Diagnosis is made when several characteristic clinical signs are observed. There is no single test to confirm the presence of Weill–Marchesani syndrome. Exploring family history or examining other family members may prove helpful in confirming this diagnosis.

Lens subluxation is also seen in dogs and is characterized by a partial displacement of the lens. It can be recognized by trembling of the iris (iridodonesis) or lens (phacodonesis) and the presence of an aphakic crescent (an area of the pupil where the lens is absent). Other signs of lens subluxation include mild conjunctival redness, vitreous humour degeneration, prolapse of the vitreous into the anterior chamber, and an increase or decrease of anterior chamber depth. Removal of the lens before it completely luxates into the anterior chamber may prevent secondary glaucoma. A nonsurgical alternative involves the use of a miotic to constrict the pupil and prevent the lens from luxating into the anterior chamber.

On photographs taken using a flash, instead of the familiar red-eye effect, leukocoria can cause a bright white reflection in an affected eye. Leukocoria may appear also in low indirect light, similar to eyeshine.

Leukocoria can be detected by a routine eye exam (see Ophthalmoscopy). For screening purposes, the red reflex test is used. In this test, when a light is shone briefly through the pupil, an orange red reflection is normal. A white reflection is leukocoria.

With posterior lens luxation, the lens falls back into the vitreous humour and lies on the floor of the eye. This type causes fewer problems than anterior lens luxation, although glaucoma or ocular inflammation may occur. Surgery is used to treat dogs with significant symptoms. Removal of the lens before it moves to the anterior chamber may prevent secondary glaucoma.

Persistent tunica vasculosa lentis is a congenital ocular anomaly. It is a form of persistent hyperplastic primary vitreous (PHPV).

It is a developmental disorder of the vitreous. It is usually unilateral and first noticed in the neonatal period. It may be associated with micropthalmos, cataracts, and increased intraocular pressure. Elongated ciliary processes are visible through the dilated pupil. A USG B-scan confirms diagnosis in the presence of a cataract.

Treatment is based

on the stage of the disease. Stage 1 does not

require treatment and

should be observed. 4

Neovascularization

(stage 2) responds well

to laser ablation or

cryotherapy.2,4 Eyes

with retinal detachments (stages

3 through 5) require surgery, with

earlier stages requiring scleral

buckles and later stages ultimately

needing vitrectomy. 2,4

More recently, the efficacy of

anti-VEGF intravitreal injections

has been studied. In one study,

these injections, as an in adjunct

with laser, helped early stages

achieve stabilization, but further

investigation is needed.6

Persistent hyperplastic primary vitreous (PHPV), also known as Persistent Fetal Vasculature (PFV), is a rare congenital developmental anomaly of the eye that results

following failure of the embryological, primary vitreous and hyaloid vasculature to regress. It can be present in three forms: purely anterior (persistent tunica vasculosa lentis and persistent posterior fetal fibrovascular sheath of the lens), purely posterior (falciform retinal septum and ablatio falcicormis congenita) and a combination of both. Most examples of PHPV are unilateral and non-hereditary. When bilateral, PHPV may follow an autosomal recessive or autosomal dominant inheritance pattern.

Causes a ‘white reflex’ in the affected eye (leukocoria), prompting further investigation.

Eye surgery has been documented to help those with ocular diseases, such as some forms of glaucoma.

However, long term medical management of glaucoma has not proven to be successful for patients with Weill–Marchesani syndrome. Physical therapy and orthopedic treatments are generally prescribed for problems stemming from mobility from this connective tissue disorder. However, this disorder has no cure, and generally, treatments are given to improve quality of life.

Imaging studies are performed before surgery or biopsy to preclude an intracranial connection. Images usually show a sharply circumscribed but expansile mass. It may be difficult to exclude the intracranial connection if the defect is small whether employing computed tomography or magnetic resonnance.

Corectopia is the displacement of the eye's pupil from its normal, central position. It may be associated with high myopia or ectopia lentis, among other conditions. Medical or surgical intervention may be indicated for the treatment of corectopia in some cases.

