Further delineation of the chromosome 14q terminal deletion syndrome

Abstract

A patient with hypotonia, blepharophimosis, ptosis, a bulbous nose, a long philtrum, upturned corners of the mouth, and mild developmental delay was found to have a small subtelomeric deletion of the long arm of chromosome 14 (q32.31-qter). In comparing her phenotype with previously reported patients with similar 14q deletions, due to either a linear deletion or to a ring chromosome 14, a clinically recognizable terminal 14q microdeletion syndrome was evident. Due to the limited number of cases reported, it was not possible to assign specific features to specific regions of terminal 14q. The comparison of features in cases with a linear deletion of 14qter (n = 19) to those in cases with a deletion due to a ring chromosome 14 (n = 23), both with the same breakpoint in 14q, showed that seizures and retinitis pigmentosa have been found only in patients with ring chromosomes. Several hypotheses are put forward to explain this difference: mitotic instability of ring chromosomes; a telomere position effect in ring chromosomes in which the 14p telomere silences nearby gene(s) on the q-arm; and dose-dependent gene(s) involved in seizures and retinitis pigmentosa located on the short arm of chromosome 14. In our opinion, only seizures may be explained by the mitotic instability of ring chromosomes, while both seizures and retinitis pigmentosa may be explained by silencing of gene(s) on 14q by the 14p telomere; the third hypothesis seems unlikely to explain either symptom.

Position effect leading to haploinsufficiency in a mosaic ring chromosome 14 in a boy with autism

“…26 It may also offer an explanation for the different phenotypic findings in individuals with terminal deletions of chromosome 14q and ring chromosome 14, despite similar breakpoints. 27 In conclusion, this case illustrates that genotypephenotype correlations derived from the physical mapping of chromosomal aberrations need to be taken with caution, given the possibility of position effects.…”

Ring chromosome formation as a novel escape mechanism in patients with inverted duplication and terminal deletion

“…The ring chromosome 14 syndrome was delineated by Schmidt et al, 24 and it was further described by van Karnebeek et al 25 A distal duplication of chromosome 14 results in a variable clinical picture that is mainly depending on the size of the duplication. 9,26 Main features that are found in distal duplications of 14q31-qter are mental and growth retardation, microcephaly, hypertelorism, abnormal ears, micrognathia and congenital heart defects.…”

“…In the case of Chen et al, an additional terminal deletion was demonstrated using FISH, next to the duplication. The small terminal deletion, which in itself can lead to a severe phenotype, 25 or an additional duplication in a ring chromosome, is sometimes only detectable by molecular techniques such as FISH and array-CGH. It emphasizes the significance of high-resolution molecular karyotyping for the establishment of accurate phenotype/genotype correlations.…”

Prenatal diagnosis of a ring chromosome 14 in a fetus with a severe skeletal dysplasia

“…Here we report on a new case of r(14) in a fetus with severe skeletal dysplasia and clinical features reminiscent of the phenotype described in paternal uniparental disomy of chromosome 14 [upd(14)pat] (Curtis et al, 2006). The clinical features observed in the present case are compared to those reported in previously published cases of r(14) and upd (14)pat (Jean et al, 1997;Van Karnebeek et al, 2002;McGowan et al, 2002;Sutton et al, 2003;Kagami et al, 2005;Curtis et al, 2006).…”

“…Ring chromosome 14 syndrome [r(14)] is a rare cytogenetic disorder associated with growth retardation, facial dysmorphism, hypotonia, seizures and retinitis pigmentosa (Van Karnebeek et al, 2002). Here we report on a new case of r(14) in a fetus with severe skeletal dysplasia and clinical features reminiscent of the phenotype described in paternal uniparental disomy of chromosome 14 [upd(14)pat] (Curtis et al, 2006).…”