Nail-patella syndrome is a genetic disease of the connective tissue that produces defects in the fingernails, bone joints, and kidneys.
Patients who have nail-patella syndrome may show a variety of physical defects. The most common features of this syndrome are missing or poorly developed fingernails, toenails, and patellae (kneecaps). Other common abnormalities include elbow deformities, abnormally shaped pelvis bone (hip bone), and kidney (renal) disease.
Less common medical findings include defects of the upper lip, the roof of the mouth, and unusual skeletal abnormalities. Skeletal abnormalities may include poorly developed shoulder blades (scapulae), sideways bent fingers (clinodactyly), clubfoot, scoliosis, and unusual neck bones. There are also other effects, such as thickening of the basement membrane in the skin and tiny clusters of capillaries (glomeruli) in the kidney. Nail-patella syndrome is associated with open-angle glaucoma, which, if untreated, may lead to blindness. Patients may also have cataracts, drooping eyelids (ptosis), or corneal problems such as glaucoma. In addition, scientists have recognized an association between nail-patella syndrome and colon cancer.
People with nail-patella syndrome may display only a few or many of the recognized signs of this disease, with symptoms varying widely from person to person. Symptoms even vary within a single family with multiple affected members.
Nail-patella syndrome is also known as Fong disease, hereditary onycho-osteodysplasia (HOOD), Iliac Horn syndrome, and Turner-Kieser syndrome.
Nail-patella syndrome is a rare genetic disease. The incidence of nail-patella syndrome is approximately one in 50,000 births. This disorder affects males and females equally. It is found throughout the world and occurs in all ethnic groups. The strongest risk factor for nail-patella syndrome is a family history of the disease.
Causes and symptoms
Nail-patella syndrome has been recognized as an inherited disorder for over a hundred years. It is caused by mutations in a gene known as LIM Homeobox Transcription Factor 1-Beta (LMX1B), located on the long arm of chromosome 9. The LMX1B gene codes for a protein that is important in organizing embryonic limb development. Mutations in this gene have been detected in many unrelated people with nail-patella syndrome. Scientists have also been able to interrupt this gene in mice to produce defects similar to those seen in human nail-patella syndrome.
Nail-patella syndrome is inherited in an autosomal dominant manner. This means that possession of only one copy of the defective gene is enough to cause disease. When a parent has nail-patella syndrome, each of the children has a 50 percent chance to inherit the disease-causing mutation.
A new mutation causing nail-patella syndrome can also occur, causing disease in a child with no family history of the syndrome. This is called a sporadic occurrence and accounts for approximately 20 percent of cases of nail-patella syndrome. The children of a person with sporadic nail-patella syndrome are also at a 50 percent risk of inheriting the disorder.
Medical signs of nail-patella syndrome vary widely between patients. Some patients with this disorder do not display symptoms. These patients are discovered to have the nail-patella syndrome only when genetic studies are conducted to trace their family history.
The most obvious sign associated with nail-patella syndrome is absent, poorly developed, or unusual fingernails. Fingernail abnormalities are found in about 98 percent of children with this disorder. Abnormalities may be found in one or more fingernails. Only rarely are all fingernails affected. This disease most commonly affects the fingernails of the thumbs and index fingers. The pinky fingernail is least likely to be affected. Fingernails may be small and concave with pitting, ridges, splits, and/or discoloration. Toenails are less often affected.
Kneecap abnormalities, present in about 92 percent of children with this disorder, are the second most common sign associated with this disorder. Either or both kneecaps may be missing or poorly formed. If present, kneecaps are likely to be dislocated. The knees of people with nail-patella syndrome may have a square appearance. Besides the kneecap, other support structures including bones, ligaments, and tendons may also be malformed. Since these support structures stabilize the knee, patients with some leg malformations may have difficulty in walking. There may also be some hip bone anomaly or other skeletal symptoms, for example, clubfoot.
Kidney disease is present in about 30 to 50 percent of people with nail-patella syndrome. Kidney disease has been reported in children with nail-patella syndrome, but renal involvement more commonly develops during adulthood, usually during the fourth decade of life.
