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Renal coloboma syndrome(PAPRS)

MedGen UID:
339002
Concept ID:
C1852759
Disease or Syndrome
Synonyms: CAKUT WITH OR WITHOUT OCULAR ABNORMALITIES; Coloboma of optic nerve with renal disease; CONGENITAL ANOMALIES OF THE KIDNEY AND URINARY TRACT WITH OR WITHOUT OCULAR ABNORMALITIES; Optic coloboma, vesicoureteral reflux, and renal anomalies; Optic nerve coloboma with renal disease; Papillorenal syndrome; PAPILLORENAL SYNDROME WITH MILD OCULAR ABNORMALITIES; PAPRS; RENAL-COLOBOMA SYNDROME WITH MACULAR ABNORMALITIES
SNOMED CT: Papillorenal syndrome (446449009); Renal coloboma syndrome (446449009)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): PAX2 (10q24.31)
 
Monarch Initiative: MONDO:0007352
OMIM®: 120330
Orphanet: ORPHA1475

Disease characteristics

Excerpted from the GeneReview: PAX2-Related Disorder
PAX2-related disorder is an autosomal dominant disorder associated with renal and eye abnormalities. The disorder was originally referred to as renal coloboma syndrome and characterized by renal hypodysplasia and abnormalities of the optic nerve; with improved access to molecular testing, a wider range of phenotypes has been recognized in association with pathogenic variants in PAX2. Abnormal renal structure or function is noted in 92% of affected individuals and ophthalmologic abnormalities in 77% of affected individuals. Renal abnormalities can be clinically silent in rare individuals. In most individuals, clinically significant renal insufficiency / renal failure is reported. End-stage renal disease requiring renal transplant is not uncommon. Uric acid nephrolithiasis has been reported. Ophthalmologic abnormalities are typically described as optic nerve coloboma or dysplasia. Iris colobomas have not been reported in any individual with PAX2–related disorder. Ophthalmologic abnormalities may significantly impair vision in some individuals, while others have subtle changes only noted after detailed ophthalmologic examination. Additional clinical findings include high-frequency sensorineural hearing loss, soft skin, and ligamentous laxity. PAX2 pathogenic variants have been identified in multiple sporadic and familial cases of nonsyndromic renal disease including renal hypodysplasia and focal segmental glomerulosclerosis. [from GeneReviews]
Authors:
Matthew A Bower  |  Lisa A Schimmenti  |  Michael R Eccles   view full author information

Additional descriptions

From OMIM
Papillorenal syndrome (PAPRS) is an autosomal dominant disorder characterized by both ocular and renal anomalies. Less common findings include high frequency hearing loss, central nervous system anomalies, soft skin, ligamentous laxity, and/or genital anomalies, consistent with the expression of PAX2 in these tissues during development (summary by Eccles and Schimmenti, 1999; Negrisolo et al., 2011). The disorder shows wide inter- and intrafamilial variability. The renal features are part of a spectrum of malformations termed congenital anomalies of the kidney and urinary tract (CAKUT; see, e.g., 610805), and some patients with PAX2 mutations may present with CAKUT without obvious ocular abnormalities. In these patients, ocular abnormalities may be subtle and difficult to detect without advanced screening methods or may be normal (summary by Negrisolo et al., 2011; Iatropoulos et al., 2012). Eye anomalies associated with PAX2 mutations consist of a wide and sometimes excavated dysplastic optic disc with the emergence of the retinal vessels from the periphery of the disc, designated optic nerve 'coloboma' or 'morning glory' anomaly. Associated findings may include a small corneal diameter, retinal coloboma, scleral staphyloma, optic nerve cyst, microphthalmia, and pigmentary macular dysplasia. The kidneys are small and abnormally formed (renal hypodysplasia), and have fewer than the normal number of glomeruli, which are enlarged (oligomeganephronia). These ocular and renal anomalies result in decreased visual acuity and retinal detachment, as well as hypertension, proteinuria, and renal insufficiency that frequently progresses to end-stage renal disease (summary by Schimmenti, 2011).  http://www.omim.org/entry/120330
From MedlinePlus Genetics
Renal coloboma syndrome (also known as papillorenal syndrome) is a condition that primarily affects kidney (renal) and eye development. People with this condition typically have kidneys that are small and underdeveloped (hypoplastic), which can lead to end-stage renal disease (ESRD). This serious disease occurs when the kidneys are no longer able to filter fluids and waste products from the body effectively. It has been estimated that approximately ten percent of children with hypoplastic kidneys may have renal coloboma syndrome. The kidney problems can affect one or both kidneys.

