Nail changes are the most constant feature of NPS (98%). In most individuals with NPS, improper development (dysplasia) of the nails is apparent at birth or early infancy. While the thumbnails are almost always affected, the other fingernails may be more mildly affected or not at all. Typically the severity of the nail dysplasia decreases from the thumb toward the 5th digit. The nails may be abnormally small and narrow (i.e., one half to one third of normal size), split, abnormally thickened, depressed, and/or discolored. In addition, in most people, the crescent-shaped pale area at the base of the nail (lunula) is malformed and/or triangular. Improper development (dysplasia) of the toenails is usually less common than the fingernails; if the toenails are involved, it is often the little toenail that is affected.
Most individuals with NPS also have abnormalities of certain bones. In most people, one or both knee caps (patellae) may be abnormally small, underdeveloped (hypoplastic), and misshaped (e.g., tripartite, polygonal). In other people, one or both knee caps may be absent. In addition, affected individuals may also demonstrate underdevelopment (hypoplasia) of the two bones that create the outer part of the knee (the top of the fibula in the lower part of the leg and/or the lower, rounded projection of the femur in the upper part of the leg). Due to such abnormalities, individuals with NPS often exhibit partial dislocation (subluxation) of the patella and a limited range of movements of the knee(s), a deformity in which one or both legs bend outward at the knee (“bow-leg” or genu varum), and/or progressive degeneration, stiffness, tenderness, and Pain of the knee(s) (osteoarthritis). In severe cases, osteoArthritis may eventually limit use of the knee(s).
Most people with NPS also have abnormalities of the elbows. The portions of bone that meet at the elbow(s) (i.e.capitellum, head of radius) may be abnormally small and underdeveloped (hypoplastic). In addition, some affected individuals may have abnormal webbing of skin at the bend of the elbow(s) (antecubital pterygium). Due to such abnormalities, affected individuals may be unable to completely extend the arms, rotate the arms inward toward the body with the palms facing down (pronation), or rotate the arms outward with the palms facing upward (supination). Some affected individuals may experience partial dislocation of the elbows (subluxation). Individuals with NPS may also develop progressive osteoArthritis of the elbows that, in severe cases, may eventually limit elbow function.
The majority of individuals with NPS also have abnormal projections of bone from the upper (superior) portion of both sides of the hipbone (bilateral iliac horns). In some cases, additional Skeletal abnormalities may be present. These may include underdevelopment (hypoplasia) of the shoulder blades (scapulae) and/or abnormal sideways curvature of the spine (scoliosis).
Some affected individuals within particular families may also have a condition in which fluid pressure of the eyes becomes abnormally increased (glaucoma). The condition results due to progressive blockage of the outflow of fluid (aqueous humor) from the front chamber of the eyes (open-angle glaucoma). Initially, affected individuals may have no apparent symptoms (asymptomatic). As fluid pressure increases, some individuals with the condition may develop mild headaches, blurred vision, and/or the appearance of “halos” around certain lights. Since Glaucoma may be asymptomatic, annual screening for this condition should be performed in all patients with NPS. Without appropriate treatment, elevated fluid pressure may lead to gradual loss of peripheral vision, increased narrowing of visual fields, and eventual blindness.
Other eye (ocular) abnormalities may also be associated with NPS. In approximately 45 percent of affected individuals, the inner margin (pupillary margin) of the colored portion of the eyes (irides) may appear abnormally dark (hyperpigmentation) and “cloverleaf shaped” (Lester’s sign). Some individuals may also have abnormal clouding of the lenses of the eyes (cataracts) and/or unusually small corneas (microcornea). The cornea is the front, clear portion of the eye through which light passes. The degree of associated visual impairment depends upon the severity and/or combination of Eye abnormalities present.
Approximately 30-50% of individuals with NPS may also experience abnormalities in kidney function (nephropathy) that may be apparent during childhood or later in life. Such kidney disease may be due to abnormal degeneration of the tiny tubes (renal tubules) that collect, conduct, and secrete urine (nephrotic kidney disease) and/or Inflammation and degeneration of the clusters of capillaries (renal glomeruli) that filter the blood passing through the kidneys (glomerular kidney disease).
In most affected individuals, the first apparent signs of nephropathy include the presence of small amounts of blood in the urine (microhematuria); high blood pressure (hypertension); and/or an abnormal accumulation of fluid between layers of tissue under the skin (edema). In most people, the nephropathy may be relatively benign. However, in about 5% of those affected, progressive kidney failure may result, causing potentially life-threatening complications.
For example, some affected individuals with nephropathy may begin to exhibit a variety of symptoms (nephrotic syndrome) including anemia, edema, and/or other characteristic, abnormal laboratory findings (see “Standard Therapies, Diagnosis” for more information). In some people, the kidneys may eventually lose their ability to excrete waste products through the urine, to regulate the balance of salt and water in the body, and to perform their other vital functions (renal failure), resulting in potentially life-threatening complications. Progression to renal failure is rare in patients with NPS, usually in adults if it occurs.