Mosaic marker chromosome 16 resulting in 16q11.2–q12.1 gain in a child with intellectual disability, microcephaly, and cerebellar cortical dysplasia

Abstract

Proximal duplications of the long arm of chromosome 16 are rare and only a few patients have been reported. Clinically, the patients do not have a distinctive syndromic appearance; however they all show some degree of intellectual disability and most have severely delayed speech development. We report on a child presenting with mild-to-moderate intellectual disability, microcephaly, language dyspraxia, and mild dysmorphisms who was found to have a mosaic gain of chromosome 16q (16q11.2-16q12.1). Magnetic resonance imaging done at the age of 4 years demonstrated cerebellar cortical dysplasia involving the vermis and hemispheres. This is the first report of cerebellar anomalies in a patient with partial trisomy 16q. The genes ZNF423 and CBLN1 found in the duplicated region play a role in the development of the cerebellum and may be responsible for the cerebellar cortical dysplasia.

Molecular characterization of 20 small supernumerary marker chromosome cases using array comparative genomic hybridization and fluorescence in situ hybridization

“…Thirdly, for the sSMC carrier associated with varying clinical features, detailed characterization of the sSMC could provide useful data to establish the phenotype-genotype correlation, and then assist in interpreting the potential phenotypic impact 5 , 7 , 9 . Finally, aCGH characterization of sSMCs in individuals with special clinical features may contribute to the search for candidate genes or a novel locus associated with unique syndromes 26 , 27 .…”

ZNF423: A New Player in Estrogen Receptor-Positive Breast Cancer

“…Mutations of the mouse ortholog Zfp423 cause reduced proliferation and abnormal development of midline neural progenitors resulting in a loss of the cerebellar vermis ( 50 , 51 ) similar to that seen in Joubert syndrome patients with cerebellar vermis hypoplasia. A mosaic gain of chromosome 16 (16q11.2–16q12.1) involving the ZNF423 and the Cerebellin-1 gene was found in a child with intellectual disability, microcephaly, and cerebellar cortical dysplasia ( 65 ).…”

Clinical and cytogenetic characterization of a boy with a de novo pure partial trisomy 16q24.1q24.3 and complex chromosome rearrangement

“…Partial trisomy 16q is a rare syndrome with a wide range of manifestations, including central nervous system malformations, developmental delay, intellectual disability, genitourinary anomalies, congenital heart defects, and dysmorphic facial features [Brisset et al, 2002; Puhl et al, 2010; Lonardo et al, 2011; Zerem et al, 2011; Laus et al, 2012]. Only eight patients with 16q24 trisomy have been reported in the literature [Maher et al, 1991; Giardino et al, 2001; Baker et al, 2002; Brisset et al, 2002; Zahn et al, 2005; Ferrero et al, 2006].…”