Vascular Anomalies and Their Clinical Presentations

OVERGROWTH

SYNDROMES

STURGE-WEBER SYNDROME BLAHBLAH PARKES WEBER SYNDROME ADDED MORE PROTEUS SYNDROME CLOVES SYNDROME KLIPPEL-TREANUNAY SYNDROME MAFFUCI SYNDROME STURGE-WEBER SYNDROME PARKES WEBER SYNDROME PROTEUS SYNDROME CLOVES SYNDROME KLIPPEL-TRENAUNAY SYNDROME MAFFUCCI SYNDROME

1 of 7 Endochonromatosis congenital lipomatosis overgrowth syndromes (subtype 2) vascular malformations epidermial,

AKA Scoliosis/skeletal/spinal anomalies (CLOVES), Spindle cell hemangioma or soft tissue vascular anomaly

incidence 1/50,000 newborns CM, VM and/or LM + assymetrical M = F VM +/- spindle-cell hemangioma + CM + VM +/- LM + limb overgrowth CM + AVF +limb overgrowth somatic overgrowth endochondroma facial + leptomeningeal CM + eye anomalies LM + VM + CM +/- AVM + lipomatous +/- bone and/or soft tissue overgrowth growth patients have normal intelligence 100 cases in literature defined by CM in V1 trigeminal nerve Lipomatosis mass associations (capillary venous component of the syndrome involvement but can also involve V2 & V3 diagnosis confirmed by detection of malformations [skin above mass] OR manifests as phlebectasia/abnormal multiple endochondromas & soft tissue General bruit or thrill neurology, opthamology, pulmonology lymphatic malformations within mass) drainage vascular lesions Increased risk for GH deficiency and central consultations needed (83%) hypothyroidism At risk of developing other tumors [brain, AVM within or around lipomatous masses commonly has soft tissue and/or bony pancreatic, ovarian, & AML M:F = 2:1 in paraspinal area (28%) pathognomonic: emrbyonic marginal overgrowth patients have subcutaneous and vein of Servelle in the subcutaneous (60-83%) intramuscular microshunting extracraniofacial capillary malformations Venous malformations (phlebectasia) tissue is isolated in the lateral calf/thigh possibly fatal due to pulmonary metastasis high risk of developing DVT (29%) involving truncal lesions (16%) from chondrosarcoma

spindle cell: head & neck (25%) Morbidity: Glaucoma ( 65-77%), opthalmologic findings (40%) = stabismus, Head & Neck blindness, retinal detachment epibulbar cysts, epibulbar dermoids endochondromas: head (18%)

neurologic problems (87-93%) & spine, neural tube defects (ex: leptomeningeal anomalies common encephalocele, spina bifida), tethered cerebral anomalies (40%) = cord Intracranial Morbidity: refractory seizures, development delays, seizures, contralateral hemiplegia, and/or delayed malformations Lipomatous mass -> infiltrate adacent motor and cognitive development, 75% of areas (retroperitoneum, mediastinum, seizures occur during the first year of life paraspinal muscles, and epidural space)

Truncal Lipomatous mass in CM distributed over lateral side of posterolateral, back or flank = all extremity, buttock, or thorax spindle cell: trunk (29%) patients Pelvic involvement can cause can develop symptomatic Trunk spine, neural tube defects --> hematuria, bladder outlet obstructure, congestive heart failure (6%) cystitis, and hematochezia

lipomatous mass --> macrocystic in pelvis/thigh endochondromas: scapula (20%), ribs (27%) Lymphatic abnormalities microcystic buttock, MSK anomalies - scoliosis abdominal wall, distal limb

