Wilms tumor, aniridia, genitourinary anomalies and mental retardation (WAGR) syndrome

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WAGR syndrome information for patients

Quick links


Synonyms of WAGR syndrome
Overview
The condition
Treatment
Further information and support

Synonyms of WAGR syndrome


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  • Chromosome 11p deletion syndrome
  • WAGR complex


Overview


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WAGR syndrome is a rare condition affecting 1 in 500,000 to 1 in 1 million people.[1] It is caused by genetic changes to genes located on chromosome 11. WAGR syndrome affects multiple body systems. WAGR is an acronym which describes its main features: Wilms tumour (a childhood kidney cancer), Aniridia, Genitourinary abnormalities (anomalies of the reproductive organs and urinary tract) and a Range of developmental disabilities. Affected individuals usually have two or more of the above features. Most cases are not inherited, but develop spontaneously within the patient themselves (when they were developing in the womb during pregnancy).

WAGR syndrome is typically diagnosed at birth or in early infancy when aniridia is first noticed, prompting further examination and investigations. Approximately one-third of children with non-inherited aniridia are diagnosed with WAGR syndrome.[1] Apart from the four main features, there are other conditions associated with WAGR syndrome as well. These conditions include medical, behavioural, and neurodevelopmental disorders.[1]


The condition


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Symptoms

1) Wilms tumour (nephroblastoma)
Wilms tumour is the most common kidney cancer in childhood. Patients affected by WAGR syndrome are at 45-60% increased risk of developing Wilms tumour.[2][3][4] Of those who develop Wilms tumour, 98% do so by age seven.[5]

Children with WAGR syndrome are monitored for the development of Wilms tumour with abdominal ultrasound every 3 months from birth or diagnosis to age 8 years. After age 8, surveillance continues throughout life with ultrasound examination every 6 to 12 months, regular blood pressure evaluation, feeling of the abdomen, and blood tests.


2) Aniridia
Aniridia is present in almost all cases of WAGR syndrome.[1] It is characterised by an under-developed or absent iris in both eyes. Other structures of the eye could be affected as well, such as the cornea, the trabecular meshwork, lens, fovea, optic disc and overall size of the eye. The symptoms experienced by patients depend on the structures affected and vary in severity. The most common symptoms associated with aniridia are glare, light sensitivity, poor vision and nystagmus.

This image demonstrates the difference between a patient with aniridia and a normal healthy individual. On the left is an eye without an iris while on the right of the image shows an eye with a fully formed iris, giving the eye a hazel colour.
An eye affected by aniridia where the iris is absent (A) and an eye with a fully developed iris (B)


3) Genitourinary abnormalities
Both males and females with WAGR syndrome may have abnormal development of their reproductive organs (gonads) and urinary tract. During pregnancy, a baby boy’s testes are normally developed in the abdomen before moving down into the scrotum about 1 to 2 months before birth. However, this might not occur in males with WAGR syndrome, leading to a condition called undescended testes or cryptorchidism. This is the most common abnormality in male WAGR patients (60% of cases).[3] Another feature in males with WAGR syndrome is hypospadias, where the opening of the penis is not at the tip. Undescended testes and hypospadias are correctable with surgery.

In females, genitourinary abnormalities can manifest as underdeveloped ovaries (streak ovaries) or malformation of the womb or vagina.

These features can affect urination, fertility and more importantly, children from both sexes with underdeveloped gonads are at increased risk of developing a rare type of cancer called gonadoblastoma.

In some patients with WAGR syndrome, the external genitals might not have fully developed, leading to difficulty in sexual assignment at birth (ambiguous genitalia).


4) Range of developmental abnormality
70% of patients with WAGR syndrome have developmental delay, learning difficulties, or intellectual disability (defined as IQ<74). Most patients are mildly to moderately affected, but the range of disability varies.[1] Some patients are profoundly delayed, while others have normal intellect.


