MR lymphangiography of lymphatic abnormalities in children and adults with Noonan syndrome

Pieper, Claus Christian; Wagenpfeil, Julia; Henkel, A; Geiger, Sergej; Köster, T; Hoss, K; Luetkens, Julian A.; Hart, Christopher; Attenberger, Ulrike; Müller, Alexandra

doi:10.1038/s41598-022-13806-w

Cited by 12 publications

(18 citation statements)

References 39 publications

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“…They include neonatal presentations with congenital lymphedema, chylothorax, or ascites, but may also occur at any age postnatally in patients without a perinatal history of lymphatic abnormalities. They likely result from a primary maldevelopment of central conducting lymphatic vessels (Kleimeier et al, 2022; Pieper et al, 2022). Notably, lymphatic abnormalities also represent the most frequent fetal manifestation of RASopathies.…”

Section: Shared Patterns Of Organ Involvement In Ns‐like Rasopathiesmentioning

confidence: 99%

Clinical overview on RASopathies

Zenker

2022

American J of Med Genetics Pt C

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RASopathies comprise a group of clinically overlapping developmental disorders caused by genetic variations affecting components or modulators of the RAS-MAPK signaling cascade, which lead to dysregulation of signal flow through this pathway. Noonan syndrome and the less frequent, clinically related disorders, Costello syndrome, cardiofaciocutaneous syndrome, Noonan syndrome with multiple lentigines, and Noonan syndrome-like disorder with loose anagen hair are part of the RASopathy spectrum and share a recognizable pattern of multisystem involvement. This review describes the "Noonan syndrome-like" phenotype as a common phenotypic signature of generalized developmental RAS pathway dysregulation. Distinctive features of the different entities are revisited against the background of the understanding of underlying genetic alterations and genotype correlations, which has evolved rapidly during the past 20 years, thereby leading to suggestions regarding the nosology of RASopathies. K E Y W O R D S cardiofaciocutaneous syndrome, Costello syndrome, LEOPARD syndrome, Noonan syndrome, Noonan syndrome with multiple lentigines, Noonan syndrome-like disorder with loose anagen hair 1 | INTRODUCTION The term "RASopathies" was coined in 2009 (Tidyman & Rauen, 2009). It denotes a group of clinically overlapping multisystem disorders that share a common molecular pathogenesis in that the underlying genetic variations affect components or modulators of the RAS-MAPK signaling cascade and lead to dysregulation of signal flow through this pathway. No generally accepted definition and definitive delineation of RASopathies exist, so far. The major classes of disorders that have been grouped under this umbrella term are summarized in Table 1. This clinical overview is focused on Noonan syndrome (NS; MIM #PS163950) and the less frequent, clinically related disorders, Costello syndrome (CS; MIM #218040), cardiofaciocutaneous syndrome (CFCS: MIM #PS115150), Noonan syndrome with multiple lentigines (NSML; MIM #151100), Noonan syndrome-like disorder with loose anagen hair (NSLH; MIM #PS607721), collectively referred to in the following as "Noonan syndrome-like RASopathies (NS-like RASopathies)." They represent disorders that are caused by a mild to moderate and generalized constitutional RAS pathway dysregulation (Figure 1a) and have a multisystem phenotype. Based on the current pathogenetic concepts and understanding it can be concluded that the "NS-like" clinical picture represents the common phenotypic signature of a systemic RAS pathway dysregulation that starts in the embryonic period. This notion is supported by the fact that all genes known to cause NS-like RASopathies encode for components or modulators of the RAS-MAPK signaling cascade. However, this does not mean that disturbed signaling through MAPKs as the sole effectors can explain all the organ-specific pathophysiology. In fact, cellular pathways are interconnected and abnormal signaling in one of them

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Section: Shared Patterns Of Organ Involvement In Ns‐like Rasopathiesmentioning

confidence: 99%

Clinical overview on RASopathies

Zenker

2022

American J of Med Genetics Pt C

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“…Although also described for peripheral lymphatics, 95 noncontrast MRL is mainly used for visualization of abdomino-thoracic lymphatics. Although only static images of lymphatic vessels can be acquired by noncontrast MRL 96,97 and differentiation of lymph vessels and smaller veins with slow flow can be challenging, noncontrast MRL has demonstrated its diagnostic use in traumatic and complex syndromatic patients, 23 as well as its prognostic role in patients with univentricular heart disease 98 . Apart from yielding only static images, a drawback of noncontrast MRL can be that lymphatics may be obscured by surrounding edema (eg, after surgery or due to the lymphatic pathology itself) as well as adjacent effusions 20,99 .…”

Section: Transnodal X-ray Lymphangiographymentioning

confidence: 99%

“…As contrast flow can be imaged with a high temporal resolution due to a lack of radiation exposure, central lymph flow can readily be evaluated dynamically on DC-MRL. Although for “simple” lymphatic pathologies (eg, postsurgical thoracic duct transection) anatomic imaging of the leakage and injured vessels is often sufficient for interventional planning, 24 dynamic information of DC-MRL is imperative to understand more complex lymphatic flow pathologies 23 …”

Section: Transnodal X-ray Lymphangiographymentioning

confidence: 99%

“…The examination time will depend largely on patient age, injection speed, and the underlying lymphatic pathology. The entire lymphatic system can already be visible after a few minutes, but typically dynamic imaging should be performed for approximately 15–30 minutes 23,36 . Depending on the individual clinical question, it can be useful to acquire higher resolution coronal or axial images after (or sometimes during) contrast application.…”

Section: Transnodal X-ray Lymphangiographymentioning

confidence: 99%

“…This will depend on whether the treatment procedure (eg, lymph vessel embolization) is to be planned in advance as a primary treatment approach or is reserved as a second-line intervention when treatment purely by XRL failed. Ultimately, the choice of the appropriate lymphangiographic technique therefore will depend largely on the individual type and location of lymphatic pathologies, the planned treatment strategy, as well as the local expertise with different imaging techniques 1,20,23,46,73,118,119 …”

Section: Transnodal X-ray Lymphangiographymentioning

confidence: 99%

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Back to the Future II—A Comprehensive Update on the Rapidly Evolving Field of Lymphatic Imaging and Interventions

Pieper

2023

Invest Radiol

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Lymphatic imaging and interventional therapies of disorders affecting the lymphatic vascular system have evolved rapidly in recent years. Although x-ray lymphangiography had been all but replaced by the advent of cross-sectional imaging and the scientific focus shifted to lymph node imaging (eg, for detection of metastatic disease), interest in lymph vessel imaging was rekindled by the introduction of lymphatic interventional treatments in the late 1990s. Although x-ray lymphangiography is still the mainstay imaging technique to guide interventional procedures, several other, often less invasive, techniques have been developed more recently to evaluate the lymphatic vascular system and associated pathologies. Especially the introduction of magnetic resonance, and even more recently computed tomography, lymphangiography with water-soluble iodinated contrast agent has furthered our understanding of complex pathophysiological backgrounds of lymphatic diseases. This has led to an improvement of treatment approaches, especially of nontraumatic disorders caused by lymphatic flow abnormalities including plastic bronchitis, protein-losing enteropathy, and nontraumatic chylolymphatic leakages. The therapeutic armamentarium has also constantly grown and diversified in recent years with the introduction of more complex catheter-based and interstitial embolization techniques, lymph vessel stenting, lymphovenous anastomoses, as well as (targeted) medical treatment options. The aim of this article is to review the relevant spectrum of lymphatic disorders with currently available radiological imaging and interventional techniques, as well as the application of these methods in specific, individual clinical situations.

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