WAGR syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

WAGR syndrome is a disorder that affects many body systems and is named for its main features: Wilms tumor, aniridia, genitourinary anomalies, and a range of developmental delays.

People with WAGR syndrome have a 45 to 60 percent chance of developing Wilms tumor, a rare form of kidney cancer. This type of cancer is most often diagnosed in children but is sometimes seen in adults. Some people with WAGR syndrome develop nephrogenic rests, which are abnormal clumps of cells in the kidneys. These can lead to Wilms tumor, but some people with nephrogenic rests never develop Wilms tumor.

Most people with WAGR syndrome have aniridia, an absence of the colored part of the eye (the iris). This can reduce the sharpness of a person's vision (visual acuity) and increase sensitivity to light (photophobia). Aniridia is typically the first noticeable sign of WAGR syndrome. Other eye problems may also develop, such as clouding of the lens of the eyes (cataracts), increased pressure in the eyes (glaucoma), and involuntary eye movements (nystagmus).

Abnormalities of the genitalia and urinary tract (genitourinary anomalies) are seen more frequently in males with WAGR syndrome than in affected females. The most common genitourinary abnormality in affected males is undescended testes (cryptorchidism). Affected females may not have functional ovaries and may instead have undeveloped clumps of tissue called streak gonads. Females with WAGR syndrome may also have a heart-shaped (bicornate) uterus, which makes it difficult to carry a pregnancy to term.

Intellectual disability and other developmental delays are also common in people with WAGR syndrome. Affected individuals often have difficulty processing, learning, and properly responding to information. Many affected individuals have difficulty speaking or understanding language. Some individuals with WAGR syndrome also have psychiatric or behavioral problems such as depression, anxiety, attention-deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), or a developmental disorder called autism spectrum disorder that affects communication and social interaction.

Other signs and symptoms of WAGR syndrome can include ongoing constipation, inflammation of the pancreas (pancreatitis), kidney failure, breathing problems, and allergies. Some affected children have obesity. When WAGR syndrome includes childhood-onset obesity, it is often referred to as WAGRO syndrome.

ORPHANET DEFINITION A rare genetic disorder characterized by the association of complete or partial congenital aniridia (and associated eyes abnormalities), genitourinary anomalies (ranging from sexual ambiguity to ectopic testis), variable degrees of intellectual disability and an increased risk of developing Wilms tumors. A minority of patients develop kidney failure. Other variable findings may include obesity and duplicated halluces.

Inheritance

From: MedlinePlus Genetics, National Library of Medicine

Not inherited

Frequency in the source

From: MedlinePlus Genetics, National Library of Medicine

Prevalence at birth: 1-9 / 1 000 000; Worldwide; Value and class. Point prevalence: Unknown; Worldwide; Class only.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Aplasia/Hypoplasia of the iris · Very frequent (99-80%)

Absence or underdevelopment of the iris.

Cataract · Frequent (79-30%)

A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule.

Cryptorchidism · Frequent (79-30%)

Testis in inguinal canal. That is, absence of one or both testes from the scrotum owing to failure of the testis or testes to descend through the inguinal canal to the scrotum.

Displacement of the urethral meatus · Frequent (79-30%)

A displacement of the external urethral orifice from its normal position (in males normally placed at the tip of glans penis, in females normally placed about 2.5 cm behind the glans clitoridis and immediately in front of that of the vagina).

Everted lower lip vermilion · Frequent (79-30%)

An abnormal configuration of the lower lip such that it is turned outward i.e., everted, with the Inner aspect of the lower lip vermilion (normally opposing the teeth) being visible in a frontal view.

Hearing abnormality · Frequent (79-30%)

An abnormality of the sensory perception of sound.

Intellectual disability · Frequent (79-30%)

The term intellectual disability or intellectual developmental disorder is used to describe significantly sub-average intellectual and adaptive functioning based on clinical assessment and as measured by individually administered, appropriately normed, standardized and validated tests of intellectual functioning and adaptive behavior, with onset during the developmental period from infancy through adolescence.

Microcephaly · Frequent (79-30%)

Head circumference below 2 standard deviations below the mean for age and gender.

Micrognathia · Frequent (79-30%)

Developmental hypoplasia of the mandible.

Nystagmus · Frequent (79-30%)

Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.

Ptosis · Frequent (79-30%)

The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).

Short stature · Frequent (79-30%)

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).

Visual impairment · Frequent (79-30%)

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.

Ambiguous genitalia · Occasional (29-5%)

A genital phenotype that is not clearly assignable to a single gender. Ambiguous genitalia can be evaluated using the Prader scale: Prader 0: Normal female external genitalia. Prader 1: Female external genitalia with clitoromegaly. Prader 2: Clitoromegaly with partial labial fusion forming a funnel-shaped urogenital sinus. Prader 3: Increased phallic enlargement. Complete labioscrotal fusion forming a urogenital sinus with a single opening. Prader 4: Complete scrotal fusion with urogenital opening at the base or on the shaft of the phallus. Prader 5: Normal male external genitalia. The diagnosis of ambiguous genitalia is made for Prader 1-4.

Other findings in the same source

From: Orphanet

Additional reported features include Glaucoma (Occasional (29-5%)); Obesity (Occasional (29-5%)); Scoliosis (Occasional (29-5%)); Dysfunction of lateral corticospinal tracts (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: MedlinePlus Genetics, National Library of Medicine

Antenatal; Neonatal

Inheritance in the source

From: MedlinePlus Genetics, National Library of Medicine

Not inherited

Frequency and the population described

From: MedlinePlus Genetics, National Library of Medicine

Prevalence at birth: 1-9 / 1 000 000; Worldwide; Value and class. Point prevalence: Unknown; Worldwide; Class only.

Which doctor should you see?

The suggested department for discussing WAGR syndrome is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for WAGR syndrome. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.