endochondromas: pelvis (25%) --> 3.8X

Groin higher risk of transformation in any area

generalized extracraniofacial capillary spindle cells hands (57%), foot (41%), most commonly involves one lower cerebriform CT nevi (palmar aspects of 10% can be hypoplastic malformations in (29%) arm (39%), leg (38%) extremity hands, plantar surface of feet, chest). Significant progression and often misdiagnosed in the extremity as pathognomonic. MSK anomalies: wide triangular feet, large Lower limb (95%), Upper extremity (5%), endochondromas: tibia/fibula (32%), foot Klippel-Trenaunay syndrome, or Parkes hands, macrodactyly (usually middle toe contralateral foot or hand may be enlarged, Extremity symmetrical enlargement (36%), femur (36%), humerus (34%), Weber syndrome or finger), widened "sandal gap" typically exhibit macrodactyly radius/ulna (29%) progressive, asymmetrical, first web space of toot disproportionate overgrowth of body unlike the other two syndromes, pts with Long bone & axial skeleton higher risk of Parkes weber via RASA1 mutation = association: thrombophlebitis (20%-45%) and Sturge-Weber do not have venous, lymphatic, parts (typically skeletal/limbs), adipose transformation (44%). hand & foot 14% upper limb (33%), lower limb (67%) PE (4-24%) or arterial anomalies in an extremity overgrowth transf.

adipose overgrowth, cystic lung disease (9%), renal.urologic anomalies (9%), bone Visceral disorders (skull hyperostoses, renal agenesis or hypoplasia megaspondylodysplasia)

overlying CM is heterogenous (single,

Multifocal? multiple, localized, diffuse)

Present at Birth? Yes Yes Yes

average age presentation: 4 yrs old Growth Progression significant progression 27% patients diagnosed at birth

78% patients present prior to puberty

Spindle cell occurs due to likely VM, blue in Differential is CLOVES syndrome: but color, and empitied with pressure/elevation. Contains phleboliths proteus patients have significant Appearance progression, cerebriform CT nevi & Endochondromas are endosteal & cause differentiated via AKT1 genetic progressive skeletal deformity such as mutation bowing, shortening of extremities, leg-length discrepancy, and scoliosis

Size

commonly have tumors: ovarian, Symptoms cystadenoma, meningioma, testicular pain with lipomatous masses see above tumor, parotid adenoma

slow flow vascular formations Blood Flow Fast flow fast flow paraspinal malformations

MRI: confirm dx & determine extent of CT/MRI: evaluate pulomnary cystic determine if spinal cord threatened by malformation lesions, intraabdominal lipomas, lipomatous lesion or AVM confirm tissues above AND below muscle fascia are CNS anomalies MRI delineates thoracic phlebectasia affected Imaging MR angiography & venography (non-specific) MRI other causes of extremity overgrowth only involve Skeletal radiographs to rule out the area above the muscle fascia magaspondylodysplasia or vertebral body Renal ultrasound: Wilm's tumor Ultrasound (non-specific) asymmetry

non-specific, biopsy if malignancy Histopathology not indicated non-specific non-specific not indicated nondiagnositc is indicated

sporadic or familial somatic mosaic PIK3CA mutations, non-familial, somatic mosaic GNAQ AKT1 with 5 specific PIK3CA mutations IDH1/IDH2 Gene activating mutation in PIK3C4 RASA1 mutation accounting for most cases

LYMPHATIC MALFOR MATION MACmaRcOrocCyYstiScTIC MICmRicOCYrocystSicTIC COMBINcoEmDb i(nMedACRO + GENERALIZEGDL ALYMPHATIC KAPOSIFORM LYMKPLHA ANGIOMATOSIS GORHgoArhMam-S sTtoOUut diTse DasIeSEASE PRIMpAirmRaYry L lyYmMphPedHemEDa EMA MICRO) ANOMALY (GLA) (KLA) cystic hygroma discontinue use of congenital,

AKA pracox, tarda to define age of onset lymphangioma

1.2/100,000 people under age 20 M:F = 2:1 high risk of infection (71%) M = F Males more likely to present in infancy [68%] M = F Females more likely present in adolescence [55%] macro > micro ratio = better Bone involvement 40% accessed by needle too small to be cannulated Mean age presentation = 8 M = F General prognosis associated w/ turner syndrome

adolescence > childhood (2.6x) appendicular > axial skeleton chronic lymphedema: predisposes to Poor prognosis/ high mortality lymphngiosarcoma (0.07-.45%), recurrence and pulmonary metastasis

