Diagnosis commonly occurs later in childhood and often occurs incidentally in asymptomatic patients or as a cause of visual impairment. The first symptoms are commonly found during routine vision screenings.

A number of examinations can be used to determine the extent of the syndrome and its severity. Fluorescein angiography is quite useful in diagnosing the disease, and the use of ultrasonography and optical coherence tomography (OCT) are helpful in confirming the disease. Neuro-ophthalmic examinations reveal pupillary defects (see Marcus Gunn Pupil). Funduscopic examinations, examinations of the fundus of the eye, allow detection of arteriovenous malformations. Neurological examinations can determine hemiparesis and paresthesias. Malformations in arteriovenous connections and irregular functions in the veins may be distinguished by fluorescein angiographies. Cerebral angiography examinations may expose AVMs in the cerebrum. MRIs are also used in imaging the brain and can allow visualization of the optic nerve and any possible atrophy. MRI, CT, and cerebral angiography are all useful for investigating the extent and location of any vascular lesions that are affecting the brain. This is helpful in determining the extent of the syndrome.

Genetic tests are available for the "ENG", "ACVRL1" and "MADH4" mutations. Testing is not always needed for diagnosis, because the symptoms are sufficient to distinguish the disease from other diagnoses. There are situations in which testing can be particularly useful. Firstly, children and young adults with a parent with definite HHT may have limited symptoms, yet be at risk from some of the complications mentioned above; if the mutation is known in the affected parent, absence of this mutation in the child would prevent the need for screening tests. Furthermore, genetic testing may confirm the diagnosis in those with limited symptoms who otherwise would have been labeled "possible HHT" (see below).

Genetic diagnosis in HHT is difficult, as mutations occur in numerous different locations in the linked genes, without particular mutations being highly frequent (as opposed to, for instance, the ΔF508 mutation in cystic fibrosis). Sequence analysis of the involved genes is therefore the most useful approach (sensitivity 75%), followed by additional testing to detect large deletions and duplications (additional 10%). Not all mutations in these genes have been linked with disease.

Mutations in the "MADH4" gene is usually associated with juvenile polyposis, and detection of such a mutation would indicate a need to screen the patient and affected relatives for polyps and tumors of the large intestine.

Identification of AVMs requires detailed medical imaging of the organs most commonly affected by these lesions. Not all AVMs cause symptoms or are at risk of doing so, and hence there is a degree of variation between specialists as to whether such investigations would be performed, and by which modality; often, decisions on this issue are reached together with the patient.

Lung AVMs may be suspected because of the abnormal appearance of the lungs on a chest X-ray, or hypoxia (low oxygen levels) on pulse oximetry or arterial blood gas determination. Bubble contrast echocardiography (bubble echo) may be used as a screening tool to identify abnormal connections between the lung arteries and veins. This involves the injection of agitated saline into a vein, followed by ultrasound-based imaging of the heart. Normally, the lungs remove small air bubbles from the circulation, and they are therefore only seen in the right atrium and the right ventricle. If an AVM is present, bubbles appear in the left atrium and left ventricle, usually 3–10 cardiac cycles after the right side; this is slower than in heart defects, in which there are direct connections between the right and left side of the heart. A larger number of bubbles is more likely to indicate the presence of an AVM. Bubble echo is not a perfect screening tool as it can miss smaller AVMs and does not identify the site of AVMs. Often contrast-enhanced computed tomography (CT angiography) is used to identify lung lesions; this modality has a sensitivity of over 90%. It may be possible to omit contrast administration on modern CT scanners. Echocardiography is also used if there is a suspicion of pulmonary hypertension or high-output cardiac failure due to large liver lesions, sometimes followed by cardiac catheterization to measure the pressures inside the various chambers of the heart.

Liver AVMs may be suspected because of abnormal liver function tests in the blood, because the symptoms of heart failure develop, or because of jaundice or other symptoms of liver dysfunction. The most reliable initial screening test is Doppler ultrasonography of the liver; this has a very high sensitivity for identifying vascular lesions in the liver. If necessary, contrast-enhanced CT may be used to further characterize AVMs. It is extremely common to find incidental nodules on liver scans, most commonly due to focal nodular hyperplasia (FNH), as these are a hundredfold times more common in HHT compared to the general population. FNH is regarded as harmless. Generally, tumor markers and additional imaging modalities are used to differentiate between FNH and malignant tumors of the liver. Liver biopsy is discouraged in people with HHT as the risk of hemorrhage from liver AVMs may be significant. Liver scans may be useful if someone is suspected of HHT, but does not meet the criteria (see below) unless liver lesions can be demonstrated.

Brain AVMs may be detected on computed tomography angiography (CTA or CT angio) or magnetic resonance angiography (MRA); CTA is better in showing the vessels themselves, and MRA provides more detail about the relationship between an AVM and surrounding brain tissue. In general, MRI is recommended. Various types of vascular malformations may be encountered: AVMs, micro-AVMs, telangiectasias and arteriovenous fistulas. If surgery, embolization, or other treatment is contemplated (see below), cerebral angiography may be required to get sufficient detail of the vessels. This procedure carries a small risk of stroke (0.5%) and is therefore limited to specific circumstances. Recent professional guidelines recommend that all children with suspected or definite HHT undergo a brain MRI early in life to identify AVMs that can cause major complications. Others suggest that screening for cerebral AVMs is probably unnecessary in those who are not experiencing any neurological symptoms, because most lesions discovered on screening scans would not require treatment, creating undesirable conundrums.

Making a correct diagnosis for a genetic and rare disease is often times very challenging. So the doctors and other healthcare professions rely on the person’s medical history, the severity of the symptoms, physical examination and lab tests to make and confirm a diagnosis.

There is a possibility of interpreting the symptoms of PWS with other conditions such as AVMs and or AVFs. This is because AVMs and AVFs also involve the characteristic overgrowth in soft tissue, bone and brain. Also PWS can be misdiagnosed with Klippel–Trenaunay syndrome (KTS). However, KTS consists of the following: triad capillary malformation, venous malformation, and lymphatic malformation.

Usually a specific set of symptoms such as capillary and arteriovenous malformations occur together and this is used to distinguish PWS from similar conditions. Arteriovenous malformations (AVMs) and arteriovenous fistulas (AVFs) are caused by RASA1 mutations as well. Therefore, if all the other tests (discussed below) fail to determine PWS, which is highly unlikely, genetic testing such as sequence analysis and gene-targeted deletion/duplication analysis can be performed to identify possible RASA1 gene mutations.

But PWS can be distinguished from other conditions because of its defining port-wine stains that are large, flat and pink. The port-wine stains and physical examination are enough to diagnose PWS. But additional testing is necessary to determine the extent of the PWS syndrome. The following tests may be ordered by physicians to help determine the appropriate next steps: MRI, ultrasound, CT/CAT scan, angiogram, and echocardiogram.

MRI: This is a high-resolution scan that is used to identify the extent of the hypertrophy or overgrowth of the tissues. This can also be used to identify other complications that may arise a result of hypertrophy.

Ultrasound: this can be necessary to examine the vascular system and determine how much blood is actually flowing through the AVMs.

CT/CAT scan: this scan is especially useful for examining the areas affected by PWS and is helpful for evaluating the bones in the overgrown limb.

Angiogram: an angiogram can also be ordered to get a detailed look at the blood vessels in the affected or overgrown limb. In this test an interventional radiologist injects a dye into the blood vessels that will help see how the blood vessels are malformed.

Echocardiogram: depending on the intensity of the PWS syndrome, an echo could also be ordered to check the condition of the heart.

And PWS often requires a multidisciplinary care. Depending on the symptoms, patients are dependent on: dermatologists, plastic surgeons, general surgeons, interventional radiologists, orthopedists, hematologists, neurosurgeons, vascular surgeons and cardiologists. Since the arteriovenous and capillary malformations cannot be completely reconstructed and depending on the extent and severity of the malformations, these patients may be in the care of physicians for their entire lives.

The causes for PWS are either genetic or unknown. Some cases are a direct result of the RASA1 gene mutations. And individuals with RASA1 can be identified because this genetic mutation always causes multiple capillary malformations. PWS displays an autosomal dominant pattern of inheritance. This means that one copy of the damaged or altered gene is sufficient to elicit PWS disorder. In most cases, PWS can occur in people that have no family history of the condition. In such cases the mutation is sporadic. And for patients with PWS with the absence of multiple capillary mutations, the causes are unknown.

