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Disease Profile

Nail-patella syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

Neonatal

ICD-10

Q87.2

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

NPS 1; Onychoosteodysplasia; Turner-Kieser syndrome;

Categories

Congenital and Genetic Diseases; Eye diseases; Kidney and Urinary Diseases;

Summary

Nail-patella syndrome causes changes in the nails, elbows, kneecaps (patellae), and hip bone. The most common symptom of the syndrome is having missing or underdeveloped fingernails and toenails. Other symptoms may include having small or missing kneecaps, underdeveloped elbows, and an extra small piece of bone on both sides of the hip (called iliac horns). People with nail-patella syndrome are at an increased risk for developing high fluid pressure in the eye (glaucoma) and kidney disease.[1][2][3] 

Nail-patella syndrome is caused by genetic changes (pathogenic variants or mutations) in the LMX1B gene. The syndrome is inherited in an autosomal dominant manner.[1] Diagnosis is usually suspected when a person has symptoms of the syndrome. The diagnosis can be confirmed by genetic testing. Treatment for nail-patella syndrome may include physical therapy or surgery for joint problems. Other treatments depend on the symptoms present in each person.[1][2][3]

Symptoms

The symptoms of nail-patella syndrome most commonly affect the way the nails, kneecaps (patellae), elbows, and hip bone form. Almost all people with nail-patella syndrome have nails that are missing, underdeveloped, discolored, split, or ridged. The fingernails are more likely to be affected than the toenails. The thumbnails tend to be the most severely affected.[1][2][3] 

Most people who have nail-patella syndrome have kneecaps that are small, absent, or irregularly shaped. This can cause problems such as frequent kneecap dislocation or early-onset arthritis. One kneecap may be affected more than the other. Most people with the syndrome also have problems with one or both of their elbows because different parts of the elbow did not develop correctly. Some people are not able to fully extend their elbows or may have a hard time turning (rotating) the lower part of the arm when their arm is straight. The elbow may dislocate easily.[1][2][3] 

Changes in the pelvic bones called iliac horns can often be seen on x-ray and are found in 70% of people with nail-patella syndrome. Iliac horns are small pointy growths of bone (bony projections) that are not normally found on people's hip bones. Although these changes do not cause any health problems, iliac horns, if present, can be used to diagnose nail-patella syndrome.[1][2][3]

Other less common symptoms may include gastrointestinal problems such as constipation or irritable bowel syndrome. There may be nerve (neurological) problems affecting the hands and feet, such as reduced sensitivity to pain and temperature, numbness, tingling, or burning sensations. The hands and feet may be unusually cold, even in warm weather. Dental problems may include weak, crumbling teeth and thin dental enamel.[2][4]

People with nail-patella syndrome are at a higher risk to develop increased pressure in the eye (glaucoma). About 30-50% of people with nail-patella syndrome have kidney disease. The most common feature of kidney disease is having high levels of protein in the urine (proteinuria). High blood pressure (hypertension) is also common in people with kidney disease. In about 5% of people with nail-patella syndrome, the kidney disease may progress to kidney failure.[2][3] 

The symptoms associated with nail-patella syndrome can vary widely, even among people in the same family. This concept is called variable expressivity.[1]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal fingernail morphology
Abnormal fingernails
Abnormality of the fingernails

[ more ]

0001231
Aplasia/Hypoplasia of the patella
Absent/small kneecap
Absent/underdeveloped kneecap

[ more ]

0006498
Concave nail
Spoon-shaped nails
0001598
Cubitus valgus
Outward turned elbows
0002967
Exostoses
Formation of new noncancerous bone on top of existing bone
0100777
Hypoplastic toenails
Underdeveloped toenails
0001800
Iliac horns
0009780
Joint hyperflexibility
Joints move beyond expected range of motion
0005692
Joint stiffness
Stiff joint
Stiff joints

[ more ]

0001387
Patellar dislocation
Dislocated kneecap
0002999
Ridged nail
Grooved nails
Nail ridging

[ more ]

0001807
Skeletal dysplasia
0002652
Thickening of the lateral border of the scapula
Thickening of the lateral border of the shoulder blade
0006650
30%-79% of people have these symptoms
Joint swelling
0001386
Nephrotic syndrome
0000100
Osteoarthritis
Degenerative joint disease
0002758
Proteinuria
High urine protein levels
Protein in urine

[ more ]

0000093
5%-29% of people have these symptoms
Cataract
Clouding of the lens of the eye
Cloudy lens

[ more ]

0000518
Glaucoma
0000501
Glomerulopathy
0100820
Hearing impairment
Deafness
Hearing defect

[ more ]

0000365
Hematuria
Blood in urine
0000790
Hypertension
0000822
Nephropathy
0000112
Renal insufficiency
Renal failure
Renal failure in adulthood

[ more ]

0000083
Vasculitis
Inflammation of blood vessel
0002633
1%-4% of people have these symptoms
Absent distal interphalangeal creases
0001032
Antecubital pterygium
0009760
Back pain
0003418
Limited elbow extension
Decreased elbow extension
Elbow limited extension
Limitation of elbow extension
Limited extension at elbows
Limited forearm extension
Restricted elbow extension