Eye problems may be present and vary from person to person. Nail-patella syndrome is thought to be associated with open-angle glaucoma, a condition caused by blockage of the outflow of fluid (aqueous humor) from the front chamber of the eyes. Nail-patella syndrome has also been associated with abnormalities of the cornea, cataracts, and astigmatism. Additionally, the irises of the eye may be multicolored.
When to call the doctor
The doctor should be called if a parent detects the symptoms of nail-patella syndrome in a child previously not diagnosed with the syndrome.
Genetic testing for nail-patella syndrome is usually available only at research institutions that are working to further characterize this disorder. However, genetic testing cannot predict which signs of the disease will develop nor predict the severity of disease symptoms.
Diagnosis of this disease is most often made on visual medical symptoms such as the characteristic abnormalities of the fingernails and kneecaps. Diagnosis is confirmed by x-ray images of the affected bones and, when indicated, kidney biopsy. The bony pelvic spurs found in children with nail-patella syndrome are not associated with any other disease.
Treatment for children affected by nail-patella syndrome depends on the child's specific symptoms.
A wheelchair may be required if walking becomes painful due to bone, tendon, ligament, or muscle defects. Orthopedic surgery may be necessary for congenital clubfoot deformity. Manipulation or surgery may be required to correct hip dislocation. Cataracts are also surgically treated. Medical treatment at early signs of glaucoma prevents progression of the disease to blindness.
Controlling blood pressure may slow the rate of deterioration of kidney function. Severe kidney disease can be treated with dialysis or a kidney transplant. Children receiving kidney transplants do not develop nail-patella-type renal complications in their new kidney.
Because many possible manifestations of nail-patella syndrome exist, parents are advised to obtain extra medical care for their child with nail-patella syndrome, including regular urinalysis to monitor blood and protein levels to detect kidney disease as well as eye exams to detect glaucoma. Children with nail-patella syndrome should be periodically screened for scoliosis and lordosis.
Symptoms vary from person to person and for one person through time. The long-term prognosis is extremely variable. One person may exhibit mild symptoms, while another person may become wheelchair-bound or require a kidney transplant.
Survival among patients with nail-patella syndrome is not decreased unless they exhibit renal complications. It is estimated that 8 percent of individuals with nail-patella syndrome who come to medical attention eventually die of kidney disease.
Genetic counseling can be offered to persons who have the disease. Parents with this disease have a 50 percent chance of passing it to each of their children.
Families may wish to seek counseling regarding the effects on relationships within the family after the birth of a child with nail-patella syndrome, for many people respond with guilt, fear, or blame when a genetic disorder is manifested within a family. Support groups are often good sources of information about nail-patella syndrome and can offer emotional and psychological support.
Chorionic villus sampling—A procedure used for prenatal diagnosis at 10–12 weeks gestation. Under ultrasound guidance a needle is inserted either through the mother's vagina or abdominal wall and a sample of the chorionic membrane. These cells are then tested for chromosome abnormalities or other genetic diseases.
Glaucoma—A common eye disease characterized by increased fluid pressure in the eye that damages the optic nerve, which carries visual impulses to the brain. Glaucoma can be caused by another eye disorder, such as a tumor or congenital malformation, or can appear without obvious cause, but if untreated it generally leads to blindness.
Glomerulus—Plural, glomeruli; a network of capillaries located in the nephron of the kidney where wastes are filtered from the blood.
Hematuria—The presence of blood in the urine.
Hypnogogic hallucination—A vivid, dream-like hallucination, such as the sensation of falling, that occurs at the onset of sleep.
Proteinuria—Abnormally large quantites of protein in the urine.
Nail Patella Syndrome: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References. San Diego, CA: Icon Health Publications, 2004.
Nail Patella Syndrome Networking/Support Group. 67 Woodlake Dr., Holland, PA 18966. Web site: <www.hometown.aol.com/pacali/npspage.html>.
National Organization for Rare Disorders Inc. 55 Kenosia >Ave., PO Box 1968, Danbury, CT 06813–1968. Web site: <www.rarediseases.org>.
Judith L. Sims, MS John T. Lohr, PhD Judy C. Hawkins, MS