Detection of a de novo duplication of 1q32-qter by fluorescence in situ hybridisation in a boy with multiple malformations: further delineation of the trisomy 1q syndrome.

Abstract

We report a dysmorphic boy with a de novo partial trisomy lq. The boy has microcephaly, bilateral cleft lip and palate, low set and dysmorphic ears, brain anomalies, pulmonary stenosis, duodenal obstruction, dysplastic kidneys, and bifid thumbs. The trisomic segment lq32-qter is duplicated with an inverted insertion at lp36.3. The aberration was initially detected at amniocentesis and confirmed and defined by GTG banding, chromosome microdissection, and FISH on postnatal blood samples. The parents had normal karyotypes. De novo partial duplications of chromosome lq have rarely been reported. Comparison of our patient with other published pure trisomy lq cases showed similarities which allowed the further delineation of the trisomy lq syndrome.

Duplication Dup(1)(q32q44) Detected by Comparative Genomic Hybridization (CGH): Further Delineation of Trisomies 1q

“…The neuropathologic basis for severe mental retardation remains unclear. Hydrocephalic dilatation of the lateral ventricle was diagnosed on CT scan or at autopsy in 7 individuals of groups I-III [15,19,21,22,25,26,29]. In two infants of group I the cerebellum was hypoplastic [14,19] and anomalies of the gyral pattern, optic tract and absence of the olfactory nerves were noted in two children from group II and III on autopsy [18,21].…”

Boy with an interstitial 1q (q31q41) duplication confirmed by fluorescent in situ hybridisation

“…The parental karyotypes were normal. From a search in the POSSUM data base a duplication of chromosome 1q was suspected, but the patient did not have a congenital malformation of the heart, hypospadias, cleft lip and palate, or thick lips, as reported in patients with this chromosomal abnormality [Duba et al, 1997;Flatz and Fonatsch, 1979]. In Table I, the clinical observations from the present case are listed together with previously reported cases with chromosomal aberrations involving 1q, but without involvement of other chromosomes.…”

“…In two cases, chromosome 18 has been involved [Liberfarb et al, 1979;Rosenthal et al, 1987] and in three cases, chromosome 15 [DuPont et al, 1994;Kennerknecht et al, 1993;Verschuuren-Bemelmans et al, 1995]. There have also been reports involving inversions and/or deletions of chromosome 1 segments together with partial trisomy of others [Clark et al, 1994;Duba et al, 1997;Mewar et al, 1994]. The phenotypic variances reported in patients in whom only a chromosome 1q duplication exist might be explained by the differences in the segments duplicated (Table I).…”

“…The phenotypic variances reported in patients in whom only a chromosome 1q duplication exist might be explained by the differences in the segments duplicated (Table I). The most common duplicated segments are in the 1q32q-qter region [Clark et al, 1994;Duba et al, 1997;Fryns et al, 1980;Rehder and Friedrich, 1979;Schinzel, 1981] or the 1q42-qter region [Chia et al, 1988;Johnson, 1991;Kennerknecht et al, 1993;Liberfarb et al, 1979]. Even among patients having certain duplicated segments in common, the observed anomalies are variable, although it must be noted that a molecular characterisation of the duplicated segment was seldom performed.…”

“…In those cases it is difficult to separate the duplication 1q phenotype from that of the other involved chromosome. Cases with duplications involving chromosome 1q alone, when a de novo structural rearrangement has occurred, are not very common [Garver et al, 1976;Palmer et al, 1977;Pan et al, 1977;Steffenssen et al, 1977;Flatz and Fonatsch, 1979;Schinzel, 1979;Lungarotti et al, 1980;Mewar et al, 1994;Duba et al, 1997], but are the most informative for delineating a duplication 1q syndrome. It is then important to identify the duplicated region in order to make a correct genotype-phenotype correlation.…”