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

Abstract

BackgroundRearrangements involving the short arm of chromosome 18 have been extensively described. Here we report a microduplication of 320.5–431.5 Kb at 18p11.31-p11.23 in a 10 year-old boy.Case presentationIn a 10 year-old boy with moderate psychomotor delay, hypoplasia of the cerebellar vermis, chorioretinal coloboma, deafness and growth hormone deficiency (GHD), an interstitial microduplication at 18p11.31-p11.23 was identified by array-CGH. This maternally inherited microduplication, encompasses three genes, namely ARHGAP28, LINC00668 and LAMA1 (a gene involved in cerebellum and retinal development).ConclusionsThe genotype-phenotype is discussed with particular attention to the LAMA1 gene, although it is difficult, as in many other similar situations, to assess the causality of the detected duplication in the absence of further studies aiming to explore the presence of co-occurring variants that could explain the incomplete penetrance.Electronic supplementary materialThe online version of this article (doi:10.1186/s13039-016-0298-9) contains supplementary material, which is available to authorized users.

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

“…All fetuses in our report shared partial duplications of the LAMA1 locus. The ultrasound abnormalities of the cerebellum in case 2 showed some resemblance to the patient described by Giordano et al 1 This microduplication was identified as arising from a paternal origin, but the father presented no apparent abnormalities. Compared with the terminated pregnancy in case 2, case 3 showed duplication of a larger microduplication was present in both tissues.…”

“…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.…”

“…Chromosomal rearrangements, such as duplications, often have close relationships with intellectual disability and related disorders. Pure duplication of chromosome 18p is rare, with clinical phenotypes ranging from normal or slight abnormalities to various degrees of mental retardation …”

Genotype-Phenotype Analysis, Neuropsychological Assessment, and Growth Hormone Response in a Patient with 18p Deletion Syndrome

“…Neuroimaging of these patients showed cerebellar dysplasia with cysts, an enlarged 4th ventricle, and hypoplasia of the cerebellar vermis [Aldinger et al, 2014;Micalizzi et al, 2016]. Some of the clinical features in our patient, such as hypoplasia of cerebellar vermis, DandyWalker malformations, cognitive impairment, language and motor delay, may be caused by LAMA1 deletions [Hasi-Zogaj et al, 2015;Abdel Razek and Castillo, 2016;Giordano et al, 2016]. TWSG1 encodes a bone morphogenetic protein antagonist and plays a role in craniofacial development [Kauvar et al, 2011;Billington et al, 2015;Huntley et al, 2015].…”

Two-Generation Transmission of Trisomy 18p: Prenatal Diagnosis in a Woman with Mild Intellectual Disability

“…Some of these triplicated genes could also be associated with mental disorders. A genotype-phenotype correlation was discussed with particular attention to the LAMA1 , ARH-GAP28 , LINC00668 , and TXNDC2 genes [Guillaume et al, 2015;Giordano et al, 2016]. However, further studies are necessary to determine whether the presence of cooccurring variants could explain the incomplete penetrance.…”