eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Genetics

Nail-Patella Syndrome

Julie Hoover-Fong, MD, PhD, FACMG, Assistant Professor, Director, Greenberg Center for Skeletal Dysplasias, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University
Iain McIntosh, PhD, Professor of Medical Genetics, Chair, Department of Molecular and Cell Biology, Director, Stephen Gaffin Research Laboratory, American University of the Carribean; Elizabeth Sweeney, MBChB, MD, Consultant Clinical Geneticist, Royal Liverpool Children's Hospital, UK

Updated: Oct 20, 2009

Introduction

Background

Nail-patella syndrome (NPS; OMIM 161200) is an autosomal dominant condition characterized by the classical clinical tetrad of nail dysplasia, patellar aplasia-hypoplasia, elbow arthrodysplasia, and iliac horns. The nails may be absent, hypoplastic, or dystrophic with ridges, pits, and/or triangular lunulae.

Nail of a patient the nail-patella syndrome.

Pathophysiology

Although the joint anomalies in nail-patella syndrome may limit range of motion (ROM), the associated glaucoma and nephropathy may be the most serious complication. Asymptomatic proteinuria may persist for years; however, end-stage renal failure occurs in less than 5%. 

Mutations in the homeodomain of LMX1B versus LIM-A or LIM-B may be associated with proteinuria. However, further investigation of a larger population of patients with nail-patella syndrome (ideally sporadic) is needed to determine if this genotype-phenotype correlation is valid outside large pedigrees of nail-patella syndrome, which may be simultaneously segregating nephropathy-related genes.

Frequency

United States

Nail-patella syndrome has been recognized for more than 100 years. It has an estimated prevalence of 1 per 50,000 live births.

International

Nail-patella syndrome has been described in multiple populations.

Mortality/Morbidity

The severity of clinical features and manifestations cannot be predicted. Orthopedic problems may be treated with analgesics, physical therapy, bracing, and/or surgery. With concurrent renal disease, nonsteroidal anti-inflammatory drugs (NSAIDs) must be used cautiously to avoid worsening renal function. If orthopedic surgery is planned, MRI prior to surgery is recommended because joint structures (ie, ligament, tendon and muscle insertions, vessel locations) are typically distorted in patients with nail-patella syndrome.

Renal disease that manifests as proteinuria with or without hematuria occurs in 30-50% of patients, but progression to end-stage renal disease occurs in less than 5%. Hypertension and renal disease are treated as in the general population, with recognition that ACE inhibitors have been shown to slow progression of proteinuria in nail-patella syndrome. Patients who have undergone renal transplantation usually have good results. Glaucoma should also be treated as in the general population, but with increased surveillance in all patients with nail-patella syndrome (eg, annual ophthalmologic examination with glaucoma screening).

Race

No race predilection has been reported.

Sex

Males and females are equally affected.

Age

Prenatal diagnosis based on ultrasonography detection of iliac horns is reported; talipes may also be detected on antenatal ultrasonography. Nail anomalies and contractures of the knees or elbows may be noted at birth. Abnormal patellae are often noted in early childhood. Renal disease may occur at any age. When present, the onset of glaucoma or ocular hypertension is usually in adulthood but at an earlier age than in the general population. Other disease manifestations span all ages.

Clinical

History

• Family history: Collect a full 3 generation pedigree to detect family history of autosomal dominant nail-patella syndrome (NPS). Currently, 88% of affected individuals have a positive family history of nail-patella syndrome. Nail-patella syndrome is fully penetrant, but significant interfamilial and intrafamilial variability is noted.
• Nail/digit anomalies: Nail anomalies are present at birth.
• Knees: Recurrent patellar dislocations, deformity of knee joint, and knee pain are noted.
• Elbows: Elbow pain, decreased flexion, pronation, and supination are reported.
• Back pain: This is common in nail-patella syndrome; underlying spinal problems such as spondylolisthesis may be observed.
• Renal disease: Proteinuria, hypertension, and/or decreased renal function may be observed in patients with nail-patella syndrome. End-stage renal disease is relatively rare and is reported in approximately 5% of patients.
• Preeclampsia: This condition is more common in patients with nail-patella syndrome than in the general population.
• Ophthalmology: Ocular hypertension or open-angle glaucoma may be observed.
• Neurology: Attention deficit disorder with and without hyperactivity (ADHD) may be more common in adults with nail-patella syndrome and does not exhibit the same increased male prevalence as in the general population. Major depressive symptoms may also be part of the syndrome. A significant proportion of patients exhibit decreased sensitivity to pain and temperature in the extremities. Signs and symptoms of chronic fatigue may be present due to maldevelopment of the serotonergic system.
• GI problems: Constipation and irritable bowel syndrome are more common in patients with nail-patella syndrome than in the general population.

