title: Phenotypic variability in a Hungarian patient with the 4q21 microdeletion syndrome.
abstract: BACKGROUND
  Interstitial deletions of 4q21 (MIM 613509) have already been reported in more than a dozen patients with deletions ranging from 2 to 15.1 Mb delineating a common phenotype including marked growth restriction, hypotonia, severe developmental delay with absent or delayed speech and distinctive facial features. A minimal critical region of 1.37 Mb accounting for the common features with 5 known genes (PRKG2, RASGEF1B, HNRNPD, HNRPDL, and ENOPH1) has been described so far.
  
  
  RESULTS
  Here we report on a 5 year-old Hungarian girl presenting with severe developmental delay, good receptive language but absent spoken speech, short stature, dystrophy, hypotonia, distinctive facies including broad forehead, frontal bossing, downward slanting palpebral fissures, hypertelorism, hypoplastic ear-lobes, anteverted nostrils, short philtrum, small mouth, higharched palate, short, small hands and feet, distally narrowing fingers and clinodactyly. Cerebral MRI showed ventricular dilation and an increase in periventricular signal intensity. After extensive metabolic tests and exclusion of subtelomeric deletions array CGH analysis was performed using the Agilent Human Genome G3 SurePrint 8x60K Microarray (Agilent Technologies, USA), which detected a 4,85 Mb de novo interstitial deletion of 4q21.21-4q21.23. The clinical symptoms only partly overlap with reported 4q21 microdeletion cases. Among multiple annotated genes our patient is also haploinsufficient for the following genes: RASGEF1B being a strong candidate for the neurodevelopmental features and PRKG2 for severe growth delay.
  
  
  CONCLUSIONS
  The first Hungarian case of 4q21 deletion adds to the phenotypic spectrum of this novel microdeletion syndrome and underlines the importance of array CGH to uncover the heterogeneous causes of intellectual disability.
authors.affiliation: Department of Medical Genetics, Clinical Centre, University of Pecs, Szigeti Street 12, Pecs, H-7624 Hungary.|Szentágothai Research Centre, University of Pecs, Ifjusag Street 20, Pecs, H-7624 Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Komlósi
authors.affiliation: Department of Medical Genetics, Clinical Centre, University of Pecs, Szigeti Street 12, Pecs, H-7624 Hungary.|Szentágothai Research Centre, University of Pecs, Ifjusag Street 20, Pecs, H-7624 Hungary.
authors.forename: Balázs
authors.initials: B
authors.lastname: Duga
authors.affiliation: Department of Medical Genetics, Clinical Centre, University of Pecs, Szigeti Street 12, Pecs, H-7624 Hungary.|Szentágothai Research Centre, University of Pecs, Ifjusag Street 20, Pecs, H-7624 Hungary.
authors.forename: Kinga
authors.initials: K
authors.lastname: Hadzsiev
authors.affiliation: Department of Medical Genetics, Clinical Centre, University of Pecs, Szigeti Street 12, Pecs, H-7624 Hungary.|Szentágothai Research Centre, University of Pecs, Ifjusag Street 20, Pecs, H-7624 Hungary.
authors.forename: Márta
authors.initials: M
authors.lastname: Czakó
authors.affiliation: Department of Medical Genetics, Clinical Centre, University of Pecs, Szigeti Street 12, Pecs, H-7624 Hungary.|Szentágothai Research Centre, University of Pecs, Ifjusag Street 20, Pecs, H-7624 Hungary.
authors.forename: György
authors.initials: G
authors.lastname: Kosztolányi
authors.affiliation: Department of Neurology, Bethesda Children's Hospital, Bethesda Street 3, Budapest, H-1146 Hungary.
authors.forename: András
authors.initials: A
authors.lastname: Fogarasi
authors.affiliation: Department of Medical Genetics, Clinical Centre, University of Pecs, Szigeti Street 12, Pecs, H-7624 Hungary.|Szentágothai Research Centre, University of Pecs, Ifjusag Street 20, Pecs, H-7624 Hungary.
authors.forename: Béla
authors.initials: B
authors.lastname: Melegh
keywords: 4q21; Array CGH; Intellectual disability; Short stature; Submicroscopic deletion