Towards mapping phenotypical traits in 18p− syndrome by array-based comparative genomic hybridisation and fluorescent in situ hybridisation

Abstract

Molecular karyotyping holds the promise of improving genotype -phenotype correlations for frequent chromosome conditions such as the 18pÀ syndrome. In spite of more than 150 reported cases with deletions in 18p, no reliable phenotype map for the characteristic clinical findings such as mental retardation, post-natal growth retardation and typical facial features has been established yet. Here, we report on four patients with partial monosomy 18p of different sizes owing to unbalanced translocations that were thoroughly characterised clinically and by molecular karyotyping. One patient had a terminal deletion of 1.6 Mb in 18p and a trisomy of 8q24.23-qter as determined by array-based comparative genomic hybridisation and large insert clone fluorescent in situ hybridisation. In two sibs and a fourth patient, cytogenetic and molecular-cytogenetic analyses showed the terminal deletions in 18p (8.0 and 13.84 Mb, respectively) to be accompanied by partial trisomies of 20p. Literature analyses of typical phenotypic features of 18pÀ, 8qþ and 20pþ syndromes allowed the attribution of clinical findings in our patients to the respective chromosomal aberration. Based on these data, we propose a phenotype map for several clinical features of the 18pÀ syndrome: Round face was tentatively mapped to the distal 1.6 Mb of 18p; post-natal growth retardation and seizures to the distal 8 Mb and ptosis and short neck to the proximal half of 18p.

Molecular cytogenetic characterization of the first reported case of inv dup del 20p compatible with a U‐type exchange model

“…Thirty-nine cases have been reported, all but two cases [Zumel et al, 1989;Molina-Gomes et al, 2006] diagnosed postnatally. Most partial trisomies result from reciprocal translocation [Taylor et al, 1976;Marcus et al, 1979;Funderburk et al, 1983;Lurie et al, 1985;Vamos et al, 1985;Zumel et al, 1989;Grammatico et al, 1992;LeChien et al, 1994;Belin et al, 1999;Oppenheimer et al, 2000;Wieczorek et al, 2003;Thomas et al, 2004;T€ umer et al, 2005;Brenk et al, 2007]. In a few cases, trisomy 20p results from parental inversion [Lucas et al, 1985;Bown et al, 1986;Molina-Gomes et al, 2006;Chaabouni et al, 2007] or the formation of isochromosomes [Sidwell et al, 2000].…”

Psychiatric syndromes in individuals with chromosome 18 abnormalities

“…Mental retardation is found in case reports of all three abnormalities (18p-, 18q-, and 18p tetrasomy), and in one study was estimated at 68% of all 18q deletion subjects [Semrud-Clikeman et al, 2005]. Abnormal EEG findings and epilepsy have been described in case reports for all three chromosomal disorders [Chudley et al, 1974;Wilson et al, 1979;Wilson and Al Saadi, 1989;Schinzel et al, 1991;Chudley et al, 1992;Krasikov et al, 1992;Poissonnier et al, 1992;Engelen et al, 1998;Tinkle et al, 2003;Linnankivi et al, 2006;Swingle et al, 2006;Brenk et al, 2007;Cody et al, 2007]. Many subjects with 18p or 18q deletions display delayed speech, mutism, or articulation difficulties [Thompson et al, 1986;Poissonnier et al, 1992;Grosso et al, 1999;Babovic-Vuksanovic et al, 2004;Wester et al, 2006;Brenk et al, 2007;Cody et al, 2007] and there has been one report of short Neuropsychiatric Genetics attention span in three out of three 18p-subjects [Thompson et al, 1986].…”

Pericentric inversion of chromosome 18 in parents leading to a phenotypically normal child with segmental uniparental disomy 18

“…22,23 Mejia-Baltodano et al 18 also reported a patient with minor dysmorphic features, small stature and obesity. Learning difficulty was noticed only after the first year of primary school and a cognitive delay of 2 years was recorded by psychometric testing at 8 years.…”