Retinal examination with scleral depression is generally recommended for patients born before 30–32 weeks gestation, or 4–6 weeks of life, whichever is later. It is then repeated every 1–3 weeks until vascularization is complete (or until disease progression mandates treatment).

The most common missed lesion is within the nasal cavity, where a fibrosed nasal polyp may be considered. However, it does not have glial tissue. Further, a polyp usually has mucoserous glands. The lesion is frequently misintrepreted as scar in the subcutaneous tissues, but scar in a <2 year old child would be uncommon. Special stains are frequently required to highlight the diagnosis.

FEVR is, as its name suggests,

familial and can be inherited in an

autosomal dominant, autosomal

recessive or X-linked recessive pattern.1-3 It is caused by mutations in

FZD4, LRP5, TSPAN12 and NDP

genes, which impact the wingless/

integrated (Wnt) receptor signaling

pathway. 3 Disruption of this path

way leads to abnormalities of vascu-

lar growth in the peripheral retina. 2,3

It is typically bilateral, but asymmetric, with varying degrees of

progression over the individual’s

lifetime. Age of onset varies, and

visual outcome can be strongly

influenced by this factor. Patients

with onset before age three have a

more guarded long-term prognosis

whereas those with later onset are

more likely to have asymmetric

presentation with deterioration of

vision in one eye only. 2-3 However,

because FEVR is a lifelong disease,

these patients are at risk even as

adults.2 Ocular findings and useful

vision typically remain stable if the

patient does not have deterioration

before age 20.2,4 Due to the variability and unpredictability of the

disease course, patients with FEVR

should be followed throughout

their lifetime.

Clinical presentation can vary

greatly. In mild variations, patients

may experience peripheral vascular

changes, such as peripheral avascular zone, vitreoretinal adhesions,

arteriovenous anastomoses and a

V-shaped area of retinochoroidal

degeneration. 4 Severe forms may

present with neovascularization,

subretinal and intraretinal hemorrhages and exudation. 4 Neovascularization is a poor prognostic

indicator and can lead to retinal

folds, macular ectopia and tractional retinal detachment. 2,4 Widefield FA has been crucial in

helping to understand this disease,

as well as helping to confirm the

diagnosis. An abrupt cessation

of the retinal capillary network

in a scalloped edge posterior to

fibrovascular proliferations can

be made using FA.2,3,5 Patients can

also show delayed transit filling on

FA as well as delayed/patchy choroidal filling, bulbous vascular terminals, capillary dropout, venous/venous shunting and abnormal

branching patterns. 2,3,5 The staging of FEVR is similar

to that of retinopathy of prematurity. The first two stages involve an

avascular retinal periphery with or

without extraretinal vascularization (stage 1 and 2, respectively). 4 Stages three through five delineate

levels of retinal detachment; stage 3

is subtotal without foveal involvement, stage 4 is subtotal with foveal

involvement and stage 5 is a total

detachment, open or closed funnel.4

Because there was neovascularization in the absence of retinal detachment, our patient was

considered to have

stage 2.

Following pupillary dilation using eye drops, the retina is examined using a special lighted instrument (an indirect ophthalmoscope). The peripheral portions of the retina are sometimes pushed into view using scleral depression. Examination of the retina of a premature infant is performed to determine how far the retinal blood vessels have grown (the zone), and whether or not the vessels are growing flat along the wall of the eye (the stage). Once the vessels have grown into Zone 3 (see below) it is usually safe to discharge the child from further screening for ROP. The stage of ROP refers to the character of the leading edge of growing retinal blood vessels (at the vascular-avascular border).

Diagnosis is made through a combination of patient history, neurological examination, and medical imaging. Magnetic resonance imaging (MRI) is considered the best imaging modality for Chiari malformation since it visualizes neural tissue such as the cerebellar tonsils and spinal cord as well as bone and other soft tissues. CT and CT myelography are other options and were used prior to the advent of MRI, but they characterize syringomyelia and other neural abnormalities less well.

