Clinical and molecular findings in nine new cases of tetrasomy 18p syndrome: FISH and array CGH characterization

Abstract

BackgroundSmall Supernumerary Marker Chromosomes (sSMC) are rare chromosomal abnormalities, which have abnormal banding arrangement and take many shapes. Several disorders have been correlated with sSMC presence. The aim of this study is to characterize the sSMC derived from chromosome 18 by Fluorescence in situ hybridization (FISH) and Array Comparative Genomic Hybridization (aCGH).ResultsNine children with dysmorphic features have been investigated. They have these features in common: a triangular face, low-set ears, a large mouth with a thin upper lip, and a horizontal palpebral fissure. Epicanthus and strabismus were present in two patients. In addition, we have noticed microcephaly and mental and/or developmental delay with low birth weight. However, two patients had standard birth weight; one patient had hypospadias; two had skin problems; and three showed different congenital heart defects. One patient had corpus callosum hypoplasia. Systematic karyotype analysis revealed a de novo supernumerary chromosome. Array CGH showed a gain in copy number on the short arm of chromosome 18 in the nine cases. In one case, the sSMC seemed to be in mosaic. The breakpoints of the marker were identified using aCGH and FISH. Thus, the sSMC led to 18p tetrasomy with approximately 14 Mb lengths, between 364344 and 14763575 based on the human genome version 18.ConclusionsThese results have been completed by FISH in order to ascertain the shape of the sSMC. Our results confirm the uniqueness and particularity of the iso18p syndrome on the phenotypic as well as on the genetic level.

Variable degree of mosaicism for tetrasomy 18p in phenotypically discordant monozygotic twins—Diagnostic implications

“…The consistent findings were global developmental delay/mental retardation, abnormal muscle tone, brain MRI abnormalities, feeding difficulties, and microcephaly. A similar but milder phenotype is present in the rare cases of high-level mosaicism (Bai et al, 2017;Slimani et al, 2019), which is consistent with a clinical picture of the proband. with our PDMZTs is given in Table S2.…”

“…We describe a pair of PDMZTs where phenotypic features of the proband are due to mosaic tetrasomy 18p, which is preferentially present in the tissues of ectodermal origin. Tetrasomy 18p [or isochromosome 18p, i(18p)] is a rare syndrome (OMIM #614290) involving feeding difficulties, neonatal respiratory distress, growth retardation, microcephaly, developmental delay, muscle tone abnormalities, various congenital anomalies, and characteristic dysmorphism (Sebold et al, 2010; Slimani et al, 2019). Most cases are de novo aberrations, although there are familial examples (Abeliovich et al, 1993; Boyle et al, 2001).…”

Molecular and cytogenetic analysis of small supernumerary marker chromosomes in prenatal diagnosis

“…No abnormality was found in the ultrasound of Case 24. Isochromosome 18p syndrome would cause growth and mental retardation, neonatal respiratory distress, and characteristic dysmorphism [ 15 , 16 ]. Case 25 was found to have r(Y).…”

“…The CMA result of Case 24 demonstrated that the CNV was pathogenic. The duplication contains 54 OMIM genes, and it has been reported that tetrasomy18p would cause developmental delay and intellectual disability [ 15 , 16 ]. Six cased continued the pregnancy and the babies were phenotypically normal at birth.…”

Anomalies in Human Sex Determination: Usefulness of a Combined Cytogenetic Approach to Characterize an Additional Case with Xp Functional Disomy Associated with 46,XY Gonadal Dysgenesis

“…CGH 4x44K micro-array was performed using the agilent platform as previously described ( 11 , 12 ). Agilent ® oligonucleotide array was performed according to the manufacturer’s instructions (Agilent Human Genome CGH Microarray kit 44K ® ).…”