De novo isochromosome 18p in a female dysmorphic child

Abstract

Isochromosome 18p results in tetrasomy 18p. Most of the i(18p) cases reported so far in the literature are sporadic due to de novo formation, while familial and mosaic cases are infrequent. It is a rare chromosomal abnormality, occurring once in every 140,000 livebirths, affecting males and females equally. In the present investigation, we report a de novo i(18p) in a female dysmorphic child. The small metacentric marker chromosome was confirmed as i(18p) in the proband by cytogenetic and FISH analysis [47,XX+i(18p)]. Cytogenetic investigations in the family members revealed normal chromosome numbers, indicating the case as a de novo event of i(18p) formation. It could be due to the somewhat advanced maternal age (32 years) and/or expression of recessive genes in the proband, who is the progeny of consanguineous marriage, which could have led to misdivision and nondisjunction of chromosome 18 in meiosis I, followed by failure in the chromatid separation of 18p in meiosis II and by inverted duplication.

Clinical Outcome: A Monosomy 18p is Better than a Tetrasomy 18p

“…Interestingly, trisomy 18p results in little phenotypic effects, and these patients have been reported to range from normal to mildly developmentally delayed [Takeda et al, 1989;Mabboux et al, 2007;Rodriguez et al, 2007;Orendi et al, 2013]. Tetrasomy 18p causes severe phenotypic effects, including moderate to severe mental retardation, hypotonia, and multiple skeletal anomalies [Ramegowda et al, 2006;Maruotti et al, 2011;Plaiasu et al, 2011]. As expected, our comparison of clinical abnormalities involving the short arm of chromosome 18 showed distinct phenotypes depending on the number of copies present ( table 1 ).…”

“…severe mental retardation, developmental delay, craniofacial anomalies, microcephaly, and an abnormal muscle tone [Ramegowda et al, 2006;Dundar et al, 2010;Plaiasu et al, 2011]. In contrast, the deletion of the short arm of chromosome 18 (del(18p), OMIM 146390) has an estimated prevalence of 1: 50,000 live births and characteristically presents with variable mental retardation, growth retardation, low height, pectus excavatum, and craniofacial malformations including long ears, ptosis, microcephaly, and a short neck.…”

Tetrasomy 18p in a male dysmorphic child in southeast Turkey

“…Prevalence of various kinds of isochromosomes range from 0.14 to 0.72 per 1000 live births (Boyle et al 2001;Ramegowda et al 2006). The presence of a supernumerary isochromosome 18p results in tetrasomy of 18p (Boyle et al 2001;Bakshi et al 2006;Ramegowda et al 2006).…”

“…Isochromosomes are supernumerary marker chromosomes, that are made up of two copies of the same arm of a chromosome, so that they form a mirror image of each other, resulting in a tetrasomy of the arm involved (Boyle et al 2001;Ramegowda et al 2006). Prevalence of various kinds of isochromosomes range from 0.14 to 0.72 per 1000 live births (Boyle et al 2001;Ramegowda et al 2006).…”

A female infant case with tetrasomy 18p

“…Her father was 29 and her mother was 28 years old. Most of the I (18p) cases are sporadic, de novo meiotic events 11 . However, familial and somatic mosaic cases have also been reported 12 .…”