According to Boston’s Children Hospital, no known food, medications or drugs can cause PWS during pregnancy. PWS is not transmitted from person to person. But it can run in families and can be inherited. PWS effects both males and females equally and as of now no racial predominance is found

At the moment, there are no known measures that can be taken in order to prevent the onset of the disorder. But Genetic Testing Registry can be great resource for patients with PWS as it provides information of possible genetic tests that could be done to see if the patient has the necessary mutations. If PWS is sporadic or does not have RASA1 mutation then genetic testing will not work and there is not a way to prevent the onset of PWS.

Treatment depends on the anatomy of the malformation as determined by angiography or Magnetic Resonance Imaging (MRI).

The treatment for Bonnet–Dechaume–Blanc syndrome is controversial due to a lack of consensus on the different therapeutic procedures for treating arteriovenous malformations. The first successful treatment was performed by Morgan et al. They combined intracranial resection, ligation of ophthalmic artery, and selective arterial ligature of the external carotid artery, but the patient did not have retinal vascular malformations.

If lesions are present, they are watched closely for changes in size. Prognosis is best when lesions are less than 3 cm in length. Most complications occur when the lesions are greater than 6 cm in size. Surgical intervention for intracranial lesions has been done successfully. Nonsurgical treatments include embolization, radiation therapy, and continued observation. Arterial vascular malformations may be treated with the cyberknife treatment. Possible treatment for cerebral arterial vascular malformations include stereotactic radiosurgery, endovascular embolization, and microsurgical resection.

When pursuing treatment, it is important to consider the size of the malformations, their locations, and the neurological involvement. Because it is a congenital disorder, there are not preventative steps to take aside from regular follow ups with a doctor to keep an eye on the symptoms so that future complications are avoided.

This is based on MRI scan, magnetic resonance angiography and CT scan. A cerebral digital subtraction angiography (DSA) enhances visualization of the fistula.

- CT scans classically show an enlarged superior ophthalmic vein, cavernous sinus enlargement ipsilateral (same side) as the abnormality and possibly diffuse enlargement of all the extraocular muscles resulting from venous engorgement.

- Selective arteriography is used to evaluate arteriovenous fistulas.

- High resolution digital subtraction angiography may help in classifying CCF into dural and direct type and thus formulate a strategy to treat it either by a balloon or coil or both with or without preservation of parent ipsilateral carotid artery.

The Cognard et al. Classification correlates venous drainage patterns with increasingly aggressive neurological clinical course.

Cerebral angiography is the diagnostic standard. MRIs are usually normal.

AVMs are diagnosed primarily by the following methods:

- Computerized tomography (CT) scan is a noninvasive X-ray to view the anatomical structures within the brain to detect blood in or around the brain. A newer technology called CT angiography involves the injection of contrast into the blood stream to view the arteries of the brain. This type of test provides the best pictures of blood vessels through angiography and soft tissues through CT.

- Magnetic resonance imaging (MRI) scan is a noninvasive test, which uses a magnetic field and radio-frequency waves to give a detailed view of the soft tissues of the brain.

- Magnetic resonance angiography (MRA) – scans created using magnetic resonance imaging to specifically image the blood vessels and structures of the brain. A magnetic resonance angiogram can be an invasive procedure, involving the introduction of contrast dyes (e.g., gadolinium MR contrast agents) into the vasculature of a patient using a catheter inserted into an artery and passed through the blood vessels to the brain. Once the catheter is in place, the contrast dye is injected into the bloodstream and the MR images are taken. Additionally or alternatively, flow-dependent or other contrast-free magnetic resonance imaging techniques can be used to determine the location and other properties of the vasculature.

AVMs can occur in various parts of the body:

- brain (cerebral AV malformation)

- spleen

- lung

- kidney

- spinal cord

- liver

- intercostal space

- iris

- spermatic cord

- extremities – arm, shoulder, etc.

AVMs may occur in isolation or as a part of another disease (for example, Von Hippel-Lindau disease or hereditary hemorrhagic telangiectasia).

AVMs have been shown to be associated with aortic stenosis.

