Two autopsy cases of siblings with alveolar capillary dysplasia: clinical and post-mortem issues

Abstract

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare but fatal lung disorder, which causes persistent pulmonary hypertension of the newborn (PPHN) and which is unresponsive to treatment. We report the case of two siblings, both of whom died a few hours after birth because of severe pulmonary failure. Post-mortem histology confirmed ACD/MPV as the cause of death in both cases, and genetic analysis identified the same 16p13.3 deletion. ACD/MPV can occur suddenly in apparently healthy newborns after a regular pregnancy, and always leads to death. Nevertheless, an autopsy is not always performed after the death of an infant. For these reasons ACD/MPV represents a challenge for diagnosis and therapeutic management with medicolegal implications. Prenatal assessment of ACD/MPV is very difficult, and it should be suspected when irreversible and persistent fetal circulation occurs rapidly in newborns. An early diagnosis during pregnancy would facilitate adequate counselling regarding treatment and prognosis. When death occurs, a complete autopsy with histological and genetic investigations is recommended in order to define the exact cause of death, and potentially inform appropriate genetic counselling of family members who could be affected by hereditary disorders.

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References

  1. 1.

    Bishop NB, Stankiewicz P, Steinhorn RH. Alveolar capillary dysplasia. Am J Respir Crit Care Med. 2011;184:172–9.

    Article  Google Scholar 

  2. 2.

    Luk HM, Tang T, Choy KWR, Tong MFT, Wong OK, Lo FMI. Maternal somatic mosaicism of FOXF1 mutation causes recurrent alveolar capillary dysplasia with misalignment of pulmonary veins in siblings. Am J Med Genet A. 2016;170:1942–4.

    Article  Google Scholar 

  3. 3.

    Eulmesekian P, Cutz E, Parvez B, Bohn D, Adatia I. Alveolar capillary dysplasia: a six-year single center experience. J Perinat Med. 2005;33:347–52.

    Article  Google Scholar 

  4. 4.

    Janney CG, Askin FB, Kuhn G. Congenital alveolar capillary dysplasia – an unusual cause of respiratory distress in the newborn. Am J Clin Pathol. 1981;76:722–7.

    CAS  Article  Google Scholar 

  5. 5.

    Miranda J, Rocha G, Soares H, Vilan A, Brandão O, Guimarães H. Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV): a case series. Case Rep Crit Care. 2013;2013:327250.

    PubMed  PubMed Central  Google Scholar 

  6. 6.

    Stankiewicz P, Sen P, Bhatt SS, Storer M, Xia Z, Bejjani BA, et al. Genomic and genic deletions of the FOX gene cluster on 16q24.1 and inactivating mutations of FOXF1 cause alveolar capillary dysplasia and other malformations. Am J Hum Genet. 2009;84:780–91.

    CAS  Article  Google Scholar 

  7. 7.

    Slot E, Edel G, Cutz E, van Heijst A, Post M, Schnater M, et al. Alveolar capillary dysplasia with misalignment of the pulmonary veins: clinical, histological, and genetic aspects. Pulm Circ. 2018;8:1–8.

    CAS  Article  Google Scholar 

  8. 8.

    Goel D, Oei JL, Shand AW, Mowat D, Loo C. FOXF1 gene mutation in alveolar capillary dysplasia associated with Hirschsprung's disease and clinical review. J Paediatr Child Health. 2016;52:787–8.

    Article  Google Scholar 

  9. 9.

    Obata-Yasuoka M, Hamada H, Ohara R, Nakao A, Miyazono Y, Yoshikawa H. Alveolar capillary dysplasia associated with duodenal atresia: ultrasonographic findings of enlarged, highly echogenic lungs and gastric dilatation in a third-trimester fetus. J ObstetGynaecol Res. 2011;37:937–9.

    Google Scholar 

  10. 10.

