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Generalized arterial calcification of infancy: Phenotypic spectrum among three siblings including one case without obvious arterial calcifications
Author(s) -
Dlamini Nomazulu,
Splitt Miranda,
Durkan Anne,
Siddiqui Ata,
Padayachee Soundrie,
Hobbins Sue,
Rutsch Frank,
Wraige Elizabeth
Publication year - 2009
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.32646
Subject(s) - sibling , calcification , phenotype , medicine , gene , biology , genetics , pathology , psychology , developmental psychology
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. © 2009 Wiley‐Liss, Inc.