Generalized arterial calcification of infancy: phenotypic spectrum among three siblings including one case without obvious arterial calcifications.
Generalized arterial calcification of infancy (GACI) (OMIM no. 208000) is characterized by calcification of the major arteries and soft tissues and associated with mutations in the ENPP1 gene. Most affected patients die within the first 6 months of life although prolonged survival is increasingly recognized. We report on three siblings with GACI and striking phenotypic variability. Two siblings (including the sibling survivor) were compound heterozygotes for mutations in exon 7 (c.783C>G (p.Y261X)) and exon 8 (c. 878_879delAA (p.K293fsX5)) of the ENPP1 gene confirming the diagnosis of GACI. The sibling survivor did not have calcification on X-ray studies or evidence of hypophosphatemic rickets. GACI may be under recognized and we emphasize consideration of this condition in patients with multiple arterial stenosis even in the absence of radiographic calcification. This adds to the expanding phenotype of GACI and supports a potential role for modifying genes.
Dlamini
Nomazulu
N
Department of Paediatric Neurology, Evelina Children's Hospital, St Thomas' Hospital, London, UK.
Splitt
Miranda
M
Durkan
Anne
A
Siddiqui
Ata
A
Padayachee
Soundrie
S
Hobbins
Sue
S
Rutsch
Frank
F
Wraige
Elizabeth
E
D001158:Arteries / Q000000981:diagnostic imaging / Q000503:physiopathology*; D002114:Calcinosis / Q000175:diagnosis / Q000235:genetics*; D005091:Exons; D006579:Heterozygote; D006801:Humans; D050498:Live Birth; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D010727:Phosphoric Diester Hydrolases / Q000235:genetics*; D011755:Pyrophosphatases / Q000235:genetics*; D035781:Siblings; D050497:Stillbirth / Q000235:genetics; D014463:Ultrasonography; D014652:Vascular Diseases / Q000235:genetics*
D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases