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Neonatal diagnosis of primary ciliary dyskinesia in a high consanguinity population: a single tertiary center experience

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Abstract

Though PCD usually presents after birth in term neonates, diagnosing PCD during the neonatal and infancy stages is uncommon, particularly in children who do not exhibit laterality defects. We report our recent experience with the diagnosis of PCD in the neonatal and early infantile period in a highly consanguine population. This was achieved by implementing a novel genetic-based diagnostic approach based on direct testing for recognized regional genetic variants. We conducted a retrospective analysis of children diagnosed with PCD at Soroka University Medical Center during the neonatal or early infantile period between 2020 and 2023. We included children under 3 months of age who had a genetic confirmation of PCD, as evidenced by the presence of two pathogenic variants in recognized genes. Genetic testing targeted regional genetic variants in previously identified PCD genes. Eight patients were included. The median age at diagnosis was 12.5 days. Three (38%) were born prematurely < 34 weeks gestational age. All patients were presented with respiratory distress and hypoxemia after birth. The median duration of oxygen support was 23 days, and upper lobe atelectasis was present in five patients (63%). Congenital cardiac malformation was present in four patients. Organ laterality defects were present in four patients. Genetic mutations identified were in the DNAAF5, DNAL1, DNAAF3, and DNAH1 genes.

     Conclusion: Neonatal diagnosis of PCD is uncommon, especially in atypical presentations such as children without laterality defects or preterms. Focusing on a genetic diagnosis of the local tribal pathogenic variants promotes a potential cost-efficient test leading to earlier diagnosis. There is a need for a standardized protocol for earlier diagnosis of PCD in high-consanguinity areas.

What is Known:

• Primary ciliary dyskinesia (PCD) typically presents after birth in term neonates.

• Diagnosing PCD during neonatal and infancy stages is challenging, particularly in children without laterality defects.

What is New:

• A novel genetic-based diagnostic approach was implemented on the neonatal population in a highly consanguine community, focusing on direct testing for regional genetic variants, leading to early and rapid diagnosis of PCD.

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No datasets were generated or analysed during the current study.

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Acknowledgements

We extend our appreciation to Dr. Shirly Amar, Ph.D., for her invaluable assistance in obtaining the genetic data for this study.

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Authors and Affiliations

  1. Pediatric Pulmonology Unit, Faculty of Health Sciences, Soroka University Medical Center, Ben Gurion University, PO box 151, Beer-Sheva, Israel

    Noga Arwas, Dvir Gatt, Micha Aviram, Guy Hazan, Aviv Goldbart & Inbal Golan-Tripto

  2. Neonatology Unit, Soroka University Medical Center, Beer-Sheva, Israel

    Ramy Abramsky

  3. Pediatric Pulmonology Unit, Dana-Dwek Children’s Hospital, Tel Aviv, Israel

    Israel Amirav

Authors
  1. Noga Arwas
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  2. Dvir Gatt
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  3. Micha Aviram
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  4. Ramy Abramsky
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  5. Guy Hazan
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  6. Aviv Goldbart
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  7. Israel Amirav
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  8. Inbal Golan-Tripto
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Contributions

I.G, D.G and I.A conceptualized the article and revised the manuscript, N.A wrote the main manuscript text and M.A, R.A., G.H and A.G provided patients data and revised the manuscript. All authors reviewed the manuscript

Corresponding author

Correspondence to Noga Arwas.

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Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Soroka University Medical Center.

Competing interests

The authors declare no competing interests.

Additional information

Communicated by Peter de Winter

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Arwas, N., Gatt, D., Aviram, M. et al. Neonatal diagnosis of primary ciliary dyskinesia in a high consanguinity population: a single tertiary center experience. Eur J Pediatr (2024). https://doi.org/10.1007/s00431-024-05574-8

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  • DOI: https://doi.org/10.1007/s00431-024-05574-8

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