Lymphatic anomalies during lifetime in patients with Noonan syndrome: Retrospective cohort study

Swarts, Jessie W.; Kleimeier, Lotte E. R.; Leenders, Erika; Rinne, Tuula; Klein, Willemijn M.; Draaisma, Jos M. Th.

doi:10.1002/ajmg.a.62955

Cited by 8 publications

(8 citation statements)

References 47 publications

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“…Patient 4 is a 10-year-old female diagnosed with NSML based on a de novo in-frame deletion-insertion in KRAS (c.194_195ins21 (p.Ser65delins8)). In an earlier study, this female was described to have NS, but subsequently, she developed multiple lentigines [ 8 ]. From an early age, she experienced pain in both hands and feet and developed a stepping gait.…”

Section: Resultsmentioning

confidence: 99%

Hypertrophic neuropathy: a possible cause of pain in children with Noonan syndrome and related disorders

Draaisma¹,

Erasmus

Braakman

et al. 2023

Eur J Pediatr

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This study is aimed at describing the findings of high-resolution nerve ultrasound in children with Noonan syndrome (NS) and related disorders experiencing pain in their legs. This retrospective cohort study was conducted in the NS expert center of the Radboud University Medical Center in the Netherlands. Patients were eligible if they were younger than 18 years, clinically and genetically diagnosed with NS or a NS related disorder, and experienced pain in their legs. Anamneses and physical examination were performed in all children. In addition, high-resolution nerve ultrasound was used to assess nerve hypertrophy and, if needed, complemented spinal magnetic resonance imaging was performed. Over a period of 6 months, four children, three with NS and one child with NS with multiple lentigines, who experienced pain of their legs were eligible for inclusion. Muscle weakness was found in two of them. High-resolution nerve ultrasound showed (localized) hypertrophic neuropathy in all patients. One child underwent additional spinal magnetic resonance imaging, which showed profound thickening of the nerve roots and plexus. Conclusion: In the four children included with a NS and related disorders, pain was concomitant with nerve hypertrophy, which suggests an association between these two findings. The use of high-resolution nerve ultrasound and spinal magnetic resonance imaging might result in better understanding of the nature of this pain and the possible association to nerve hypertrophy in patients with NS and related disorders. What is Known:• Children with Noonan syndrome and related disorders may report pain in their legs, which is often interpreted as growing pain.• Some adults with Noonan syndrome and related disorders have hypertrophic neuropathy as a possible cause of neuropathic pain. What is New:• This is the first study using high-resolution nerve ultrasound in children with Noonan syndrome and related disorders experiencing pain in their legs.• Hypertrophic neuropathy was diagnosed as possible cause of pain in four children with Noonan syndrome and related disorders.

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Section: Resultsmentioning

confidence: 99%

Hypertrophic neuropathy: a possible cause of pain in children with Noonan syndrome and related disorders

Draaisma¹,

Erasmus

Braakman

et al. 2023

Eur J Pediatr

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“…The father, who was not available for clinical evaluation, denied having hearing loss and lentigines [13]. In a large-scale study of the clinical presentation and prevalence of lymphatic anomalies in patients with NS, patients with sporadic NS (16/40) have a high predisposition for developing lymphatic anomalies during life, compared to inherited NS (3/17, paternally inherited 1/6 and maternally inherited 2/11) [33].…”

Section: Discussionmentioning

confidence: 99%

Paternally Inherited Noonan Syndrome Caused by a PTPN11 Variant May Exhibit Mild Symptoms: A Case Report and Literature Review

Han,

Park

2024

Genes

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Background: Noonan syndrome (NS)/Noonan syndrome with multiple lentigines (NSML) is commonly characterized by distinct facial features, a short stature, cardiac problems, and a developmental delay of variable degrees. However, as many as 50% of individuals diagnosed with NS/NSML have a mildly affected parent or relative due to variable expressivity and possibly incomplete penetrance of the disorder, and those who are recognized to have NS only after a diagnosis are established in a more obviously affected index case. Methods: In order to collect intergenerational data reported from previous studies, electronic journal databases containing information on the molecular genetics of PTPN11 were searched from 2000 to 2022. Results: We present a case of a proband with a PTPN11 variant (c.1492C > T/p.Arg498Trp) inherited from an asymptomatic father, displaying only mild intellectual disability without classical symptoms of NS. Among our cases and the reported NS cases caused by the PTPN11 p.Arg498Trp variant, cardiac abnormalities (6/11), facial dysmorphism (7/11), skin pigmentation (4/11), growth problems (4/11), and sensorineural hearing loss (2/11) have been observed. NS/NSML patients with the PTPN11 p.Arg498Trp variant tend to exhibit relatively lower frequencies of skin pigmentation, facial dysmorphism and cardiac abnormalities and mild symptoms compared to those carrying any other mutated PTPN11. Conclusions: Paternally inherited NS/NSML caused by a PTPN11 p.Arg498Trp variant, including our cases, may exhibit relatively lower frequencies of abnormal features and mild symptoms. This could be ascribed to potential gene–gene interactions, gene–environment interactions, the gender and phenotype of the transmitting parent, or ethnic differences that influence the clinical phenotype.

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“…The prevalence of lymphatic disease in NS is estimated to be 37% during lifetime. 2 The underlying mechanism may be an abnormal development of the central lymphatic system leading to a central conducting lymphatic anomaly (CCLA). 3 CCLA affects large lymphatic vessels in the middle of the torso, resulting in central flow problems and subsequent backward flow or leakage of lymph fluid.…”

Section: Introductionmentioning

confidence: 99%

Trametinib restores the central conducting lymphatic flow in a premature infant with Noonan syndrome

Leenders,

Kleimeier,

Weeke

et al. 2024

Clinical Case Reports

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Lymphatic anomalies during lifetime in patients with Noonan syndrome: Retrospective cohort study

Cited by 8 publications

References 47 publications

Hypertrophic neuropathy: a possible cause of pain in children with Noonan syndrome and related disorders

Hypertrophic neuropathy: a possible cause of pain in children with Noonan syndrome and related disorders

Paternally Inherited Noonan Syndrome Caused by a PTPN11 Variant May Exhibit Mild Symptoms: A Case Report and Literature Review

Trametinib restores the central conducting lymphatic flow in a premature infant with Noonan syndrome

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