5) Other associated features
Apart from the four main features, a variety of other conditions have been reported in WAGR syndrome:

  • Chronic kidney disease
It affects approximately 60% of patients with WAGR syndrome, most often developing in adolescence or young adulthood. The cause of kidney disease is FSGS (focal segmental glomerulosclerosis). FSGS attacks the kidney's filtering units (glomeruli) causing serious scarring which leads to permanent kidney damage. Symptoms of FSGS include high blood pressure and protein in the urine. FSGS may progress to kidney failure, requiring dialysis or kidney transplant.[4]
  • Behavioural, neurodevelopmental, and psychiatric disorders
These are common in patients with WAGR syndrome. They may include attention-deficit disorder (ADD), attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder, anxiety, depression, and obsessive-compulsive disorder (OCD).
  • Neurological abnormalities
Problems with muscle tone (too much or too little) and seizures are commonly found in WAGR patients
  • Central auditory processing disorder (CAPD)
90% of patients with WAGR syndrome have some degree of CAPD. It affects the brain’s ability to filter and interpret sounds.[6]
  • Early onset obesity (before the age of 10)
50% of patients with WAGR syndrome have a deletion of one copy of the BDNF gene.[7]Loss of one copy of this gene is associated with early onset obesity. Symptoms of BDNF gene deletion include constant hunger, food-seeking behaviour, and a decreased behavioural response to pain.[8]
  • Dyslipidaemia (elevated levels of fat in the blood)
  • Sleep disorders and sleep apnoea
These conditions are common in WAGR syndrome.[9] People with WAGR syndrome may have small or absent pineal glands, an organ in the brain which produces a hormone called melatonin. This hormone helps the brain to know when to sleep and when to wake up. Too little melatonin may result in difficulty falling asleep or staying asleep. Sleep apnoea is a disorder in which breathing repeatedly stops and starts. Sleep apnoea may cause high blood pressure or heart problems, and may increase the risk of developing type 2 diabetes.


This list of associated features is not exhaustive. Please visit the International WAGR Syndrome Association (IWSA) website for more information.


Cause

WAGR syndrome is caused by deletion of a section of genetic material on chromosome 11. This deletion occurs during the formation of the sperm or egg or in the early stages of the baby’s development in the womb. This section of genetic material involves the PAX6 and WT1 genes as well as many other genes.

The PAX6 gene provides instructions for the development of multiple vital organs during early pregnancy including the eyes, the brain and the spinal cord.[10] When the PAX6 gene is not working properly, the development of these vital organs are affected, leading to some main features seen in WAGR syndrome such as aniridia and intellectual disability.

The WT1 gene is responsible for the development of the kidneys and gonads before birth. After birth, it provides instructions for a protein that maintains normal growth of kidney cells.[11] Absence of the WT1 gene results in kidney malformation and unregulated growth of these cells, increasing the risk of developing Wilms tumour. It also leads to abnormal development of the gonads and genitals, causing genitourinary anomalies.

The BDNF gene provides instructions for making a protein found in the brain and spinal cord called brain-derived neurotrophic factor. This protein helps regulate synaptic plasticity, which is important for learning and memory, and is found in regions of the brain that control eating, drinking, and body weight, as well as perception of pain.[12] People with deletion of this gene may have learning difficulties, early onset obesity, and a decreased response to pain.

More research is needed to determine whether other genes that are deleted in patients with WAGR syndrome are responsible for other features of the disorder.


How is it diagnosed?

WAGR syndrome is suspected based on the four main clinical features although not every feature has to be present. The diagnosis is confirmed with genetic testing by identifying deletions in the PAX6 and WT1 genes.


How is it inherited?

  • Sporadic
WAGR syndrome most often develops spontaneously during the early stages of the baby’s development in the womb. In very rare cases, it can be inherited through complex genetic abnormalities in an unaffected parent.

If your child is affected by WAGR syndrome, it is advisable to see a genetic counsellor to obtain more information and advice on inheritance and family planning options including prenatal testing and preimplantation diagnosis.


Treatment


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Is there any treatment?

There is currently no treatment for the gene deletions causing WAGR syndrome. Treatment is mainly focused on a patient’s presenting symptoms. Frequent observations are advised so that any associated physical or mental issues can be addressed at the earliest instance. Children affected with WAGR syndrome should be managed by a multidisciplinary team of healthcare professionals.