FOXC2 mutation = Lymphedema Distichiases: extra row eyelashes

Head & Neck most common is neck face cranium, cervical spine Hypotrichosis-Lymphedema-Telangiectasia [sparse hair & cutaneous telangiectasias]

SOX18 mutation Hennekam Syndrome [generalized, developmental delay, flat fase, hypertelorism, broad nasal bridge

Intracranial

most common ribs Mediastinum (95%0 most common is ribs Trunk axilla (most common) axilla thoracic spine Retroperotineum (30%) clavicle

Groin 4% isolated genital involvement

DIstal limb is ALWAYS effected & swelling can migrate proximally humerus

91.7% lower extremity [50% unilateral, 50% Extremity extremities common bilateral], 16% upper extremity

femur positive stemmer sign: inability to pinch dorsal skin of hand/foot due to edema + dermal thickening

Hennekam Syndrome: visceral involvement

Milroy Disease: infant with lower extremity lymphedema presents at Spleen 35% Visceral birth. + family OR VEGFR3mutation

Meige Disease: adolescent with lower extremity lymphedema. Only with family history.

multiple bones (mean 30 bones inolved), multiple bones (mean 7 bones involved =

Multifocal? non-contagious always contagious)

Present at Birth? Yes Yes Yes Yes Yes Yes Yes Yes

progressive: overtime edema replaced with subcutaneous adipose tissue, increasing Growth Progression increase circumference of limb

[Infancy 49.2%], [Childhood 9.5%], Adolescence [55%] Occurrence

disappearing bones soft and compressible, blueish 56% overlying soft tissue abonormality see above Appearance hue, pink vesicles 95% overlying soft tissue abnormality

Size 5 mm or larger <5 mm

Thrombocytopenia (30%) Discrete lytic areas/radiolucency psychosocial morbidity pain & pathologic fractures confined to medullary cavity Cough/dyspnea (55%) painless, progressive, risk of bleeding & leaking Symptoms infection & cellulitis, distal limb [cutaneous vessel] Pericardial/pleural effusion (85%) always effected, ulceration rare 50% macrocystic, 63% splenic lesions, pleural effusion (42%), splenic/hepatic infection & bleeding 50% pleural effusion lesions (21%) Cutaneous stain/nodule (25%)

Blood Flow Slow Slow Slow Slow Slow Slow Slow Slow

Imaging osteolysis, cortical loss Lymphoscintigraphy

Histopathology

FOXC2, SOX18, VEGFR3, PIK3CA of lymphatic PIK3CA of lymphatic PIK3CA of lymphatic PIK3CA Somatic Mutation NRAS Gene endothelial cells endothelial cells endothelial cells CCBE1 [Hennekam]

CAPILLARY MALFOR MATION MA MACROCEPHALY-CAPILLARYCROCEHALY CAPILLARY MALFOR M CCLLAAPO D IIFFFFUUSSEE C CAAPPILILALRAYR YM AMLAFOLFROMRATMIOANT ICOMNO FADINGFADING CAPILLARY CAPILLARY S STAINTAIN HEHTEETREOROTOTOPPICIC N NEEUURAL NOODDUULELE CUTIS MCAMRTMCORATA CUTISCUTIS MARMORATA MARMORATA MALFORMATION (M-CM) W/ OVERGROWTH (DCMO) TELANGIECTATICA CONGENITA port-wine stain (CMTC) AKA capillary hemangioma

7 Phenoypic Subtypes >> lower lip CM + face and neck LM + asymmetry & partial/generalized ring of long hair cutaneous marbling at birth low temperature induced Lesion does not ulcerate of fade ( overgrowth overgrowth of soft tissue and bony most common vascular birthmark Involves integument General unlike CMTC) overgrowth of limbs (50% of whitenewborns) contains heterotopic lympathic malformation = pronounced in low temperature not pathologic M = F microcystic and oral cavity leptomeningeal tissue

dermatomal distribution, more Philtrum/upper lip 75% and neuro 'angel kiss' on forehead, eyelids, parietal of occipital scalp nodule progression nose, upper lip Head & Neck lower lip is pathognomic CLAPO, Fading capillary stain , M- macrocephaly Overlying alopecia CM 'Stork Bite' on posterior neck

