Congenital Limb Overgrowth Syndromes Associated with Vascular Anomalies

Bertino, Frederic J.; Braithwaite, Kiery; Hawkins, C. Matthew; Gill, Anne E.; Briones, Michael; Swerdlin, Rachel; Milla, Sarah Sarvis

doi:10.1148/rg.2019180136

Cited by 50 publications

(82 citation statements)

References 76 publications

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“…NGS‐based somatic genetic testing at high‐depth is able to detect low‐level mosaicism that may have been missed by traditional sequencing methods, PCR‐based assays, or exome (or genome) sequencing (Lee et al, 2014). It also allows for sequencing many targets simultaneously, which is appropriate in case of overlapping features of somatic overgrowth syndromes (Bertino et al, 2019). Thus, in individuals in whom the diagnosis of PDGFRB activating variants‐associated mosaic condition is suspected, testing multiple affected tissues with NGS‐based somatic genetic testing that includes PGDFRB gene can be beneficial.…”

Section: Discussionmentioning

confidence: 99%

Segmental overgrowth and aneurysms due to mosaic PDGFRB p.(Tyr562Cys)

Chenbhanich

Hetts

et al. 2021

American J of Med Genetics Pt A

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Activating variants in the platelet‐derived growth factor receptor β gene (PDGFRB) have been associated with Kosaki overgrowth syndrome, infantile myofibromatosis, and Penttinen premature aging syndrome. A recently described phenotype with fusiform aneurysm has been associated with mosaic PDGFRB c.1685A > G p.(Tyr562Cys) variant. Few reports however have examined the vascular phenotypes and mosaic effects of PDGFRB variants. We describe clinical characteristics of two patients with a recurrent mosaic PDGFRB p.(Tyr562Cys) variant identified via next‐generation sequencing‐based genetic testing. We observed intracranial fusiform aneurysm in one patient and found an additional eight patients with aneurysms and phenotypes associated with PDGFRB‐activating variants through literature search. The conditions caused by PDGFRB‐activating variants share overlapping features including overgrowth, premature aged skin, and vascular malformations including aneurysms. Aneurysms are progressive and can result in morbidities and mortalities in the absence of successful intervention. Germline and/or somatic testing for PDGFRB gene should be obtained when PDGFRB activating variant‐related phenotypes are present. Whole‐body imaging of the arterial tree and echocardiography are recommended after diagnosis. Repeating the imaging study within a 6‐ to 12‐month period after detection is reasonable. Finally, further evaluation for the effectiveness and safety profile of kinase inhibitors in this patient population is warranted.

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Section: Discussionmentioning

confidence: 99%

Segmental overgrowth and aneurysms due to mosaic PDGFRB p.(Tyr562Cys)

Chenbhanich

Hetts

et al. 2021

American J of Med Genetics Pt A

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“…KTS is a disorder combining vascular malformations and an affected overgrowth of a limb. It is believed to be caused by somatic mosaicism in the phosphoinositide 3-kinase/PIK3CA signaling pathway [3], with an incidence of 1 per 100,000 [4]. Common clinical presentations include limb hypertrophy (limb-length asymmetry and soft tissue hypertrophy), varices and vascular nevus, commonly termed a classic triad.…”

Section: Discussionmentioning

confidence: 99%

Gastrointestinal bleeding with Klippel–Trenaunay syndrome: a case report

2021

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Background Gastrointestinal bleeding caused by gastrointestinal tract involvement in patients with Klippel–Trenaunay syndrome (KTS) is extremely rare and often overlooked. Case presentation A 9-year-old girl who presented with chronic gastrointestinal bleeding was admitted to our hospital. Laboratory examinations revealed microcytic hypochromic anemia and a positive fecal occult blood test. Computed tomography (CT) of the lower limbs combined with physical examination confirmed KTS. The pelvic CT showed concentric thickening of the sigmoid colon and rectum, with progressive enhancement after the administration of a contrast agent. Colonoscopy demonstrated vascular malformations of the sigmoid colon and rectum. The patient was finally diagnosed with KTS with gastrointestinal tract involvement. The patient improved after receiving conservative treatment. Conclusions A suspicion of gastrointestinal tract involvement as an etiology for gastrointestinal bleeding should not be overlooked in patients with KTS. Endoscopy and imaging modalities can synergistically help diagnose this condition.

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“…Artery steal syndromes can also occur due to the presence of AVMs, resulting in underperfusion of tissues. Moreover, a large AVM closely related to a long bone can result in limb-length discrepancy either by limb undergrowth or overgrowth [4].…”

Section: Discussionmentioning

confidence: 99%

Peripheral Arteriovenous Malformations and Their Response to Treatment Modalities: A Single Surgeon’s Experience at Tertiary Care Hospitals

Rashid

Hussain

Malik

et al. 2021

Preprint

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Background Peripheral arteriovenous malformations (AVMs) are congenital defects resulting in abnormal connections between veins and arteries. We investigated a group of patients with peripheral AVMs to determine whether there were any gender differences in disease presentation and the response of AVMs to various modalities of treatment. Methodology The patients in this cross-sectional study were divided into two groups based on gender and their demographic data, clinical presentation at the time of diagnosis and response to treatment was assessed. Both surgical and nonsurgical treatment options were used. Nonsurgical options employed in the study included immunotherapy, embolotherapy and ultrasound-guided foam sclerotherapy (UGFS) Results Out of 43 patients, 74.4% were females with a male to female ratio of 1:3. The mean age at presentation in males was 27 years and 17 years in females. 60% of the male patients presented with high-flow AVMs while 81% of the female patients presented with low-flow lesions instead. Half of the AVMs in males were on the trunk whereas, in females, 93.9% were on the extremities. UGFS alone was used in 95.3% of patients while 32.5% of patients underwent UGFS followed by surgical excision. One patient was treated with sirolimus. In 4.6% of cases, embolization followed by surgical excision was performed. Recurrence was recorded in 20.9% of cases. Conclusions The clinical presentation of AVMs is notably different among the two genders. Sclerotherapy and embolotherapy proved to be effective treatment options. Larger studies, however, are needed to substantiate these claims. Keywords arteriovenous malformations, vascular malformations, sclerotherapy, embolotherapy, sirolimus

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Congenital Limb Overgrowth Syndromes Associated with Vascular Anomalies

Cited by 50 publications

References 76 publications

Segmental overgrowth and aneurysms due to mosaic PDGFRB p.(Tyr562Cys)

Segmental overgrowth and aneurysms due to mosaic PDGFRB p.(Tyr562Cys)

Gastrointestinal bleeding with Klippel–Trenaunay syndrome: a case report

Peripheral Arteriovenous Malformations and Their Response to Treatment Modalities: A Single Surgeon’s Experience at Tertiary Care Hospitals

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