    Shimizu T, Fukuda T, Inomata S, Satsumae T, Tanaka M. A novel association of alveolar capillary dysplasia, atypical duodenal atresia, and subglottic stenosis. J Anesth. 2011;25:298–300.

    Article  Google Scholar 

  11. 11.

    Uhrikova Z, Matasova K, Jurko A Jr, Zibolen M. Alveolar capillary dysplasia with anorectal anomaly. Indian Pediatr. 2011;48:803–4.

    PubMed  Google Scholar 

  12. 12.

    Bellamkonda-Athmaram V, Sulman CG, Basel DG, Southern J, Konduri GG, Basir MA. Alveolar capillary dysplasia with multiple congenital anomalies and bronchoscopic airway abnormalities. J Perinatol. 2014;34:326–8.

    CAS  Article  Google Scholar 

  13. 13.

    Antao B, Samuel M, Kiely E, Spitz L, Malone M. Congenital alveolar capillary dysplasia and associated gastrointestinal anomalies. Fetal Pediatr Pathol. 2006;25:137–45.

    CAS  Article  Google Scholar 

  14. 14.

    Razak A, Mohanty PK, Nagesh KN. Alveolar capillary dysplasia as a cause of persistent pulmonary hypertension. Indian Pediatr. 2015;52:984–6.

    Article  Google Scholar 

  15. 15.

    Inwald D, Brown K, Gensini F, Malone M, Goldman A. Open lung biopsy in neonatal and paediatric patients referred for extracorporeal membrane oxygenation (ECMO). Thorax. 2004;59:328–33.

    CAS  Article  Google Scholar 

  16. 16.

    Abu-Shaweesh M. Respiratory disorders in preterm and term infants. In: Martin RJ, Fanaroff AA, Walsh MC, editors. Fannaroff and Martin’s neonatal-perinatal medicine. Diseases of the fetus and infant. St Louis: Elsevier Mosby; 2011. p. 1141–70.

    Google Scholar 

  17. 17.

    Shankar V, Haque A, Johnson J, Pietsch J. Late presentation of alveolar capillary dysplasia in an infant. Pediatr Crit Care Med. 2006;7:177–9.

    Article  Google Scholar 

  18. 18.

    Michalsky MP, Arca MJ, Groenman F, Hammond S, Tibboel D, Caniano DA. Alveolar capillary dysplasia: a logical approach to a fatal disease. J Pediatr Surg. 2005;40:1100–5.

    Article  Google Scholar 

  19. 19.

    Al-Hathlol K, Phillips S, Seshia MK, Casiro O, Alvaro RE, Rigatto H. Alveolar capillary dysplasia. Report of a case of prolonged life without extracorporeal membrane oxygenation (ECMO) and review of the literature. Early Hum Dev. 2000;57:85–94.

    CAS  Article  Google Scholar 

  20. 20.

    Edwards JJ, Murali C, Pogoriler J, Frank DB, Handler SS, Deardorff MA, et al. Histopathologic and genetic features of alveolar capillary dysplasia with atypical late presentation and prolonged survival. J Pediatr. 2019;210:214–9.

    Article  Google Scholar 

  21. 21.

    Ma Y, Jang M, Yoo HS, Ahn SY, Sung SI, Chang YS, et al. A novel de novo pathogenic variant in FOXF1 in a newborn with alveolar capillary dysplasia with misalignment of pulmonary veins. Yonsei Med J. 2017;58:672–5.

    Article  Google Scholar 

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Correspondence to Lucia Tattoli.

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Petetta, C., Tattoli, L., Botta, G. et al. Two autopsy cases of siblings with alveolar capillary dysplasia: clinical and post-mortem issues. Forensic Sci Med Pathol 16, 180–183 (2020). https://doi.org/10.1007/s12024-019-00153-y

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Keywords

  • Alveolar capillary dysplasia
  • Pulmonary veins
  • Autopsy
  • Neonatal death
  • Pulmonary hypertension