Three patients with hallucal polydactyly and WAGR syndrome, including discordant expression of Wilms tumor in MZ twins.
The WAGR contiguous gene deletion syndrome is a combination of Wilms tumor, Aniridia, Genito-urinary abnormalities, and growth and mental retardation which is invariably associated with an 11p13 deletion. We report two monozygotic twins and a third, unrelated patient with WAGR syndrome and additional clinical features not usually associated with WAGR. Both twins had developmental delay, growth deficiency, severe ocular involvement (nystagmus, aniridia, cataracts), atrial septal defect and two uncommon findings: agenesis of the corpus callosum and duplication of the halluces. One twin developed Wilms tumors aged 19 months while her sister remained tumor free by the age of 6.5 years. The singleton patient showed typical WAGR syndrome and preaxial hallucal polydactyly. Molecular cytogenetic studies refined the identification of the extent of the deleted segments, which were not identical in the two families. The two deletions included the PAX6 and WT1 genes as previously reported in typical WAGR patients. The unusual anomalies described in this report, may represent the expression of low penetrant traits associated with haploinsufficency of one or more of the genes present in the deletion (PAX6 is expressed in CNS) or may indicate epistatic influences of modifier genes on the expression of gene(s) present in the WAGR region.
Brémond-Gignac
Dominique
D
Department of Ophthalmology, Robert Debré Hospital, Paris, France. dominique.bremond@rdb.ap-hop-paris.fr
Gérard-Blanluet
Marion
M
Copin
Henri
H
Bitoun
Pierre
P
Baumann
Clarisse
C
Crolla
J A
JA
Benzacken
Brigitte
B
Verloes
Alain
A
D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002871:Chromosome Banding; D002872:Chromosome Deletion; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006214:Hallux; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007621:Karyotyping; D008297:Male; D018895:Microsatellite Repeats; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D017689:Polydactyly / Q000473:pathology*; D012097:Repressor Proteins / Q000235:genetics; D014430:Twins, Monozygotic; D017624:WAGR Syndrome / Q000473:pathology*; D025721:WT1 Proteins / Q000235:genetics; D009396:Wilms Tumor / Q000473:pathology*
D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D025721:WT1 Proteins