Additionally, people with renal coloboma syndrome may have a malformation in the optic nerve, a structure that carries information from the eye to the brain. Optic nerve malformations are sometimes associated with a gap or hole (coloboma) in the light-sensitive tissue at the back of the eye (the retina). The vision problems caused by these abnormalities can vary depending on the size and location of the malformation. Some people have no visual problems, while others may have severely impaired vision.

Less common features of renal coloboma syndrome include backflow of urine from the bladder (vesicoureteral reflux), multiple kidney cysts, loose joints, and mild hearing loss.  https://medlineplus.gov/genetics/condition/renal-coloboma-syndrome

Clinical features

From HPO
Hematuria
MedGen UID:
5488
Concept ID:
C0018965
Disease or Syndrome
The presence of blood in the urine. Hematuria may be gross hematuria (visible to the naked eye) or microscopic hematuria (detected by dipstick or microscopic examination of the urine).
Proteinuria
MedGen UID:
10976
Concept ID:
C0033687
Finding
Increased levels of protein in the urine.
Vesicoureteral reflux
MedGen UID:
21852
Concept ID:
C0042580
Disease or Syndrome
Vesicoureteral reflux (VUR) is characterized by the reflux of urine from the bladder into the ureters and sometimes into the kidneys. It is a risk factor for urinary tract infections. Primary VUR results from a developmental defect of the ureterovesical junction (UVJ). In combination with intrarenal reflux, the resulting inflammatory reaction may result in renal injury or scarring, also called reflux nephropathy (RN). Extensive renal scarring impairs renal function and may predispose patients to hypertension, proteinuria, and renal insufficiency (summary by Lu et al., 2007). Genetic Heterogeneity of Vesicoureteral Reflux A locus designated VUR1 maps to chromosome 1p13. VUR2 (610878) is caused by mutation in the ROBO2 gene (602431) on chromosome 3p12; VUR3 (613674) is caused by mutation in the SOX17 gene (610928) on chromosome 8q11; VUR4 (614317) maps to chromosome 5; VUR5 (614318) maps to chromosome 13; VUR6 (614319) maps to chromosome 18; VUR7 (615390) maps to chromosome 12; and VUR8 (615963) is caused by mutation in the TNXB gene (600985) on chromosome 6p21. A possible X-linked form has been reported (VURX; 314550).
Horseshoe kidney
MedGen UID:
65140
Concept ID:
C0221353
Congenital Abnormality
A connection of the right and left kidney by an isthmus of functioning renal parenchyma or fibrous tissue that crosses the midline.
Renal malrotation
MedGen UID:
68662
Concept ID:
C0238210
Congenital Abnormality
An abnormality of the normal developmental rotation of the kidney leading to an abnormal orientation of the kidney.
Renal hypoplasia
MedGen UID:
120571
Concept ID:
C0266295
Congenital Abnormality
Hypoplasia of the kidney.
Nephrolithiasis
MedGen UID:
98227
Concept ID:
C0392525
Disease or Syndrome
The presence of calculi (stones) in the kidneys.
Chronic kidney disease
MedGen UID:
473458
Concept ID:
C1561643
Disease or Syndrome
Functional anomaly of the kidney persisting for at least three months.
Absence of renal corticomedullary differentiation
MedGen UID:
342352
Concept ID:
C1849765
Finding
A lack of differentiation between renal cortex and medulla on diagnostic imaging.
Stage 5 chronic kidney disease
MedGen UID:
384526
Concept ID:
C2316810
Disease or Syndrome
A degree of kidney failure severe enough to require dialysis or kidney transplantation for survival characterized by a severe reduction in glomerular filtration rate (less than 15 ml/min/1.73 m2) and other manifestations including increased serum creatinine.
Multicystic kidney dysplasia
