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Lowe syndrome(OCRL)

MedGen UID:
18145
Concept ID:
C0028860
Disease or Syndrome
Synonyms: Lowe oculocerebrorenal syndrome; OCRL; Oculocerebrorenal Syndrome; Phosphatidylinositol 4,5-bisphosphate 5-phosphatase deficiency
Modes of inheritance:
X-linked recessive inheritance
MedGen UID:
375779
Concept ID:
C1845977
Finding
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
X-linked recessive inheritance (HPO, OMIM, Orphanet)
SNOMED CT: Oculocerebrorenal dystrophy (79385002); Cerebro-oculorenal dystrophy (79385002); Lowe disease (79385002); Lowe syndrome (79385002); Oculocerebrorenal syndrome (79385002); Renal-oculocerebrodystrophy (79385002); Lowe-Terrey-MacLachlan syndrome (79385002); Lowe-Bickel syndrome (79385002)
 
Gene (location): OCRL (Xq26.1)
OMIM®: 309000
Orphanet: ORPHA534

Disease characteristics

Excerpted from the GeneReview: Lowe Syndrome
Lowe syndrome (oculocerebrorenal syndrome) is characterized by involvement of the eyes, central nervous system, and kidneys. Dense congenital cataracts are found in all affected boys and infantile glaucoma in approximately 50%. All boys have impaired vision; corrected acuity is rarely better than 20/100. Generalized hypotonia is noted at birth and is of central (brain) origin. Deep tendon reflexes are usually absent. Hypotonia may slowly improve with age, but normal motor tone and strength are never achieved. Motor milestones are delayed. Almost all affected males have some degree of intellectual disability; 10%-25% function in the low-normal or borderline range, approximately 25% in the mild-to-moderate range, and 50%-65% in the severe-to-profound range of intellectual disability. Affected males have varying degrees of proximal renal tubular dysfunction of the Fanconi type, including bicarbonate wasting and renal tubular acidosis, phosphaturia with hypophosphatemia and renal rickets, aminoaciduria, low molecular-weight (LMW) proteinuria, sodium and potassium wasting, and polyuria. Fanconi syndrome is usually not clinically apparent in the first few months of life, but symptoms may appear by age six to 12 months. Glomerulosclerosis associated with chronic tubular injury usually results in slowly progressive chronic renal failure and end-stage renal disease after age ten to 20 years. [from GeneReviews]
Authors:
Richard Alan Lewis  |  Robert L Nussbaum  |  Eileen D Brewer   view full author information

Additional description

From GHR
Lowe syndrome is a condition that primarily affects the eyes, brain, and kidneys. This disorder occurs almost exclusively in males.Infants with Lowe syndrome are born with thick clouding of the lenses in both eyes (congenital cataracts), often with other eye abnormalities that can impair vision. About half of affected infants develop an eye disease called infantile glaucoma, which is characterized by increased pressure within the eyes.Many individuals with Lowe syndrome have delayed development, and intellectual ability ranges from normal to severely impaired. Behavioral problems and seizures have also been reported in children with this condition. Most affected children have weak muscle tone from birth (neonatal hypotonia), which can contribute to feeding difficulties, problems with breathing, and delayed development of motor skills such as sitting, standing, and walking.Kidney (renal) abnormalities, most commonly a condition known as renal Fanconi syndrome, frequently develop in individuals with Lowe syndrome. The kidneys play an essential role in maintaining the right amounts of minerals, salts, water, and other substances in the body. In individuals with renal Fanconi syndrome, the kidneys are unable to reabsorb important nutrients into the bloodstream. Instead, the nutrients are excreted in the urine. These kidney problems lead to increased urination, dehydration, and abnormally acidic blood (metabolic acidosis). A loss of salts and nutrients may also impair growth and result in soft, bowed bones (hypophosphatemic rickets), especially in the legs. Progressive kidney problems in older children and adults with Lowe syndrome can lead to life-threatening renal failure and end-stage renal disease (ESRD).  https://ghr.nlm.nih.gov/condition/lowe-syndrome

