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Imaging findings in a distinct lethal inherited arteriopathy syndrome associated with a novel mutation in the FBLN4 gene

  • Pediatric
  • Published:
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Abstract

Objectives

We present the imaging findings of a newly identified lethal arteriopathy associated with a novel mutation in the gene encoding fibulin-4, occurring in a distinct community from southern India.

Material and methods

A total of 31 children from a distinct population subgroup who presented with characteristic arterial dilatation and tortuosity were studied. All children except one belonged to unrelated families from an ethno-religious group (Muslim) from the northern coastal belt of southern India. CT angiography was performed in 30 children and contrast MRA in one.

Results

Impressive dilatation and elongation of ascending aorta, arch, descending aorta and main pulmonary arteries with characteristic narrowing of aortic isthmus were seen in all patients. Stenosis of arch branches, abdominal visceral branches and pulmonary artery branches was observed in 21 (68 %), 23 (62.5 %) and 20 (65 %) patients respectively. Genetic studies revealed an identical mutation in exon 7 of the FBLN4 gene. On follow-up, 27 of them had died before the age of 3 years and only two children were alive after the age of 4 years.

Conclusions

FBLN4-associated vasculopathy is a highly lethal disease characterized by severe aneurysmal dilatation of thoracic aorta, its branches and pulmonary arteries with stenoses at typical locations.

Key points

• Homozygous mutations in exon 7 of the FBLN4 gene can produce lethal vasculopathy.

• Fibulin-4 is a critical determinant in human elastogenesis.

• Imaging findings can give a clue to underlying connective tissue disorders

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Abbreviations

MDCT:

Multidetector computed tomography

MRA:

Magnetic resonance angiography

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Acknowledgements

The scientific guarantor of this publication is Dr. Srikanth Moorthy. The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article. This work was supported by grant nr. G.0094.06 from the Fund for Scientific Research-Flanders to A. De Paepe and by a Methusalem grant BOF08/ 01 M01108 from Ghent University to A. De Paepe. No complex statistical methods were necessary for this paper. Institutional review board approval was obtained. Written informed consent was obtained from all subjects (patients) in this study. Some study subjects or cohorts have been previously reported in Orphanet Journal of Rare Diseases 7:61, 2012. Methodology: prospective, observational, multicentre study.

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Authors and Affiliations

  1. Department of Radiology, Amrita Institute of Medical Sciences, AIMS (PO), Ernakulam, India, 682041

    Ramiah Rajeshkannan, Chinmay kulkarni & Srikanth Moorthy

  2. Department of pediatric cardiology, Amrita Institute of Medical Sciences, AIMS (PO), Ernakulam, India, 682041

    Mahesh Kappanayil

  3. Department of Pediatric Genetics, Amrita Institute of Medical Sciences, AIMS (PO), Ernakulam, India, 682041

    Sheela Nampoothiri

  4. Center for Medical Genetics, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium

    Fransiska Malfait & Anne De Paepe

Authors
  1. Ramiah Rajeshkannan
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  2. Chinmay kulkarni
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  3. Mahesh Kappanayil
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  4. Sheela Nampoothiri
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  5. Fransiska Malfait
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  6. Anne De Paepe
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Correspondence to Ramiah Rajeshkannan.

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Rajeshkannan, R., kulkarni, C., Kappanayil, M. et al. Imaging findings in a distinct lethal inherited arteriopathy syndrome associated with a novel mutation in the FBLN4 gene. Eur Radiol 24, 1742–1748 (2014). https://doi.org/10.1007/s00330-014-3205-y

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  • DOI: https://doi.org/10.1007/s00330-014-3205-y

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