Phenotypic variability in a Hungarian patient with the 4q21 microdeletion syndrome

Molecular Cytogenetics

Béla Melegh²  András Fogarasi¹  György Kosztolányi²  Márta Czakó²  Kinga Hadzsiev²  Balázs Duga²  Katalin Komlósi² 

[1]Department of Neurology, Bethesda Children’s Hospital, Bethesda Street 3, Budapest H-1146, Hungary

[2]Szentágothai Research Centre, University of Pecs, Ifjusag Street 20, Pecs H-7624, Hungary

关键词: Intellectual disability;    Short stature;    4q21;    Array CGH;    Submicroscopic deletion;   

Others  :  1139688
DOI  :  10.1186/s13039-015-0118-7

 received in 2014-11-17, accepted in 2015-02-13,  发布年份 2015

【 摘 要 】

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.

Conclusion

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.

【 授权许可】

   
2015 Komlosi et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

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