Congenital lymphedema as a rare and first symptom of tuberous sclerosis complex

Klinner, Jürgen; Krüger, M.; Brunet, Theresa; Makowski, Christine; Riedhammer, Korbinian; Mollweide, Andreas; Wagner, Matias; Hoefele, Julia

doi:10.1016/j.gene.2020.144815

Cited by 10 publications

(7 citation statements)

References 14 publications

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“…We also found lymphatic malformations in the abdomen at 1–2% based on the patient’s risk factors (female sex and TSC2 mutation). This is consistent with the already known association of congenital lymphatic problems and TSC [ 32 , 33 ]. Additionally, cysts within multiple abdominal organs were found, regardless of the status of TSC2-PKD1 contiguous gene syndrome diagnosis, suggesting that this could be the result of TSC-specific pathways.…”

Section: Discussionsupporting

confidence: 93%

Prevalence of thoracoabdominal imaging findings in tuberous sclerosis complex

Ritter

Fessler

Ebrahimi‐Fakhari

et al. 2022

Orphanet J Rare Dis

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Background Tuberous sclerosis complex (TSC) results in neurodevelopmental phenotypes, benign tumors, and cysts throughout the body. Recent studies show numerous rare findings in TSC. Guidelines suggest routine abdominal and chest imaging to monitor these thoracoabdominal findings, but imaging is not uniformly done across centers. Thus, the prevalence of many findings is unknown. To answer this, we categorized the clinical reads of 1398 thoracoabdominal scans from 649 patients of all ages in the Cincinnati Children’s Hospital TSC Repository Database. Results Typical TSC findings were present in many patients: kidney cysts (72%), kidney fat-containing angiomyolipomas (51%), kidney lipid-poor angiomyolipomas (27%), liver angiomyolipomas (19%), and lung nodules thought to represent multifocal micronodular pneumocyte hyperplasia (MMPH) (18%). While many features were more common in TSC2 patients, TSC1 patients had a higher prevalence of MMPH than TSC2 patients (24% versus 13%, p = 0.05). Many rare findings (e.g., lymphatic malformations and liver masses) are more common in TSC than in the general population. Additionally, most thoracoabdominal imaging findings increased with age except kidney cysts which decreased, with the 0–10 years age group having the highest percentage (69% 0–10 years, 49% 10–21 years, 48% 21 + years, p < 0.001). Finally, in our population, no patients had renal cell carcinoma found on abdominal imaging. Conclusions These results show that regular thoracoabdominal scans in TSC may show several findings that should not be ignored or, conversely, over-reacted to when found in patients with TSC. Female sex, TSC2 mutation, and age are risk factors for many thoracoabdominal findings. The data suggest novel interactions of genetic mutation with pulmonary nodules and age with renal cysts. Finally, in agreement with other works, these findings indicate that several rare thoracoabdominal imaging findings occur at higher rates in the TSC population than in the general population. This work supports obtaining detailed thoracoabdominal imaging in patients with TSC.

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Section: Discussionsupporting

confidence: 93%

Prevalence of thoracoabdominal imaging findings in tuberous sclerosis complex

Ritter

Fessler

Ebrahimi‐Fakhari

et al. 2022

Orphanet J Rare Dis

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“…Primary congenital lymphedema has been described in 13 cases of TSC. 35 Both of our patients with TSC had a lymphedema present at birth. Lymphedema is also linked with chromosome 22 anomalies; it has been described in 25% of Phelan-McDermid syndromes, 36 and rarely in DiGeorge syndrome.…”

Section: Discussionmentioning

confidence: 67%

Pediatric Lymphedema: Study of 180 Patients Referred to a Tertiary Lymphedema Clinic

et al. 2022

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Background Lymphedema is due to dysfunction of the lymphatic system. It can be primary or secondary. Pediatric lymphedema is more often primary and is a chronic disease with a heavy burden on quality of life. Methods Medical records of patients under 18 years of age referred between 1996 and 2021 to the specialized lymphedema clinic at the Sainte-Justine University Hospital Center were reviewed. Demographic data, sex, age at presentation, location of the lymphedema, clinical features, genetic testing, symptoms, complications, investigations, and treatment were collected. Results Of 180 referred patients, lymphedema was confirmed in 151, and 137 were primary lymphedema. Median age of apparition of primary lymphedema was 7.00 years and was significantly lower in boys than in girls. Primary congenital lymphedema was more frequent in boys (51.0%, 27.3% in girls, P = .007), and onset of primary lymphedema during adolescence was more frequent in girls (53.4%, 25.0% in boys, P = .001). Lower limbs were the most impacted (88.3%). Sixty patients had genetic testing, and 38 (63.3%) of them were discovered to have a pertinent genetic mutation. The most common mutated gene was the FLT4 gene (in 9 patients). Seven patients (5.1%) had associated extensive/central lymphatic malformation and 24 (17.6%) had a polymalformative syndrome/syndromic lymphedema. Conclusions Pediatric lymphedema is more frequent in girls, usually involves lower limb, and is most often sporadic, but often associated with a genetic mutation, and genetic testing should be performed.

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“…The cumulative ultrafiltration in peritoneal dialysis represents net fluid removal across the capillary walls, considering the reduction due to lymphatic reabsorption. Peritoneal ultrafiltration failure (UFF) is a consequential outcome characterized by increased peritoneal solute transport and reduced ultrafiltration capacity [ 74 ]. This factor significantly contributes to the discontinuation of peritoneal dialysis, which is strongly linked to heightened mortality rates.…”

Section: Lymphangiogenesis and Peritoneal Ultrafiltration Failurementioning

confidence: 99%

“…Inhibition of lymphangiogenesis using a soluble VEGFR-3 inhibitor enhanced compromised ultrafiltration in mice. Lymphangiogenesis in peritoneal uremic fluid is strongly associated with peritoneal fibrosis progression [ 74 , 75 , 76 , 77 , 78 ].…”

Section: Lymphangiogenesis and Peritoneal Ultrafiltration Failurementioning

confidence: 99%

Lymphatic System and the Kidney: From Lymphangiogenesis to Renal Inflammation and Fibrosis Development

Stasi,

Sciascia,

Naretto

et al. 2024

IJMS

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The lymphatic kidney system plays a crucial role in managing interstitial fluid removal, regulating fluid balance, and tuning immune response. It also assists in the reabsorption of proteins, electrolytes, cytokines, growth factors, and immune cells. Pathological conditions, including tissue damage, excessive interstitial fluid, high blood glucose levels, and inflammation, can initiate lymphangiogenesis—the formation of new lymphatic vessels. This process is associated with various kidney diseases, including polycystic kidney disease, hypertension, ultrafiltration challenges, and complications post-organ transplantation. Although lymphangiogenesis has beneficial effects in removing excess fluid and immune cells, it may also contribute to inflammation and fibrosis within the kidneys. In this review, we aim to discuss the biology of the lymphatic system, from its development and function to its response to disease stimuli, with an emphasis on renal pathophysiology. Furthermore, we explore how innovative treatments targeting the lymphatic system could potentially enhance the management of kidney diseases.

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Congenital lymphedema as a rare and first symptom of tuberous sclerosis complex

Cited by 10 publications

References 14 publications

Prevalence of thoracoabdominal imaging findings in tuberous sclerosis complex

Prevalence of thoracoabdominal imaging findings in tuberous sclerosis complex

Pediatric Lymphedema: Study of 180 Patients Referred to a Tertiary Lymphedema Clinic

Lymphatic System and the Kidney: From Lymphangiogenesis to Renal Inflammation and Fibrosis Development

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