Intracranial heterotopic neural nodul, m-cm Extends intracranially

Diffuse capillary malformation Trunk less progression Axial overgrowth Yes, common location Patchy and reticular

Groin

Diffuse capillary malformation DCMO (lower > upper, increased CMTC (69%) common location, less progression circumfrence & possible axial Extremity limb commonly hypoplastic overgrowth)

Visceral

localized, extensive, multiple,

Multifocal? generalized

Present at Birth? Yes (0.3% newborns) Yes Yes Yes Yes Yes Yes Yes

Growth Progression lesion darkens, more purple lightens over first 2 years of life improves during first year

overgrowth of soft tissue & bony depressed, purple serpiginous lesion does not ulcerate or fade ( overgrowth of limbs reticulated pattern unlike CMTC) generally most have pink-purple Midline, symmetrical, Accentuated normal cutaneous Appearance port wine stain-colored birth mark skin discoloration smooth, well defined Extremity has increased Subtopic 11 vascularity pattern circumfrence and may have axial patchy and reticular overgrowth usually unilateral

Size

Symptoms

Blood Flow Slow Slow Slow Slow Slow Slow Slow Slow

not needed for diagnosis Imaging MRI to check for dura involvement MRI for dura involvement)

contain heterotopic Histopathology rarely indicated leptomeningeal tissue

GNAQ (Sturge-Weber Syndrome), PIK3CA PIK3CA GNA11 ARL6IP6 Gene GNA11

VENOUS MAL FORMATION BRLUBNES R BULBUBEE RRU BBLBEEBR FIBROADIPOFASVEA VASCULAR GLOMUGVMENOUS CUTANECOMMVMUC VOESNAOLU VSENOUS CERCECBMR MAALL CFOARVMERANTIONUS VERRUCOVUVSM VENOUS DIFFUSBEO PCHKLEENBHEECIMTEARSIA OF FAM FILAIAMLI LINIATRLA IONSTSREAOOUSSS VEAOSUCSU LAR NEVUS SYNDROME ANOMALY (FAVA) MALFORMATION (GVM) MALFORMATION (CMVM) MALFORMATION (CCM) MALFORMATION BOCKENHEIMER VASCULAR MALFORMATION ( V V M ) (VMOS)

AKA phlebectasia verrucous hemangioma

severe blood vessel expansion within may be part of a combined shares clinical, radiographic, craniofacial bones accompanied by malformation, particularly histologic w/ intramuscular venous low temperature induced midline abonormalities (diastasis recti & lymphatic supraumblibical raphe) malformation similar to hyperkeratoic venous M = F less common than GVM malformation clincally, General hereditary, documented in literature sporadic phlebectasia (congenital) radiographically, hisologically within families associated with lymphatic malformation different: significant pain (89%), 3 forms nonspongiform venous cutanous part ( not pathologic syndromic (lateral embryonal vein in Klippel- 44%), poor response to sclerotherapy very rare. intraosseous vascular Trenaunay syndrome) malformations 0.2% all bony tumors

47% lesions involve skin, mucosa, subcutaneous tissue 10% skin & subcutaneous tissue

50% affect muscle, bone, joints, 50%; affect skin and oral mucosa CCM defined by effecting brain and Head & Neck viscera 60% skin and soft tissue (muscle maybe) spinal cord

primary morbiity psychosocial. 50% intramuscular lesions airway or orbital compromise due to bleeding

Intracranial May present in brain brain & spinal cord affected

13% lesions involve skin, mucosa 14% skin $ subcutaneous 9% skin lesions affect the skin & subcutis of tunk ( Trunk 80% skin and soft tissue 13%; skin & possible muscle 50% affect muscle, bone, joint, Association: risk for new intracranial 95) viscera 50% intramuscular lesion lesions, seizures, hemorrhages