Clinical features

Aggressive behavior
MedGen UID:
1375
Concept ID:
C0001807
Individual Behavior
A verbal or physical act of hostility.
Cataract, congenital
MedGen UID:
3202
Concept ID:
C0009691
Congenital Abnormality
A congenital cataract.
Constipation
MedGen UID:
1101
Concept ID:
C0009806
Sign or Symptom
Infrequent or difficult evacuation of FECES. These symptoms are associated with a variety of causes, including low DIETARY FIBER intake, emotional or nervous disturbances, systemic and structural disorders, drug-induced aggravation, and infections.
Cryptorchidism
MedGen UID:
8192
Concept ID:
C0010417
Congenital Abnormality
Cryptorchidism, or failure of testicular descent, is a common human congenital abnormality with a multifactorial etiology that likely reflects the involvement of endocrine, environmental, and hereditary factors. Cryptorchidism can result in infertility and increases risk for testicular tumors. Testicular descent from abdomen to scrotum occurs in 2 distinct phases: the transabdominal phase and the inguinoscrotal phase (summary by Gorlov et al., 2002).
Hypoplasia of dental enamel
MedGen UID:
3730
Concept ID:
C0011351
Disease or Syndrome
A form of amelogenesis imperfecta characterized by incomplete formation of the dental enamel and transmitted as an X-linked or autosomal dominant trait.
Pathologic fracture
MedGen UID:
42095
Concept ID:
C0016663
Pathologic Function
A pathologic fracture occurs when a bone breaks in an area that is weakened secondary to another disease process such as tumor, infection, and certain inherited bone disorders. A pathologic fracture can occur without a degree of trauma required to cause fracture in healthy bone.
Glaucoma
MedGen UID:
42224
Concept ID:
C0017601
Disease or Syndrome
Glaucoma is a group of eye disorders in which the optic nerves connecting the eyes and the brain are progressively damaged. This damage can lead to reduction in side (peripheral) vision and eventual blindness. Other signs and symptoms may include bulging eyes, excessive tearing, and abnormal sensitivity to light (photophobia). The term "early-onset glaucoma" may be used when the disorder appears before the age of 40.In most people with glaucoma, the damage to the optic nerves is caused by increased pressure within the eyes (intraocular pressure). Intraocular pressure depends on a balance between fluid entering and leaving the eyes.Usually glaucoma develops in older adults, in whom the risk of developing the disorder may be affected by a variety of medical conditions including high blood pressure (hypertension) and diabetes mellitus, as well as family history. The risk of early-onset glaucoma depends mainly on heredity.Structural abnormalities that impede fluid drainage in the eye may be present at birth and usually become apparent during the first year of life. Such abnormalities may be part of a genetic disorder that affects many body systems, called a syndrome. If glaucoma appears before the age of 5 without other associated abnormalities, it is called primary congenital glaucoma.Other individuals experience early onset of primary open-angle glaucoma, the most common adult form of glaucoma. If primary open-angle glaucoma develops during childhood or early adulthood, it is called juvenile open-angle glaucoma.
Hip dislocation
MedGen UID:
42455
Concept ID:
C0019554
Injury or Poisoning
A congenital or traumatic abnormality in which the femoral head slips out of the acetabulum.
Hypercholesterolaemia
MedGen UID:
5687
Concept ID:
C0020443
Disease or Syndrome
A condition with abnormally high levels of CHOLESTEROL in the blood. It is defined as a cholesterol value exceeding the 95th percentile for the population.
Kyphosis
MedGen UID:
44042
Concept ID:
C0022821
Anatomical Abnormality
Abnormally increased curvature of the thoracic portion of the spine.
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.People 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.People 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.Between 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.
Osteomalacia
MedGen UID:
14533
Concept ID:
C0029442
Disease or Syndrome
A metabolic bone disease that results from either a deficiency in vitamin D, or an abnormality in the metabolism of vitamin D, or a deficiency of calcium in the diet. The most common symptoms are bone pain and muscle weakness. When it occurs in children it is commonly referred to as rickets. (Diagnostic Surgical Pathology, 3rd ed.) --2003
Proteinuria
MedGen UID:
10976
Concept ID:
C0033687
Finding
Increased levels of protein in the urine.
Rickets
MedGen UID:
48470
Concept ID:
C0035579
Disease or Syndrome
Bone softening and weakening usually caused by deficiency or impaired metabolism of vitamin D. Deficiency of calcium, magnesium, or phosphorus may also cause rickets. It predominantly affects children who suffer from severe malnutrition. It manifests with bone pain, fractures, muscle weakness, and skeletal deformities.
Seizures
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or "seizure disorder."
Stereotypy
MedGen UID:
21320
Concept ID:
C0038273
Mental or Behavioral Dysfunction
A stereotypy is a repetitive, simple movement that can be voluntarily suppressed. Stereotypies are typically simple back-and-forth movements such as waving of flapping the hands or arms, and they do not involve complex sequences or movement fragments. Movement is often but not always rhythmic and may involve fingers, wrists, or more proximal portions of the upper extremity. The lower extremity is not typically involved. Stereotypies are more commonly bilateral than unilateral.
