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


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.


CONCLUSIONS
• 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.
Department of Radiology, Amrita Institute of Medical Sciences, AIMS (PO), Ernakulam, India, 682041, rajeshkannanmdrd@gmail.com.
Ramiah
R
Rajeshkannan
Chinmay
C
kulkarni
Mahesh
M
Kappanayil
Sheela
S
Nampoothiri
Fransiska
F
Malfait
Anne
A
De Paepe
Srikanth
S
Moorthy
D000792:Angiography; D001158:Arteries / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D003952:Diagnostic Imaging / Q000379:methods*; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018810:Magnetic Resonance Angiography; D008297:Male; D061330:Multidetector Computed Tomography; D009154:Mutation; D015203:Reproducibility of Results; D013577:Syndrome; D061205:Vascular Calcification / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism
C403672:EFEMP2 protein, human; D016326:Extracellular Matrix Proteins; D004247:DNA