  • Wilms tumour
Children with confirmed WAGR syndrome should have an ultrasound scan of their abdomen performed every 3 months from birth or diagnosis until the age of 8.[1] In addition, parents can be taught how to feel the abdomen for any masses or swelling when at home. After age 8, the interval between ultrasound scans may be increased, and other monitoring including regular blood pressure and urine checks may be added.
If Wilms tumour is diagnosed, the affected child is referred to a paediatric oncologist for treatment. Treatment may include a combination of chemotherapy, radiation therapy and surgery depending on the location and stage of the tumour. Lifelong observation of kidney function through blood tests is advised.[4]
Patients affected with WAGR syndrome are normally monitored by an ophthalmologist for visual development and eye conditions typically associated with aniridia, such as glaucoma, cataract and aniridia-related keratopathy. Regular check-ups are important to monitor these conditions so that treatment, either in the form of eye drops or surgery can be initiated as soon as possible to preserve sight. Patients with visual impairment are referred to low vision services to help optimise their vision so that they can remain independent.
This image demonstrates a patient affected by aniridia-related keratopathy. The usually transparent cornea is now covered with blood vessels from the conjunctiva, causing it to be opaque.
Aniridia-related keratopathy (ARK)
The usually transparent cornea is now opaque after being replaced by tissues from the conjunctiva
  • Genitourinary anomalies
This is usually managed by a urologist or a gynaecologist.
  • Undescended testes/cryptorchidism
An operation called orchidopexy can be performed to move the undescended testes to the scrotum. Untreated cryptorchidism can result in fertility issues and increased risk of testicular cancer.
  • Hypospadias
An operation can be performed to create a new opening at the tip of the penis. Although it is not a life-threatening problem, surgery is usually performed for reproductive purposes or to correct problems with urination.
  • Abnormal development of gonads
Due to the increased risk of gonadoblastoma, children with WAGR syndrome should be regularly evaluated to detect abnormalities in the gonads. In males, this risk may be decreased by orchidopexy surgery. If this is not possible, the testicle may be removed. Females, may be managed by monitoring the ovaries with ultrasound or MRI (magnetic resonance imaging) and with blood tests. As the ovaries might not be able to produce adequate level of hormones for the development of puberty and menstruation, hormone replacement therapy might be required.
  • Intellectual disability, behavioural and neurodevelopmental disorders
Children are usually managed in specialist centres alongside community paediatric services to cater to the complex health, developmental and social needs of children affected by WAGR syndrome. Professionals such as community nurses, therapists (speech and language therapists, occupational health therapists and physiotherapists), social workers, child and adolescent mental health service (CAMHS) and schools work together to provide holistic care for each individual.
As children may be seen by many different services, parents may find it helpful to speak to their paediatrician to help coordinate care.
Find out more about educational support that is available for children with special needs.
  • Chronic kidney disease
Early diagnosis of kidney disease and aggressive treatment with medication may preserve kidney function for long periods in some patients. When kidney function declines below the level needed to sustain life, dialysis or kidney transplant is required.[4]
  • Neurological abnormalities
Physiotherapy is helpful for problems with muscle tone, coordination, and strength. Seizure disorders may be effectively treated with medication.
  • Central Auditory Processing Disorder (CAPD)
Environmental modifications at home and at school, such as the use of listening devices, and working with a speech and language therapist.
  • BDNF gene deletion
Some patients may respond to careful control of calorie intake and increased physical activity. Restricting access to food may be necessary. Patients with decreased response to pain should be observed closely for altered behaviour that may indicate injury or illness, such as limping or refusing to use an arm or a hand, swelling or redness of the skin, or fever.
  • Dyslipidaemia
Patients may benefit from medication to lower the level of lipids (fats) in the blood. These patients should also avoid propofol if possible. Propofol is a common medication given during general anaesthesia.
  • Sleep disorders and sleep apnoea
Supplemental melatonin is helpful for some people with WAGR syndrome and sleep disorders. Sleep apnoea may be treated with CPAP (continuous positive airway pressure), a machine which uses a hose and mask or nosepiece to deliver constant and steady air pressure.