Physical

• Nail/digit anomalies: Nails may be absent, hypoplasia, or dystrophic; triangular lunulae may be the sole nail anomaly. Typically, the thumb is most severely affected, with possible decreasing severity progressing to the fifth digit. Decreased creases over the distal interphalangeal (DIP) joints are noted.
• Patellar anomalies: Patellae may be absent or hypoplastic. Dislocation in the superior and lateral direction is common. Pain is also common and osteoarthritis may be present.
• Iliac horns: These bony prominences are typically asymptomatic and may be palpable on the posterolateral iliac bones. If not palpable, they are often detected using radiography. They are present in about 70% of patients and are pathognomonic of nail-patella syndrome.
• Elbow anomalies: Decreased flexion, supination, and pronation are noted. The radius may be hypoplastic and posteriorly placed. Skin webbing (pterygia) may be present.
• Renal disease: Proteinuria with or without hematuria may be present in 30-50% of patients. This progresses to end-stage renal disease in approximately 5%. No evidence suggests that renal transplantation has different outcome in patients with nail-patella syndrome than in the general population.
• Open-angle glaucoma: Optic nerve and visual field damage can be prevented with early detection of elevated intraocular pressure and appropriate treatment.
• Lester sign: A hyperpigmented, irregular ring in the iris may be noted.

Causes

• The LMX1B gene is a transcription factor involved in the dorsoventral patterning of vertebrate limbs (including patterning of the nails, digits, elbows and patellae), the differentiation and function of kidney podocytes, development of the anterior eye structures, and the CNS. 
• The loss of function of one allele of LMX1B is the only known cause of nail-patella syndrome.

Differential Diagnoses

Genitopatellar syndrome
Meier-Gorlin syndrome
Patellar aplasia-hypoplasia
Radial and patellar aplasia/hypoplasia, cleft or high arched palate, infantile diarrhea and dislocated joints, little size and limb malformations, long slender nose and normal intelligence (RAPADILINO) syndrome
Small patella syndrome (ischiopatellar dysplasia, Scott-Taor syndrome)

Workup

Laboratory Studies

• Annual screening urinalysis with microscopy is indicated in patients with nail-patella syndrome (NPS) to evaluate for proteinuria and hematuria. A urine protein-to-creatinine ratio or albumin-to-creatinine ratio is also indicated.
• Annual blood pressure measurements and annual BUN and creatinine level assessments are indicated.
• Consider 24-hour urine collection to quantitate protein and creatinine excretion if above screening results are abnormal.

Imaging Studies

• Radiography may reveal iliac horns, hypoplastic patellae or abnormal radial heads.
• If joint surgery planned, conduct MRI of that joint to identify abnormal tendon, ligament, and/or muscle insertions and vessel distribution prior to surgery. Anatomy of joints in patients with nail-patella syndrome is typically abnormal.

Other Tests

• Perform annual dilated ophthalmologic examination including slit-lamp quantification of intraocular pressure and visual fields. 
• Consider dual energy x-ray absorptiometry (DEXA) scanning to evaluate bone mineral content and density as surrogate indicator of bone strength. Bone mineral density is decreased by 8-20% in the hips of patients with nail-patella syndrome, and increased fractures have been reported.

Procedures

• Renal biopsy may be indicated after referral to nephrologist for evaluation of progressive renal insufficiency, proteinuria, and hypertension in nail-patella syndrome.
• Light microscopy reveals glomerulonephritis and basement membrane thickening; however, negative results do not rule out pathological processes in the kidney.
• Electron microscopy can reveal ultrastructural changes, such as irregularities and thickening of the basement membrane and the presence of collagen-like fibrils within the basement membrane, which cannot be seen with light microscopy. These appearances are pathognomonic.

Histologic Findings

• Increased lucency of the glomerular basement membrane resembles a moth-eaten appearance. A typical lesion consists of irregular basement membrane thickening, epithelial foot process fusion, and the presence of fibrillar collagenlike material within the basement.
• Histological features are present even in patients without clinically evident renal involvement.