Groin affects gluteal area (7%)

defines disease: all tissues of an 40% skin, mucosa, 76% skin & subcutaneous tissue extremity affects calf (70%), thigh (12%), forearm ( affect the skin & subcutis of Extremity 93% skin and soft tissue 37%; skin & possible muscle 9% skin lesions 8%), ankle/foot (3%) extremity (9%) Association: hypoplastic limb, 50% muscle, bone, joint, viscera 50% intramuscular lesion arthiritis

GI (usually small intestine) association w/ chronic bleeding/ Visceral May present in GI, lung anemia 75% bleeding requiring transfusion

8% glomuvenous (GVM) can have hundreds of lesions 73% lesions are multiple 73% Multifocal? 10% multifocal 2% cutaneomucosal (CMVM)

Present at Birth? Yes Yes Yes Yes Yes Yes Yes Yes Yes

2.6x more likely adolescence than prior to puberty malformation & bone during childhood englargement restricted to mandibular/ maxillary region Growth Progression

26% before adolescence, 75% after puberty rapid expansion to all cranial before adulthood bones

blue, soft, compressible. becomes hyperkeratotic and Appearance hard, calcified phleboliths may be frequently bleeds palpable

Size >5 cm (56%) < 2cm <5cm (66.6%) <5 cm (76%) 2-8 cm

differentiated via pain & Symptoms pain painful particularly on palpation pain contractures

Blood Flow Slow Slow Slow Slow Slow Slow Slow Slow Slow

MRI to differentiate FAVA

Imaging FAVA more fat or fibrosis, not as bright on no findings yet T2 images, hetergenous, smaller/less defined channels, nonspongiform- appearing vessels

FAVA infiltrative & greater fibroadipose critical to determine differential diagnosis Histopathology tissue

CCM1/KR1T1, CCM2/malcavernin, loss-of-function mutations in ELMO2 via Gene TIE2, PIK3CA TIE2 PIK3CA LOF of glomulin gene TIE2 CCM3/PDCD10 impaired RAC1 signaling INFANTILE HEMANGIOMA

CONGE NITAL INFANTILE HEMANGIOMA INFAINNFATNITLIELE M MYOFFIBIBRORMOAMA PYOPYGOEGNEINCIC G GRRAANUULOLMOAMA TUFTUTFETDE DA ANNGIOMMA A(T A()TA) KAPOKSHIFEORM ENZIN ENGEZRIN INGTERRA MINUTSRCUALMARU SHCEUMALNAGRI OMA CUTANE COUVTISACNEREOALV AISNCGEIORMAALT OSIS W/ EPITHELIOID E HPEIMTAHNEGLIIOOEINDD OTHELIOMA ANGIOANSGAIORSCOMA HEMANGIOMA (IM) HEMANGIOENDOTHELIOMA HEMANGIOMA ANGIOMATOSIS W/ HEMANGIOENDOTHELIOMA (EHE) ( K H E ) THROMBOCYTOPENIA (CAT) capillary/ cavernous,/strawberry hemangioma AKA hemangioma infantile myofibromatosis capillary hemangioma

Locally aggressive (no metastasis) M = F M: F = 1.6:1 Less aggressive than Kaposiform Benign tumor of skeletal muscle Affects skin & GI tract 99% affects adults in 70s most prevalent in white F:M = 4:1 Hangloendothelioma counterpart Malignant endothelial tumor 1/100,000 children M = F 80% male in adult onset Benign fibrous tumor of infancy General RICH [rapidly involuting] Age 6-7 onset Locally invasive 25% pediatrics Thrombocytopenia 1% Pediatrics Kasabach-Merritt (K-M) Phenomenon: 85% increased risk 40% increased risk in prematurity 3 Types: solitary, multifocal, Affecting Skin, bone, liver, and lung Kasabach-Merritt (K-M) retroperitoneal, intrathoracic, NICH [non involuting] generalized Median age diagnosis 25 yrs Hematemesis/Melena M = F phenomenon muscle involvement