Further information and support


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References

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  1. 1.0 1.1 1.2 1.3 1.4 1.5 Moosajee M, Hingorani M, Moore AT. PAX6-Related Aniridia. In: GeneReviews®[Internet]. University of Washington, Seattle; 2018.
  2. Muto R, Yamamori S, Ohashi H, Osawa M. Prediction by FISH analysis of the occurrence of Wilms tumor in aniridia patients. Am J Med Genet. 2002;108(4):285-289.
  3. 3.0 3.1 Fischbach BV, Trout KL, Lewis J, Luis CA, Sika M. WAGR syndrome: a clinical review of 54 cases. Pediatrics. 2005;116(4):984-988.
  4. 4.0 4.1 4.2 4.3 Breslow NE, Norris R, Norkool PA, et al. Characteristics and outcomes of children with the Wilms tumor-Aniridia syndrome: a report from the National Wilms Tumor Study Group. J Clin Oncol. 2003;21(24):4579-4585.
  5. Beckwith JB. Nephrogenic rests and the pathogenesis of Wilms tumor: developmental and clinical considerations. Am J Med Genet. 1998;79(4):268-273.
  6. Bobilev AM, Hudgens-Haney ME, Hamm JP, et al. Early and late auditory information processing show opposing deviations in aniridia. Brain Res. 2019;1720:146307
  7. Han JC, Liu QR, Jones M, et al. Brain-derived neurotrophic factor and obesity in the WAGR syndrome. N Engl J Med. 2008;359(9):918-927.
  8. Sapio MR, Iadarola MJ, LaPaglia DM, et al. Haploinsufficiency of the brain-derived neurotrophic factor gene is associated with reduced pain sensitivity. Pain. 2019;160(5):1070-1081.
  9. Hanish AE, Butman JA, Thomas F, Yao J, Han JC. Pineal hypoplasia, reduced melatonin and sleep disturbance in patients with PAX6 haploinsufficiency. J Sleep Res. 2016;25(1):16-22.
  10. US National Libray of Medicine. PAX6 gene. https://ghr.nlm.nih.gov/gene/PAX6. Published 2019. Updated July 2014. Accessed 30/10/19.
  11. US National Libray of Medicine. WT1 gene. https://ghr.nlm.nih.gov/gene/WT1. Published 2019. Updated September 2018. Accessed 30/10/19.
  12. U.S. National Library of Medicine. BDNF gene. https://ghr.nlm.nih.gov/gene/BDNF. Published 2019. Updated March 2013. Accessed 10 November 2019.

WAGR syndrome information for doctors

Quick links


Synonyms of WAGR syndrome
Overview
Clinical phenotype
Genetics
Diagnosis
Management
Further information for patients

Synonyms of WAGR syndrome


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  • Chromosome 11p deletion syndrome
  • WAGR complex


Overview


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WAGR syndrome (OMIM #194072) is a rare condition characterised by its four main features, Wilms tumour, Aniridia, Genitourinary anomalies (gonadoblastoma, cryptorchidism and hypospadias in males; streak ovaries and bicornate uterus in females) and intellectual disability (previous known as mental Retardation). Apart from these main features, it is also associated with chronic kidney disease, neurodevelopmental disorders, neurological abnormalities, central auditory processing and sleep disorders. WAGR syndrome has a prevalence of 1 in 500,000 to 1 in one million.[1] It is mainly due to de novo sporadic contiguous gene deletion on chromosome 11p13 involving the PAX6 and WT1 genes. Very rarely, it is inherited in an autosomal dominant pattern due to mosaicsm in either parent. Treatment is based on the presenting features.


Clinical phenotype


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1) Wilms tumour (nephroblastoma)

Patients affected by WAGR syndrome are at 45-60% increased risk of developing Wilms tumour.[2][3]Compared to patients with isolated Wilms tumour not associated with a WT1 gene deletion, WAGR patients often have a younger age of diagnosis and tend to have bilateral involvement.[4] Of those who develop Wilms tumour, 98% do so by age seven.[5]

In the early stages, Wilms tumour usually does not cause any symptoms. Later on, patients might experience haematuria, abdominal pain and swelling, anaemia, low-grade fever, loss of appetite, weight loss and lethargy. About 30% of children with Wilms tumour also have hypertension.


