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
, 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
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
with multiple affected members.
Nail-patella syndrome is also known as Fong disease, hereditary
onycho-osteodysplasia (HOOD), Iliac Horn syndrome, and Turner-Kieser
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
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,
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.
The doctor should be called if a parent detects the symptoms of
nail-patella syndrome in a child previously not diagnosed with the
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
Illustration of bones around the knees showing absence of the
patella in nail-patella syndrome.
(Illustration by Argosy, Inc.)
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
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
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
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.
—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.
—Plural, glomeruli; a network of capillaries located in the
nephron of the kidney where wastes are filtered from the blood.
—The presence of blood in the urine.
—A vivid, dream-like hallucination, such as the sensation of
falling, that occurs at the onset of sleep.
—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:
National Organization for Rare Disorders Inc.
55 Kenosia >Ave., PO Box 1968, Danbury, CT 06813–1968. Web site: