eMedicine Specialties > Dermatology > Nails

Nail-Patella Syndrome

Author: Anna Choczaj-Kukula, MD, PhD, Locum Consultant Dermatologist, St John's Institute of Dermatology, St Thomas' Hospital, UK
Coauthor(s): Camila K Janniger, MD, Clinical Professor of Dermatology, Clinical Associate Professor of Pediatrics, Chief of Pediatric Dermatology, New Jersey Medical School
Contributor Information and Disclosures

Updated: Apr 21, 2009

Introduction

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

Nail-patella syndrome 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 nail-patella syndrome locus has been linked to the locus of the alpha1 chain of type 5 collagen.1,2,3,4,5,6,7,8,9,10,11,12,13,14,15

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 nail-patella syndrome 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 nail-patella syndrome who had immune complex nephropathy and altered collagen, and they remarked that the patients with nail-patella syndrome were indistinguishable from patients with Goodpasture disease.16

Numerous other skeletal and eye anomalies are also described in patients with nail-patella syndrome.

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

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.17
  • 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.18
  • 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.19

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.20,21 Renal complications and ophthalmologic problems can accompany nail-patella syndrome.22

  • 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 nail-patella syndrome include splitting, longitudinal ridging, koilonychia, poor lunula formation, and discoloration.23
    • In the absence of other nail changes, V-shaped triangular lunulae with a distal peak in the midline are pathognomonic for nail-patella syndrome.24,25
  • 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.
  • Kidneys26,27
    • Renal disorders may result in only asymptomatic proteinuria, although hematuria, nephrotic syndrome,28 and progression to renal failure have been observed.18
    • Ankle edema and recurrent urinary tract infections can also be manifestations of renal involvement.
    • Nephropathy is the only manifestation of nail-patella syndrome in some cases.
  • Eyes
    • Hyperpigmentation of the pupillary margin of the iris, the Lester iris, occurs in 45% of patients with nail-patella syndrome. 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.29
  • 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.30

Causes

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

  • Nail-patella syndrome 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 Nail-patella syndrome.

More on Nail-Patella Syndrome

Overview: Nail-Patella Syndrome
Differential Diagnoses & Workup: Nail-Patella Syndrome
Treatment & Medication: Nail-Patella Syndrome
Follow-up: Nail-Patella Syndrome
References
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References

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Further Reading

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Keywords

nail-patella syndrome, NPS, hereditary osteo-onychodysplasia, HOOD, Fong syndrome, Osterreicher-Turner syndrome, fingernail dysplasia, absent patellae, hypoplastic patellae, posterior conical iliac horns, radial head deformation, radial head luxation, Goodpasture disease, congenital permanent dislocation of the patella, CPDP

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Contributor Information and Disclosures

Author

Anna Choczaj-Kukula, MD, PhD, Locum Consultant Dermatologist, St John's Institute of Dermatology, St Thomas' Hospital, UK
Disclosure: Johnson & Johnson Salary Management position

Coauthor(s)

Camila K Janniger, MD, Clinical Professor of Dermatology, Clinical Associate Professor of Pediatrics, Chief of Pediatric Dermatology, New Jersey Medical School
Camila K Janniger, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

Medical Editor

Catharine Lisa Kauffman, MD, FACP, Georgetown Dermatology and Georgetown Dermpath
Catharine Lisa Kauffman, MD, FACP is a member of the following medical societies: American Academy of Dermatology, American Medical Association, Royal Society of Medicine, Society for Investigative Dermatology, and Women's Dermatologic Society
Disclosure: Nothing to disclose.

Pharmacy Editor

David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic
David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Managing Editor

Paul Krusinski, MD, Director of Dermatology, Professor, Department of Internal Medicine, Fletcher Allen Health Care, University of Vermont
Paul Krusinski, MD is a member of the following medical societies: American Academy of Dermatology, American College of Physicians, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

CME Editor

Glen H Crawford, MD, Assistant Clinical Professor, Department of Dermatology, University of Pennsylvania School of Medicine; Chief, Division of Dermatology, The Pennsylvania Hospital
Glen H Crawford, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Phi Beta Kappa, and Society of USAF Flight Surgeons
Disclosure: Nothing to disclose.

Chief Editor

William D James, MD, Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System
William D James, MD is a member of the following medical societies: American Academy of Dermatology and Society for Investigative Dermatology
Disclosure: elsevier Royalty Other; american college of physicians Honoraria Other

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