2) Aniridia

An eye with an underdeveloped iris, typical of aniridia. There is also some spoke-wheel like cloudiness of the lens, representing cataract.
Iris hypoplasia with associated lens opacity

Aniridia is almost universally present in WAGR patients and tends to be severe.[1] It is usually the first sign detected by clinicians at birth or early infancy, leading to further examination and investigations. Approximately 1/3 of patients presenting with aniridia have WAGR syndrome.

It is a pan-ocular condition characterised by iris hypoplasia, early-onset nystagmus and foveal and/or optic nerve hypoplasia. There are other frequently associated ocular abnormalities, often of later onset, which include cataract, glaucoma, aniridia-related keratopathy (ARK), and retinal involvement including exudative vascular retinopathy or chorioretinal degeneration. Microphthalmia and ocular coloboma can also be found in association with aniridia. Patients with aniridia typically have impaired vision (VA 6/30 or worse) and photophobia but milder forms of aniridia with subtle changes to the iris architecture, good vision, and normal foveal structure do occur.[6]


3) Genitourinary anomalies

Both males and females might suffer from abnormal development of their gonads, external genitalia and urinary tract. Cryptorchidism is the most common manifestation among males with WAGR syndrome (60% of cases) followed by hypospadias. In females, uterine abnormalities such as bicornate uterus (Figure X) and streak ovaries can occur. These gonadal malformations lead to an increased risk of gonadoblastoma development in WAGR patients.

Other features include ambiguous genitalia, urtheral strictures and ureteric abnormalities.


4) Intellectual disability

This is defined as having an IQ<74. 70% of patients with WAGR syndrome suffer from intellectual disability but the severity varies between individuals. Some patients can even have normal intellect.


5) Other associated features

  • Chronic kidney disease
It affects approximately 60% of patients with WAGR syndrome, most often developing in adolescence or young adulthood. The cause of kidney disease is FSGS (focal segmental glomerulosclerosis). Symptoms of FSGS include high blood pressure and protein in the urine. FSGS may progress to kidney failure, requiring dialysis or kidney transplant[4]
  • Behavioural, neurodevelopmental, and psychiatric disorders
These are common in patients with WAGR syndrome. They may include attention-deficit disorder (ADD), attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder, anxiety, depression, and obsessive-compulsive disorder (OCD).
  • Neurological abnormalities
Hyper- or hypotonia and seizures are commonly found in WAGR patients.
  • Central auditory processing disorder (CAPD)
90% of patients with WAGR syndrome have some degree of CAPD. It affects the brain’s ability to filter and interpret sounds.[7]
  • Early onset obesity (before the age of 10)
50% of patients with WAGR syndrome have a deletion of one copy of the BDNF gene.[8]Loss of one copy of this gene is associated with early onset obesity. Symptoms of BDNF gene deletion include constant hunger, food-seeking behaviour, and a decreased behavioural response to pain.[9]
  • Dyslipidaemia
  • Sleep disorders and sleep apnoea
These conditions are common in WAGR syndrome.[10] People with WAGR syndrome may have small or absent pineal glands, disrupting the production of melatonin. Sleep apnoea may cause high blood pressure or heart problems, and may increase the risk of developing type 2 diabetes.


This list of associated features is not exhaustive. Please visit the International WAGR Syndrome Association (IWSA) website for more information.


Genetics


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Genes involved: PAX6 (OMIM 607108), ELP4 (OMIM 606985), WT1 (OMIM 194072), BDNF (OMIM 113505)

WAGR syndrome is associated with contiguous gene deletions involving both PAX6 and the adjacent WT1 gene on chromosome 11p13.

The PAX6 gene codes for highly conserved transcriptional factors that are involved in the early development of the eye, brain, olfactory bulb, neural tube, pancreas and gut in the embryo. 99% of isolated aniridia are due to mutations in the PAX6 gene.