Treatment

Medical Care

• ACE inhibitors for proteinuria, hypertension, or both are indicated in patients with nail-patella syndrome (NPS). Consultation with a nephrologist may permit implementation of prophylactic treatment with ACE inhibitors.
• Dialysis and/or renal transplant may be indicated in as many as 5% of patients who have renal involvement that progresses to end-stage renal disease.
• Physical therapy, bracing, and analgesics may be needed for joint pain. Caution is necessary in using analgesics, particularly nonsteroidal anti-inflammatory drugs (NSAIDs) because renal disease may also be part of this condition.

Surgical Care

• Renal transplantation has proven successful in patients with nail-patella syndrome who develop end-stage renal disease.
• Patella realignment surgery may help in cases of recurrent dislocation.
• Joint replacement may be beneficial in cases of severe osteoarthritis of the knee or elbow.
• Excision of the radial head should only be undertaken after careful consideration and only for pain relief as range of movement is not usual improved significantly by surgery.
• MRI is necessary to reveal the abnormal muscle and nerve insertions that may complicate orthopedic procedures.

Consultations

• Geneticist
• Orthopaedist
• Ophthalmologist
• Nephrologist

Diet

• No dietary restrictions are necessary unless hypertension or nephrotic syndrome develop.

Activity

• Joint abnormalities and pain may limit physical activity.

Medication

ACE inhibitors should be used to treat proteinuria, hypertension, or both in nail-patella syndrome (NPS). Consultation with a nephrologist may permit implementation of prophylactic treatment with ACE inhibitor medication prior to overt proteinuria or hypertension.

Vitamin D analogs, thiazides, and prednisone are effective in alleviating the complicating symptoms of nephrotic syndrome and end-stage renal failure (ESRF) in nail-patella syndrome as in all patients with ESRF.⁴

Vitamin D Analog

Vitamin D is necessary to maintain the correct amount of calcium needed for strong bones and teeth and is needed throughout the body.

Calcitriol (Rocaltrol)

Increases calcium levels by promoting absorption of calcium in intestines and retention in kidneys. The beneficial effects of vitamin D replacement in renal osteodystrophy appear to result from correction of hypocalcemia and secondary hyperparathyroidism.

Dosing

Adult

0.25 mcg/d PO initially
If the response in the biochemical parameters and clinical manifestations of the disease state is not satisfactory, dosage may be increased by 0.25 mcg/d q4-8wk; typical dosage range is 0.5-1 mcg/d

Pediatric

<3 years: 10-15 ng/kg/d PO
>3 years: Administer as in adults

Interactions

Cholestyramine and colestipol decrease absorption of calcitriol; magnesium-containing antacids and thiazide diuretics can increase calcitriol effects

Contraindications

Documented hypersensitivity; hypercalcemia; malabsorption syndrome

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Hypercalcemia, hypercalciuria, and hyperphosphatemia

Thiazide diuretics

These agents are used to treat edema caused by renal dysfunction (eg, nephrotic syndrome, chronic renal failure).

Hydrochlorothiazide (Hydro-Diuril, Microzide)

Inhibits reabsorption of sodium in distal tubules, increasing excretion of sodium, water, and potassium and hydrogen ions.

Dosing

Adult

25-100 mg PO qd or divided bid

Pediatric

1-2 mg/kg PO qd or divided bid; not to exceed 37.5 mg/d (age <2 y) or 100 mg/d (age 2-12 y)

Interactions

May decrease effects of anticoagulants, antigout agents, or sulfonylureas; may increase toxicity of allopurinol, anesthetics, antineoplastics, calcium salts, loop diuretics, lithium, diazoxide, digitalis, amphotericin B, or nondepolarizing muscle relaxants

Contraindications

Documented hypersensitivity; anuria or renal decompensation

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in renal or hepatic disease, gout, diabetes mellitus, or erythematosus

Corticosteroids

These agents induce diuresis or remission of proteinuria in nephrotic syndrome.

Prednisone (Deltasone, Orasone)

Acts as an anti-inflammatory agent and immunosuppressant.
Dose depends on specific disease entity being treated; in situations of less severity, lower doses generally suffice, whereas, in selected patients, higher initial doses may be required; initial dosage should be maintained or adjusted prn.
Alternate day therapy (ADT) PO is a corticosteroid-dosing regimen in which twice the usual daily dose of corticoid is administered every other morning.
The purpose of this mode of therapy is to provide the patient who requires long-term pharmacologic dose treatment with the beneficial effects of corticoids while minimizing certain undesirable effects, including pituitary-adrenal suppression, the Cushingoid state, corticoid withdrawal symptoms, and growth suppression in children.

