Del5p/dup5q in a ‘cri du chat’ patient without parental chromosomal rearrangement

Abstract

To the Editor:‘‘Criduchatsyndrome’’(CDCS/[OMIM#123450])isone of the most common deletion syndromes,involving the short arm of chromosome 5, with anestimated incidence of 1 in 50,000 live births [Levyetal.,2002].Thesizesofthedeletionsrangefromtheentire short arm to only 5p15.3 [Overhauser et al.,1994; Gersh et al., 1995; Sreekantaiah et al., 1999].Although the latter is responsible for the character-istic cat-like cry, the typical cri du chat syndrome iscaused by deletion of the band 5p15.2 [Gersh et al.,1994; Church et al., 1995; Mainardi et al., 2001].Clinical manifestations of the syndrome include adiagnostic high pitched, monotonous cry similar tothemewingofacat,microcephaly,aroundfacewithhypertelorism, epicanthic folds, micrognathia, pro-minentnasalbridge,abnormaldermatoglyphics,anddelayed growth, and severe psychomotor andmental delay [Lejeune et al., 1963; Niebuhr, 1978].Approximately 85% of the cases are caused by denovodeletions(themajorityareofpaternalinorigin[Overhauser et al., 1990]), whereas 10–15% of casesare familial and result from unbalanced segregationof parental translocation chromosomes. Further-more,onlyabout5%ofthefamilialcasesarecausedby meiotic recombination aneusomy [Niebuhr,1978], which occurs when a parental inversion ofchromosome5recombinestoproduceagametewithpartial monosomy of the short arm and partialtrisomy of the long arm [Beemer et al., 1984;Schroeder et al., 1986; Kumar et al., 1987; Dobbsetal.,1988;Sonodaetal.,1989;Chernosetal.,1992;Onoetal.,1993;Goodartetal.,1996;Levyetal.,2002;Bocian et al., 2005].In this report, we describe a new case of ‘‘cri duchat syndrome’’ having distal deletion of 5p anddistal duplication of 5q defined by the molecularcytogenetic techniques of fluorescence in situhybridization (FISH) and comparative genomichybridization (CGH). This is the first patient with‘‘cri du chat syndrome’’ born to parents without adetectablepericentricinversionofchromosome5intheir blood cells.Theindexpatientwas a full term male infant borntononconsanguineous healthyparents(motherandfather: 24 and 33 years old, respectively) after anuneventful gestation. The pedigree revealed amiscarriageatthe3rdmonthofgestation.Thepatientwas referred to Medical Genetics Department ofAnkaraUniversityFacultyofMedicinewithmultiplecongenital abnormalities and distinctive high-pitched mewing cry. He was 2,350 g by weight (3rdcentile) (2,600 g at birth), 46 cm in length (3rdcentile), and had a 31.5 cm head circumferences(3rd centile) at 11th day. The physical examinationshowed a round face, hypertelorism, epicanthalfolds, downward slanting of the palpebral fissures,microretrognathia,bilateralincompletehelicalarchi-tecture of horizontally asymmetric low set ears,preauricular skin tag on the left, long philtrum,bilateralsingletransversecrease,andbilateralhallux