10qter deletion: A new case

Vertebrate telomeres consist of tandem repeats of the TTAGGG sequence that cap the ends of chromosomes, protecting them from degradation and fusion. Extensive evidence has shown that telomere shortening and erosion lead to chromosome end-to-end fusions and genomic instability, causing mental retardation and/or malformation syndromes. So far, over 19,000 patients with mental retardation have been tested and reported of whom 2.5% appeared to have a subtelomeric rearrangement [Ravnan et al., 2006; Ballif et al., 2007; Ledbetter and Martin, 2007]. Since the identification of submicroscopic subtelomeric rearrangements as a major cause of mental retardation [Flint et al., 1995], testing for subtelomeric abnormalities among patients with mental retardation has become an important diagnostic tool. Although widespread screening among patients with mental retardation might be desirable, the current cost of testing is considered too expensive to allow unselected testing. Therefore clinical preselection is important. So far, selection for subtelomere testing has often been based on the checklist proposedbyDeVries et al. [2001]. (1, Family history of mental retardation; 2, prenatal onset growth retardation; 3, postnatal growth abnormalities; 4,>2 facial dysmorphic features; 5, one or more non-facial dysmorphic features and/or congenital abnormality). Some of the submicroscopic subtelomeric deletions result in a specific phenotype which may direct the clinician towards the diagnosis; the common forms of subtelomeric deletions such as 1p, 4p, 5p, 9p, 22q are quite consistent and the mental retardation is a typical feature [De Vries et al., 2003]. Patients with 10q26-qter deletion seem to have a consistent phenotype including psychomotor delay, growth retardation (preand/or postnatal), microcephaly, triangular face, hypertelorism, strabismus, prominent nasal bridge, low-set/malformed/large/ posteriorly rotated ears, micrognathia, short neck, cryptorchidism, ano/genital defects, congenital heart malformation and urinary tract/renal anomalies [Waggoner et al., 1999; Lukusa and Fryns, 2000; Courtens et al., 2006]. In contrast to these findings, normal individuals (at least 1% of the population [Ledbetter and Martin, 2007]) can also carry subtelomeric aberration like 10qter deletion and do not have any disability or dysmorphic features [Ravnan et al., 2006; Balikova et al., 2007]. Several mechanisms may explain the presence of subtelomeric imbalance in these people: (1) some recurrent chromosomal deletions, such as VCFS syndrome, have variable expressivity [McDonald-McGinn et al., 2001]. (2) The presence of an unmasked recessive allele in the affected patients may determine the phenotypic difference with the normal individuals [Lesnik Oberstein et al., 2006]. (3) Somatic mosaicism, with normal cell lines in the unaffected individuals, may explain the difference. (4) Epigenetic modifications could induce a phenotypic difference between affected patients and normal people. Moreover at present the size of most reported deletions has not been well molecularly characterized, thus complicating accurate genotype–phenotype correlations for these patients [Ledbetter and Martin, 2007]. Here we report on a patient with a 10 q26-10qter deletion. Our patient is a male, the first-born child of healthy non-consanguineous parents, with no family history of mental retardation or birth defects. He was born by caesarean delivery at 38 weeks of gestation. Birth weight was 2,980 g (3rd–10th centile), length was 48 cm (3rd–10th centile), and occipitofrontal head circumference (OFC) was 34 cm (10th–25th