Combination of WAGR and Potocki-Shaffer contigous deletion syndromes in a patient with an 11p11.2-p14 deletion

Department of Ophthalmology, Robert Debré Hospital, AP-HP, Paris, France.
European Journal of HumanGenetics (Impact Factor: 4.35). 05/2005; 13(4):409-13. DOI: 10.1038/sj.ejhg.5201358
Source: PubMed


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.

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Available from: Dominique Bremond-Gignac, Mar 04, 2014
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    • "However, the genotype-phenotype correlation was clear enough for the diagnosis of PSS. So far, 46 patients from 31 families affected by PSS have been described [Francke et al., 1977; Gustavson et al., 1984; Lorenz et al., 1990; Shaffer et al., 1993; McGaughran et al., 1995; Bartsch et al., 1996; Potocki and Shaffer, 1996; Wuyts et al., 1999, 2004; Hall et al., 2001; Yamamoto et al., 2001; Chien et al., 2003; Brémond-Gignac et al., 2005; Chuang et al., 2005; Wakui et al., 2005; Romeike and Wuyts, 2007; Almind et al., 2009; Swarr et al., 2010]. The clinical phenotype of PSS is extremely heterogeneous, from normal development and intelligence to severe developmental delay and other abnormalities, including WAGR syndrome, due to the size of the deletion. "
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    ABSTRACT: We describe the case of an adult patient affected by multiple exostoses, severe mental retardation, epilepsy and facial dysmorphisms with a deletion of ∼2.3 Mb on chromosome 11p11.21, correlated to Potocki-Shaffer syndrome (PSS). PSS is a rare contiguous gene deletion syndrome, mainly characterized by multiple exostoses and bilateral parietal foramina. Mental retardation and craniofacial dysmorphisms have often been reported, too. Although the patient showed many signs of PSS since early childhood, the diagnosis was suggested only when we examined her at adult age. This case highlights how frequently rare diseases remain undiagnosed till adulthood and is an excellent example of the need for a timely and correct diagnosis.
    Full-text · Article · Apr 2012 · Molecular syndromology
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    • "This patient exhibited features of both WAGR as well as PSS; developmental delay but no seizures. Bremond-Gignac et al described a further case with 11p deletion encompassing EXT2, ALX4, WT1 and PAX6 genes showing features of both WAGR and PSS [15]. In addition, the patient showed obesity. "
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    ABSTRACT: WAGR syndrome (Wilms' tumor, aniridia, genitourinary abnormalities and mental retardation) and Potocki-Shaffer syndrome are rare contiguous gene deletion syndromes caused by deletions of the 11p14-p12 chromosome region. We present a patient with mental retardation, unilateral cataract, bilateral ptosis, genital abnormalities, seizures and a dysmorphic face. Cytogenetic analysis showed a deletion on 11p that was further characterized using FISH and MLPA analyses. The deletion (11p13-p12) located in the area between the deletions associated with the WAGR and Potocki-Shaffer syndromes had a maximum size of 8.5 Mb and encompasses 44 genes. Deletion of WT1 explains the genital abnormalities observed. As PAX6 was intact the cataract observed cannot be explained by a deletion of this gene. Seizures have been described in Potocki-Shaffer syndrome while mental retardation has been described in both WAGR and Potocki-Shaffer syndrome. Characterization of this patient contributes further to elucidate the function of the genes in the 11p14-p12 chromosome region.
    Full-text · Article · Mar 2009 · Molecular Cytogenetics
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    • "t(11;15) AND WAGR reported to have ptosis as an additional feature suggesting that ptosis is a relatively rare complication of PAX6 mutations that cause aniridia. In contrast, ptosis was present in our patient and was specifically mentioned in the reports of at least two of the six individuals previously reported to have WAGR and obesity [Bremond-Gignac et al., 2005; POSSUM case #1242]. "
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    ABSTRACT: 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.
    Full-text · Article · Jun 2006 · American Journal of Medical Genetics Part A
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