MedGen UID:
811388
Concept ID:
C3714581
Disease or Syndrome
Multicystic dysplasia of the kidney is characterized by multiple cysts of varying size in the kidney and the absence of a normal pelvicaliceal system. The condition is associated with ureteral or ureteropelvic atresia, and the affected kidney is nonfunctional.
Renal cyst
MedGen UID:
854361
Concept ID:
C3887499
Disease or Syndrome
A fluid filled sac in the kidney.
Mild proteinuria
MedGen UID:
868438
Concept ID:
C4022832
Finding
Mildly increased levels of protein in the urine (150-500 mg per day in adults).
Hypertensive disorder
MedGen UID:
6969
Concept ID:
C0020538
Disease or Syndrome
The presence of chronic increased pressure in the systemic arterial system.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Sensorineural hearing loss disorder
MedGen UID:
9164
Concept ID:
C0018784
Disease or Syndrome
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
Gliosis
MedGen UID:
4899
Concept ID:
C0017639
Pathologic Function
Gliosis is the focal proliferation of glial cells in the central nervous system.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Chiari type I malformation
MedGen UID:
196689
Concept ID:
C0750929
Congenital Abnormality
Arnold-Chiari type I malformation refers to a relatively mild degree of herniation of the posteroinferior region of the cerebellum (the cerebellar tonsils) into the cervical canal with little or no displacement of the fourth ventricle. It is characterized by one or both pointed (not rounded) cerebellar tonsils that project 5 mm below the foramen magnum, measured by a line drawn from the basion to the opisthion (McRae Line)
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Joint hypermobility
MedGen UID:
336793
Concept ID:
C1844820
Finding
The capability that a joint (or a group of joints) has to move, passively and/or actively, beyond normal limits along physiological axes.
Edema
MedGen UID:
4451
Concept ID:
C0013604
Pathologic Function
An abnormal accumulation of fluid beneath the skin, or in one or more cavities of the body.
Elevated circulating creatinine concentration
MedGen UID:
148579
Concept ID:
C0700225
Finding
An increased amount of creatinine in the blood.
Orbital cyst
MedGen UID:
56359
Concept ID:
C0155285
Finding
Presence of a cyst in the region of the periorbital tissues. Orbital cysts can be derived from epithelial or glandular tissue within or surrounding the orbit (lacrimal glands, salivary glands, conjunctival, oral, nasal, or sinus epithelium).
Hyperextensible skin
MedGen UID:
66023
Concept ID:
C0241074
Finding
A condition in which the skin can be stretched beyond normal, and then returns to its initial position.
Soft skin
MedGen UID:
336730
Concept ID:
C1844592
Finding
Subjective impression of increased softness upon palpation of the skin.
Lens luxation
MedGen UID:
6043
Concept ID:
C0023309
Injury or Poisoning
Complete dislocation of the lens of the eye.
Macular degeneration
MedGen UID:
7434
Concept ID:
C0024437
Disease or Syndrome
A nonspecific term denoting degeneration of the retinal pigment epithelium and/or retinal photoreceptor cells of the macula lutea.
Microphthalmia
MedGen UID:
10033
Concept ID:
C0026010
Congenital Abnormality