Bleeding from an AVM can be relatively mild or devastating. It can cause severe and less often fatal strokes. If a cerebral AVM is detected before a stroke occurs, usually the arteries feeding blood into the nidus can be closed off to avert the danger. However, interventional therapy may also be relatively risky.

Testing for a malformed vein of Galen is indicated when a patient has heart failure which has no obvious cause. Diagnosis is generally achieved by signs such as cranial bruits and symptoms such as expanded facial veins. The vein of Galen can be visualized using ultrasound or Doppler. A malformed Great Cerebral Vein will be noticeably enlarged. Ultrasound is a particularly useful tool for vein of Galen malformations because so many cases occur in infancy and ultrasound can make diagnoses prenatally. Many cases are diagnosed only during autopsy as congestive heart failure occurs very early.

Kaposiform hemangioendothelioma (KHE) is a rare vascular neoplasm that is locally aggressive but without metastatic potential. It occurs particularly in the skin, deep soft tissue, retroperitoneum, mediastinum, and rarely in bone. Although lesions occur solitary, they often involve large areas of the body, such as the head/neck region (40%), trunk (30%), or extremity (30%).

Usually, it is present at birth as a flat, reddish-purple, tense and edematous lesion.

Although half of lesions are congenital, 58% of KHE develop during infancy, 32% between age 1 and 10 years (32%) and 10% after 11 years of age. Moreover, adult onset has been described too with mainly males being affected. Both sexes are affected equally in children.

Lesions are often greater than 5 cm in diameter and can cause visible deformity and pain. During early childhood, KHE may enlarge and after 2 years of age, it may partially regress. Though, it usually persists longterm. In addition, 50% of patients suffer from coagulopathy due to thrombocytopenia (<25,000/mm3), presenting with petechiae and bleeding. This is called the Kasabach-Merritt Phenomenon, which is caused by trapping of platelets and other clotting factors within the tumor. Kasabach-Merritt Phenomenon is less likely in patients with lesions less than 8 cm. As two-thirds of adult-onset KHE tumors are less than 2 cm, KHE in adults is rarely associated with Kasabach-Merritt Phenomenon.

Patients with KHE and Kasabach-Merritt Phenomenon present with petechiae and ecchymosis.

Most KHE tumors are diffuse involving multiple tissue planes and important structures. Resection of KHE is thus often difficult. Treatment of kaposiform hemangioendothelioma is therefore medical. The primary drug is interferon alfa, which is successful in 50% of children. Another option is vincristine, which has lots of side-effects, but has a response rate of 90%. Drug therapy is often used in shrinking the tumor and treating the coagulopathy. However, many of these kaposiform hemangioendotheliomas do not completely regress and remain as a much smaller asymptomatic tumor. However, KHE still has a high mortality rate of 30%. Although complete surgical removal with a large margin has the best reported outcome, it is usually not done because of the risk of bleeding, extensiveness, and the anatomic site of the lesion.

Operative management may be possible for small or localized lesions. Removal of larger areas also may be indicated for symptomatic patients or for patients who have failed farmacotherapy. Resection is not required for lesions that are not causing functional problems, because KHE is benign and because resection could cause deformity.

Congenital hemangioma can be distinguished from infantile hemangioma because it is fully developed at birth. It forms during prenatal life and has reached its maximal size at birth. Congenital hemangioma can even be diagnosed in utero by prenatal ultrasound. Unlike IH, CH is more common in the extremities, has an equal sex distribution, and is solitary, with an average diameter of 5 cm. It commonly presents in the head and neck and in the lower extremities.

Congenital hemangioma are divided into 2 subgroups: the rapidly involuting congenital hemangiomas (RICHs) and the non-involuting congenital hemangiomas(NICHs).

The rapidly involuting congenital hemangioma, RICH, presents at birth as a solitary raised tumor with a central depression, scar, or ulceration surrounded by a rim of pallor. It is noted for its involution, which typically begins several weeks after birth and is completed no later than 14 months of age. After regression RICH may cause a residual deformity, such as atrophic skin and subcutaneous tissue. It mainly affects the limbs (52%), but also the head and neck region (42%) and the trunk (6%).

