Klippel-Trenaunay syndrome (KTS) is a rare slow-flow congenital vascular disorder with an incidence of 1:100,000. 1 , 2 KTS is classically characterized by a clinical triad of capillary malformation, venous malformation, and bony or soft tissue hypertrophy. RAD50 and POLE genes act directly on deoxyribonucleicacid (DNA) and genome stability. Although distinct from the more studiedphosphatidylinositol-4,5-bisphosphate3-kinase catalytic subunit alpha (PIK3CA)gene, RAD50 and POLE genes coexist as a deficient gene in few vascular malformations and papillary thyroid carcinoma (PTC).

This is a case of a 7-month-old Filipino female patient clinically and radiologically diagnosed as KTS presenting with multiple capillary malformations and left limb length-girth discrepancies. Dermoscopy showed various vessel patterns in all affected areas. Soft tissue ultrasound and magnetic resonance imaging/angiography (MRI/MRA) of the left extremities revealed subcutaneous capillary malformations, hypertrophy of the subcutaneous structures and compartment muscles. Strong family history of PTC was elicited and genetic sequencing revealed detected RAD50 and POLE genes. She was treated using the mammalian target of rapamycin inhibitor sirolimus with careful monitoring of trough levels and radiographic tests. A significant outcome one year post-sirolimus revealed no abnormal vessels on ultrasound, a lesser degree of hypertrophy and capillary malformations were no longer appreciated in MRI/MRA of left extremities. Port-wine stains (PWS) and affected limbs showed a decrease in erythema and growth rate during the treatment period.

KTS detected with RAD50 and POLE genes successfully treated with sirolimus with trough-level monitoring. Radiographic evaluation and regular anthropometric assessment remain valuable in the diagnosis and monitoring.

Humans ; Neuroendocrine Tumors/pathology* ; Pancreatic Neoplasms/pathology* ; Neoplasms, Second Primary ; von Hippel-Lindau Disease/pathology*

Klippel-Trenaunay syndrome (KTS) is a rare disorder characterized by a triad of abnormal bone and soft tissue growth, the presence of a port-wine stain, and venous malformations. Gastrointestinal (GI) manifestations of KTS are relatively common and generally do not cause significant problems. However, persistence can lead to chronic GI blood loss or even massive bleeding in rare cases. The majority of the severe GI manifestations associated with KTS present as vascular malformations around the GI tract and exposed vessels can lead to serious bleeding into the GI tract. Herein, we report a case of a 16-year-old boy with severe iron deficiency anemia who was previously misdiagnosed as hemorrhoid due to small amount of chronic bleeding. The actual cause of chronic GI bleeding was from an uncommon GI manifestation of KTS as rectal polyposis.]]>
Adolescent ; Anemia, Iron-Deficiency ; Gastrointestinal Hemorrhage ; Gastrointestinal Tract ; Hemorrhage ; Hemorrhoids ; Humans ; Klippel-Trenaunay-Weber Syndrome ; Male ; Polyps ; Port-Wine Stain ; Vascular Malformations

A 58-year-old male patient with severe claudication due to thrombosis of the left ilio-femoro-popliteal artery aneurysm. He also had a venous stasis ulcer with a history of multiple embolotherapy of arteriovenous malformation. Duplex sonography revealed reflux and varicose veins of the left great saphenous vein (GSV). A sequential bypass surgery was performed that consisted of excision of the left external iliac and common femoral artery aneurysm, external iliac to deep femoral interposition with an expanded polytetrafluoroethylene graft, and femoro-posterior tibial artery bypass with the reversed left GSV. Symptoms of claudication were alleviated and the chronic ulcer was healed in time. To our knowledge, this is the first report of successful bypass in a patient with arterial aneurysm, arteriovenous malformation, and venous insufficiency that can be diagnosed as an atypical case of Parkes Weber syndrome. Long-term follow-up is needed to define the fate of aneurysms and varicose vein graft.
Aneurysm ; Arteries ; Arteriovenous Fistula ; Arteriovenous Malformations ; Embolization, Therapeutic ; Femoral Artery ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Polytetrafluoroethylene ; Popliteal Artery ; Saphenous Vein ; Sturge-Weber Syndrome ; Thrombosis ; Tibial Arteries ; Transplants ; Ulcer ; Varicose Ulcer ; Varicose Veins ; Venous Insufficiency

