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Nail-patella syndrome

Patrick Niaudet, MD
Section Editors
Tej K Mattoo, MD, DCH, FRCP
Helen V Firth, DM, FRCP, DCH
Deputy Editor
Melanie S Kim, MD


The nail-patella syndrome (NPS, MIM #161200) or hereditary osteo-onychodysplasia (HOOD syndrome) is a rare autosomal dominant disorder. It is characterized by limb and pelvic skeletal abnormalities (eg, hypoplastic or absent patella, dysplasia of elbows, including pterygia, and iliac horns), nail and distal digital abnormalities, and renal disease.

The clinical manifestations, diagnosis, and management of children with NPS will be reviewed here.


The estimated incidence of NPS is 1 per 50,000 [1,2]. The disease has been reported in patients all around the world.


NPS is an autosomal dominant disorder with full gene penetrance but variability of expression even within families [3,4].

Approximately 85 percent of families with NPS present with mutations of the LMX1B gene located at the distal end of the long arm of chromosome 9 [5-7]. LMX1B is a transcription factor of the LIM-homeodomain type that plays an important role for limb and renal development in vertebrates; however, it is expressed lifelong within the podocyte and it is essential for the maintenance the structured actin cytoskeleton in podocytes [8]. More than 140 heterozygous mutations in LMX1B have been reported, including missense, splicing, deletions, and nonsense mutations. Most mutations result in protein truncation [3,7,9-11]. The identification of entire LMX1B deletions confirms that haploinsufficiency is the principal pathogenetic mechanism of NPS [12]. Studies in homozygous knock-out mice and in vitro assays demonstrated that LMX1B protein expressed in glomerular podocytes helps control the transcription of multiple genes integral for proper glomerular basement membrane (GBM) formation, and/or glomerular podocyte differentiation and function during the early stages of renal development [5,13-16]. Putative target genes include COL4A3 and COLA4, genes for alpha-4 chains of collagen type IV [13,14], and NPHS2 and CD2AP genes, which encode podocyte proteins [14,15]. (See "Clinical manifestations, diagnosis, and treatment of Alport syndrome (hereditary nephritis)" and "Steroid-resistant idiopathic nephrotic syndrome in children", section on 'NPHS2 mutations' and "Steroid-resistant idiopathic nephrotic syndrome in children", section on 'Other genes'.)

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Literature review current through: Nov 2017. | This topic last updated: Nov 15, 2016.
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