The WT1 gene encodes for a protein involved in the development of kidneys and gonads before birth. Postnatally, the WT1 protein regulates renal cell division, differentiation and apoptosis. Deletion of the WT1 gene leads to unregulated cell growth and thus increases the risk Wilms tumour formation.

The BDNF gene encodes for a protein found in the brain and spinal cord. This protein helps regulate synaptic plasticity, which is important for learning and memory, and is found in regions of the brain that control eating, drinking, and body weight, as well as perception of pain.[11] People with deletion of this gene may have learning difficulties, early onset obesity, and a decreased response to pain.[9]


Diagnosis


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Patients are usually referred due to the presence of aniridia. Therefore, general ophthalmologists should be vigilant about its association with Wilms tumour and other systemic features.

New patients should be under joint care with a paediatrician and have genetic testing done urgently either by a clinical geneticist or an ophthalmologist specialising in genetic eye disease. Patients should be tested for WT1 and PAX6 deletions with chromosomal microarray in the first instance to exclude WAGR syndrome. If this is negative, PAX6 is then screened using sequence analysis to identify a causative mutation as per isolated aniridia.


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Management


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Patient management

Patients diagnosed with WAGR syndrome often have complex physical, mental and social needs. Therefore, a multidisciplinary approach is key.

  • Wilms tumour
Patients with confirmed WT1 gene deletion should be referred to a paediatrician for Wilms tumour surveillance. Serial 3 monthly abdomen ultrasound scans are performed until the age of 8 where the risk of tumour development is low. Patients who did not get or refused genetic testing should be monitored similarly. The same is applied to aniridia patients until absence of WT1 gene deletion is confirmed. If Wilms tumour is diagnosed, treatment usually involves a combination of nephrectomy, chemotherapy and radiotherapy.
Due to the significant risk of renal failure especially in patients with bilateral Wilms tumour[4], lifelong monitoring of renal function and blood pressure is recommended.
Patients should be followed-up regularly by a glaucoma specialist as they are at increased risk of developing secondary glaucoma. They may also need input, monitoring and intervention from the cornea specialists if they have evidence of limbal stem cell deficiency and their cornea is affected by epithelial defects and scarring.
Due to the multiple ocular co-morbidities associated with aniridia, regular refraction is recommended to maximise visual development. Treatment for amblyopia should be commenced urgently if detected. Consider referral to low vision services if there is significant visual impairment. Family support services can help patients connect with their local education authority for access to qualified teachers for children with visual impairment (QTVI) and social services.
  • Genitourinary anomalies
This is usually managed by a combination of urologists, gynaecologists and endocrinologists
  • Cryptorchidism
Orchidopexy is performed to move the undescended testes to the scrotum. Untreated cryptorchidism can result in fertility issues and increased risk of testicular cancer.
  • Hypospadias
An operation can be performed to create a new meatus at the tip of the penis. Although it is not a life-threatening problem, surgery is usually performed for reproductive purposes or to correct problems with urination.
  • Abnormal development of gonads
Due to the increased risk of gonadoblastoma, children with WAGR syndrome should be regularly evaluated to detect abnormalities in the gonads. In males, this risk may be decreased by orchidopexy surgery. If this is not possible, the testicle may be removed. Females, may be managed by monitoring the ovaries with ultrasound or MRI and with blood tests. As the ovaries might not be able to produce adequate level of hormones for the development of puberty and menstruation, hormone replacement therapy might be required.
  • Intellectual disability, behavioural and neurodevelopmental disorders
Children are usually managed in specialist centres alongside community paediatric services to cater to the complex health, developmental and social needs of children affected by WAGR syndrome. Professionals such as community nurses, therapists (speech and language therapists, occupational health therapists and physiotherapists), social workers, child and adolescent mental health service (CAMHS) and schools work together to provide holistic care for each individual.
As children may be seen by many different services, parents may find it helpful to speak to their paediatrician to help coordinate care.
Find out more about educational support that is available for children with special needs.
  • Chronic kidney disease
Early diagnosis of kidney disease and aggressive treatment with medication may preserve kidney function for long periods in some patients. When kidney function declines below the level needed to sustain life, dialysis or kidney transplant is required.[4]
  • Neurological abnormalities
Physiotherapy is helpful for problems with muscle tone, coordination, and strength.
  • Central Auditory Processing Disorder (CAPD)
Environmental modifications at home and at school, such as the use of listening devices, and working with a speech and language therapist.
  • BDNF gene deletion
Some patients may respond to careful control of calorie intake and increased physical activity. Restricting access to food may be necessary. Patients with decreased response to pain should be observed closely for altered behaviour that may indicate injury or illness, such as limping or refusing to use an arm or a hand, swelling or redness of the skin, or fever.
  • Dyslipidaemia
Patients may benefit from lipid lowering medications. These patients should also avoid propofol if possible. Propofol is a common medication given during general anaesthesia.
  • Sleep disorders and sleep apnoea
Supplemental melatonin is helpful for some people with WAGR syndrome and sleep disorders. Sleep apnoea may be treated with CPAP (continuous positive airway pressure) machine.