The non-involuting congenital hemangioma, NICH, presents as a solitary, well-circumscribed reddish-pink to purple plaque with central telangiectasia and hypopigmented rim. In contrast to RICH, NICH does not involute and rarely ulcerates. It persists into late childhood and can even mimic a vascular malformation by growing commensurately with the child. Although NICH can resemble RICH in its external appearance, it can be differentiated from RICH by a greater elevation and coarse telangiectases. It mainly affects the head and neck region (43%), but also the limbs (38%) and the trunk (19%).

Surgical resection for congenital hemangiomas is rarely needed, because RICH undergoes postnatal regression and NICH is benign and often asymptomatic. Resection may be indicated to improve the appearance of the affected area, as long as the surgical scar is less noticeable than the lesion. Other indications are problematic ulcers with persistent bleeding or chronic infection.

Although most NICH lesions are non-problematic and do not cause significant deformity, the threshold for resection of NICH is lower, because it neither involutes, nor responds to pharmacotherapy. RICH tumors are observed until involution is completed. Involuted RICH may leave behind atrophic tissue, which can be reconstructed with autologous grafts. It is often best to postpone excision until regression is complete.

There are effective pharmacologic treatments, which include intralesional corticosteroid injection, systemic corticosteroid injection, interferon α-2a or α-2b and angiogenic inhibitors. The use of corticosteroids leads to accelerated regression in 30%, stabilization of growth in 40%, lightening of color and softening of the tumor. However, 30% shows minimal or no response. Another drug treatment is interferon α-2a or α-2b. It is often used for patients who did not respond to corticosteroids. Although the response rate is much slower, it has been successful for 80% of children treated. The most serious side effect of interferon is a spastic diplegia. Other therapeutic options are embolization and pulsed-dye laser, which improves residual telangiectasias in RICH and in NICH.

An AVM diagnosis is established by neuroimaging studies after a complete neurological and physical examination. Three main techniques are used to visualize the brain and search for AVM: computed tomography (CT), magnetic resonance imaging (MRI), and cerebral angiography. A CT scan of the head is usually performed first when the subject is symptomatic. It can suggest the approximate site of the bleed. MRI is more sensitive than CT in the diagnosis of AVMs and provides better information about the exact location of the malformation. More detailed pictures of the tangle of blood vessels that compose an AVM can be obtained by using radioactive agents injected into the blood stream. If a CT is used in conjunctiangiogram, this is called a computerized tomography angiogram; while, if MRI is used it is called magnetic resonance angiogram. The best images of an AVM are obtained through cerebral angiography. This procedure involves using a catheter, threaded through an artery up to the head, to deliver a contrast agent into the AVM. As the contrast agent flows through the AVM structure, a sequence of X-ray images are obtained.

Treatment for brain AVMs can be symptomatic, and patients should be followed by a neurologist for any seizures, headaches, or focal neurologic deficits. AVM-specific treatment may also involve endovascular embolization, neurosurgery or radiosurgery.

Embolization, that is, cutting off the blood supply to the AVM with coils, particles, acrylates, or polymers introduced by a radiographically guided catheter, may be used in addition to neurosurgery or radiosurgery, but is rarely successful in isolation except in smaller AVMs. Gamma knife may also be used.

Low-output fistula: < 200 mL/day

Moderate-output fistula: 200-500 mL/day

High-output fistula: > 500 mL/day

A limitation of the Spetzler-Martin Grading system is that it does not include the following factors: Patient age, hemorrhage, diffuseness of nidus, and arterial supply. In 2010 a new supplemented Spetzler-Martin system (SM-supp, Lawton-Young) was devised adding these variables to the SM system. Under this new system AVMs are classified from grades 1 - 10. It has since been determined to have greater predictive accuracy that Spetzler-Martin grades alone.

The mainstay of treatment for CCF is endovascular therapy. This may be transarterial (mostly in the case of direct CCF) or transvenous (most commonly in indirect CCF). Occasionally, more direct approaches, such as direct transorbital puncture of the cavernous sinus or cannulation of the draining superior orbital vein are used when conventional approaches are not possible. Spontaneous resolution of indirect fistulae has been reported but is uncommon. Staged manual compression of the ipsilateral carotid has been reported to assist with spontaneous closure in selected cases.

Direct CCF may be treated by occlusion of the affected cavernous sinus (coils, balloon, liquid agents), or by reconstruction of the damaged internal carotid artery (stent, coils or liquid agents).