Subcutaneous nodule
MedGen UID:
101803
Concept ID:
C0151811
Pathologic Function
A small palpable mass in the subcutaneous tissues.
Areflexia
MedGen UID:
115943
Concept ID:
C0234146
Finding
A finding indicating the complete absence of neurological reflexes.
Reduced visual acuity
MedGen UID:
65889
Concept ID:
C0234632
Finding
Visual impairment (or vision impairment) is vision loss (of a person) to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive correction, medication, or surgery.
Aminoaciduria
MedGen UID:
116067
Concept ID:
C0238621
Disease or Syndrome
An increased concentration of an amino acid in the urine.
Finger swelling
MedGen UID:
65989
Concept ID:
C0239598
Finding
Enlargement of the soft tissues of one or more fingers.
Wrist swelling
MedGen UID:
116125
Concept ID:
C0241760
Finding
Hyperphosphaturia
MedGen UID:
78638
Concept ID:
C0268079
Disease or Syndrome
An increased excretion of phosphates in the urine.
Proximal renal tubular acidosis
MedGen UID:
82804
Concept ID:
C0268435
Disease or Syndrome
A type of renal tubular acidosis characterized by a failure of the proximal tubular cells to reabsorb bicarbonate, leading to urinary bicarbonate wasting and subsequent acidemia.
Fanconi renotubular syndrome 1
MedGen UID:
137960
Concept ID:
C0341703
Disease or Syndrome
Fanconi renotubular syndrome is a consequence of decreased solute and water reabsorption in the proximal tubule of the kidney. Patients have polydipsia and polyuria with phosphaturia, glycosuria, and aminoaciduria. They may develop hypophosphatemic rickets or osteomalacia, acidosis, and a tendency toward dehydration. Some will eventually develop renal insufficiency. Common laboratory abnormalities include glucosuria with a normal serum glucose, hyperaminoaciduria, hypophosphatemia, progressive renal insufficiency, renal sodium and potassium wasting, acidosis, uricosuria, and low-molecular-weight proteinuria (summary by Lichter-Konecki et al., 2001). Genetic Heterogeneity of Fanconi Renotubular Syndrome Fanconi renotubular syndrome-1 has been mapped to chromosome 15q15.3. See also FRTS2 (613388), caused by mutation in the SLC34A1 gene (182309) on chromosome 5q35; FRTS3 (615605), caused by mutation in the EHHADH gene (607037) on chromosome 3q27; and FRTS4 (616026), which is associated with maturity-onset diabetes of the young (MODY), caused by mutation in the HNF4A gene (600281) on chromosome 20q13.
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).
Camptodactyly of finger
MedGen UID:
98041
Concept ID:
C0409348
Finding
The distal interphalangeal joint and/or the proximal interphalangeal joint of the fingers cannot be extended to 180 degrees by either active or passive extension.
Genu valgum
MedGen UID:
154364
Concept ID:
C0576093
Anatomical Abnormality
An inward slant of the thigh in which the knees are close together and the ankles far apart. Genu valgum can develop due to skeletal and joint dysplasias (e.g., OSTEOARTHRITIS; HURLER SYNDROME); and malnutrition (e.g., RICKETS; FLUORIDE POISONING).
Scoliosis
MedGen UID:
195976
Concept ID:
C0700208
Finding
The presence of an abnormal lateral curvature of the spine.
Elevated maternal serum alpha-fetoprotein
MedGen UID:
152853
Concept ID:
C0740927
Laboratory or Test Result
An elevation of alpha-feto protein in the maternal serum.
Renal insufficiency
MedGen UID:
332529
Concept ID:
C1565489
Disease or Syndrome
A reduction in the level of performance of the kidneys in areas of function comprising the concentration of urine, removal of wastes, the maintenance of electrolyte balance, homeostasis of blood pressure, and calcium metabolism.
Periventricular cysts
MedGen UID:
326980
Concept ID:
C1839858
Finding
Elevated amniotic fluid alpha-fetoprotein
MedGen UID:
333423
Concept ID:
C1839860
Finding
An elevation of alpha-feto protein measured in the amniotic fluid.
Bicarbonaturia
MedGen UID:
326596
Concept ID:
C1839865
Finding
Abnormally increased concentration of hydrogencarbonate in the urine.
Elevated serum acid phosphatase
MedGen UID:
326597
Concept ID:
C1839866
Finding
Platyspondyly
MedGen UID:
335010
Concept ID:
C1844704
Finding
A flattened vertebral body shape with reduced distance between the vertebral endplates.
Joint hypermobility
MedGen UID:
336793
Concept ID:
C1844820
Finding
The ability of a joint to move beyond its normal range of motion.
Neonatal hypotonia
MedGen UID:
412209
Concept ID:
C2267233
Disease or Syndrome
Muscular hypotonia (abnormally low muscle tone) manifesting in the neonatal period.
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Ventriculomegaly
MedGen UID:
480553
Concept ID:
C3278923
Finding
An increase in size of the ventricular system of the brain.
Visual impairment
MedGen UID:
777085
Concept ID:
C3665347
Finding
Visual impairment (or vision impairment) is vision loss (of a person) to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive correction, medication, or surgery.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Subnormal intellectual functioning which originates during the developmental period. Intellectual disability, previously referred to as mental retardation, has been defined as an IQ score below 70.
Dense posterior cortical cataract
MedGen UID:
870324
Concept ID:
C4024767
Finding
A type of posterior cortical cataract characterized by dense lenticular opacities.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Lowe syndrome in Orphanet.

