Isolated 6q terminal deletions: An emerging new syndrome

Abstract

Deletions of the distal part of the 6q chromosome have not been associated with a clearly distinctive and recognizable phenotype. In order to determine if a "6q terminal deletion syndrome" could be delineated, we compared the phenotype of two new cases with those patients reported in literature presenting with a similar deletion. Cases with more complex karyotypes were excluded. The deletion in our patients was accurately analyzed by loss of heterozygosity (LOH) and fluorescence in situ hybridization (FISH) with a panel of probes located around the putative breakpoint. Interestingly, the breakpoints were located in 6q26 in both our patients, distally to clone RP11-150P20 and proximally to clone RP11-152P19, with a deletion size of approximately 8 Mb. The breakpoints fall within the fragile site FRA6E. From a careful evaluation of the selected patients, a common phenotype emerged, including psychomotor retardation, hypotonia, seizures, short neck, and typical facial anomalies, along with nonspecific anomalies. While these features are shared by other chromosome syndromes and are not sufficient on their own for a clinical diagnosis, when considered together, the pattern can allow the identification of the "6q terminal deletion syndrome." Moreover, the potential role of FRA6E in generating these deletions is suggested.

6q27 subtelomeric deletions: Is there a specific phenotype?

“…Our patients displayed only mild joint laxity (which is likely related to hypotonia rather than to a connective tissue abnormality). Both had 6q27 deletions smaller than the one detected in the patient of Mosca et al [2010] (5.65 Mb); however deletion size also in this case is apparently unrelated to the presence of EDS-like features since the two patients published by Bertini et al [2006] and three out of five patients of Striano et al [2006] had deletions larger than 6 Mb but apparently lacked features of EDS.…”

Delineation of candidate genes responsible for structural brain abnormalities in patients with terminal deletions of chromosome 6q27

“…[1][2][3][4][5][6][7][8][9]15,16 Though the clinical phenotypes associated with this deletion are quite variable, reports in unrelated subjects from independent investigators have shown that ACC, PNH, polymicrogyria, hydrocephalus, and cerebellar malformations are the consistently observed features. A recent analysis of a comprehensive map of loci for ACC from 374 patients revealed that chromosome 6q27 was one of the few loci wherein six or more subjects with ACC have been reported.…”

“…Structural brain malformations are consistently observed in these patients and include agenesis of the corpus callosum (ACC), periventricular nodular heterotopia (PNH), polymicrogyria, hydrocephalus, and cerebellar malformations. [1][2][3][4][5][6][7][8][9][10] Whereas previous studies have attempted to delineate the critical region responsible for brain malformations in patients with terminal 6q27 deletions, the sensitivity of the methodologies used has prevented the fine-mapping of the critical region. 1,6 A detailed genomic analysis of the subtelomeric chromosome 6q region would help identify the putative genes involved in the causation of brain malformations.…”

Dirençli epilepsi olgusunda mozaik ring kromozom 6 ve klinik önemi

“…Very significant dysmorphic characteristics are present in most chromosamal disorders associated with epilepsy (3). We presented a 7-year old male patient who was referred to our clinic because of resistant epilepsy and whose chromosomal analysis on peripheral blood revealed mos 47,XY,+r (6)[3]/ 46,XY, r (6)[40]/ 45,XY,-6 [7]. Based on this case we aimed to discuss the significance of use of cytogenetic techniques and multidiciplinary study in understanding clinical and basic mechanisms of epilepsy.…”

“…Afterwards, cases from different areas have been reported occasionally. These diseases reported have generally been diagnosed postnatally, but there are also patients who have been diagnosed prenatally (3,4,5,6). Chilren with ring chromosome 6 who have been reported until the present time in the literature have been observed to display a wide clinical spectrum ranging from normal intelligence level to neurologic and dysmorphic findings including epilepsy, hydrocephaly, microcephaly and mental retardation (5,6).…”