Cheek 29%, Lips 9% RICH 42% 40% PHACES: Eye/Endocrine Oral Cavity 14% Sun & Radiation Head & Neck 1 most common common location 30% exposed 60% 62% LUMBAR: Myelopathy Scalp 11%, Eyelid 9% Association with K-M, muscle areas in adults NICH 43% involvement Forehead 10%

PHACES: posterior fosa brain Intracranial malformation, arterial cerebrovascular anomalies

RICH 6% PHACES: sternal clefting, 20% Association: Hx of 30% Association K-M: Breast (13%) Trunk supralumbilical raphe second most common trauma/ common location retroperitoneal, intrathoracic, 32% Yes 25% NICH 19% underlying cutaneous condition muscle involvement Mesentery ( %)

Check for spinal anomaly. Groin LUMBAR: urogential anomalies, Peds: Pelvis (7%) anorectal malformation

RICH 52% Upper 13% Upper Limb 23% 30% . Association K-M muscle 15% third most common Peds: Upper (7%) Extremity involvement NICH 38% Lower 5% Lower Extremity 15%

Peds: Heart & pericardium (46%) Hepatic = Check thyroid levels. PHACES: coarctation of aorta & 25-40% with multifocal subtype GI tract , Melena, Lung Liver Peds: Liver (13%) Visceral cardiac defects. LUMBAR: renal have visceral involvement involvement causes hemoptysis anomaly Peds: Spleen (7%)

Multifocal? No Yes Affects viscera Usually solitary No - solitary Yes Yes

Present at Birth? Yes Yes Yes (60% cases) No During early infancy & childhood Yes

In utero 60% noted neonatal 93% in Grows during infancy Grows rapidly & forms stalk Proliferating Phase: 80% growth by infancy Rapidly Involuting: 50% regression 3 Growth Progression by 7 months unpredictable Malignant, High Mitotic Index months Involuting Phase: begins 9-12 Mean age 42.9 onset month, cont. 3.5 yrs Diagnose before 2 yrs (80% cases) Age 6-7 onset Enlarges until age 2, then partially Non Involuting: no postnatal regresses regression

ALWAYS SOLITARY 80% Superficial [bright Pink-red, violaceous plaque red] reddish-brown w/ blue macules Violaceous with coarse reddish-pruple small, red, bleeding lesion reddish-purple painless soft tissue welling Appearance 20% Deep [blue] and pupules telangiectasia and a peripheral 80% Single Lesion Solitary tumor, diffuse stain pale halo

6.5 mm (2-20 mm range) Mean 8 cm Infants with >5 lesions [<5mm] = 0.5-7 cm > 5 cm Size 16% risk visceral lesion 75% <1 cm range 3.5 - 13 cm

may ulcerate during infancy (16%) chronic pain, stiffness & ulcerate Bleeding (64.2%), Ulcerate (36.3%) K-M phenomenon melena/hemoptysis Symptoms rarely bleeds contractures

Blood Flow Fast Fast Fast Fast Fast Flow & Enhancement Fast Fast N/A

Rarely Ultrasonography [first line, check MRI for diagnosis confirmation & indicated, Doppler, MRI, Ultrasound findings = tumor Imaging for hepatic lesions], Doppler, MRI severity Prenatal ultrasonography, Doppler

"cannonballs" or indicated (racemose Histopathology Rarely indicated GLUT1 positivity often necessary to diagnose indicated round indicated biopsy required for dx indicated vessels vascular nodules and solid sheet of cells)

Gene GNA11 PDGFR-β RAF(BRAF), GNA14 GNA14 GNA14 CAMTA1 & WWTR1?