Recent clinical studies

Etiology

Gao Y, Jiang F, Ou ZY
World J Pediatr 2016 Nov;12(4):484-488. Epub 2016 Apr 8 doi: 10.1007/s12519-016-0017-y. PMID: 27059748
Liu T, Yue Z, Wang H, Tong H, Sun L
Indian J Pediatr 2015 Jan;82(1):89-92. Epub 2014 Oct 10 doi: 10.1007/s12098-014-1581-6. PMID: 25297642
Zhang YQ, Wang F, Ding J, Yan H, Yang YL
World J Pediatr 2013 Feb;9(1):53-7. Epub 2013 Feb 7 doi: 10.1007/s12519-013-0406-4. PMID: 23389333
Ke YH, He JW, Fu WZ, Zhang ZL
Nephrology (Carlton) 2012 Jan;17(1):20-5. doi: 10.1111/j.1440-1797.2011.01514.x. PMID: 21854507
Lasne D, Baujat G, Mirault T, Lunardi J, Grelac F, Egot M, Salomon R, Bachelot-Loza C
Br J Haematol 2010 Sep;150(6):685-8. doi: 10.1111/j.1365-2141.2010.08304.x. PMID: 20629659

Diagnosis

Nakanishi K, Nozu K, Hiramoto R, Minamikawa S, Yamamura T, Fujimura J, Horinouchi T, Ninchoji T, Kaito H, Morisada N, Ishimori S, Nakanishi K, Morioka I, Awano H, Matsuo M, Iijima K
Eur J Med Genet 2017 Dec;60(12):631-634. Epub 2017 Aug 9 doi: 10.1016/j.ejmg.2017.08.001. PMID: 28803024
Rendu J, Montjean R, Coutton C, Suri M, Chicanne G, Petiot A, Brocard J, Grunwald D, Pietri Rouxel F, Payrastre B, Lunardi J, Dorseuil O, Marty I, Fauré J
Hum Mutat 2017 Feb;38(2):152-159. Epub 2016 Nov 21 doi: 10.1002/humu.23139. PMID: 27790796
Gao Y, Jiang F, Ou ZY
World J Pediatr 2016 Nov;12(4):484-488. Epub 2016 Apr 8 doi: 10.1007/s12519-016-0017-y. PMID: 27059748
Recker F, Zaniew M, Böckenhauer D, Miglietti N, Bökenkamp A, Moczulska A, Rogowska-Kalisz A, Laube G, Said-Conti V, Kasap-Demir B, Niemirska A, Litwin M, Siteń G, Chrzanowska KH, Krajewska-Walasek M, Sethi SK, Tasic V, Anglani F, Addis M, Wasilewska A, Szczepańska M, Pawlaczyk K, Sikora P, Ludwig M
Pediatr Nephrol 2015 Jun;30(6):931-43. Epub 2014 Dec 6 doi: 10.1007/s00467-014-3013-2. PMID: 25480730
Ke YH, He JW, Fu WZ, Zhang ZL
Nephrology (Carlton) 2012 Jan;17(1):20-5. doi: 10.1111/j.1440-1797.2011.01514.x. PMID: 21854507

