Nail-Patella Syndrome

Clinical characteristics: Nail-patella syndrome (NPS) (previously referred to as Fong's disease), encompasses the classic clinical tetrad of changes in the nails, knees, and elbows, and the presence of iliac horns. Nail changes are the most constant feature of NPS. Nails may be absent, hypoplastic, or dystrophic; ridged longitudinally or horizontally; pitted; discolored; separated into two halves by a longitudinal cleft or ridge of skin; and thin or (less often) thickened. The patellae may be small, irregularly shaped, or absent. Elbow abnormalities may include limitation of extension, pronation, and supination; cubitus valgus; and antecubital pterygia. Iliac horns are bilateral, conical, bony processes that project posteriorly and laterally from the central part of the iliac bones of the pelvis. Renal involvement, first manifest as proteinuria with or without hematuria, occurs in 30%-50% of affected individuals; end-stage kidney disease occurs up to 15% of affected individuals. Primary open-angle glaucoma and ocular hypertension occur at increased frequency and at a younger age than in the general population.

Diagnosis/testing: The diagnosis of nail-patella syndrome is established in a proband with suggestive findings and/or a heterozygous pathogenic variant in LMX1B identified by molecular genetic testing

Management: Treatment of manifestations: Orthopedic problems may be helped by analgesics, physiotherapy, splinting, bracing, or surgery; MRI of joints to identify abnormal anatomy is important prior to surgery so that appropriate surgical treatment can be planned in advance; ACE inhibitors to control blood pressure and possibly to slow progression of proteinuria; kidney transplantation as needed; standard treatment for decreased bone mineral density, hypertension, constipation/inflammatory bowel disease, glaucoma, epilepsy, and dental anomalies.

Surveillance: At least annually: monitoring of blood pressure for hypertension; assessment of urinalysis and first-morning urine albumin-to-creatinine ratio for kidney disease; screening for glaucoma (as soon as a child is compliant). Dental examination at least every six months and DXA scan as needed.

Agents/circumstances to avoid: Chronic use of NSAIDs because of the detrimental effect on kidney function.

Pregnancy management: The risk of developing preeclampsia may be increased in pregnant women with NPS; hence, frequent urinalysis and blood pressure measurement is recommended during pregnancy. For women taking an ACE inhibitor, transitioning to an alternative treatment ideally prior to pregnancy, or at least as soon as pregnancy is recognized, is recommended to avoid potential adverse effects of ACE inhibitors on the developing fetus.

Genetic counseling: Nail-patella syndrome is inherited in an autosomal dominant manner. Eighty-eight percent of individuals with NPS have an affected parent; 12% of affected individuals have a de novo pathogenic variant. The offspring of an affected individual are at a 50% risk of inheriting NPS. Prenatal testing and preimplantation genetic testing are possible if the pathogenic variant in the family has been identified.