Clinical characterization of a girl with trisomy 20q13.2qter and monosomy 13q33.1qter: Delineating phenotype–genotype correlations

Abstract

Array comparative genomic hybridization (aCGH) is a techniqueenabling high-resolution, genome-wide screeningof genomic seg-mentalcopynumbervariations(CNVs)[Solinas-Toldoetal.,1997;Pinkeletal.,1998].Itisbecominganessentialandaroutineclinicaldiagnostic tool and is gradually replacing cytogenetic methods.Most of the clinically available aCGH platforms are designed todetectaneuploidies,well-characterizedmicrodeletion/microdupli-cation syndromes and subtelomeric or other unbalanced chromo-somal rearrangements [Ballif et al., 2006; Shinawi and Cheung,2008]. The aim of the present paper is to present the clinical andmolecular description of a patient with a submicroscopic rear-rangement resulting in trisomy 20q and monosomy 13q andtherebytodelineatethephenotypeassociatedtoaspecificchromo-somal region.Thepatient,a6-year-oldgirl,istheproductofthefirstpregnancyofhealthy,nonconsanguineousparents,aged45years(mother)and51 years (father). The pregnancy was complicated by reduced fetalmovement and vaginal infection.Intrauterine diagnosis at the 7th month of pregnancy showedhypoplasia of the corpus callosum during the final month severeIUGR was diagnosed.Thepatientwasdeliveredat38weeksgestationviainducedlabor.The weight was 1,400g (<10th centile), length 45.5cm (10thcentile), and the OFC was 30cm (3rd centile). Examinationsimmediately after birth revealed that the patient had hyporeflexia,hypoactivity, and flattened occiput. The cerebral ultrasoundshowedthatshehadhypogenesisofthecorpuscallosum.Echocar-diographyand subsequent cardiac catheterization showed an osti-um secundum atrial septal defect and branch pulmonary stenosis.Congenital tracheal stenosis was diagnosed by a bronchoscopy.Fundus and evoked potentials were both normal.Significant psychomotor developmental delay was observed ininfancyandattheageof6years,shewasstillunabletostandalone.Vocalizations began at 4 years and at 6 years she said disyllabicnon-referentialwordsandcommunicatedwithsimplegestures.Shehad no developmental regression Since 3 years of age, she hasexperiencedsporadicseizures(5or6episodes)andreceivedfurthertreatment with valproic acid or clonazepam. No deterioration wasseeninassociationwiththeepisodes.Shehadslowweightgainandlongitudinal growth.Amongtheillnesshad,shewasadmittedat22monthsoldduetoan episode of acute gastroenteritis with severe hypernatremicdehydration and prerenal acute renal failure. In addition, she hashad several urinary tract infections with normal renal findings onsonogram.