It is important to remember that a given individual with WAGR syndrome may or may not have or develop the condition listed below. |
Obesity (defined as an excessively high amount of body fat in relation to lean body mass) has become an epidemic in the United States and in many other countries. In both children and adults, obesity increases the risk of diabetes and many other serious health problems. We now know that increased risk for obesity in the general population can be attributed to genetic factors as well as less than optimal lifestyle choices in the areas of diet and exercise.
Individuals with WAGR syndrome are at risk for obesity. It appears that there may be several factors contributing to this, especially those with "early-onset overweight," (being overweight at a very young age). One factor under study involves a protein called "brain-derived neurotrophic factor," or BDNF. BDNF is found in a wide range of tissues and cell types in the body. It is especially important in the brain, but has effects in many other areas as well. It is thought that one of the effects of BDNF may be to help regulate appetite and eating.
Some people with WAGR syndrome have a genetic deletion which includes the gene for BDNF, so they may have low levels of BDNF in their bloodstream. Research investigators are currently trying to determine whether these low levels of BDNF may contribute to early-onset overweight and obesity in WAGR syndrome. In time, this research may lead to effective treatment for these problems.
In people with WAGR syndrome, this genetic predisposition can be compounded by low activity level due to other health conditions. They may also have a less than optimal diet, especially those who have medical, behavioral and/or developmental issues that might promote or require limited food choices. This combination of risk factors creates a difficult situation for some people with WAGR syndrome and it is important to take these challenges into account when encouraging a person with the syndrome to make the healthiest possible lifestyle choices. |
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OBESITY IN WAGR SYNDROME
WAGR(O?) syndrome and congenital ptosis caused by an unbalanced t(11;15)(p13;p11.2)dn demonstrating a 7 megabase deletion by FISH.
· Lennon PA,
· Scott DA,
· Lonsdorf D,
· Wargowski DS,
· Kirkpatrick S,
· Patel A,
· Cheung SW.
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77021, USA.
Aniridia usually occurs in isolation, but may also occur as part of the WAGR contiguous gene deletion syndrome, which includes Wilms tumor, aniridia, genitourinary abnormalities, and mental retardation.
The aniridia and predisposition for Wilms tumor seen in WAGR are caused by haploinsufficiency for PAX 6 and WT1, respectively.
We present a female infant with aniridia, bilateral ptosis, bilateral posterior capsular cataracts, nystagmus, left-sided glaucoma, microcephaly, mild unilateral hydronephrosis, poor linear growth, and gross motor delay consistent with a clinical diagnosis of WAGR syndrome. In addition, weight-for-height ratio at 12 months is at the 94th centile, raising the possibility of a diagnosis of WAGRO (WAGR + Obesity).
Chromosome analysis revealed a translocation (11;15)(p13;p11.2) which has not been previously associated with a diagnosis of WAGR.
Subsequent clinical WAGR fluorescent in situ hybridization (FISH) analysis demonstrated a deletion of 11p13 including PAX6 and WT1. A complete FISH-mapping of the breakpoints on chromosome 11 revealed a 7 Mb deletion within 11p13-11p14.
The patient is examined in light of other reported patients with deletions and/or translocations involving the regions between 11p12 --> 11p14 including patients with WAGR + obesity (WAGRO) as well as with other reported patients with aniridia and congenital ptosis.
Copyright 2006 Wiley-Liss, Inc.
PMID: 16646034 [PubMed - indexed for MEDLINE]
Combination of WAGR and Potocki-Shaffer contiguous deletion syndromes in a patient with an 11p11.2-p14 deletion.
· Bremond-Gignac D,
· Crolla JA,
· Copin H,
· Guichet A,
· Bonneau D,
· Taine L,
· Lacombe D,
· Baumann C,
· Benzacken B,
· Verloes A.
Department of Ophthalmology, Robert Debre Hospital, AP-HP, Paris, France.
Aniridia, Wilms tumor, genitourinary abnormalities, growth and mental retardation are the cardinal features of the WAGR 11p13 deletion syndrome.
The Potocki-Schaffer syndrome or proximal 11p deletion syndrome (previously DEFECT11 syndrome) is a contiguous gene syndrome associated with deletions in 11p11.2, principal features of which are multiple exostoses and enlarged parietal foramina. Mental handicap, facial dysmorphism and craniosynostosis may also be associated.
We report a patient with combined WAGR and Potocki-Shaffer syndromes, and obesity.
She presented with aniridia, cataract, nystagmus, corneal ulcers and bilateral congenital ptosis.
A left nephroblastoma was detected at 15 months.
Other features included moderate developmental delay, growth deficiency, facial dysmorphism, multiple exostoses and cranial lacunae.
High-resolution and molecular cytogenetics confirmed a del(11)(p11.2p14.1) deletion with a proximal breakpoint between the cosmid DO8153 and the BAC RP11-104M24 to a distal breakpoint between cosmids CO8160 (D11S151) and F1238 (D11S1446).
The deletion therefore includes EXT2, ALX4, WT1 and PAX6.
This case appears to be the second patient reported with this combined deletion syndrome and confirms the association of obesity in the WAGR spectrum, a feature previously reported in four cases, and for which the acronym WAGRO has been suggested.
Molecular and follow-up data on the original WAGRO case are briefly presented.
PMID: 15702131 [PubMed - indexed for MEDLINE]
Clinical, cytogenetic and molecular characterization of a patient with combined succinic semialdehyde dehydrogenase deficiency and incomplete WAGR syndrome with obesity.
· Jung R,
· Rauch A,
· Salomons GS,
· Verhoeven NM,
· Jakobs C,
· Michael Gibson K,
· Lachmann E,
· Sass JO,
· Trautmann U,
· Zweier C,
· Staatz G,
· Knerr I.
Children and Youth Hospital, University of Erlangen-Nuremberg, Erlangen, Germany.
We describe the clinical course, as well as cytogenetic and molecular findings, of a 3-year-old obese boy with psychomotor retardation who exhibited two rare conditions: succinic semialdehyde dehydrogenase deficiency (SSADH deficiency, MIM 271980), a disorder of gamma-aminobutyric acid metabolism with a heterogeneous clinical spectrum, and partial Wilms' tumor, aniridia, genital abnormalities, and mental retardation (WAGR) syndrome, an association between Wilms' tumor, aniridia, genitourinary malformations, and mental retardation due to mutations involving the short arm of chromosome 11, particularly deletions at the chromosomal region 11p13 (MIM 194072).
Diagnosis of SSADH deficiency in our patient was established by demonstration of absent enzyme activity in isolated leucocytes, and was associated with a novel missense mutation (c.587G>A; p.Gly196Asp) in the SSADH coding sequence.
We further confirmed an incomplete WAGR syndrome in this boy [karyotype 46, XY, del (11) (p13p14.2)] with a normal WT1 (Wilms' tumor) gene and an absence of pathology in the genitourinary tract, but with obesity (WAGR syndrome with obesity, WAGRO syndrome).
The patient also exhibited distinctive cerebral anomalies such as increased signals of the globi pallidi, internal hydrocephalus and cerebellar vermian atrophy.
However, treatment options for this patient are limited, including supportive treatment, physiotherapy, special educational training, and vigabatrin.
In summary, we report the first patient with the exceptional rare findings of both SSADH deficiency and partial WAGR/WAGRO syndrome.
PMID: 16545979 [PubMed - indexed for MEDLINE] |
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