This finding implies the activation of the PI3K-AKT pathway in the characteristic clinical findings of overgrowth and tumor susceptibility in patients with Proteus syndrome [22]. (c–e) Gray-scale (c) and color Doppler (d) US images of the lesion (arrow in e) over the calf, and a conventional radiograph (e) were obtained in the 10-year-old girl. This congenital overgrowth syndrome is characterized by a triad of major features: macroglossia, pre- or postnatal gigantism (> 90th percentile), and anterior abdominal wall defects (exomphalos, umbilical hernia, or diastasis recti). PTEN mutation spectrum in a 10-year-old boy. AVMs associated with RASA1 mutations have a high recurrence rate and are treated only when the patient becomes symptomatic. Documentation regarding a patient’s deep venous system is important for planning treatment of KTS, and arteriography is used to rule out high-flow malformations, as these may reflect PWS with a KTS phenotype. Therefore, serial physical and imaging examinations are required to monitor and control progression (36,72). (b, c) Photographs show the limb phenotype, which may comprise asymmetric limb overgrowth (b), dysregulated adipose overgrowth (c), and/or epidermal nevi (c). Calcification, phleboliths, and osseous involvement can be assessed with MRI, CT, and conventional film hard-copy radiography (3). MRI and MR angiography (Fig 10h), or CT angiography can help to identify the low-flow malformations and achieve greater soft-tissue resolution when evaluating vasculature and overgrowth, respectively. Figure 5c. Figure 10g. These malformations are more frequently low-flow anomalies; they are rarely high-flow or true arteriovenous anomalies. However, extensive networks of the venous malformation can extend to involve visceral organs of the pelvis and spinal structures. The “café-au-lait” spots are present in approximately 95% of diseased patients and are usually congenital; they occur in different sizes and are distributed throughout the body surface [50, 54]. PTEN mutation spectrum in a 10-year-old boy. FAVA lesions contain echogenic solid components that correspond to the fibroadipose nature of the mass, and the dominant solid component with phlebectasia helps to differentiate this anomaly from the venous malformation seen at US and MRI (35). Treatment and Follow-up.—Treatments for PTEN spectrum disorders are often multifactorial and are focused on treatment of the vascular anomaly, as well as suppression of tumoral growth. (f) Coronal T2-weighted MR image of the chest, abdomen, and left upper extremity shows lipomatous overgrowth. Deficiency of vitamin B 12 can occur in bacterial overgrowth. The authors declare that there is no conflict of interests regarding the publication of this paper. However, velocity imaging or phase-contrast imaging is not performed, as the rate of blood flow through these lesions is very dynamic, often based on the patient’s positioning, and varies with the degree of physical activity. 10.1 BECKWITH-WIEDEMANN SYNDROME Print Section Listen EPIDEMIOLOGY/GENETICS Definition Beckwith-Wiedemann syndrome (BWS) is a somatic overgrowth syndrome characterized by macrosomia, omphalocele, macroglossia, and ear creases. The recently developed therapy ARQ-092, and ARQ751 are examples of such treatments that are being investigated, and they may be of expanded clinical use in the treatment of other syndromes in the PI3K/AKT/mTOR pathway (80,81). (g, h) In the same girl, note the high signal intensity of the calf lesion on the sagittal T2-weighted MR image (g) and the iso- to hypointense signal of the lesion on the nonenhanced T1-weighted MR image (h). Figure 3f. Soft-tissue hyperplasia or hypertrophy is a common radiographic finding, although it might be more easily detected on axial MR images in more subtle cases. (b–d) Coronal T1-weighted MR image (b), proton density–weighted fat-saturated MR image (c), and dynamic gadobutrol-enhanced MR venogram (d) show a large enhancing lateral draining vein in the affected leg. (a, b) Photographs show clinical findings of the PTEN mutation spectrum, confirmed by means of genetic testing, with the CLOVES phenotype. (f) Axial nonenhanced head CT image shows asymmetric widening of the external auditory meatus on the left. Auto-brewery syndrome (ABS), also known as gut fermentation syndrome, is a rarely diagnosed medical condition in which the ingestion of carbohydrates results in endogenous alcohol production. Figure 4. (g–i) Right lower extremity lateral marginal vein of Servelle venograms obtained with pedal venous access 2 months later show successful coil (arrows in i) and sodium tetradecyl sulfate foam embolization of the right lateral marginal vein of Servelle, with patency of the deep femoral venous system. These complex shunts deny or steal blood from the distal tissues and lead to ischemic changes. Phlebectasia and venous thrombosis can be evaluated on Doppler US images and are easily identifiable when they are present. ), Children’s Healthcare of Atlanta, Atlanta, Ga. These agents offer the benefit of causing extensive endothelial damage to the anomaly on contact with endothelial cells. Sclerotherapy and embolization techniques