{
  "abstract": "To evaluate the association between pupillary signs and the risk of late-diagnosed Hirschsprung disease (HD) and Malignant Neoplasm of the Adrenal Gland (MNAG) in pediatric patients with Congenital Central Hypoventilation Syndrome (CCHS), and to systematically review ocular manifestations in CCHS. We performed a retrospective cohort analysis with integrated systematic literature review. A cohort of 680 pediatric CCHS patients (2004–2024) was identified from the TriNetX US Collaborative Network. Patients with pre-existing HD or MNAG were excluded. CCHS patients with pupillary signs (ICD-10 codes H21.56, H57.0, G90.2) were compared to those without. Primary outcomes were subsequent HD diagnosis or MNAG at 3 and 5 years, assessed using adjusted Hazard Ratios (aHRs). A PRISMA-compliant systematic review of CCHS ocular findings was also performed. Among 680 CCHS patients (mean age 3.4 years), 38 (5.6%) had pupillary abnormalities. The presence of pupillary signs was significantly associated with an increased risk of subsequent HD diagnosis [5-year aHR, 4.93 (95% CI: 2.72–8.84; p < .001)] and MNAG [5-year aHR, 5.72 (95% CI: 2.31–14.33; p < .001)]. The systematic review (8 studies, n = 32 patients) found pupillary signs were present in 100% of tumor-positive patients and co-occurred with HD in 56%. Pupillary signs in pediatric CCHS were significantly associated with increased risk of subsequent HD diagnosis and MNAG. These findings are hypothesis-generating and support the incorporation of structured pupillary assessment into the multidisciplinary evaluation of pediatric CCHS patients, pending prospective validation.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "name": "Taher K. Eleiwa"
    },
    {
      "name": "Ahmed S. Bayoumy"
    },
    {
      "name": "Jamal O. Azhari"
    },
    {
      "name": "Ibrahim Abboud"
    },
    {
      "name": "Davina Malek"
    },
    {
      "name": "Eric D. Gaier"
    },
    {
      "name": "Paul H. Phillips"
    },
    {
      "name": "Abdelrahman M. Elhusseiny"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/52kdytrmcdwdj.bib",
  "cited_by": 0,
  "doi": "10.1038/s41598-026-67332-0",
  "fulltext_url": "https://doi.org/10.1038/s41598-026-67332-0",
  "id": "52kdytrmcdwdj",
  "issns": [
    "2045-2322"
  ],
  "landing_url": "https://www.nature.com/articles/s41598-026-67332-0",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "Q"
    ],
    [
      "lcc",
      "R"
    ],
    [
      "openalex",
      "2746|Congenital gastrointestinal and neural anomalies"
    ]
  ],
  "openalex": "W7223252484",
  "pdf_url": "https://www.nature.com/articles/s41598-026-67332-0.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-22",
  "publisher": "Springer Science and Business Media LLC",
  "ris": "https://research.draconitic.com/paper/52kdytrmcdwdj.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:33Z",
      "native_id": "10.1038/s41598-026-67332-0",
      "source": "crossref",
      "url": "https://www.nature.com/articles/s41598-026-67332-0"
    },
    {
      "first_seen": "2026-10-30T13:45:45Z",
      "native_id": "5e632c0c781f421b87bfcdaf91ea44e0",
      "source": "doaj",
      "url": "https://doi.org/10.1038/s41598-026-67332-0"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2746|Congenital gastrointestinal and neural anomalies",
      "subfield": "surgery"
    }
  ],
  "title": "Pupillary signs are associated with subsequent Hirschsprung disease diagnosis and malignant adrenal neoplasm in congenital central hypoventilation syndrome",
  "title_text": "Pupillary signs are associated with subsequent Hirschsprung disease diagnosis and malignant adrenal neoplasm in congenital central hypoventilation syndrome",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:45:45Z",
  "url": "https://research.draconitic.com/paper/52kdytrmcdwdj",
  "venue": "Scientific Reports",
  "versions": []
}