6q subtelomeric deletion: is there a recognizable syndrome?

Abstract

We report on a girl with an abnormal hybridization pattern for the subtelomeric fluorescence in-situ hybridization (FISH) probe panel showing deletion of the long arm telomeric region of chromosome 6. All other subtelomere DNA probes showed normal hybridization patterns. Metaphase cells analysed from cultures of peripheral blood revealed a normal female chromosome complement at the 650-band level. The deletion was further characterized using genomic microarray analysis. Clinical findings include: developmental delay, seizures, hypoplasia of the corpus callosum, dextrocardia, unusual dimpling of knees and elbows, and minor anomalies. We are aware of only two other reports of isolated cryptic 6q subtelomeric deletions not associated with other chromosomal abnormalities. The absence of retinal abnormalities in our case supports the theory that genes responsible for the retinal abnormalities in other terminal 6q deletions are proximal to 6q27. Subtelomeric FISH probes were useful in establishing a diagnosis in our patient. As more cases are reported, we may be able to establish discrete phenotypes and natural histories that can aid in counselling families.

Isolated 6q terminal deletions: An emerging new syndrome

“…It is interesting to note that our two cases, like the other two patients more recently reported [Stevenson et al, 2004;Eash et al, 2005], present with abnormalities in the corpus callosum (agenesis or hypoplasia), an aspect which had never been highlighted before in cases presenting a similar deletion extent. This discrepancy may be due either to a more precise ascertainment of more subtle brain malformations in the recent years or to the genetic background.…”

“…For this reason, a thorough ophthalmologic evaluation in all patients with 6qter deletions was recommended. The two most recent cases reported [Stevenson et al, 2004;Eash et al, 2005], which presented an isolated 6q subtelomeric deletion, did not show any retinal problems; the authors suggest that the gene(s) responsible for the retinal abnormalities in 6q deletion patients is proximal to the breakpoint, localized in these patients in 6q27. Neither of our two patients presents retinal problems, and this observation seems to exclude the putative genes from the region distal to RP11-150P20.…”

“…Cystic areas References: A: Milosevic and Kalicanin [1975]; B: Liberfarb et al [1978]; C: Bartoshesky et al [1978]; D: Rivas et al [1986]; E: Stevens et al [1988], patient 2; F: Oliveira-Duarte et al [1990], patient 1; G: Oliveira-Duarte et al [1990], patient 2; H: Valtat et al [1992], patient 3; I: Valtat et al [1992], patient 4; J: Meng et al [1992], patient 2; K: Evers et al [1996], patient 2; L: Hopkin et al [1997], patient 3; M: Koh and Boles [1998]; N: Hagemeijer et al [1977]; O: McLeod et al [1990], patient 1; P: the present patient 1; Q: the present patient 2; R: Stevenson et al [2004]; Eash et al [2005]; S: Eash et al [2005].…”

“…To our knowledge, only 17 cases with these characteristics have been reported [Milosevic and Kalicanin, 1975;Hagemeijer et al, 1977;Bartoshesky et al, 1978;Liberfarb et al, 1978;Rivas et al, 1986;Stevens et al, 1988;McLeod et al, 1990;OliveiraDuarte et al, 1990;Meng et al, 1992;Valtat et al, 1992;Evers et al, 1996;Hopkin et al, 1997;Koh and Boles, 1998;Stevenson et al, 2004;Eash et al, 2005]. A common phenotype emerges from these reports, including typical facial dysmorphisms, short neck, psychomotor retardation, hypotonia, and seizures, along with various nonspecific malformations.…”

Idiopathic learning disability and genome imbalance

“…The most striking example of this was the elucidation of the '1p36 deletion syndrome' (Shapira et al, 1997;Knight-Jones et al, 2000). This was followed by clinically identifiable phenotypes being put forward for a number of other subtelomeric imbalances, for example, 1qter syndrome, 2q37.3 monosomy, 3q29 microdeletion syndrome, 5q35.3 subtelomeric deletion syndrome, 6q subtelomeric deletion syndrome, subtelomeric 9q microdeletion syndrome, 14q terminal deletion syndrome, 19p13.3-pter subtelomeric deletion syndrome and 22q deletion syndrome (de Vries et al, 2001a;van Karnebeek et al, 2002;Heilstedt et al, 2003;Rauch et al, 2003;Wilson et al, 2003;Aldred et al, 2004;Stevenson et al, 2004;Stewart et al, 2004;Archer et al, 2005;Eash et al, 2005; van Bever et Willatt et al, 2005). In most cases these studies were aided by the detailed phenotypic characterisation of a series of patients with similar regions of imbalance.…”