Objective To analyze the clinical features of Von-Hippel-Lindau(VHL)syndrome and explore the diagnostic value of abdominal ultrasound for this disease.Methods The clinical features including age at first diagnosis,symptoms,signs,affected organs,number of operations,and diagnostic examinations of 35 patients with VHL syndrome admitted to our center from January 1994 to December 2017 were retrospectively analyzed.The diagnostic value of abdominal ultrasound for VHL syndrome was analyzed.Results Pheochromocytoma(=14)and nervous system hemangioblastoma(=13)were the common firstly-identified tumors.Nervous system hemangioblastoma(=21),pheochromocytoma(=19),renal carcinoma(=17),and pancreatic mass(=15)were common tumors.The main surgical reasons were nervous system hemangioblastoma(=22),pheochromocytoma(=23)and renal carcinoma(=13).Abdominal organ involvements were found in 33 patients,which were first detected by abdominal ultrasound in 20 patients and were found accidently during routine health checkups in 6 patients.The ultrasound results were accurate in 27 of 33 adrenal gland scans,13 of 16 pancreas scans,and 8 of 19 kidney scans.Conclusions When multiple tumors are detected in the kidney,adrenal gland,and pancreas by ultrasound,the possibility of VHL syndrome should be considered.When the clinical findings suggest the possibility of VHL syndrome,ultrasound can discover and diagnose the abdominal tumors and can also be used for the long-term follow-up of the tumors.Therefore,ultrasound is an important method in the screening and follow-up of patients with VHL syndrome.
Abdomen ; diagnostic imaging ; Adrenal Gland Neoplasms ; diagnostic imaging ; Hemangioblastoma ; diagnostic imaging ; Humans ; Pheochromocytoma ; diagnostic imaging ; Retrospective Studies ; Ultrasonography ; von Hippel-Lindau Disease ; complications ; diagnostic imaging

Hemangioblastoma (HBL) in the suprasellar region is very rare and a few cases have been reported. Suprasellar HBL without von Hippel-Lindau disease is much rarer. A 76-year old male patient presented progressively deteriorating visual disturbance. MRI demonstrated solid suprasellar mass of 20 mm in diameter, broadly based to planum sphenoidale and diaphragm sella and dural tail sign after the administration of gadolinium diethylene triamine penta-acetic acid (Gd-DTPA). Preoperative diagnosis was meningioma. Total resection of the tumor was not accomplished because of massive hemorrhage, and the histopathologic examination revealed the tumor to be HBL. The visual disturbance of the patient was not improved. The authors reviewed the literature and considered a differential diagnosis of suprasellar tumors and treatment of suprasellar HBL.
Diagnosis ; Diagnosis, Differential ; Diaphragm ; Gadolinium ; Hemangioblastoma ; Hemorrhage ; Humans ; Magnetic Resonance Imaging ; Male ; Meningioma ; Tail ; Temazepam ; von Hippel-Lindau Disease

OBJECTIVE: To detect VHL gene mutation in a pedigree affected with von Hippel-Lindau syndrome (VHL). METHODS: Clinical data of the pedigree was reviewed. Patients were subjected to Sanger sequencing to detect mutation of the VHL gene. Structure of pVHL was predicted by 3D modeling using the swiss-model. RESULTS: A novel c.426delT(p.V142fs) [NM_000551] mutation was found in exon 2 of the VHL gene. 3D modeling suggested that the alpha-structure of pVHL is completely absent. CONCLUSION The novel c.426delT(p.V142fs) mutation probably underlies the VHL in this pedigree.
DNA Mutational Analysis ; Exons ; Humans ; Mutation ; Pedigree ; Von Hippel-Lindau Tumor Suppressor Protein ; genetics ; von Hippel-Lindau Disease ; genetics

Parkes Weber syndrome is a rare congenital vascular anomaly, related to the RAS p21 protein activator 1 (RASA1) gene. It is characterized by capillary cutaneous malformations, bony and soft tissue hyperplasia, and multiple arteriovenous fistulas throughout the affected upper or lower extremity. These arteriovenous fistulas can be associated with life-threatening complications such as bleeding, thrombosis, and high output heart failure. In this report, we present a neonate who had a disproportionately hypertrophied left upper limb with port-wine stain, dystrophy of the left humerus, and hypertrophy of the left clavicle on X-ray, and arteriovenous malformation and massive dilatation of the left subclavian artery on magnetic resonance angiography. Exome sequencing analysis revealed a novel heterozygous splicing mutation (c.1776+2T>A) in the RASA1 gene. To the best of our knowledge, this report is the first case of RASA1-related Parkes Weber syndrome in Korea.
Arteriovenous Fistula ; Arteriovenous Malformations ; Capillaries ; Clavicle ; Dilatation ; Exome ; Heart Failure ; Hemorrhage ; Humans ; Humerus ; Hyperplasia ; Hypertrophy ; Infant, Newborn* ; Korea ; Lower Extremity ; Magnetic Resonance Angiography ; Port-Wine Stain ; Sturge-Weber Syndrome* ; Subclavian Artery ; Thrombosis ; Upper Extremity

