WAGR is an acronym for: Wilms tumor, Aniridia, Genitourinary
anomalies and mental Retardation. A combination of
two or more of these clinical features is normally required for
an individual to be diagnosed with WAGR syndrome
6. The
patient described in this report meets the diagnostic criteria
for WAGR syndrome, both clinically and cytogenetically.
Karyotypic examination revealed a deletion in p11.2-p13. In
addition to, the cytogenetic results were confirmed with FISH
analysis. It was used for FISH analysis that the PAX6 probe
which obtained from clone RP11-26B16. Similar deletions
were previously reported
2,4,7,8. The microdeletion is de
novo in most cases, but it may result from an inherited parental
translocation. The karyotype of the patient should be
determined to detect the presence of such a translocation
9.
The parents of our case had no chromosomal rearrangement.
Children with WAGR syndrome generally present in
the newborn period with sporadic aniridia6. The feature
invariably present in all documented cases is aniridia. Only
one patient who had WAGR without aniridia has published10. Aniridia occurs in 1 in 50–100,000 newborns7 and it
exists both as sporadic cases and as familial cases with an
autosomal dominant mode of inheritance. Approximately one
third of patients with sporadic aniridia will have WAGR
syndrome. Both forms of aniridia are caused by mutations in
the PAX6 gene6,7. The combination of sporadic aniridia
along with genital anomalies may alert the clinician to the
possibility of WAGR syndrome, although genitourinary
anomalies are not always present, particularly in girls. For
this reason, it is recommended that all infants with sporadic
aniridia be evaluated carefully for WAGR syndrome. The
most common abnormality of the genitourinary tract was
cryptorchidism, found in 60% of male patients6.
According to recent research, deficiencies in the PAX6
gene result in abnormalities not only of the eye but also
possibly of the central nervous system and endocrine pancreas11,12. Mental retardation was the most common neurologic manifestation of WAGR syndrome and was found
in 70% of patients6. The genetic basis of mental retardation
in WAGR remains to be explained. There is great variability
in the cognitive abilities of children with WAGR syndrome,
from profound mental retardation to “borderline” or even
normal IQ.
The majority of these cases with FISH detected cryptic
deletions involving WTI were reported to have developed
Wilms tumors. It has been suggested that about 1 in 70–90
children with Wilms tumor has aniridia2. Wilms' tumor is
an embryonal tumor that normally affects approximately 1 in
10 000 children. In patients with WAGR syndrome, the risk
has been estimated to be up to 45%13. The development of
Wilms tumor in patients with WAGR syndrome has a more
rapid time course than of a sporadic Wilms tumor. Mean age
at diagnosis of Wilms tumor in WAGR syndrome is 28.6
months (median: 17months) compared to a mean of 36
months and a median of 33 months in unilateral, nonsyndromic
Wilms tumor2. Wilms' tumor is considered
unusual after age 5, renal ultrasound is recommended every 3
months from birth until age 6. After age 6, a thorough physical
examination should be performed to assess for abdominal
masses every 6 months until age 8 and every 6 to 12 months
thereafter. Clinicians should maintain a high index of suspicion
for Wilms' tumor in patients of any age with WAGR
syndrome. The cumulative risk of renal failure in patients
with WAGR syndrome at 20 years of age is 53%6. The
majority of patients who have a sporadic Wilms' tumor and
subsequent nephrectomy do not develop renal failure. This
suggests that additional factors may contribute to the development
of renal disease in patients with WAGR syndrome.
Bernard et al. (2005) showed the ratio of nonclassical
clinical findings in 54 cases with WAGR Syndrome in literature6. The patient reported here had some of these rare
manifestations such as cataracts [36], nystagmus [22], macular
hypoplasia [7], ptosis [2], cryptorchidism [19], inguinal
hernia [3], hypotonia [7], epilepsy [4], tonsillectomy and
adenoidectomy [22], kyphosis [8]. These unusual anomalies
could be very low penetrant traits associated with haploinsufficency
of one of the genes present in the critical WAGR
region. There are four cases had duplication of halluces in
literature2,4 but to our knowledge, this is the first case
with postaxial polydactyly. This finding may be unrelated
and a familial feature as his sister also had postaxial polydactyly.
On the other hand, this may be a new feature of this
syndrome. Cytogenetic analysis showed a deletion more
proximal than that observed in the cases with thumb duplication
in this case. This may be the reason of this and other
additional features.
In summary; we are presenting a case with very rare
features including postaxial polydactyly, epilepsy and ptosis.
To our knowledge, this is the first case with postaxial polydactyly.
This is very important to know, WAGR syndrome
cases may have very rare additional features and these features
may mislead during diagnostic studies.
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