Inherited duplication of the short arm of chromosome 18p11.32–p11.31 associated with developmental delay/intellectual disability

Abstract

Duplications of 18p have been reported in the literature associated with a range of different abnormalities and also in patients with normal phenotypes. The majority of these reports are based solely on G-banded cytogenetic evaluation. The use of arrayCGH characterization has improved the ability to define regions of imbalance and is helping to identify potential underlying triplosufficiency of any duplicated genes. We report on a family where the father and his two daughters all have a duplication 18p11.32-p11.31 characterized by microarray. They present with variable levels of intellectual disability/developmental delay and behavioural difficulties without any physical anomalies. This family contributes toward the growing knowledge of pure duplications of 18p and provides information on interpretation of novel array findings in the context of family history. It also reiterates the importance of elucidating a detailed learning and developmental phenotype and family pedigree in aiding interpretation of genetic testing results. Clin Dysmorphol 25:19-22

A 18p11.23-p11.31 microduplication in a boy with psychomotor delay, cerebellar vermis hypoplasia, chorioretinal coloboma, deafness and GH deficiency

“…To the best of our knowledge, there are only three interstitial submicroscopic duplications reported involving 18p and none of them overlaps with the one described here [6–8]. In all of these cases, the microduplication was either inherited from a healthy parent [7, 8], as in the here presented case, or it was present in unaffected family members [6], in accordance with a dominant model of inheritance with incomplete penetrance. The variability in the phenotype of patients carrying the same unbalances, ranging from severe disorders to healthy phenotype, might be explained with the presence of additional anomalies in the affected patients.…”

“…An 18p11.31-p11.32 duplication of 429.5 Kb, including four genes, among which the likely causative EMILIN2 , has been identified in a family with porokeratosis of Mibelli [6]. In the same region, other authors [7] detected a larger overlapping 2.6 Mb microduplication involving at least nine genes in two siblings with variable levels of intellectual disability/developmental delay and behavioral difficulties. Finally, Kashevarova et.…”

Prenatal detection of interstitial 18p11.31‐p11.22 microduplications: Phenotypic diversity and literature review

“…Pure chromosomal 18p duplication is a rare aberration. The main clinical features in previously described patients were a range of different abnormalities, including a nonspecific facial appearance, and mental development ranging from normal to moderate retardation . Patients with normal phenotypes can also carry this chromosomal rearrangement …”

“…3, 5, and 10) presented abnormal characteristics that differed from their phenotypically normal parents, and three (Nos. 6‐8) shared partial but increased abnormal features compared with their phenotypically abnormal parents: the father of the siblings only presented learning and behavioral difficulties, and the apparently healthy mother of the 10‐year‐old boy showed some mild clinical features, such as partial hearing loss and mild micrognathia . In addition, Srebniak et al described a male fetus with a maternally inherited 18p11.32 microduplication with no phenotypic effect, whose mother had a normal phenotype (No.…”

“…The main clinical features in previously described patients were a range of different abnormalities, including a nonspecific facial appearance, and mental development ranging from normal to moderate retardation. [15][16][17] What's already known about this topic?…”