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Case Reports
. 2016 Jun;24(6):830-7.
doi: 10.1038/ejhg.2015.202. Epub 2015 Sep 23.

9q33.3q34.11 microdeletion: new contiguous gene syndrome encompassing STXBP1, LMX1B and ENG genes assessed using reverse phenotyping

Sophie Nambot  1   2 , Alice Masurel  1 , Salima El Chehadeh  1 , Anne-Laure Mosca-Boidron  2 , Christel Thauvin-Robinet  1   3 , Mathilde Lefebvre  1 , Nathalie Marle  2 , Julien Thevenon  1   2 , Stéphanie Perez-Martin  4 , Véronique Dulieu  5 , Frédéric Huet  4 , Ghislaine Plessis  6 , Joris Andrieux  7 , Pierre-Simon Jouk  8   9 , Gipsy Billy-Lopez  8 , Charles Coutton  10 , Fanny Morice-Picard  11 , Marie-Ange Delrue  11 , Delphine Heron  12 , Caroline Rooryck  13 , Alice Goldenberg  14 , Pascale Saugier-Veber  14 , Géraldine Joly-Hélas  15 , Patricia Calenda  16 , Paul Kuentz  3 , Sylvie Manouvrier-Hanu  17   18 , Sophie Dupuis-Girod  19 , Patrick Callier  2   3 , Laurence Faivre  1   3
Affiliations
Case Reports

9q33.3q34.11 microdeletion: new contiguous gene syndrome encompassing STXBP1, LMX1B and ENG genes assessed using reverse phenotyping

Sophie Nambot et al. Eur J Hum Genet. 2016 Jun.

Abstract

The increasing use of array-CGH in malformation syndromes with intellectual disability could lead to the description of new contiguous gene syndrome by the analysis of the gene content of the microdeletion and reverse phenotyping. Thanks to a national and international call for collaboration by Achropuce and Decipher, we recruited four patients carrying de novo overlapping deletions of chromosome 9q33.3q34.11, including the STXBP1, the LMX1B and the ENG genes. We restrained the selection to these three genes because the effects of their haploinsufficency are well described in the literature and easily recognizable clinically. All deletions were detected by array-CGH and confirmed by FISH. The patients display common clinical features, including intellectual disability with epilepsy, owing to the presence of STXBP1 within the deletion, nail dysplasia and bone malformations, in particular patellar abnormalities attributed to LMX1B deletion, epistaxis and cutaneous-mucous telangiectasias explained by ENG haploinsufficiency and common facial dysmorphism. This systematic analysis of the genes comprised in the deletion allowed us to identify genes whose haploinsufficiency is expected to lead to disease manifestations and complications that require personalized follow-up, in particular for renal, eye, ear, vascular and neurological manifestations.

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Figures

Figure 1
Figure 1
Facial dysmorphism of the four patients. (a) Patient 1 at 3 years and 9 months: Round face, prominent metopic ridge, large and high forehead, highly arched eyebrows, horizontal palpebral fissures, telecanthus, strabismus, bulbous nose, small mouth, thin upper lip, prominent cheeks, and square chin. (b) Patient 2 at 4 years: Round face, large and high forehead, highly arched eyebrows, horizontal palpebral fissures, telecanthus, strabismus, dysplastic and low-set ears, bulbous nose, small mouth, thin upper lip, prominent cheeks, and square chin. (c) Patient 3 at 9.5 years: Brachycephaly, round face, prominent metopic ridge, large and high forehead, highly arched eyebrows, horizontal palpebral fissures, enophtalmia, bulbous nose, small mouth, thin lips, prominent cheeks, and square chin. (d) Patient 4 at 1 year: Asymmetric plagiocephaly, round face, high hairline at the temples, horizontal palpebral fissures, strabismus, low-set ears, wide saddle nose, bulbous nose, convex philtrum, prominent cheeks, thin lips, square chin, and short and webbed neck. A full color version of this figure is available at the European Journal of Human Genetics journal online.
Figure 2
Figure 2
Features of NPS and HHT1 of patient 4. (a) Cutaneous telangiectasias; (b) fingernail dysplasia; (c) absence of patella; (d) scoliosis. A full color version of this figure is available at the European Journal of Human Genetics journal online.
Figure 3
Figure 3
Alignment of the 9q33.3q34.11 deletion of the four index patients.
See this image and copyright information in PMC

References

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