have been shown to be effective in the treatment of macrocystic lymphatic malformations and large venous malformations, respectively, and are often first-line therapies. (m) Repeat angiogram obtained 1 month later in the girl shows aberrant vessel growth, which suggests recurrence. (h) This patient was found to have soft-tissue overgrowth of the left lower extremity, which manifested on the coronal gadofosveset-enhanced lower-extremity MR venogram as hypervascularity of the left kidney and left-thigh soft tissues. (f) Axial T2-weighted fat-saturated MR image shows the large lateral embryonic vein of Servelle. Importantly, disproportionate asymmetric overgrowth can be a clue to the differential diagnosis of other diseases of osseous overgrowth in which the enlarged bones retain their normal proportional relationships [24–26]. Conventional radiography of the affected limb also is recommended for evaluation of FAVA lesions, given their association with osseous cortical abnormalities and in some cases, deformity (Fig 6e). Most FAVA lesions are low-flow lesions. (c, d) Lateral (c) and posteroanterior (d) chest radiographs show excessive soft-tissue growth in the back. (b, c) Photographs show the limb phenotype, which may comprise asymmetric limb overgrowth (b), dysregulated adipose overgrowth (c), and/or epidermal nevi (c). Documentation regarding a patient’s deep venous system is important for planning treatment of KTS, and arteriography is used to rule out high-flow malformations, as these may reflect PWS with a KTS phenotype. Individual overgrowth syndromes have been shown to overlap with regard to clinical and radiologic features. PTEN mutation was first described in several families who had Cowden syndrome (an autosomal dominant disorder) and was quickly characterized as a hamartomatous syndrome (32) and one of many PTEN-associated hamartoma tumor syndromes. (a, b) Clinical photographs show a painful lump arrow) in the calf of a 10-year-old girl (a) and an adolescent boy (age withheld) (b). Key features of CLOVES syndrome are summarized in Table 5. (d) Anteroposterior chest radiograph shows asymmetry of the humeral heads. It is a rare condition that is possibly related to alcohol consumption and leads to denervation and subsequent adipocyte hypertrophy [41, 42]. The presence of calcified phleboliths in a slow-flow vascular anomaly, which are occasionally identified incidentally on film hard-copy images obtained in cases of trauma, is almost always diagnostic for a venous malformation. PWS in a 4-year-old boy. (g–i) Right lower extremity lateral marginal vein of Servelle venograms obtained with pedal venous access 2 months later show successful coil (arrows in i) and sodium tetradecyl sulfate foam embolization of the right lateral marginal vein of Servelle, with patency of the deep femoral venous system. Embolization and surgical strategies are often combined to avoid permanent neurologic and spinal complications (29,58). Letícia da Silva Lacerda, Úrsula David Alves, José Fernando Cardona Zanier, Dequitier Carvalho Machado, Gustavo Bittencourt Camilo, Agnaldo José Lopes, "Differential Diagnoses of Overgrowth Syndromes: The Most Important Clinical and Radiological Disease Manifestations", Radiology Research and Practice, vol. (d) MR angiogram of the lower extremities shows an arterial blush adjacent to the larger-caliber superficial femoral artery and peroneal artery (arrows), consistent with high-flow malformations. (a) Photograph shows the facial phenotype: dolichocephaly, down-slanting palpebral fissures, low nasal bridge, wide nares, and resting open mouth. Most FAVA lesions are low-flow lesions. Figure 10c. Owing to the increased risk of tumor growth associated with PTEN syndromes involving limb overgrowth, especially those in the gastrointestinal tract (PTEN-associated hamartoma tumor, Peutz-Jeghers syndrome, and juvenile polyposis syndrome) and central nervous system (Proteus and SOLAMEN [segmental overgrowth, lipomatosis, AVM, and epidermal nevus] syndromes, tuberous sclerosis), these conditions should not be mistaken as PROS spectrum disorders (67,69). Radiologists who are aware of congenital limb length discrepancies can make specific diagnoses based on imaging findings. (b–d) Coronal T1-weighted MR image (b), proton density–weighted fat-saturated MR image (c), and dynamic gadobutrol-enhanced MR venogram (d) show a large enhancing lateral draining vein in the affected leg. These patients do not fit the diagnostic criteria of the other disorders marked by capillary malformations and overgrowth such as KTS or Parkes-Weber syndrome. (a) Photograph shows the facial phenotype: dolichocephaly, down-slanting palpebral fissures, low nasal bridge, wide nares, and resting open mouth. The differentiation of CLOVES syndrome from KTS is strongly based on the phenotypic appearance of the patient (29,55,56). (c) Photograph shows a protuberant abdominal mass, suggesting truncal overgrowth. Computed tomography (CT) is important for a Madelung’s diagnosis because it can identify the key symptoms, such as lipomatosis in the characteristic regions (Figure 4), the calcification of lipomas, tracheal narrowing, and venous stasis in the chest wall, while confirming the absence of masses in other sites [46]. There is also a second domain that consists of the CDKN1C gene, which acts as an in-utero negative regulator of cell growth. Most FAVA lesions are low-flow lesions. 