Dosing

Adult

5-60 mg/d PO

Pediatric

1-2 mg/kg/d PO

Interactions

Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics

Contraindications

Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections; fungal or tubercular skin infections; GI disease

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use

Angiotensin-converting Enzyme (ace) Inhibitor

ACE inhibitors are preferred for treating hypertension and proteinuria associated with nail-patella syndrome.

Captopril (Capoten)

Captopril is an example of an ACE inhibitor used off-label for hypertension and proteinuria in neonates, infants, and children. Prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone secretion.

Dosing

Adult

12.5-25 mg PO bid/tid initially, may increase according to control of blood pressure and proteinuria
Administer 1 h ac or 2 h pc

Pediatric

Off-label
Neonates: 0.01-0.05 mg/kg/dose PO q8-12h
Infants: 0.15-0.3 mg/kg/dose PO initially; titrate upward, not to exceed 6 mg/kg/day divided bid/qid
Children: 0.3-0.5 mg/kg/dose PO initially; titrate upward, not to exceed 6 mg/kg/day divided bid/qid
Older children: 6.25-12.5 mg/dose PO q12-24h initially; titrate upward, not to exceed 6 mg/kg/day divided bid/qid
Administer 1 h ac or 2 h pc

Interactions

NSAIDs may reduce hypotensive effects of captopril; ACE inhibitors may increase digoxin, lithium, and allopurinol levels; rifampin decreases captopril levels; probenecid may increase captopril levels; the hypotensive effects of ACE inhibitors may be enhanced when given concurrently with diuretics

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

May cause chronic cough; decrease dose by 50% if dehydrated or sodium depleted; caution in renal impairment, valvular stenosis, or severe congestive heart failure

Follow-up

Further Inpatient Care

• Admit patients with nail-patella syndrome (NPS) for testing and renal transplantation if end-stage renal disease is progressive.
• If the patient has severe joint problems, surgery such as joint replacement or patellar realignment may be required.

Further Outpatient Care

• Annual renal function screening with urinalysis, blood testing for BUN and creatinine levels, and blood pressure assessment is indicated. 
• Annual ophthalmological evaluation is indicated for detection of glaucoma.
• Orthopedic consultations are indicated as needed.

Inpatient & Outpatient Medications

• ACE inhibitors should be used to treat proteinuria and/or hypertension in nail-patella syndrome. Consultation with a nephrologist may permit implementation of prophylactic treatment with ACE inhibitor medication prior to overt proteinuria or hypertension.
• Prednisone, vitamin D replacement, and thiazides are appropriate to manage nephrotic syndrome and end-stage renal failure (ESRF).

Transfer

• Transfer may be required for further evaluation and renal transplantation.

Complications

• Glaucoma
• Osteoarthritis
• Nephrotic syndrome
• ESRF

Prognosis

• Approximately 30-55% of patients with nail-patella syndrome develop nephropathy, which may lead to ESRF in about 5% of patients.
• Prognosis after renal transplantation is good.

Patient Education

• Genetic counseling is recommended because the risk of having affected offspring is 50%. Prenatal diagnosis using molecular analysis is possible but because of the marked intrafamilial variability, the severity of the condition in an affected child cannot be predicted.
• Stress the importance of regular assessment of renal function to the patient.
• The patient should receive annual glaucoma checks.

Miscellaneous

Medicolegal Pitfalls

• Failure to recognize associated conditions such as renal disease or glaucoma
• Failure to recommend genetic counseling

Special Concerns

• Nephropathy may occur at any age from birth onwards.

Multimedia

Media file 1: Nail of a patient the nail-patella syndrome.

References

1. Sweeney E, Fryer A, Mountford R, Green A, McIntosh I. Nail patella syndrome: a review of the phenotype aided by developmental biology. J Med Genet. Mar 2003;40(3):153-62. [Medline].

2. Bongers EM, van Kampen A, van Bokhoven H, Knoers NV. Human syndromes with congenital patellar anomalies and the underlying gene defects. Clin Genet. Oct 2005;68(4):302-19. [Medline].

3. McIntosh I, Dunston JA, Liu L, Hoover-Fong JE, Sweeney E. Nail patella syndrome revisited: 50 years after linkage. Ann Hum Genet. Jul 2005;69(Pt 4):349-63. [Medline].

