Rieger syndrome with multiple chromosomal breaks and chromosome 4 deletion

Abstract

Rieger syndrome (RS) is a rare autosomal dominant disorder with variable expressivity and complete penetrance. Axenfeld-Rieger syndrome (ARS) shows genetic heterogeneity with mutations in several chromosomal loci being implicated including PITX2, FOXC1 and PAX6. Cytogenetic analysis was done in this case. Patient had de novo 46,XY,del(4q25-q27) karyotype with a high percentage (>35%) of chromosomal breaks. The breaks were on different chromosomes and not related to disease phenotype of RS. Such chromosomal breaks are diagnostic of chromosomal instability syndromes. Available literature does not report chromosomal breaks in RS or due to culture condition. Such a high percentage of chromosomal breaks are associated with development of certain cancers. In the present case we did not find any features consistent with any of the chromosomal instability syndromes like Fanconi's anaemia and Blooms syndrome, but such cases need to be under regular follow-up. Thus RS cases with multiple chromosomal breaks need regular follow-up and genetic counselling.

A de novo Pericentric Inversion in Chromosome 4 Associated with Disruption of<b><i> PITX2</i></b> and a Microdeletion in 4p15.2 in a Patient with Axenfeld-Rieger Syndrome and Developmental Delay

“…The PITX2 gene plays a major role in the pathogenesis of ARS, accounting for 40% of classical ARS [Lines et al, 2004;Footz et al, 2009]. In addition to the PITX2 point mutations, several cases of chromosomal aberrations such as interstitial deletions and/or translocations involving the chromosome 4q25 region have been described in patients with clinical features of 7 ARS [Kamnasaran et al, 2003;Trembath et al, 2004;Engenheiro et al, 2007;Tanwar et al, 2009]. Reported balanced translocations disrupt the coding region [Kamnasaran et al, 2003] or the 5 ′ genomic region of the PITX2 gene [Trembath et al, 2004].…”

Axenfeld‐Rieger syndrome: Further clinical and array delineation of four unrelated patients with a 4q25 microdeletion

“…Twenty‐four patients with ARS have been described with deletions encompassing 4q25 [Mitchell et al, ; Chudley et al, ; Raczenbek et al, ; Fryns and Van Den Berghe, ; Vaux et al, ; Kulharya et al, ; Flomen et al, ; Schinzel et al, ; Ogilvie et al, ; Becker et al, ; Kamnasaran et al, ; Lines et al, ; de la Houssaye et al, ; Engenheiro et al, ; Tanwar et al, ; Moreira et al, ; Volkmann et al, ; Strehle et al, ]. Only seven had their deletions precisely characterized [Kamnasaran et al, ; Lines et al, ; Engenheiro et al, ; Moreira et al, ; Strehle et al, ].…”