Microphthalmia is an eye abnormality that arises before birth. In this condition, one or both eyeballs are abnormally small. In some affected individuals, the eyeball may appear to be completely missing; however, even in these cases some remaining eye tissue is generally present. Such severe microphthalmia should be distinguished from another condition called anophthalmia, in which no eyeball forms at all. However, the terms anophthalmia and severe microphthalmia are often used interchangeably. Microphthalmia may or may not result in significant vision loss.\n\nPeople with microphthalmia may also have a condition called coloboma. Colobomas are missing pieces of tissue in structures that form the eye. They may appear as notches or gaps in the colored part of the eye called the iris; the retina, which is the specialized light-sensitive tissue that lines the back of the eye; the blood vessel layer under the retina called the choroid; or in the optic nerves, which carry information from the eyes to the brain. Colobomas may be present in one or both eyes and, depending on their size and location, can affect a person's vision.\n\nPeople with microphthalmia may also have other eye abnormalities, including clouding of the lens of the eye (cataract) and a narrowed opening of the eye (narrowed palpebral fissure). Additionally, affected individuals may have an abnormality called microcornea, in which the clear front covering of the eye (cornea) is small and abnormally curved.\n\nBetween one-third and one-half of affected individuals have microphthalmia as part of a syndrome that affects other organs and tissues in the body. These forms of the condition are described as syndromic. When microphthalmia occurs by itself, it is described as nonsyndromic or isolated.
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.
Retinal detachment
MedGen UID:
19759
Concept ID:
C0035305
Disease or Syndrome
Primary or spontaneous detachment of the retina occurs due to underlying ocular disease and often involves the vitreous as well as the retina. The precipitating event is formation of a retinal tear or hole, which permits fluid to accumulate under the sensory layers of the retina and creates an intraretinal cleavage that destroys the neurosensory process of visual reception. Vitreoretinal degeneration and tear formation are painless phenomena, and in most cases, significant vitreoretinal pathology is found only after detachment of the retina starts to cause loss of vision or visual field. Without surgical intervention, retinal detachment will almost inevitably lead to total blindness (summary by McNiel and McPherson, 1971).
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.
Cataract
MedGen UID:
39462
Concept ID:
C0086543
Disease or Syndrome
A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule.
Coloboma of optic nerve
MedGen UID:
57832
Concept ID:
C0155299
Disease or Syndrome
A cleft of the optic nerve that extends inferiorly.
Scleral staphyloma
MedGen UID:
509933
Concept ID:
C0155359
Disease or Syndrome
A staphyloma is a localized defect in the eye wall with protrusion of uveal tissue due to alterations in scleral thickness and structure.
Reduced visual acuity
MedGen UID:
65889
Concept ID:
C0234632
Finding
Diminished clarity of vision.
High myopia
MedGen UID:
78759
Concept ID:
C0271183
Disease or Syndrome
A severe form of myopia with greater than -6.00 diopters.
Macular hyperpigmentation
MedGen UID:
488933
Concept ID:
C0745109
Finding
Increased amount of pigmentation in the macula lutea.
Retinal coloboma
MedGen UID:
761889
Concept ID:
C3540764
Disease or Syndrome
A notch or cleft of the retina.
Morning glory syndrome
MedGen UID:
767635
Concept ID:
C3554721
Congenital Abnormality
An abnormality of the optic nerve in which the optic nerve is large and funneled and displays a conical excavation of the optic disc. The optic disc appears dysplastic.
Chorioretinal atrophy
MedGen UID:
884881
Concept ID:
C4048273
Disease or Syndrome
Atrophy of the choroid and retinal layers of the fundus.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVRenal coloboma syndrome
Follow this link to review classifications for Renal coloboma syndrome in Orphanet.

