Major feeding difficulties in the first reported case of interstitial 20q11.22‐q12 microdeletion and molecular cytogenetic characterization

Abstract

We report on a 4-year-old female presenting with intrauterine growth retardation, facial dysmorphic features, major feeding difficulties with severe diarrhea and vomiting, mental retardation with abnormal behavior and hypertonia. Feeding difficulties were the most invalidating features with absent oral intake requiring persistent enteral feeding. Standard cytogenetic studies were normal, but high-resolution chromosome analyses revealed a small de novo interstitial deletion of the long arm of chromosome 20, 46,XX,del(20)(q11.21q12). The deletion was confirmed using metaphase comparative genomic hybridization (CGH) and multicolor high resolution banding (mBAND). The deletion breakpoints were characterized using FISH analyses with YACs, PACs, and BACs clones located in the deleted and adjacent regions. A 6.6-Mb deleted region between markers D20S815 (20q11.22) and D20S435 (20q12) could be delineated. None of the nine previously reported cases with interstitial 20q deletion found in the literature involve the same breakpoints. This report further emphasizes the indication of high-resolution chromosome analyses in children with syndromic mental retardation. The description of additional cases would be useful in order to better characterize the phenotype of patients with proximal interstitial 20q deletion.

First Report of Low-Rate Mosaicism for 20q11.21q12 Deletion and Delineation of the Associated Disorder

“…GHRH haploinsufficiency may lead to isolated growth hormone deficiency (GHD) and justify the marked prenatal and postnatal growth retardation found in our patient and in about half of the published cases [Callier et al, 2006;Iqbal and Al-Owain, 2007;Hiraki et al, 2011;Gervasini et al, 2013;Posmyk et al, 2014;Jedraszak et al, 2015]. This hypothesis seems to be supported by the reduced IGF1 levels in our patient.…”

“…Mutations and deletions of SAMHD1 have been associated with systemic lupus erythematosus, and recently homozygous mutations in SAMHD1 were found in 8.3% of Jedraszak et al, 2015Callier et al, 2006Iqbal et al, 2007Hiraki et al, 2011Gervasini et al, 2013Posmyk et al, 2014 Total reported patients Our case (DECIPHER…”

“…No cerebral MRI was performed in our patient. In a minority of patients with 20q11.2 deletion encompassing SAMHD1 , cerebral abnormalities were reported, with cortical atrophy being the most common finding at brain MRI (4/12) [Jedraszak et al, 2015;Callier et al, 2006;Iqbal and Al-Owain, 2007;Hiraki et al, 2011]. However, these cerebral abnormalities do not seem to be related to haploinsufficiency of SAMHD1 , according to the role previously attributed to this gene.…”

“…To date, 24 unrelated patients have been reported [Fraisse et al, 1981;Petersen et al, 1987;Porfirio et al, 1987;Shabtai et al, 1993;Aldred et al, 2002;Chen et al, 2005;Genevieve et al, 2005;Callier et al, 2006;Borozdin et al, 2007;Iqbal and Al-Owain, 2007;Hiraki et al, 2011;Gervasini et al, 2013;Iourov et al, 2013;Santoro et al, 2013;Posmyk et al, 2014;Jedraszak et al, 2015;Meredith et al, 2017], including 12 with deletions involving the proximal 20q11.2 region [Callier et al, 2006;Iqbal and Al-Owain, 2007;Hiraki et al, 2011;Gervasini et al, 2013;Iourov et al, 2013;Posmyk et al, 2014;Jedraszak et al, 2015;Meredith et al, 2017]. The clinical phenotype shared by these latter patients includes prenatal and postnatal growth retardation, feeding difficulties, psychomotor retardation and intellectual disability of variable degree, craniofacial dysmorphisms (high forehead, frontal bossing, deep-set eyes, midface hypoplasia), and hand/ feet anomalies such as brachydactyly and clinodactyly.…”

A de novo deletion of 20q11.2–q12 in a boy presenting with abnormal hands and feet, retinal dysplasia, and intractable feeding difficulty

“…To our knowledge, a total of 12 patients have been reported in the literature [Petersen et al, 1987;Shabtai et al, 1993;Aldred et al, 2002;Genevieve et al, 2005;Callier et al, 2006;Borozdin et al, 2007;Iqbal and Al-Owain, 2007]. Among them, only two cases showed the proximal q deletion (20q11-q12), not extending to q13 [Callier et al, 2006;Iqbal and Al-Owain, 2007]. One patient had a 6.6-Mb deletion at 20q11.21-q11.23 [Callier et al, 2006], and the other [Iqbal and Al-Owain, 2007] showed a 6.8-Mb deletion at 20q11.2-q12.…”