Nail-patella syndrome

Nail-patella syndrome (NPS), also known as hereditary osteo-onychodysplasia (HOOD syndrome), Fong disease, or Turner-Kieser syndrome, is a rare genetic disorder caused by mutations in the LMX1B gene located on chromosome 9q34. This gene encodes a transcription factor critical for the development of the limbs, kidneys, and eyes. NPS is characterized by a classic tetrad of abnormalities affecting the nails, knees, elbows, and pelvis. Nail changes are the most consistent feature and typically include absent, hypoplastic, or dystrophic fingernails, most severely affecting the thumbnails and index fingernails. The patellae (kneecaps) are often small, irregularly shaped, or completely absent, leading to knee instability and recurrent dislocations. Skeletal manifestations also include iliac horns — bony projections from the posterior iliac bones that are virtually pathognomonic for the condition — as well as limited elbow extension, cubitus valgus, and radial head subluxation or dislocation. Beyond the musculoskeletal system, NPS can affect the kidneys, with approximately 30–50% of patients developing nephropathy characterized by proteinuria and, in a smaller percentage (roughly 5–10%), progression to end-stage renal disease. Ocular involvement includes open-angle glaucoma and ocular hypertension, which may develop at a younger age than in the general population. Some patients also experience peripheral neuropathy and vasomotor disturbances. There is currently no cure for nail-patella syndrome, and management is symptomatic and multidisciplinary. Orthopedic interventions may be needed for joint instability or skeletal deformities. Regular monitoring of kidney function (urinalysis and blood pressure) is essential, and nephropathy is managed with ACE inhibitors or angiotensin receptor blockers when proteinuria is detected. Ophthalmologic screening for glaucoma is recommended. Genetic counseling is important given the autosomal dominant inheritance pattern, with each affected individual having a 50% chance of passing the condition to their offspring. The clinical expression is highly variable, even within the same family.

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