By convention the cerebellar tonsil position is measured relative to the basion-opisthion line, using sagittal T1 MRI images or sagittal CT images. The selected cutoff distance for abnormal tonsil position is somewhat arbitrary since not everyone will be symptomatic at a certain amount of tonsil displacement, and the probability of symptoms and syrinx increases with greater displacement, however greater than 5 mm is the most frequently cited cutoff number, though some consider 3–5 mm to be "borderline," and symptoms and syrinx may occur above that. One study showed little difference in cerebellar tonsil position between standard recumbent MRI and upright MRI for patients without a history of whiplash injury. Neuroradiological investigation is used to first rule out any intracranial condition that could be responsible for tonsillar herniation. Neuroradiological diagnostics evaluate the severity of crowding of the neural structures within the posterior cranial fossa and their impact on the foramen magnum. Chiari 1.5 is a term used when both brainstem and tonsillar herniation through the foramen magnum are present.

The diagnosis of a Chiari II malformation can be made prenatally through ultrasound.

Crossed dystopia (syn.unilateral fusion cross fused renal ectopia) is a rare form of renal ectopia where both kidneys are on the same side of the spine. In many cases, the two kidneys are fused together, yet retain their own vessels and ureters. The ureter of the lower kidney crosses the midline to enter the bladder on the contralateral side. Both renal pelvis can lie one above each other medial to the renal parenchyma (unilateral long kidney) or the pelvis of the crossed kidney faces laterally (unilateral "S" shaped kidney). Urogram is diagnostic.

The anomaly can be diagnosed through ultrasound of urography, but surgical intervention is only necessary if there are other complications, such as tumors or pyelonephritis.

In the late 19th century, Austrian pathologist Hans Chiari described seemingly related anomalies of the hindbrain, the so-called Chiari malformations I, II and III. Later, other investigators added a fourth (Chiari IV) malformation. The scale of severity is rated I – IV, with IV being the most severe. Types III and IV are very rare.

Other conditions sometimes associated with Chiari malformation include hydrocephalus, syringomyelia, spinal curvature, tethered spinal cord syndrome, and connective tissue disorders such as Ehlers-Danlos syndrome and Marfan syndrome.

Chiari malformation is the most frequently used term for this set of conditions. The use of the term Arnold–Chiari malformation has fallen somewhat out of favor over time, although it is used to refer to the type II malformation. Current sources use "Chiari malformation" to describe four specific types of the condition, reserving the term "Arnold-Chiari" for type II only. Some sources still use "Arnold-Chiari" for all four types.

Chiari malformation or Arnold–Chiari malformation should not be confused with Budd-Chiari syndrome, a hepatic condition also named for Hans Chiari.

In Pseudo-Chiari Malformation, Leaking of CSF may cause displacement of the cerebellar tonsils and similar symptoms sufficient to be mistaken for a Chiari I malformation.

Photophobia may also affect patients' socioeconomic status by limiting their career choices, since many workplaces require bright lights for safety or to accommodate the work being done. Sufferers may be shut out of a wide range of both skilled and unskilled jobs, such as in warehouses, offices, workshops, classrooms, supermarkets and storage spaces. Some photophobes are only able to work night shifts, which reduces their prospects for finding work.

The best treatment for light sensitivity is to address the underlying cause. Once the triggering factor is treated, photophobia disappears in many but not all cases.

People with photophobia will avert their eyes from direct light, such as sunlight and room lights. They may seek the shelter of a dark room. They may wear sunglasses designed to filter peripheral light and wide-brimmed sun hats.

Wearing sunglasses indoors can make symptoms worse over time as it will dark-adapt the retina which aggravates sensitivity to light. Indoor photophobia symptoms may be relieved with the use of precision tinted lenses which block the green-to-blue end of the light spectrum without blurring or impeding vision.

A paper by Stringham and Hammond, published in the "Journal of Food Science", reviews studies of effects of consuming Lutein and Zeaxanthin on visual performance, and notes a decrease in sensitivity to glare.

