Antenatal diagnosis of idiopathic infantile arterial calcification (IIAC): a single centre experience and review of the literature

Abstract

Background: Idiopathic infantile arterial calcification (IIAC) is a rare autosomal recessive disorder characterised by extensive calcification and proliferation of the intimal layer of the large and medium size arteries. Case presentation: We report 4 antenatal cases of IIAC in our institution over a 10 year period from 2006 to 2016. Clinical outcomes, prenatal ultrasound findings, radiological and postmortem investigations are summarized. A literature review of this rare autosomal recessive disease is presented. The possible aetiology of this condition and the role of biphosphonates in the management of this condition are discussed. Conclusions: This case series highlights the frequent poor outcome of IIAC, consistent with the literature, the phenotypical variability of the disease even within the same family and the role of biphosphonates in one prenatally diagnosed case. Hyperechogenicity of the fetal vasculature detected on prenatal ultrasound particularly if there is a history of IIAC in an index pregnancy may aid earlier prenatal diagnosis. A multidisciplinary approach to parental counselling can then occur in order to optimise a plan of care in the neonatal period.

Severe early-onset manifestations of generalized arterial calcification of infancy (mimicking severe coarctation of the aorta) with ABCC6 gene variant — Case report and literature review

“…In most cases (67%), causal mutations have been identified in the genes ENPP1 (GACI-1) ( 1 ). There are many studies reporting the mutations in ENPP1 in patients with GACI ( 2 , 4 , 17 – 20 ). In 9% of cases, GACI results from biallelic inactivating variants in ABCC6 (GACI-2) ( 1 ).…”

“…Generalized arterial calcification of infancy (GACI) is an autosomal recessive condition characterized by extensive calcification and intimal proliferation of the large and medium arteries, including the aorta, coronary arteries, and renal arteries, leading to vascular stenosis ( 1 , 2 ). The most frequent complications include severe systemic hypertension, heart failure, myocardial infarction, respiratory distress, and sudden death.…”

ENPP1 deficiency: A clinical update on the relevance of individual variants using a locus‐specific patient database

“…The clinical presentation of ENPP1 Deficiency in infants, typically described as GACI, is characterized by arterial calcification, stenosis of large and medium‐sized vessels and severe CV problems such as systemic hypertension, pulmonary hypertension, heart failure, cardiomyopathy or myocardial ischemia/infarction (Ferreira, Hackbarth, et al, 2021; Rutsch et al, 2008). Infants may also present with seizures or stroke, attributed to calcification of the cerebral arteries (Ferreira, Hackbarth, et al, 2021; Ferreira, Kintzinger, et al, 2021; Mulcahy et al, 2019). Calcification of organs and joints are also observed (Ferreira, Hackbarth, et al, 2021).…”

Editorial: Case reports in pediatric cardiology 2022

“…Generalized arterial calcification of infancy (GACI) is an autosomal recessive condition characterized by extensive calcification and intimal proliferation of the large and medium arteries, including the aorta, coronary arteries, and renal arteries ( 2 ). This leads to vascular stenosis and a range of complications, such as severe systemic hypertension and heart failure.…”