PURPOSE: To characterize the development of glaucoma, age of glaucoma onset, and treatments for patients with a facial port-wine stain (PWS). METHODS: We performed a retrospective analysis of the medical records of 58 patients (116 eyes) with facial PWS between January 2000 and August 2016. We noted patients' age at the initial examination, cup-to-disc ratio, corneal diameter, occurrence of ocular hypertension, development of glaucoma, age of glaucoma onset, and treatments. We compared the clinical features of eyes that developed glaucoma with those that did not develop glaucoma. Among those eyes with glaucoma, we investigated the differences between eyes that underwent surgery and those that did not undergo surgery. RESULTS: Among the 58 patients with a facial PWS (116 eyes), glaucoma was diagnosed in 38 patients (46 eyes; 39.66%). Of these, 26 patients (27 eyes; 58.69%) underwent glaucoma surgery. PWS-associated glaucoma usually developed by the age of 2 years (85.61%). In all patients, glaucoma developed on the same side of the face as the PWS. Of the 58 patients, 19 (32.76%) showed neurological symptoms, including seizures, developmental delays, intellectual disabilities, or hemiplegia, and 32 (55.17%) were diagnosed with Sturge-Weber syndrome. The mean number of glaucoma surgeries was 1.55 ± 0.93. The initial surgery included trabeculectomy (7 eyes), trabeculotomy (5 eyes), combined trabeculotomy/trabeculectomy (13 eyes), and aqueous drainage device insertion (2 eyes). The mean age at the first surgery was 35.14 ± 50.91 months. In 18 of 27 eyes (66.67%), the postoperative intraocular pressure (IOP) was controlled to below 21 mmHg, but 9 eyes (33.33%) showed elevated IOP and required a reoperation. CONCLUSIONS: PWS can be accompanied by ocular hypertension or glaucoma, so patients require regular ophthalmic examinations. When glaucoma occurs, it often does not respond to medication, making it difficult in some cases to control the IOP, so appropriate glaucoma surgery is necessary.
Drainage ; Glaucoma* ; Hemiplegia ; Humans ; Intellectual Disability ; Intraocular Pressure ; Medical Records ; Ocular Hypertension ; Port-Wine Stain* ; Reoperation ; Retrospective Studies ; Seizures ; Sturge-Weber Syndrome ; Trabeculectomy

STUDY DESIGN: Retrospective cohort study. PURPOSE: To examine the clinical profile and surgical complications in patients with spinal hemangioblastomas and to evaluate the long-term outcome in them. OVERVIEW OF LITERATURE: Although considered to be histologically benign, hemangioblastomas may cause significant neurological deficits. The proportion of spinal hemangioblastomas associated with von Hippel–Lindau (VHL) disease has been estimated be 13%–59%. Preoperative neurological function correlates with postoperative neurological status. Studies have shown no difference in outcomes between sporadic and VHL-associated spinal hemangioblastomas. METHODS: This retrospective study included 14 consecutive patients treated for spinal hemangioblastomas at our institute between January 2000 and June 2013. The mean follow-up period was 5 years. Magnetic resonance imaging of the complete neuraxis was performed in all cases, and preoperative embolization was performed in two cases. RESULTS: In total, 14 patients underwent 18 surgeries, of which 15 were for spinal hemangioblastomas. Of all the patients, 86% had motor weakness and 79% presented with sensory disturbances. Preoperative McCormick functional grades were grade I in 7 (50%), grade II in 3 (21%), and grade III in 4 (29%) patients; 50% patients were diagnosed with VHL disease. All patients underwent complete resection of the tumor. Eight patients experienced deterioration in their neurological status in the immediate postoperative period; among them, five had gradual improvement. At 5-year follow-up, 11 (78.57%) patients showed good functional outcomes. CONCLUSIONS: Microsurgical excision of spinal hemangioblastomas can cause postoperative morbidity, mainly in the form of neurological deterioration. Almost half of our patients had deterioration in the McCormick grade in the immediate postoperative period. However, a complete microsurgical excision can result in good long-term functional outcomes, as most of the immediate postoperative neurological deterioration in our patients was reversible. There was no difference in the long-term functional outcomes between sporadic and VHL-associated spinal hemangioblastomas.
Cohort Studies ; Follow-Up Studies ; Hemangioblastoma* ; Humans ; Magnetic Resonance Imaging ; Microsurgery ; Postoperative Period ; Retrospective Studies ; Spinal Cord ; Spinal Cord Neoplasms ; von Hippel-Lindau Disease*