Nail-Patella Syndrome

Updated: Sep 21, 2016
  • Author: Anna Choczaj-Kukula, MD, PhD; Chief Editor: Dirk M Elston, MD  more...
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Overview

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. See the image below.

Nail of a patient the nail-patella syndrome. Nail of a patient the nail-patella syndrome.
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Pathophysiology

Nail-patella syndrome (NPS) is inherited as an autosomal dominant trait with a high degree of penetrance but variable expression. Autosomal recessive mode of inheritance has also been reported [1] ; 88% of individuals with NPS have an affected parent. [2] The responsible gene was described by Dreyer et al in 1998. [3] The protein encoded by LMX1B is responsible for the normal dorsoventral patterning of the limb, morphogenesis of the glomerular basement membrane and anterior segment of the eye. [4, 5, 6]

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. LMX1B is involved in the regulation of collagen IV expression and in the transcriptional regulation of podocyte specification and differentiation. At present, no evidence for a correlation between the presence and severity of the clinical anomalies and the LMX1B genotype has been found. [7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 2, 20, 21, 22, 23, 24, 25, 26] A hypothesis of genetic heterogenicity was raised by Ghoumid et al, with 38 different LMX1B variants or deletions identified. [27]

The diagnostic tetrad includes fingernail dysplasia, absent or hypoplastic patellae, presence of posterior conical iliac horns, and deformation or luxation (ie, hypoplasia) of the radial heads. The clinical manifestations are extremely variable in both frequency and severity, with interfamilial and intrafamilial variability. [28] Kidney disease (focal segmental glomerulosclerosis) and glaucoma are now recognized as part of the syndrome. [29] The most serious complication associated with NPS is nephropathy. [30, 31]

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. [32]

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

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Epidemiology

Frequency

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

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.

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Prognosis

Prognosis is determined by the associated abnormalities, mainly nephropathy. The incidence of nephropathy in nail-patella syndrome (NPS) is reported to be approximately 40% among patients with various degrees of dysfunction. Of these patients, 10% die of renal insufficiency.

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Patient Education

Genetic counseling is recommended.

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