Contributed by
UZ Gent
Helena Maes, and Koen Mermuys.
History
A six-month-old boy was referred for evaluation due to congenital flexion contractures of both knees. Clinical examination revealed bilateral fixed knee flexion, absent patellar palpation and vertical splitted nail (onychoschizia) of both thumbnails.
Images (Click any image to enlarge)
Question
Which syndrome would you suggest based on these three characteristic findings?
Your answer
Please log in to see your results.
Correct answer
Nail-patella syndrome
Discussion
Nail-patella syndrome (NPS), also known as hereditary onycho-osteodystrophy, Fong disease and LMX1B-related nail-patella syndrome, is a rare autosomal dominant disorder caused by mutations in the LMX1B gene [1]. This gene plays a critical role in skeletal and renal development. The prevalence of NPS has been estimated at 1:50000 but may be higher because of undiagnosed individuals with a mild phenotype [1]. The classic clinical tetrad of NPS includes abnormalities in the iliac bones, patella, elbow, and nails, with additional renal and ophthalmologic manifestations [1].
The typical clinical presentation of NPS includes a combination of musculoskeletal, renal, and ophthalmologic symptoms. The iliac horns, which are present in 70-76% of cases, are often the first sign noted on imaging [1]. Patellar abnormalities, seen in 74% of patients, include patellas that are small, irregular, or absent [1]. Elbow deformities such as radial head dysplasia, hypoplasia of the lateral epicondyle, and prominence of the medial epicondyle are present in about 70% of patients [1]. Nail changes, especially in the form of nail dysplasia, are observed in 96-98% of individuals with NPS [1]. In addition to these musculoskeletal findings, renal involvement (such as proteinuria) occurs in 30-50% of cases, and ophthalmologic issues (like glaucoma) are seen in 10-25% of patients [1].
Imaging plays a crucial role in diagnosing NPS by identifying these characteristic skeletal abnormalities. Posterior iliac horns (Fong prongs), which are considered a pathognomonic feature, are usually bilateral and are conical, osseous projections from the central part of the iliac bones on conventional radiography. Additionally, imaging of the patella should be performed to assess for hypoplasia or absence, which is another hallmark of the syndrome. Note that patella ossification centers appear between the age of three and six years. Advanced imaging techniques, including MRI, may be used for a more detailed evaluation of the skeletal deformities. The final diagnosis of NPS is made through a combination of clinical features, radiographic findings, and genetic testing.
Differential diagnosis
Small patella syndrome
Coffin-Siris syndrome
Meier-Gorlin Syndrome
References
- Sweeney E, Hoover-Fong JE, McIntosh I (2003, updated in 2023) Nail-Patella Syndrome. GeneReviews® (PMID: 20301311)