[ more ]

0001377
Lumbar hyperlordosis
Excessive inward curvature of lower spine
0002938
Patellar aplasia
Absent kneecap
0006443
Patellar hypoplasia
Small kneecap
Underdeveloped kneecap

[ more ]

0003065
Pes planus
Flat feet
Flat foot

[ more ]

0001763
Talipes equinovarus
Club feet
Club foot
Clubfeet
Clubfoot

[ more ]

0001762
Percent of people who have these symptoms is not available through HPO
Absence of pectoralis minor muscle
0005255
Anonychia
Absent nails
Aplastic nails

[ more ]

0001798
Autosomal dominant inheritance
0000006
Biceps aplasia
Absent biceps
0009783
Cleft palate
Cleft roof of mouth
0000175
Cleft upper lip
Harelip
0000204
Clinodactyly of the 5th finger
Permanent curving of the pinkie finger
0004209
Disproportionate prominence of the femoral medial condyle
0006437
Elongated radius
0006424
Glenoid fossa hypoplasia
0006633
Glomerulonephritis
0000099
Hypoplasia of first ribs
Small first rib
Underdeveloped first rib

[ more ]

0006657
Hypoplastic radial head
0003997
Keratoconus
Bulging cornea
0000563
Lester's sign
0009781
Microcornea
Cornea of eye less than 10mm in diameter
0000482
Microphakia
Small lens
0012376
Pectus excavatum
Funnel chest
0000767
Ptosis

Cause

Nail-patella syndrome is caused by genetic changes (pathogenic variants or mutations) in the LMX1B gene in about 95% of people with the syndrome. The LMX1B gene gives the body instructions to make a protein that is thought to control when other genes are "turned on." These other genes make proteins important for the development of the nails, kneecaps, elbows, kidneys, and eyes. However, the exact function of the LMX1B gene, and the effect of pathogenic variants on its function, are not completely understood.[1][2]

In rare cases, people who have symptoms of nail-patella syndrome do not have a pathogenic variant in the LMX1B gene. Therefore it is thought that there may be other genes in which pathogenic variants cause nail-patella syndrome.[3]

Diagnosis

Nail-patella syndrome is diagnosed based on the signs and symptoms present (this is called a "clinical diagnosis" and means that laboratory or genetic testing is not necessary for the diagnosis). The diagnosis may be made when a person has a thorough clinical exam and/or imaging studies that identify symptoms such as fingernail or toenail abnormalities (present in 98% of people with the syndrome), small or absent kneecaps, elbow abnormalities, and/or iliac horns (a bone finding common in people with this syndrome but uncommon in people who do not have the syndrome). The diagnosis can be made when a person has at least one (but usually more than one) characteristic symptom.[1][2] Because about 95% of people with this syndrome have a mutation in the LMX1B gene, genetic testing that identifies a mutation in this gene can confirm the diagnosis both in people with a clinical diagnosis, and in cases where the clinical diagnosis is uncertain.[2]

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Treatment

After a diagnosis of nail-patella syndrome, a person may be recommended to undergo screening for health problems that are more common in people with the syndrome. This may include having regular blood pressure checks, urine tests to watch for the development of kidney problems, and examinations by a medical eye doctor (ophthalmologist) to check for signs of glaucoma.[2]

Symptoms of nail-patella syndrome affecting the knee and elbow (orthopedic problems) may be treated with physical therapy, braces, splints, or surgeries. Before a person with nail-patella syndrome has surgery for orthopedic problems, an MRI is recommended to make sure the doctors understand the unique anatomy of the joint or body part. Other symptoms of the syndrome, such as glaucoma or high blood pressure (hypertension), can be treated with medications as the medical problem would in people who do not have the syndrome. In some cases, people with nail-patella syndrome may require a kidney transplant.[2] It is recommended that people with the syndrome avoid non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, due to their increased risk of kidney problems.[2]

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
    Nail-Patella Syndrome
    Genetics of Nail-Patella Syndrome
  • The Merck Manual for health care professionals provides information on Nail-patella syndrome.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Nail-patella syndrome. Click on the link to view a sample search on this topic.

References

  1. Nail-patella syndrome. Genetics Home Reference. April 2013; https://ghr.nlm.nih.gov/condition/nail-patella-syndrome.
  2. Sweeney E, Hoover-Fong J, McIntosh I. Nail-Patella Syndrome. GeneReviews. November 13, 2014; https://www.ncbi.nlm.nih.gov/books/NBK1132/.
  3. Vazquez P and Hoover-Fong J. Nail Patella Syndrome. National Organization for Rare Disorders. 2017; https://rarediseases.org/rare-diseases/nail-patella-syndrome/.
  4. Choczaj-Kukula A and Janniger CK. Nail-Patella Syndrome. Medscape. September 21, 2016; https://emedicine.medscape.com/article/1106294-overview.

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