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Open Access Research

Twenty patients including 7 probands with autosomal dominant cutis laxa confirm clinical and molecular homogeneity

Smail Hadj-Rabia1*, Bert L Callewaert2*, Emmanuelle Bourrat3, Marlies Kempers4, Astrid S Plomp5, Valerie Layet6, Deborah Bartholdi7, Marjolijn Renard2, Julie De Backer2, Fransiska Malfait2, Olivier M Vanakker2, Paul J Coucke2, Anne M De Paepe2 and Christine Bodemer1

Author Affiliations

1 Service de Dermatologie – Centre de référence national des Maladies Génétiques à Expression Cutanée (MAGEC), INSERM U781, Hôpital Necker - Enfants Malades, Université Paris V-Descartes, 149, rue de Sèvres 75743 Paris Cedex 15, Paris, France

2 Center for Medical Genetics, Ghent University Hospital, De Pintelaan 185, B-9000, Ghent, Belgium

3 Service de Dermatologie, MAGEC Hôpital Saint-Louis, Paris, France

4 University Medical Center St. Radboud, Nijmegen, the Netherlands

5 Academic Medical Center, Amsterdam, the Netherlands

6 Groupe Hospitalier Du Havre – Department of Medical Genetics, Le Havre, France

7 Institute of Medical Genetics, University of Zürich, Zürich, Switzerland

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Orphanet Journal of Rare Diseases 2013, 8:36  doi:10.1186/1750-1172-8-36

Published: 25 February 2013

Abstract

Background

Elastin gene mutations have been associated with a variety of phenotypes. Autosomal dominant cutis laxa (ADCL) is a rare disorder that presents with lax skin, typical facial characteristics, inguinal hernias, aortic root dilatation and pulmonary emphysema. In most patients, frameshift mutations are found in the 3’ region of the elastin gene (exons 30-34) which result in a C-terminally extended protein, though exceptions have been reported.

Methods

We clinically and molecularly characterized the thus far largest cohort of ADCL patients, consisting of 19 patients from six families and one sporadic patient.

Results

Molecular analysis showed C-terminal frameshift mutations in exon 30, 32, and 34 of the elastin gene and identified a mutational hotspot in exon 32 (c.2262delA). This cohort confirms the previously reported clinical constellation of skin laxity (100%), inguinal hernias (51%), aortic root dilatation (55%) and emphysema (37%).

Conclusion

ADCL is a clinically and molecularly homogeneous disorder, but intra- and interfamilial variability in the severity of organ involvement needs to be taken into account. Regular cardiovascular and pulmonary evaluations are imperative in the clinical follow-up of these patients.

Keywords:
Elastin; ELN; Autosomal dominant cutis laxa; Genotype; Phenotype