Abstract
Abstract
Background
Small supernumerary marker chromosomes (sSMC) are a heterogeneous group of structurally abnormal chromosomes, with an incidence of 0,044% in newborns that increases up to almost 7 times in developmentally retarded patients. sSMC from all 24 chromosome have been described, most of them originate from the group of the acrocentric, with around half deriving from the chromosome 15. Non-acrocentric sSMC are less common and, in the 30 percent of the cases, are associated with phenotypic effect. Complex sSMC consist of chromosomal material derived from more than one chromosome. Genotype–phenotype correlations in patients with sSMC are difficult to assess. Clinical features depend on factors such as its size, genetic content, the involvement of imprinted genes which may be influenced by uniparental disomy and the level of mosaicism. Trisomy of the short arm of chromosome 18 (18p) is an infrequent finding and does not appear to be associated with a specific syndrome. However, mild intellectual disability with or without other anomalies is reported in almost one-third of the patients.
Case presentation
Here we present clinical and molecular characterization of a new case of de novo complex sSMC consisting of the entire short arm of chromosome 18p associated with a centromere of either chromosome 13 or 21, evidenced in a 5-year-old boy during diagnostic workup for moderate intellectual disability and dysmorphisms. To date, only seven cases of isolated trisomy 18p due to a sSMC have been reported, three of which have been characterized by array CGH. In two of them the breakpoints and the size of the duplication have been described. In the manuscript we also reviewed cases reported in the DECIPHER database carrying similar duplication and also considered smaller duplications within the region of interest, in order to evaluate the presence of critical regions implicated in the pathological phenotype.
Conclusions
Our case provides additional information about phenotypic effects of pure trisomy 18p, confirms chromosomal microarray analysis as gold standard to characterize complex sSMC, and supplies additional elements for genetic counselling.
Publisher
Springer Science and Business Media LLC
Subject
Biochemistry (medical),Genetics (clinical),Genetics,Molecular Biology,Molecular Medicine,Biochemistry
Reference22 articles.
1. Liehr T, Weise A. Frequency of small supernumerary marker chromosomes in prenatal, newborn, developmentally retarded and infertility diagnostics. Int J Mol Med. 2007;19(5):719–31.
2. Liehr T, Claussen U, Starke H. Small supernumerary marker chromosomes (sSMC) in humans. Cytogenet Genome Res. 2004;107(1–2):55–67.
3. Crolla JA, Youings SA, Ennis S, Jacobs PA. Supernumerary marker chromosomes in man: parental origin, mosaicism and maternal age revisited. Eur J Hum Genet. 2005;13(2):154–60.
4. Dennis NR, Veltman MW, Thompson R, Craig E, Bolton PF, Thomas NS. Clinical findings in 33 subjects with large supernumerary marker(15) chromosomes and 3 subjects with triplication of 15q11-q13. Am J Med Genet A. 2006;140(5):434–41.
5. Crolla JA. FISH and molecular studies of autosomal supernumerary marker chromosomes excluding those derived from chromosome 15: II. Review of the literature. Am J Med Genet. 1998;75(4):367–81.
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