Nail-Patella Syndrome

Updated: Feb 19, 2019
  • Author: Anna Choczaj-Kukula, MD, PhD; Chief Editor: Dirk M Elston, MD  more...
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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. [1] See the image below.

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


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 [2] ; 88% of individuals with NPS have an affected parent. [3] The responsible gene was described by Dreyer et al in 1998. [4] 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. [5, 6, 7] Heterozygous variants in LMX1B are responsible for NPS, and it has been postulated that the variable expressivity is due to the interaction of LMX1B with other developmental genes. [8]

Numerous studies have demonstrated that the NPS locus is linked to that of the ABO blood group [9] and the enzyme adenylate kinase. [10] 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 [11] (LMX1B regulates genes, which encode proteins associated with the actin cytoskeleton important for podocyte function). [12] At present, no evidence for a correlation between the presence and severity of the clinical anomalies and the LMX1B genotype has been found. [13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 3, 26, 27, 28, 29, 30, 31, 32] A hypothesis of genetic heterogenicity was raised by Ghoumid et al, with 38 different LMX1B variants or deletions identified. [33] More recently, missense mutations in the homeodomain of LMX1B have been identified to cause a kidney-limited phenotype of NPS without extrarenal manifestations. [34, 35] Pathogenic mutations in the LMXB1 gene explain approximately 95% of NPS cases, with 5% of cases remaining unexplained. Mutation of WiF1, involved in mesoderm segmentation, was reported as a suspected cause of NPS in a family negative for the LMX1B mutation. [36]

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. [37] Kidney disease (focal segmental glomerulosclerosis) and glaucoma are now recognized as part of the syndrome. [38] The most serious complication associated with NPS is nephropathy. [39, 40]

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. [41]

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



The mechanisms underlying the different manifestations and severity of the symptoms in nail-patella syndrome (NPS) remain uncertain.

NPS is known to be an autosomal dominant hereditary disease affecting development of the limbs, kidneys, and eyes. A genetic abnormality is believed to lead to altered connective-tissue metabolism with widespread structural defects in collagen.

Abnormal collagen type 3 deposition in the glomeruli probably causes the nephropathy associated with NPS. [42, 43]




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


No clear racial predominance is recognized.


Both sexes are equally affected.


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



Prognosis is determined by the associated abnormalities, mainly nephropathy. [44] 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.


Patient Education

Genetic counseling is recommended.