Professional guidelines

PubMed

Bower M, Eccles M, Heidet L, Schimmenti LA
Eur J Hum Genet 2011 Sep;19(9) Epub 2011 Feb 16 doi: 10.1038/ejhg.2011.16. PMID: 21326282Free PMC Article

Curated

Bower M, Eccles M, Heidet L, Schimmenti LA
Eur J Hum Genet 2011 Sep;19(9) Epub 2011 Feb 16 doi: 10.1038/ejhg.2011.16. PMID: 21326282Free PMC Article

Recent clinical studies

Etiology

Shimabukuro W, Chinen Y, Imanaga N, Yanagi K, Kaname T, Nakanishi K
Pediatr Nephrol 2024 Aug;39(8):2351-2353. Epub 2024 Mar 11 doi: 10.1007/s00467-024-06347-z. PMID: 38467926
Yang X, Li Y, Fang Y, Shi H, Xiang T, Liu J, Liu J, Tang X, Fang X, Chen J, Zhai Y, Shen Q, Bi Y, Qian Y, Wu B, Wang H, Zhou W, Ma D, Bai H, Mao J, Chen L, Wang X, Gao X, Zhang R, Zhuang J, Zhang A, Jiang X, Xu H, Rao J
BMC Med Genomics 2021 Oct 25;14(1):250. doi: 10.1186/s12920-021-01102-x. PMID: 34696790Free PMC Article
Sels L, Dirven W, Devriendt K, Leys A
Retin Cases Brief Rep 2020 Winter;14(1):77-81. doi: 10.1097/ICB.0000000000000625. PMID: 28820764
Vivante A, Chacham OS, Shril S, Schreiber R, Mane SM, Pode-Shakked B, Soliman NA, Koneth I, Schiffer M, Anikster Y, Hildebrandt F
Pediatr Nephrol 2019 Sep;34(9):1607-1613. Epub 2019 Apr 17 doi: 10.1007/s00467-019-04256-0. PMID: 31001663Free PMC Article
Dureau P, Attie-Bitach T, Salomon R, Bettembourg O, Amiel J, Uteza Y, Dufier JL
Ophthalmology 2001 Oct;108(10):1912-6. doi: 10.1016/s0161-6420(01)00722-9. PMID: 11581073

Diagnosis

Nagano C, Nozu K, Morisada N, Yazawa M, Ichikawa D, Numasawa K, Kourakata H, Matsumura C, Tazoe S, Tanaka R, Yamamura T, Minamikawa S, Horinouchi T, Nakanishi K, Fujimura J, Sakakibara N, Nozu Y, Ye MJ, Kaito H, Iijima K
Clin Exp Nephrol 2018 Aug;22(4):881-888. Epub 2018 Jan 25 doi: 10.1007/s10157-018-1534-x. PMID: 29372472
Okumura T, Furuichi K, Higashide T, Sakurai M, Hashimoto S, Shinozaki Y, Hara A, Iwata Y, Sakai N, Sugiyama K, Kaneko S, Wada T
PLoS One 2015;10(11):e0142843. Epub 2015 Nov 16 doi: 10.1371/journal.pone.0142843. PMID: 26571382Free PMC Article
Schimmenti LA
Eur J Hum Genet 2011 Dec;19(12):1207-12. Epub 2011 Jun 8 doi: 10.1038/ejhg.2011.102. PMID: 21654726Free PMC Article
Dureau P, Attie-Bitach T, Salomon R, Bettembourg O, Amiel J, Uteza Y, Dufier JL
Ophthalmology 2001 Oct;108(10):1912-6. doi: 10.1016/s0161-6420(01)00722-9. PMID: 11581073
Woolf AS
Kidney Int 2000 Aug;58(2):500-12. doi: 10.1046/j.1523-1755.2000.00196.x. PMID: 10916073