Family management and counselling

WAGR syndrome usually arise sporadically but very rarely, it is inherited with an autosomal dominant pattern due to mosaicsm in either parent. Patients and families require genetic counselling and can seek advice for family planning including prenatal testing and preimplantation genetic diagnosis.


Further information for patients


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References

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  1. 1.0 1.1 Moosajee M, Hingorani M, Moore AT. PAX6-Related Aniridia. In: GeneReviews®[Internet]. University of Washington, Seattle; 2018.
  2. Muto R, Yamamori S, Ohashi H, Osawa M. Prediction by FISH analysis of the occurrence of Wilms tumor in aniridia patients. Am J Med Genet. 2002;108(4):285-289.
  3. Fischbach BV, Trout KL, Lewis J, Luis CA, Sika M. WAGR syndrome: a clinical review of 54 cases. Pediatrics. 2005;116(4):984-988.
  4. 4.0 4.1 4.2 4.3 Breslow NE, Norris R, Norkool PA, et al. Characteristics and outcomes of children with the Wilms tumor-Aniridia syndrome: a report from the National Wilms Tumor Study Group. J Clin Oncol. 2003;21(24):4579-4585.
  5. Beckwith JB. Nephrogenic rests and the pathogenesis of Wilms tumor: developmental and clinical considerations. Am J Med Genet. 1998;79(4):268-273.
  6. Hingorani M, Hanson I, Van Heyningen V. Aniridia. European Journal of Human Genetics. 2012;20(10):1011.
  7. Bobilev AM, Hudgens-Haney ME, Hamm JP, et al. Early and late auditory information processing show opposing deviations in aniridia. Brain Res. 2019;1720:146307
  8. Han JC, Liu QR, Jones M, et al. Brain-derived neurotrophic factor and obesity in the WAGR syndrome. N Engl J Med. 2008;359(9):918-927.
  9. 9.0 9.1 Sapio MR, Iadarola MJ, LaPaglia DM, et al. Haploinsufficiency of the brain-derived neurotrophic factor gene is associated with reduced pain sensitivity. Pain. 2019;160(5):1070-1081.
  10. Hanish AE, Butman JA, Thomas F, Yao J, Han JC. Pineal hypoplasia, reduced melatonin and sleep disturbance in patients with PAX6 haploinsufficiency. J Sleep Res. 2016;25(1):16-22.
  11. U.S. National Library of Medicine. BDNF gene. https://ghr.nlm.nih.gov/gene/BDNF. Published 2019. Updated March 2013. Accessed 10 November 2019.


A thread-like structure in our cells that contains all our genetic characteristics

A thread-like structure in our cells that contains all our genetic characteristics

Commonly known as "wobbly eyes". It is a condition where the eyes make constant and repetitive involuntary movements which could affect vision. The eyes can move from side to side, up and down, in a circular fashion or a combination of these.

A doctor who specialises childhood cancers

An unhealthy or dysfunctional cornea

A doctor who specialises in disorders of the urinary tract and male reproductive organs

A doctor who specialises in the diagnosis and management of disorders involving the female reproductive organs

A doctor who specialises in the diagnosis and management of genetic disorders