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CT-defined phenotype of pulmonary artery stenoses in Alagille syndrome

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Abstract

Background

Alagille syndrome is a rare disorder commonly associated with pulmonary artery stenosis. Studies exist discussing the cardiovascular sequela but no consistent phenotype, or pattern of pulmonary artery stenosis, has been described.

Objective

The objective of this study was to characterize the distribution and severity of pulmonary artery stenosis in patients with Alagille syndrome based on computed tomography angiography.

Materials and methods

A retrospective chart review identified patients with Alagille syndrome who had undergone CT angiography. Pulmonary trunk (MPA), left main pulmonary artery (LPA) and right main pulmonary artery (RPA) diameters in Alagille patients were compared with those from matched control subjects. Stenoses at lobar and segmental pulmonary arteries were categorized as: Grade 1 (<33% stenosis), Grade 2 (33-66% stenosis) or Grade 3 (>66% stenosis). Involvement among the different lung regions was then compared.

Results

Fifteen patients ages 6 months to 17 years were identified; one had surgical augmentation of the central pulmonary arteries and was excluded from the central (main, right and left) pulmonary artery analysis. The proximal LPA and RPA, but not the MPA, were significantly smaller than those of the control subjects (P<0.01). The proximal LPA was significantly smaller than the proximal RPA (P<0.01) in the Alagille group (0.55 LPA:RPA ratio). Within the Alagille group, 75% of the lobar and segmental branches showed mild or no stenoses (Grade 1), 17% showed moderate stenosis (Grade 2) and 8% showed severe stenosis (Grade 3). While not statistically significant, the right lung demonstrated a greater percentage of Grades 2 and 3 stenoses (28%, right vs. 20% left, P=0.1). The right middle and lingula lobes of both lungs showed more Grade 2 and 3 stenoses (33% upper/middle vs. 18% lower, P<0.01).

Conclusion

We describe a common pattern pulmonary artery stenosis in Alagille patients consisting of severe proximal LPA stenosis, heavy involvement of the lobar and segmental branches (more often right than left), and a greater involvement of the upper lobes. Knowledge of this phenotypic pattern can help in the diagnosis of Alagille syndrome in patients presenting with pulmonary artery stenosis.

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References

  1. Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: 118450: 1/30/2014. World Wide Web URL: http://omim.org/

  2. Crosnier C, Attié-Bitach T, Encha-Razavi F et al (2004) JAGGED1 gene expression during human embryogenesis elucidates the wide phenotypic spectrum of Alagille syndrome. Hepatology 32:574–581

    Article  Google Scholar 

  3. McElhinney DB, Krantz ID, Bason L et al (2002) Analysis of cardiovascular phenotype and genotype–phenotype correlation in individuals with a JAG1 mutation and/or Alagille syndrome. Circulation 106:2567–2574

    Article  PubMed  Google Scholar 

  4. Alagille D, Estrada A, Hadchouel M et al (1987) Syndromic paucity of interlobular bile ducts (Alagille syndrome or arteriohepatic dysplasia): review of 80 cases. J Pediatr 110:195–200

    Article  CAS  PubMed  Google Scholar 

  5. Kamath BM, Bason L, Piccoli DA et al (2003) Consequences of JAG1 mutations. J Med Genet 40:891–895

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Oda T, Elkahloun AG, Pike BL et al (1997) Mutations in the human Jagged1 gene are responsible for Alagille syndrome. Nat Genet 16:235–242

    Article  CAS  PubMed  Google Scholar 

  7. Emerick KM, Rand EB, Goldmuntz E et al (1999) Features of Alagille syndrome in 92 patients: frequency and relation to prognosis. Hepatology 29:822–829

    Article  CAS  PubMed  Google Scholar 

  8. Tzakis AG, Reyes J, Tepetes K et al (1993) Liver transplantation for Alagille’s syndrome. Arch Surg 128:337–339

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Bauer RC, Laney AO, Smith R et al (2010) Jagged1 (JAG1) mutations in patients with tetralogy of Fallot or pulmonic stenosis. Hum Mutat 31:594–601