ARTERIOVENOUS MALFORMATION PTEN- PATVEAN A-NAOSMSOALCYI AVATSEDCU VLAASRC AUSLSAORC IATED CAPILLARYC MMA-ALVFOMRMATION- HEREDITARY HHHETMORRHAGIC COBcoBb bS sYyNDndroRmOMe E WYBURWNY-MBUARSNO NMA SSYONNDROME ANOMALY (PTEN-AVA) ARTERIOVENOUS MALFORMATION TELANGIECTASIA (HHT) (CM-AVM)

bonnet-dechaume-blanc PTEN hamartoma tumor syndrome arteriovenous hemangioma osler-weber-rendu syndrome syndrome; retinocephalofacial AKA cowden syndrome, bannayan-riley- vascular malformation syndrome ruvalcaba syndrome

m = f progresses over time clinical hht: epistaxis, 1/100,000 prevalence 85% are intramuscular mucocutaneous telangiectasias extremely rare (121 cases in General I. Quiescence: warm, pink-blue Doppler Lesions replace muscle with disorganized patients likely has CLOVES or CM-AVM fat (non syndromic musclular AVMs cause literature) II. Expansion: enlargement & pulsation symmetrical overgrowth without adipose clinical hht: visceral AVM, 1st Schobinger Staging III. Destruction: ulceration, bleeding tissue) parkes weber syndrome (12%) degree relative IV: Decompensation: cardiac failure Genetic testing is confirmatory

80% mucocutaneous telangiectasias (lips, oral cavity, Macrocephaly seen in PTEN fingers, nose) defined by retinal arteriovenous malformations Head & Neck most common, risk of CHF with or without a brain (47%) AVM or facial Hamartoma Syndrome vascular malformation spinal arteriovenous lesions morbidity: chronic anemia from epistaxis

intracerebral AVM (7%): associated with vein of Galen aneurysmal malformations, seizures, cerebral arteriovenous malformations hydrocephalus, developmental delay

22% have retinal AVM with brain arteriovenous

Intracranial Extra cerebral AVM (11%) malformation and facial vascular malformation Morbidity: stroke and brain abscess , 5% tumor of CNS (neurofibroma, optic flioma) hemorrhage

Trunk risk of CHF

Penile freckling seen in hamartoma

Groin syndrome

Parkes weber - diffuse extremity AVM causes overgrowth of limb. One lower extremity usually Extremity risk of chf affected & capillary malformation present over AVM

Morbidity: upper GI bleeding (25%) & high- Visceral risk of CHF thyroid lesions (31%) GI polyps 30% output heart failure/portal HTN

as many as 53 CM. 6% only have 1 57% of patients Multifocal? lesion

Present at Birth? Yes Yes Yes Yes Yes Yes

enlarges, becomes symptomatic Patients at risk for developmental delay/autism ( 19%), thyroid lesions (31%), GI polyps (30%) Growth Progression Twofold risk of progression in Patients should be followed closely for tumors of adolescence endocrine and GI origin

small, multifocal, round, pinkish- pink-red cutaneous stain, warm, red Appearance palpable thrill/bruit 50% surrounded by pale halo

Pink-red cutaneous stain, warm, 1- 15 cm range Size palpable thrill/bruit

Disfigurement, destruction of tissues, obstruction of vital structures Exam should be done to determine PTEN Symptoms Harmatoma Syndrome: macrocephaly, penile pain, ulceration, bleeding, CHF, arteries may freckling rupture

Blood Flow Fast Fast Fast Fast Fast Fast

if dx equivocal after doppler & HPE = confirm doppler ultrasound first line MRI to Often found after MRI or angiogram of MRI usually indicated for brain/spine using Ultrasound, MRI. Use Angiogram if still Imaging patient thought to have sporadic AVM associated lesions confirm angiogram CT (when unclear after all options. involving bone)

can aid diagnosis

rarely indicated. Only if dx equivocal/ Histopathology tortuous vessels with arterialized veins, malignancy suspected fibromyxoid areas, adipose tissue, lymphoid clusters . arteries have transmural muscular hyperplasia & small lumens

genetic testing should be done. patients should be genetic MAP2K1 LOF mutation RASA1 Gene counseled about transmitting disease to offspring