Therapy

Vivante A, Chacham OS, Shril S, Schreiber R, Mane SM, Pode-Shakked B, Soliman NA, Koneth I, Schiffer M, Anikster Y, Hildebrandt F
Pediatr Nephrol 2019 Sep;34(9):1607-1613. Epub 2019 Apr 17 doi: 10.1007/s00467-019-04256-0. PMID: 31001663Free PMC Article
Kobayashi Y, Hayashi T, Ishii T, Uemura H
Exp Clin Transplant 2014 Apr;12(2):162-4. Epub 2013 Jul 30 doi: 10.6002/ect.2013.0005. PMID: 23902562
Gucev ZS, Kirovski I, Jancevska A, Popjordanova N, Tasic V
Ren Fail 2009;31(7):602-5. doi: 10.1080/08860220902968862. PMID: 19839859
Porteous S, Torban E, Cho NP, Cunliffe H, Chua L, McNoe L, Ward T, Souza C, Gus P, Giugliani R, Sato T, Yun K, Favor J, Sicotte M, Goodyer P, Eccles M
Hum Mol Genet 2000 Jan 1;9(1):1-11. doi: 10.1093/hmg/9.1.1. PMID: 10587573

Prognosis

Yang X, Li Y, Fang Y, Shi H, Xiang T, Liu J, Liu J, Tang X, Fang X, Chen J, Zhai Y, Shen Q, Bi Y, Qian Y, Wu B, Wang H, Zhou W, Ma D, Bai H, Mao J, Chen L, Wang X, Gao X, Zhang R, Zhuang J, Zhang A, Jiang X, Xu H, Rao J
BMC Med Genomics 2021 Oct 25;14(1):250. doi: 10.1186/s12920-021-01102-x. PMID: 34696790Free PMC Article
Sels L, Dirven W, Devriendt K, Leys A
Retin Cases Brief Rep 2020 Winter;14(1):77-81. doi: 10.1097/ICB.0000000000000625. PMID: 28820764
Kobayashi Y, Hayashi T, Ishii T, Uemura H
Exp Clin Transplant 2014 Apr;12(2):162-4. Epub 2013 Jul 30 doi: 10.6002/ect.2013.0005. PMID: 23902562
Alur RP, Vijayasarathy C, Brown JD, Mehtani M, Onojafe IF, Sergeev YV, Boobalan E, Jones M, Tang K, Liu H, Xia CH, Gong X, Brooks BP
PLoS Genet 2010 Mar 5;6(3):e1000870. doi: 10.1371/journal.pgen.1000870. PMID: 20221250Free PMC Article
Gucev ZS, Kirovski I, Jancevska A, Popjordanova N, Tasic V
Ren Fail 2009;31(7):602-5. doi: 10.1080/08860220902968862. PMID: 19839859

Clinical prediction guides

Rossanti R, Morisada N, Nozu K, Kamei K, Horinouchi T, Yamamura T, Minamikawa S, Fujimura J, Nagano C, Sakakibara N, Ninchoji T, Kaito H, Ito S, Tanaka R, Iijima K
J Hum Genet 2020 Jun;65(6):541-549. Epub 2020 Mar 16 doi: 10.1038/s10038-020-0741-y. PMID: 32203253
Sels L, Dirven W, Devriendt K, Leys A
Retin Cases Brief Rep 2020 Winter;14(1):77-81. doi: 10.1097/ICB.0000000000000625. PMID: 28820764
Deng H, Zhang Y, Xiao H, Yao Y, Liu X, Su B, Zhang H, Xu K, Wang S, Wang F, Ding J
Mol Genet Genomic Med 2019 Jun;7(6):e701. Epub 2019 May 6 doi: 10.1002/mgg3.701. PMID: 31060108Free PMC Article
Dureau P, Attie-Bitach T, Salomon R, Bettembourg O, Amiel J, Uteza Y, Dufier JL
Ophthalmology 2001 Oct;108(10):1912-6. doi: 10.1016/s0161-6420(01)00722-9. PMID: 11581073
Torban E, Eccles MR, Favor J, Goodyer PR
Am J Pathol 2000 Sep;157(3):833-42. doi: 10.1016/S0002-9440(10)64597-X. PMID: 10980123Free PMC Article

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