4. [Guideline] Papnicolaou N, Francis IR, Casalino DD, et al. ACR Appropriateness Criteria renal failure. [online publication]. Reston (VA): American College of Radiology (ACR); 2008. [Full Text].

5. Azouz EM, Kozlowski K. Small patella syndrome: a bone dysplasia to recognize and differentiate from the nail-patella syndrome. Pediatr Radiol. May 1997;27(5):432-5. [Medline].

6. Bennett WM, Musgrave JE, Campbell RA, et al. The nephropathy of the nail-patella syndrome. Clinicopathologic analysis of 11 kindred. Am J Med. Mar 1973;54(3):304-19. [Medline].

7. Bongers EM, Huysmans FT, Levtchenko E, et al. Genotype-phenotype studies in nail-patella syndrome show that LMX1B mutation location is involved in the risk of developing nephropathy. Eur J Hum Genet. Aug 2005;13(8):935-46. [Medline].

8. Browning MC, Weidner N, Lorentz WB Jr. Renal histopathology of the nail-patella syndrome in a two-year-old boy. Clin Nephrol. Apr 1988;29(4):210-3. [Medline].

9. Chen H, Lun Y, Ovchinnikov D, et al. Limb and kidney defects in Lmx1b mutant mice suggest an involvement of LMX1B in human nail patella syndrome. Nat Genet. May 1998;19(1):51-5. [Medline].

10. Cormier-Daire V, Chauvet ML, Lyonnet S, et al. Genitopatellar syndrome: a new condition comprising absent patellae, scrotal hypoplasia, renal anomalies, facial dysmorphism, and mental retardation. J Med Genet. Jul 2000;37(7):520-4. [Medline].

11. Cottereill CP, Jacobs P. Hereditary Arthro-osteo-onchyodysplasia associated with iliac horns. Br J Clin Pract. 1961;15(11):933-941.

12. Curtis JJ, Bhathena D, Leach RP, Galla JH, Lucas BA, Luke RG. Goodpasture's syndrome in a patient with the Nail-Patella syndrome. Am J Med. Sep 1976;61(3):401-6. [Medline].

13. Dai JX, Johnson RL, Ding YQ. Manifold functions of the Nail-Patella Syndrome gene Lmx1b in vertebrate development. Dev Growth Differ. Apr 2009;51(3):241-50. [Medline].

14. Darlington D, Hawkins, CF. Nail patella syndrome with iliachorns and hereditary nephropathy: necropsy report and anatomical dissection. J Bone Joint Surg [Am]. Jan 1967;49B:164-74. [Medline].

15. Dreyer SD, Zhou G, Baldini A, et al. Mutations in LMX1B cause abnormal skeletal patterning and renal dysplasia in nail patella syndrome. Nat Genet. May 1998;19(1):47-50. [Medline].

16. Dunston JA, Hamlington JD, Zaveri J, et al. The human LMX1B gene: transcription unit, promoter, and pathogenic mutations. Genomics. Sep 2004;84(3):565-76. [Medline].

17. Dunston JA, Reimschisel T, Ding YQ, et al. A neurological phenotype in nail patella syndrome (NPS) patients illuminated by studies of murine Lmx1b expression. Eur J Hum Genet. Mar 2005;13(3):330-5. [Medline].

18. Eisenberg KS, Potter DE, Bovill EG Jr. Osteo-onychodystrophy with nephropathy and renal osteodystrophy. A case report. J Bone Joint Surg [Am]. Sep 1972;54(6):1301-5. [Medline].

19. Feingold M, Itzchak Y, Goodman RM. Ultrasound prenatal diagnosis of the Nail-Patella syndrome. Prenat Diagn. Aug 1998;18(8):854-6. [Medline].

20. Fong EE. 'Iliac horns' (symmetrical bilateral central posterior iliac processes):a case report. Radiology. 1946;47:517-518.

21. Galloway G, Vivian A. An ophthalmic screening protocol for nail-patella syndrome. J Pediatr Ophthalmol Strabismus. Jan-Feb 2003;40(1):51-3. [Medline].

22. Krawchuk D, Kania A. Identification of genes controlled by LMX1B in the developing mouse limb bud. Dev Dyn. Apr 2008;237(4):1183-92. [Medline].

23. Leahy MS. The hereditary nephropathy of osteo-onychodysplasia. Nail-patella syndrome. Am J Dis Child. Sep 1966;112(3):237-41. [Medline].