768 operated cases,”, L. A. Favorito, “Vesical hemangioma in patient with Klippel-Trenaunay-Weber syndrome,”, N. Revencu, L. M. Boon, A. Dompmartin et al., “Germline mutations in RASA1 are not found in patients with Klippel-Trenaunay syndrome or capillary malformation with limb overgrowth,”, P. Gloviczki and D. J. Driscoll, “Klippel-Trenaunay syndrome: current management,”, R. L. G. Flumignan, D. G. Cacione, S. I. Lopes et al., “Klippel-Trenaunay-Weber syndrome: association of operative treatment with foam sclerotherapy,”, A. G. Jacob, D. J. Driscoll, W. J. Shaughnessy, A. W. Stanson, R. P. Clay, and P. Gloviczki, “Klippel-Trénaunay syndrome: spectrum and management,”, M. M. Al-Salman, “Klippel-Trenaunay Syndrome: clinical features, complications, and management,”, K. T. Delis, P. Gloviczki, P. W. Wennberg, T. W. Rooke, and D. J. Driscoll, “Hemodynamic impairment, venous segmental disease, and clinical severity scoring in limbs with Klippel-Trenaunay syndrome,”, M. C. Garzon, J. T. Huang, O. Enjolras, and I. J. Frieden, “Vascular malformations. Patients with low-flow malformations benefit from anticoagulation for the prevention of thromboembolic disease (56). Jul 22, 2020 - Explore بدرالسادات موسوي's board "Brain images" on Pinterest. Venous thromboembolic disease and phlebectasia may occur, given the presence of low-flow vascular malformations (63–65). Figure 10d. Neurofibromatosis type I is the most common type of phakomatosis or neurocutaneous syndrome, occurring in one out of every 2000 live births with no predilection for gender or race [49, 50]. Key features of KTS are summarized in Table 4. CLOVES syndrome in a 3-year-old boy. (c–e) Gray-scale (c) and color Doppler (d) US images of the lesion (arrow in e) over the calf, and a conventional radiograph (e) were obtained in the 10-year-old girl. Overgrowth syndromes comprise a heterogeneous group of diseases that are characterized by excessive tissue development. Clinical photographs of a patient with PTEN syndrome manifesting as the CLOVES phenotype are seen in Figure 7a–7c. It is most effective in the evaluation of smaller superficial vascular anomalies. Embryology BWS is caused by an imbalance of gene dosage involving a number of genes clustered at … Figure 6j. (d) MR angiogram of the lower extremities shows an arterial blush adjacent to the larger-caliber superficial femoral artery and peroneal artery (arrows), consistent with high-flow malformations. With the direct inhibition of mTOR that results from the use of newer therapies such as sirolimus treatment, sirolimus has become vital in the treatment of many patients with limb overgrowth syndromes associated with vascular anomalies (24). (a, b) Photographs show clinical findings of the PTEN mutation spectrum, confirmed by means of genetic testing, with the CLOVES phenotype. Figure 3h. (g, h) In the same girl, note the high signal intensity of the calf lesion on the sagittal T2-weighted MR image (g) and the iso- to hypointense signal of the lesion on the nonenhanced T1-weighted MR image (h). In this review, four overgrowth syndromes—Proteus syndrome, Klippel-Trenaunay-Weber syndrome, Madelung’s disease, and neurofibromatosis type I—are described. (d) Posteroanterior radiograph obtained in the patient at age 3 years shows soft-tissue overgrowth of the trunk. (g–i) Right lower extremity lateral marginal vein of Servelle venograms obtained with pedal venous access 2 months later show successful coil (arrows in i) and sodium tetradecyl sulfate foam embolization of the right lateral marginal vein of Servelle, with patency of the deep femoral venous system. The tortuous and typically dilated channels manifest as atypical venous structures or a combination of venous and lymphatic channels. The tissue overgrowth in Klippel-Trénaunay syndrome is usually associated with vascular malformations, whereas in Proteus syndrome the overgrowth of bone and other tissues may occur independently of vascular malformations. Yachelevich 78 and Pappas 79 in this issue, is mainly known for hypertrophy and cancer predisposition. Specific clinical signs and symptoms can be used to define a syndrome as KTS, FAVA, or CLOVES syndrome. (g, h) Coronal T2-weighted (g) and gadobutrol-enhanced T1-weighted (h) MR images show a high-signal-intensity enhancing mass in the right lower extremity, with similar findings in the partially imaged left upper extremity. Treatment with antifungal agents allowed … Limb overgrowth is primarily lipomatous and sequestered within the extrafascial and subcutaneous compartments. (f) Sagittal gadobutrol-enhanced T1-weighted MR image obtained in the girl shows avid enhancement of the calf lesion, in line with the muscle fascicles. (a) Photograph shows the facial phenotype: dolichocephaly, down-slanting palpebral fissures, low nasal bridge, wide nares, and resting open mouth. (f) Axial T2-weighted fat-saturated MR image shows the large lateral embryonic vein of Servelle.