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kamath BM, Spinner NB, Emerick KM et al (2004) Vascular anomalies in Alagille syndrome a significant cause of morbidity and mortality. Circulation 109:1354–1358

    Article  PubMed  Google Scholar 

  11. Deak PD, Smal Y, Kalender WA (2010) Multisection CT protocols: sex- and age-specific conversion factors used to determine effective dose from dose-length product. Radiology 257:158–166

    Article  PubMed  Google Scholar 

  12. Boone J, Strauss K, Cody D et al (2011) Size-specific dose estimates (SSDE) in pediatric and adult body CT exams. Report of AAPM Task Group 204

  13. Sluysmans T, Colan SD (2009) Structural measurements and adjustment for growth. In: Lai WW, Cohen MS, Geva T, Mertens L (eds) Echocardiography in pediatric and congenital heart disease. Wiley-Blackwell, West Sussex, UK, pp 53–63

  14. Morrow D, Guha S, Sweeney C et al (2008) Notch and vascular smooth muscle cell phenotype. Circ Res 103:1370–1382

    Article  CAS  PubMed  Google Scholar 

  15. Tricarico F, Hlavacek AM, Schoepf UJ et al (2013) Cardiovascular CT angiography in neonates and children: image quality and potential for radiation dose reduction with iterative image reconstruction techniques. Eur Radiol 23:1306–1315

    Article  PubMed  Google Scholar 

  16. Mayo J, Thakur Y (2013) Pulmonary CT angiography as first-line imaging for PE: image quality and radiation dose considerations. AJR Am J Roentgenol 200:522–528

    Article  PubMed  Google Scholar 

  17. Nawaz A, Litt HI, Stavropoulos SW et al (2008) Digital subtraction pulmonary arteriography versus multidetector CT in the detection of pulmonary arteriovenous malformations. J Vasc Interv Radiol 19:1582–1588

    Article  PubMed  Google Scholar 

  18. Chandrashekhar G, Sodhi KS, Saxena AK et al (2012) Correlation of 64 row MDCT, echocardiography and cardiac catheterization angiography in assessment of pulmonary arterial anatomy in children with cyanotic congenital heart disease. Eur J Radiol 81:4211–4217

    Article  PubMed  Google Scholar 

  19. Lee EY, Jenkins KJ, Muneeb M et al (2013) Proximal pulmonary vein stenosis detection in pediatric patients: value of multiplanar and 3-D VR imaging evaluation. Pediatr Radiol 43:929–936

    Article  PubMed  Google Scholar 

  20. Monge MC, Mainwaring RD, Sheikh AY et al (2013) Surgical reconstruction of peripheral pulmonary artery stenosis in Williams and Alagille syndromes. J Thorac Cardiovasc Surg 145:476–481

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatrics (Cardiology), Packard Children’s Hospital, Stanford University Medical Center, 750 Welch Road, Suite 305, Palo Alto, CA, 94304, USA

    Renee M. Rodriguez & Jeffrey A. Feinstein

  2. Department of Bioengineering, Stanford University, Palo Alto, CA, USA

    Jeffrey A. Feinstein

  3. Department of Radiology, Stanford University, Palo Alto, CA, USA

    Frandics P. Chan

Authors
  1. Renee M. Rodriguez
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  2. Jeffrey A. Feinstein
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  3. Frandics P. Chan
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Correspondence to Jeffrey A. Feinstein.

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Rodriguez, R.M., Feinstein, J.A. & Chan, F.P. CT-defined phenotype of pulmonary artery stenoses in Alagille syndrome. Pediatr Radiol 46, 1120–1127 (2016). https://doi.org/10.1007/s00247-016-3580-4

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  • DOI: https://doi.org/10.1007/s00247-016-3580-4

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