Indirect CCF may be treated by occlusion of the affected cavernous sinus with coils, liquid agents or a combination of both.

Low-output fistula: < 500 mL/day

High-output fistula: > 500 mL/day

Due to the rarity of different types of vascular conditions, angiokeratomas may be misdiagnosed. A biopsy of the lesion can produce a more accurate diagnosis.

The radiocephalic arteriovenous fistula (RC-AVF) is a shortcut between cephalic vein and radial artery at the wrist. It is the recommended first choice for hemodialysis access. Possible underlying causes for failure are stenosis and thrombosis especially in diabetics and those with low blood flow such as due to narrow vessels, arteriosclerosis and advanced age. Reported patency of fistulae after 1 year is about 62.5%.

Outpatient treatments such as interventional radiology, lasers, and physical therapy are employed to reduce the severity of the vascular lesions. However, in some cases lasers have caused a reaction in the tissue causing it to expand and become exposed to infection. Excision and grafting may be necessary to remove the lesion. Recovery time on such an operation ranges from 3 to 12 weeks depending on location of the graft, healing time and the possibility of complications.

Cobb syndrome is a rare congenital disorder characterized by visible skin lesions with underlying spinal angiomas or arteriovenous malformations (AVMs). The skin lesions of Cobb syndrome typically are present as port wine stains or angiomas, but reports exist of angiokeratomas, angiolipomas, and lymphangioma circumscriptum. The intraspinal lesions may be angiomas or AVMs and occur at levels of the spinal cord corresponding to the affected skin dermatomes. They may in turn produce spinal cord dysfunction and weakness or paralysis.

The disorder was first described by Berenbruch in 1890, but became widely known only after Cobb's report in 1915. Cobb syndrome is thought to be more common in males and have no racial predilection, but only a few dozen cases are known. It is believed to be due to a sporadic mutation, since parents of affected children usually have no evidence of the disease.

Smith (2015) conducted a study that looked into specific biological markers that correlate to Moyamoya disease. Some of the categories of these biomarkers include phenotypes - conditions commonly related to Moyamoya, radiographical markers for the diagnosis of Moyamoya, and proteins as well as cellular changes that occur in cases of Moyamoya.

Similar to Moyamoya Disease, there are conditions that are closely associated with Moyamoya Syndrome. Some of the more common medical conditions that are closely associated with Moyamoya Syndrome include trisomy 21 (Down's Syndrome), sickle cell disease, and neurofibromatosis type 1. There is also evidence that identifies hyperthyroidism and congenital dwarfing syndromes as two of the more loosely associated syndromes that correlate with the possibility of being diagnosed with Moyamoya Disease later in life.

There is also research that has shown that certain radiographic biomarkers that lead to the diagnosis of Moyamoya Disease have been identified. The specific radiographic markers are now considered an acceptable key component to Moyamoya Disease and have been added to the INternational Classification of Diseases (ICD). These biomarkers of Moyamoya are "stenosis of the distal ICA's up to and including the bifurcation, along with segments of the proximal ACA and MCA...dilated basal collateral vessels must be present" Some other common findings that have not been added to the classification index of those with Moyamoya Disease which are found using radiography involve very distinct changes in the vessels of the brain. These changes include newly formed vessels made to compensate for another change noted, ischemia and cerebrovascular reserve, both found on MRI. Functional changes include evidence of ischemia in vessels of the brain (ICA, ACA, MCA, specifically). It is important to also note that the radiographic biomarkers, in order to be classified as Moyamoya Disease, all findings must be bilateral. If this is not the case and the findings are unilateral, it is diagnosed as Moyamoya Syndrome.

There are also several protein biomarkers that have been linked to the Moyamoya Disease diagnosis. Although the sample size of the studies performed are small due to the rarity of the disease, the findings are indicative of a correlation between the disease and several specific protein biomarkers. Other studies have confirmed the correlation of Moyamoya and adhesion molecule 1 (ICAM-1) being increased as compared to normal vascular function counterparts Furthermore, it has been concluded that the localization of inflammatory cells suggests that the inflammation stimulus iteself may be responsible for the proliferation and occlusion in the ICA, ACA, and MCA found in those with Moyamoya Disease.