24. Lemley KV. Kidney disease in nail-patella syndrome. Pediatr Nephrol. Jun 6 2008;[Medline].

25. Looij BJ Jr, te Slaa RL, Hogewind BL, van de Kamp JJ. Genetic counselling in hereditary osteo-onychodysplasia (HOOD, nail- patella syndrome) with nephropathy. J Med Genet. Oct 1988;25(10):682-6. [Medline].

26. McIntosh I, Clough MV, Gak E. Prenatal diagnosis of nail-patella syndrome [letter]. Prenat Diagn. Mar 1999;19(3):287-8. [Medline].

27. Mimiwati Z, Mackey DA, Craig JE, Mackinnon JR, Rait JL, Liebelt JE. Nail-patella syndrome and its association with glaucoma: a review of eight families. Br J Ophthalmol. Dec 2006;90(12):1505-9. [Medline].

28. Morita T, Laughlin LO, Kawano K, et al. Nail-Patella syndrome. Light and electron microscopic studies of the kidney. Arch Intern Med. Feb 1973;131(2):271-7. [Medline].

29. Sabnis SG, Antonovych TT, Argy WP, et al. Nail-patella syndrome. Clinical Nephrology. Sep 1980;14(3):148-53. [Medline].

30. Schulz-Butulis BA, Welch MD, Norton SA. Nail-patella syndrome. J Am Acad Dermatol. Dec 2003;49(6):1086-7. [Medline].

Keywords

nail-patella syndrome, NPS, Fong disease, NPS 1, onycho-osteodysplasia, hereditary onycho-osteodysplasia disease, HOOD, Turner-Kieser syndrome, arthro-onychodysplasia, nephrotic syndrome, end-stage renal disease, ESRD, end-stage renal failure, ESRF, , proteinuria, spondylolisthesis, attention deficit disorder, ADD, attention deficit hyperactivity disorder, ADHD, constipation, irritable bowel syndrome, IBS, osteoarthritis, treatment, diagnosis

Contributor Information and Disclosures

Author

Julie Hoover-Fong, MD, PhD, FACMG, Assistant Professor, Director, Greenberg Center for Skeletal Dysplasias, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University
Julie Hoover-Fong, MD, PhD, FACMG is a member of the following medical societies: American College of Medical Genetics, American Society of Human Genetics, and International Skeletal Dysplasia Society
Disclosure: Nothing to disclose.

Coauthor(s)

Iain McIntosh, PhD, Professor of Medical Genetics, Chair, Department of Molecular and Cell Biology, Director, Stephen Gaffin Research Laboratory, American University of the Carribean
Iain McIntosh, PhD is a member of the following medical societies: American Society of Human Genetics
Disclosure: Nothing to disclose.

Elizabeth Sweeney, MBChB, MD, Consultant Clinical Geneticist, Royal Liverpool Children's Hospital, UK
Elizabeth Sweeney, MBChB, MD is a member of the following medical societies: British Society of Human Genetics
Disclosure: Nothing to disclose.

Medical Editor

Christian J Renner, MD, Consulting Staff, Department of Pediatrics, University Hospital for Children and Adolescents, Erlangen, Germany
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Leonard G Feld, MD, PhD, MMM, FAAP, Sara H Bissell and Howard C Bissell Endowed Chair in Pediatrics, Chief Medical Officer, Levine Children's Hospital, Carolinas Medical Center
Leonard G Feld, MD, PhD, MMM, FAAP is a member of the following medical societies: American Academy of Pediatrics, American College of Physician Executives, American Society of Nephrology, American Society of Pediatric Nephrology, International Society of Nephrology, and Juvenile Diabetes Foundation International
Disclosure: Nothing to disclose.

CME Editor

Daniel Rauch, MD, FAAP, Director, Pediatric Hospitalist Program, Associate Professor, Department of Pediatrics, New York University School of Medicine
Daniel Rauch, MD, FAAP is a member of the following medical societies: Ambulatory Pediatric Association, American Academy of Pediatrics, and Society of Hospital Medicine
Disclosure: Baxter Honoraria Consulting

Chief Editor

Bruce Buehler, MD, Professor, Department of Pediatrics, Pathology and Microbiology, Executive Director, Hattie B Munroe Center for Human Genetics, University of Nebraska Medical Center
Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association
Disclosure: Nothing to disclose.

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors Suzanne M Carter, MS, and Susan J Gross, MD, FRCS(C), FACOG, FACMG, to the original writing and development of this article.

© 1994- by Medscape.
All Rights Reserved
(http://www.medscape.com/public/copyright)