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Lymphatic Abnormalities in Noonan Syndrome Extend Beyond Clinically Apparent Disease.

Inger Norlyk Sheyanth1,2, Benjamin Kelly1, Sheyanth Mohanakumar3,4

  • 1Department of Cardiothoracic Surgery, Rigshospitalet, Copenhagen, Denmark.

American Journal of Medical Genetics. Part A
|May 3, 2026
PubMed
Summary

Central lymphatic abnormalities are common in Noonan syndrome (NS), even without symptoms. Peripheral lymphatic conduction issues develop later, indicating lymphatic imaging is key for diagnosis and monitoring NS patients.

Keywords:
Noonan syndromeT2‐weighted magnetic resonance lymphangiographycentral conducting lymphatic anomalylymphatic anomaliesnear‐infrared fluorescence imaging

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Area of Science:

  • Cardiovascular Imaging
  • Lymphatic Physiology
  • Genetic Syndromes

Background:

  • Lymphatic disease is a known Noonan syndrome (NS) manifestation, but its full spectrum, particularly in asymptomatic individuals, is not well understood.
  • Understanding lymphatic system involvement in NS is crucial for comprehensive patient care and diagnosis.

Purpose of the Study:

  • To investigate central and peripheral lymphatic system abnormalities in individuals with Noonan syndrome.
  • To determine if lymphatic abnormalities are present in asymptomatic NS individuals.
  • To correlate lymphatic findings with clinical presentation, specifically lymphedema.

Main Methods:

  • Cross-sectional study comparing 10 NS individuals (4 with lymphedema, 6 without) and 10 healthy controls.
  • Central lymphatic anatomy assessed via non-contrast T2-weighted MR-lymphangiography.
  • Peripheral lymphatic morphology and function evaluated using near-infrared fluorescence (NIRF) imaging and strain gauge plethysmography (SGP).

Main Results:

  • Significant variations in thoracic duct morphology (89% in NS vs. 20% in controls) and thoracic lymphatic classifications were observed in NS individuals.
  • Central lymphatic abnormalities were present in 5/9 NS individuals, including 3 without clinical signs of lymphatic disease.
  • Abnormal peripheral lymphatic conduction (retrograde or absent flow) was detected in all NS individuals with lymphedema, but not in asymptomatic NS individuals or controls.

Conclusions:

  • Central lymphatic abnormalities are prevalent in Noonan syndrome, irrespective of clinical symptoms.
  • Abnormal peripheral lymphatic conduction appears to be a later development associated with clinically evident lymphedema.
  • Lymphatic imaging offers valuable diagnostic and monitoring insights, extending the known phenotype of Noonan syndrome.