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This 33-year-old Guatemalan man presented to a medical mission camp with generalized bilateral knee pain and inability to extend his leg without pain. The 4-ft 11-in patient had mild scoliosis, increased elbow carrying angles, and hypoplastic patellae. He had had dysplasia of the nails with triangular lunulae since birth. The fingernails were absent on the first and second digits of both hands. His mother had had similar physical findings. He had not had regular medical care.
The classic clinical tetrad of nail-patella syndrome (also known as Fong disease, Turner syndrome, and hereditary onycho-osteodysplasia) involves the nails, knees, and elbows, and the presence of iliac horns.1 This autosomal dominant condition is associated with the LMX1B gene on chromosome 9 (9q34).2,3 The incidence is roughly estimated at 1 in 50,000. The syndrome has been reported in a variety of ethnic groups.
The diagnosis of nail-patella syndrome is based on clinical manifestations, which vary in frequency and severity and between family members:
•Nails. The nails are absent or dystrophic in 80% to 90% of patients.4 Affected nails can be hypoplastic, ridged longitudinally or horizontally, pitted, or discolored. Nail changes may be observed at birth and are most often bilateral and symmetric. The thumbnails are the most severely affected; the severity decreases toward the little finger. The nail changes may be limited to triangular lunulae—a characteristic feature of nail-patella syndrome. Hyperextension of the proximal interphalangeal joints with flexion of the distal interphalangeal joints that results in "swan-necking" and fifth finger clinodactyly may be seen.
•Knees. Patellae may be small, irregularly shaped, or asymmetric. They are absent or hypoplastic in 60% of patients.2 Recurrent subluxation or dislocation of the patella is common, causes significant pain, and may be associated with poor development of the vastus medialis muscle. The displacement of the patella is lateral and superior; the hypoplastic patella is often located laterally and superiorly even when not actually dislocated. Osteochondritis dissecans, synovial plicae, and absence of the anterior cruciate ligament may also be noted. Early degeneration arthritis is not uncommon.
•Elbows. Abnormalities of the elbow are rare but may result in limited motion. Typical radiologic findings include dysplasia of the radial head, hypoplasia of the lateral epicondyle and capitellum, and prominence of the medial epicondyle.
•Spine and chest wall. Half of patients have back pain. An increased lumbar lordosis, scoliosis (usually mild), spondylolisthesis, spondylolysis, or pectus excavatum may be present.
•Kidney. The first sign of renal involvement is usually proteinuria, with or without hematuria (in 30% to 50% of patients).2 Proteinuria may present at any age from birth onward and may be intermittent. It may remit spontaneously, remain asymptomatic, or progress to nephritic syndrome and occasionally to renal failure. Renal failure occurs in about 5% of patients and may develop rapidly or after years of asymptomatic proteinuria.4 Nephritis also may occur.
•Eyes. Primary open-angle glaucoma and ocular hypertension develop more frequently in patients with nail-patella syndrome and at a younger age than in the general population. Hyperpigmentation of the pupillary margin of the iris (Lester sign) occurs in 45% of patients.3,4
•Pelvis. The iliac bone may have horns or spurs, which are only detected radiographically. This finding is pathognomonic for nail-patella syndrome.
Nail-patella syndrome is associated with hypothyroidism, irritable bowel syndrome, attention deficit hyperactivity disorder, and thin tooth enamel. The precise nature of these associations remains unclear.
Ideally, treatment of patients with nail-patella syndrome involves a multidisciplinary approach, including nephrology, orthopedics, rheumatology, and psychology. Close management and surveillance are essential to prevent and treat renal complications. The prognosis is usually benign, although end-stage renal disease requiring renal transplantation develops in about 30% of patients at a mean age of 33 years.2
1. Kasper DL, Braunwald E, Fauci A, et al. Harrison's Principles of Internal Medicine. 16th ed. New York: McGraw-Hill; 2005:1676,1692.
2. Sweeney E, Fryer A, Mountford R, et al. Nail patella syndrome: a review of the phenotype aided by developmental biology. J Med Genet. 2003;40:153-162.
3. McIntosh I, Dreyer SD, Clough MV, et al. Mutation analysis of LMX1B gene in nail-patella syndrome patients. Am J Hum Genet. 1998;63:1651-1658.
4. James WD. Andrews' Diseases of the Skin: Clinical Dermatology. 10th ed. Philadelphia: Saunders Elsevier; 2006:786-787.