Therapy

Mikhail M, Modabber M, Koenekoop RK, Braverman N, Khan A
Eye (Lond) 2016 Sep;30(9):1272-3. Epub 2016 May 27 doi: 10.1038/eye.2016.100. PMID: 27229703Free PMC Article
Hou JW
J Formos Med Assoc 2009 Sep;108(9):730-5. doi: 10.1016/S0929-6646(09)60397-1. PMID: 19773212
Rodrigues Santos MT, Watanabe MM, Manzano FS, Lopes CH, Masiero D
Spec Care Dentist 2007 May-Jun;27(3):108-11. PMID: 17658186
Cau M, Addis M, Congiu R, Meloni C, Cao A, Santaniello S, Loi M, Emma F, Zuffardi O, Ciccone R, Sole G, Melis MA
J Hum Genet 2006;51(11):1030-6. Epub 2006 Sep 6 doi: 10.1007/s10038-006-0049-6. PMID: 16955230
Spierer A, Desatnik H
Metab Pediatr Syst Ophthalmol (1985) 1998;21(1-4):19-21. PMID: 11548790

Prognosis

Gao Y, Jiang F, Ou ZY
World J Pediatr 2016 Nov;12(4):484-488. Epub 2016 Apr 8 doi: 10.1007/s12519-016-0017-y. PMID: 27059748
Recker F, Zaniew M, Böckenhauer D, Miglietti N, Bökenkamp A, Moczulska A, Rogowska-Kalisz A, Laube G, Said-Conti V, Kasap-Demir B, Niemirska A, Litwin M, Siteń G, Chrzanowska KH, Krajewska-Walasek M, Sethi SK, Tasic V, Anglani F, Addis M, Wasilewska A, Szczepańska M, Pawlaczyk K, Sikora P, Ludwig M
Pediatr Nephrol 2015 Jun;30(6):931-43. Epub 2014 Dec 6 doi: 10.1007/s00467-014-3013-2. PMID: 25480730
Pirruccello M, Swan LE, Folta-Stogniew E, De Camilli P
Nat Struct Mol Biol 2011 Jun 12;18(7):789-95. doi: 10.1038/nsmb.2071. PMID: 21666675Free PMC Article
Draaken M, Giesen CA, Kesselheim AL, Jabs R, Aretz S, Kugaudo M, Chrzanowska KH, Krajewska-Walasek M, Ludwig M
Hum Genet 2011 May;129(5):513-9. Epub 2011 Jan 12 doi: 10.1007/s00439-010-0944-y. PMID: 21225285
Loi M
Orphanet J Rare Dis 2006 May 18;1:16. doi: 10.1186/1750-1172-1-16. PMID: 16722554Free PMC Article

Clinical prediction guides

Inoue K, Balkin DM, Liu L, Nandez R, Wu Y, Tian X, Wang T, Nussbaum R, De Camilli P, Ishibe S
J Am Soc Nephrol 2017 May;28(5):1399-1407. Epub 2016 Nov 28 doi: 10.1681/ASN.2016080913. PMID: 27895154Free PMC Article
Recker F, Zaniew M, Böckenhauer D, Miglietti N, Bökenkamp A, Moczulska A, Rogowska-Kalisz A, Laube G, Said-Conti V, Kasap-Demir B, Niemirska A, Litwin M, Siteń G, Chrzanowska KH, Krajewska-Walasek M, Sethi SK, Tasic V, Anglani F, Addis M, Wasilewska A, Szczepańska M, Pawlaczyk K, Sikora P, Ludwig M
Pediatr Nephrol 2015 Jun;30(6):931-43. Epub 2014 Dec 6 doi: 10.1007/s00467-014-3013-2. PMID: 25480730
Montjean R, Aoidi R, Desbois P, Rucci J, Trichet M, Salomon R, Rendu J, Fauré J, Lunardi J, Gacon G, Billuart P, Dorseuil O
Hum Mol Genet 2015 Feb 15;24(4):994-1006. Epub 2014 Oct 9 doi: 10.1093/hmg/ddu514. PMID: 25305077
Bökenkamp A, Böckenhauer D, Cheong HI, Hoppe B, Tasic V, Unwin R, Ludwig M
J Pediatr 2009 Jul;155(1):94-9. doi: 10.1016/j.jpeds.2009.01.049. PMID: 19559295
Sethi SK, Bagga A, Gulati A, Hari P, Gupta N, Lunardi J
Clin Exp Nephrol 2008 Oct;12(5):358-362. Epub 2008 May 24 doi: 10.1007/s10157-008-0059-0. PMID: 18500547

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