.

CLINICAL

Section 3 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

History

The correct diagnosis is rarely established during childhood because the nail and patella abnormalities may not become apparent until later in life.

• The first symptom that usually causes the patient to seek medical care is knee pain or an inability to completely extend the knee joint. The patellae may be hypoplastic or absent, and they are frequently dislocated.
• Limitation of elbow motion or subluxation of the radius often occurs as a result of hypoplasia of the radial head. Other joints tend to be hyperflexible.
• Renal involvement may result in proteinuria and recurrent urinary tract infections.
• Cutaneous manifestations are nail changes that involve mainly the thumbs and progressively decrease in severity in the second to fifth fingers.
• Patients often complain of palmoplantar hyperhidrosis.

Physical

Nail dysplasia and patellar hypoplasia are essential findings for diagnosis. Other diagnostic features are hypoplasia of the radial head and iliac prominences, which are known as iliac horns. Renal complications and ophthalmologic problems can accompany NPS.

• Nails
• • Patients have different degrees of nail dysplasia.
  • The nails, especially those on the thumbs, are typically absent or short and never reach the free edge of the finger.
  • Nail dysplasia, a typical feature, is more severe on the ulnar side than on the radial side.
  • The toenails are rarely affected.
  • Other nail abnormalities in patients with NPS include splitting, longitudinal ridging, koilonychia, poor lunula formation, and discoloration.
  • In the absence of other nail changes, V-shaped triangular lunulae with a distal peak in the midline are pathognomonic for NPS.
• Bones and joints
• • Patellar involvement is present in approximately 90% of patients; however, patellar aplasia occurs in only 20%.
  • In instances in which the patellae are smaller or luxated, the knees may be unstable.
  • The elbows may have limited motion (eg, limited pronation, supination, extension).
  • Subluxation of the radial head may occur.
  • Arthrodysplasia of the elbows is reported in approximately 90% of patients.
  • General hyperextension of the joints can be present.
  • Exostoses arising from the posterior aspect of the iliac bones are present in as many as 80% of patients; this finding is considered pathognomonic for the syndrome.
  • Other reported bone changes include scoliosis, scapular hypoplasia, and the presence of cervical ribs.
• Kidneys
• • Renal disorders may result in only asymptomatic proteinuria, although hematuria, nephrotic syndrome, and progression to renal failure have been observed.
  • Ankle edema and recurrent urinary tract infections can also be manifestations of renal involvement.
  • Nephropathy is the only manifestation of NPS in some cases.
• Eyes
• • Hyperpigmentation of the pupillary margin of the iris, the Lester iris, occurs in 45% of patients with NPS. This can be a helpful diagnostic sign.
  • Other abnormalities, such as heterochromia of the iris with cloverleaf deformity, cataracts, microcornea, and glaucoma, have also been reported.
• Other
• • Skin laxity may be present.
  • Webbing of the elbows and absent skin creases in the distal parts of the fingers are described in some patients.

Causes

The mechanisms underlying the different manifestations and severity of the symptoms in this disorder remain uncertain.

• NPS is known to be an autosomal dominant hereditary disease.
• A genetic abnormality is believed to lead to altered connective tissue metabolism with widespread structural defects in collagen.
• Abnormal collagen deposition in the glomeruli probably causes the nephropathy associated with NPS.

DIFFERENTIALS

Section 4 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Congenital ectodermal defects

WORKUP

Section 5 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Lab Studies

• Perform urinalysis to detect proteinuria or hematuria.
• Further urologic evaluation may be necessary.

Imaging Studies

• Perform radiologic examination to search for diagnostic and minor signs.
• Diagnostic radiographic findings include the following:
• • Hypoplastic patellae
  • Bilateral posterior iliac horns
  • Hypoplasia of the radial head or capitulum
• The following findings are also reported:
• Scapular hypoplasia
• Scoliosis
• Hypoplastic lateral humerus epicondyle

Procedures

• In patients with proteinuria, percutaneous renal biopsy may be useful in evaluating renal involvement.
• The features of NPS nephropathy at light, immunofluorescence, and electron microscopy have been detailed, with an emphasis on the presence of characteristic ultrastructural collagen fibrils in the glomerular basement membrane.

Histologic Findings

The literature includes descriptions of numerous histologic abnormalities in the kidneys of patients with NPS. These findings include chronic glomerulonephritis, focal glomerular necrosis, diffuse hydropic degeneration of the tubular epithelium, and localized basement membrane thickening with mild proliferation of the endothelial and epithelial cells.

TREATMENT

Section 6 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Medical Care

• No treatment is available for the cutaneous findings.
• Associated abnormalities require appropriate care from specialists.

Surgical Care

• Although more than 90% of patients with NPS have patellar involvement, most patients are asymptomatic and rarely require surgical treatment.
• However, congenital permanent dislocation of the patella (CPDP) should be treated with surgical procedures. Preferably, orthopedic correction should be performed when the patient is aged approximately 2-3 years to prevent secondary deformities and growth-related disability.

Consultations

• Consult an orthopedist, nephrologist, and ophthalmologist, as determined by the patient's history and physical examination.
• Consult a genetic counselor.

FOLLOW-UP

Section 7 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• No further inpatient care is necessary except that indicated by the associated abnormalities.

Further Outpatient Care

• Despite long periods of stable renal function, long-term follow-up care is essential in patients with NPS.

Deterrence/Prevention

• Genetic counseling is recommended because NPS is an autosomal dominant disease.

Complications

• Complications may arise because of associated abnormalities, especially in patients with renal involvement.
• The most serious complication associated with NPS is nephropathy, which occurs in approximately 40% of patients; 10% of the patients die of renal insufficiency.

Prognosis

• Prognosis is determined by the associated abnormalities, mainly nephropathy.

Patient Education

• Genetic counseling is recommended.

MISCELLANEOUS

Section 8 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to perform a thorough evaluation to identify any associated anomalies, especially renal involvement
• Failure to suggest family genetic counseling (The autosomal dominant mode of inheritance implies the need for this consultation.)
• Failure to recognize NPS

REFERENCES

Section 9 of 9

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

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Article Last Updated: Nov 8, 2006