Familial dysautonomia is inherited in an autosomal recessive pattern, which means 2 copies of the gene in each cell are altered. If both parents are shown to be carriers by genetic testing, there is a 25% chance that the child will produce FD. Prenatal diagnosis for pregnancies at increased risk for FD by amniocentesis (for 14–17 weeks) or chorionic villus sampling (for 10–11 weeks) is possible.

Leukocoria (also leukokoria or white pupillary reflex) is an abnormal white reflection from the retina of the eye. Leukocoria resembles eyeshine, but leukocoria can occur in humans and other animals that lack eyeshine because their retina lacks a "tapetum lucidum".

Leukocoria is a medical sign for a number of conditions, including Coats disease, congenital cataract, corneal scarring, melanoma of the ciliary body, Norrie disease, ocular toxocariasis, persistence of the tunica vasculosa lentis (PFV/PHPV), retinoblastoma, and retrolental fibroplasia.

Because of the potentially life-threatening nature of retinoblastoma, a cancer, that condition is usually considered in the evaluation of leukocoria. In some rare cases (1%) the leukocoria is caused by Coats' disease (leaking retinal vessels).

A diagnosis of pentalogy of Cantrell can often be made before birth (prenatally) sometimes using a fetal ultrasound. An ultrasound is an exam that uses high-frequency sound waves to produce an image of the developing fetus. A fetal ultrasound can detect some of the defects associated with pentalogy of Cantrell. An echocardiography is usually performed to evaluate the extent of the involvement of the heart. An echocardiography is an exam that uses sound waves to produce images of the heart

Magnetic resonance imaging (MRI) may also be performed to assess the degree of certain anomalies such as abdominal wall and pericardial defects. An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues.

Genetic testing is performed on a small sample of blood from the tested individual. The DNA is examined with a designed probe specific to the known mutations. The accuracy of the test is above 99%. Dr. Anat Blumenfeld of the Hadasah Medical center in Jerusalem identified chromosome number 9 as the responsible chromosome.

In 2010 the Ghent nosology was revised, and new diagnostic criteria superseded the previous agreement made in 1996. The seven new criteria can lead to a diagnosis:

In the absence of a family history of MFS:

1. Aortic root Z-score ≥ 2 AND ectopia lentis

2. Aortic root Z-score ≥ 2 AND an FBN1 mutation

3. Aortic root Z-score ≥ 2 AND a systemic score* > 7 points

4. Ectopia lentis AND an FBN1 mutation with known aortic pathology

In the presence of a family history of MFS (as defined above):

1. Ectopia lentis

2. Systemic score* ≥ 7

3. Aortic root Z-score ≥ 2

- Points for systemic score:

- Wrist AND thumb sign = 3 (wrist OR thumb sign = 1)

- Pectus carinatum deformity = 2 (pectus excavatum or chest asymmetry = 1)

- Hindfoot deformity = 2 (plain pes planus = 1)

- Dural ectasia = 2

- Protrusio acetabuli = 2

- pneumothorax = 2

- Reduced upper segment/lower segment ratio AND increased arm/height AND no severe scoliosis = 1

- Scoliosis or thoracolumbar kyphosis = 1

- Reduced elbow extension = 1

- Facial features (3/5) = 1 (dolichocephaly, enophthalmos, downslanting palpebral fissures, malar hypoplasia, retrognathia)

- Skin striae (stretch marks) = 1

- Myopia > 3 diopters = 1

- Mitral valve prolapse 1⁄4 1

The thumb sign (Steinberg's sign) is elicited by asking the patient to flex the thumb as far as possible and then close the fingers over it. A positive thumb sign is where the entire distal phalanx is visible beyond the ulnar border of the hand, caused by a combination of hypermobility of the thumb as well as a thumb which is longer than usual.

The wrist sign (Walker's sign) is elicited by asking the patient to curl the thumb and fingers of one hand around the other wrist. A positive wrist sign is where the little finger and the thumb overlap, caused by a combination of thin wrists and long fingers.