Longer Term Survival of a Child With Autosomal Recessive Cutis Laxa Due to a Mutation in FBLN4
Article first published online: 26 MAR 2013
Copyright © 2013 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 161, Issue 5, pages 1148–1153, May 2013
How to Cite
2013. Longer term survival of a child with autosomal recessive cutis laxa due to a mutation in FBLN4. Am J Med Genet Part A 161A:1148–1153., , , , , , , .
- Issue published online: 22 APR 2013
- Article first published online: 26 MAR 2013
- Manuscript Accepted: 4 DEC 2012
- Manuscript Received: 8 MAY 2012
- autosomal recessive cutis laxa;
- FIBULIN 4;
- homozygosity mapping;
- arterial tortuosity
Autosomal recessive cutis laxa (ARCL) is a clinically and genetically heterogeneous group of disorders characterized by loose, inelastic skin and variable systemic involvement and severity. Mutations in the FBLN4 gene are associated with ARCL1B. Fibulin-4 is important in elastic fiber formation and smooth muscle cell differentiation. We describe herein an 8-year-old boy who presented with severe aortic root dilatation and arterial tortuosity at 1 year of age which required surgical repair. His parents were consanguineous and there was a family history of three brothers who died early in life with an unknown type of connective tissue disorder in the 1960s. Both parents of the patient reported here were related to these three boys. We used a homozygosity mapping strategy with a 900K SNP array and identified FBLN4 as a candidate gene in an extended region of homozygosity. We sequenced this gene in the patient and identified a homozygous non-synonymous mutation at c.376G>A (p.Glu126Lys) in exon 5 that was predicted to be damaging. ARCL1B has most typically been associated with early demise but our report suggests that long-term survival is possible. With this longer term survival we are learning more about the natural history of this disorder, which includes baroreceptor reflex failure and low bone mineral density in this patient. © 2013 Wiley Periodicals, Inc.