Since the original identification of Schimmelpenning syndrome, the number of findings has expanded to the point that the syndrome is associated with a considerable constellation of abnormalities. The abnormalities may occur in a variety of combinations, and need not include all three aspects of the classic triad of sebaceous nevus, seizures and mental retardation. In 1998, a literature review by van de Warrenburg et al. found:

- seizures in 67% of cases

- mental retardation in 61% of cases

- ophthalmological abnormalities in 59% of cases

- involvement of other organ systems in 61% of cases

- structural abnormality of cerebrum or cranium in 72% of cases

The major neurological abnormalities include mental retardation to varying extent, seizures, and hemiparesis. Seizures, when present, typically begin during the first year of life. The most common structural central nervous system abnormalities in Schimmelpenning syndrome are hemimegalencephaly and ipselateral gyral malformations.

The major ocular abnormalities are colobomas and choristomas.

Skeletal abnormalities may include dental irregularities, scoliosis, vitamin D-resistant rickets and hypophosphatemia. Cardiovascular abnormalities include ventricular septal defect and co-arctation of the aorta; urinary system issues include horseshoe kidney and duplicated urinary collection system.

Individuals with Stickler syndrome experience a range of signs and symptoms. Some people have no signs and symptoms; others have some or all of the features described below. In addition, each feature of this syndrome may vary from subtle to severe.

A characteristic feature of Stickler syndrome is a somewhat flattened facial appearance. This is caused by underdeveloped bones in the middle of the face, including the cheekbones and the bridge of the nose. A particular group of physical features, called the Pierre Robin sequence, is common in children with Stickler syndrome. Robin sequence includes a U-shaped or sometimes V-shaped cleft palate (an opening in the roof of the mouth) with a tongue that is too large for the space formed by the small lower jaw. Children with a cleft palate are also prone to ear infections and occasionally swallowing difficulties.

Many people with Stickler syndrome are very nearsighted (described as having high myopia) because of the shape of the eye. People with eye involvement are prone to increased pressure within the eye (ocular hypertension) which could lead to glaucoma and tearing or detachment of the light-sensitive retina of the eye (retinal detachment). Cataract may also present as an ocular complication associated with Stickler's Syndrome. The jelly-like substance within the eye (the vitreous humour) has a distinctive appearance in the types of Stickler syndrome associated with the COL2A1 and COL11A1 genes. As a result, regular appointments to a specialist ophthalmologist are advised. The type of Stickler syndrome associated with the COL11A2 gene does not affect the eye.

People with this syndrome have problems that affect things other than the eyes and ears. Arthritis, abnormality to ends of long bones, vertebrae abnormality, curvature of the spine, scoliosis, joint pain, and double jointedness are all problems that can occur in the bones and joints. Physical characteristics of people with Stickler can include flat cheeks, flat nasal bridge, small upper jaw, pronounced upper lip groove, small lower jaw, and palate abnormalities, these tend to lessen with age and normal growth and palate abnormalities can be treated with routine surgery.

Another sign of Stickler syndrome is mild to severe hearing loss that, for some people, may be progressive (see hearing loss with craniofacial syndromes). The joints of affected children and young adults may be very flexible (hypermobile). Arthritis often appears at an early age and worsens as a person gets older. Learning difficulties, not intelligence, can also occur because of hearing and sight impairments if the school is not informed and the student is not assisted within the learning environment.

Stickler syndrome is thought to be associated with an increased incidence of mitral valve prolapse of the heart, although no definitive research supports this.

Stickler syndrome (hereditary progressive arthro-ophthalmopathy) is a group of genetic disorders affecting connective tissue, specifically collagen. Stickler syndrome is a subtype of collagenopathy, types II and XI. Stickler syndrome is characterized by distinctive facial abnormalities, ocular problems, hearing loss, and joint problems. It was first studied and characterized by Gunnar B. Stickler in 1965.

Schimmelpenning syndrome is a neurocutaneous condition characterized by one or more sebaceous nevi, usually appearing on the face or scalp, associated with anomalies of the central nervous system, ocular system, skeletal system, cardiovascular system, and genitourinary system.

Synonyms include: "Linear nevus sebaceous syndrome (LNSS)", "Schimmelpenning-Feuerstein-Mims syndrome", "Feuerstein-Mims syndrome", "sebaceous nevus syndrome", "Solomon syndrome", and "Jadassohn's nevus phakomatosis". "Nevus" is sometimes spelled "naevus" and "sebaceous" may also be spelled "sebaceus". "Epidermal nevus syndrome" is sometimes used as a synonym, but more often as a broader term referring to Schimmelpenning syndrome in addition to nevus comedonicus syndrome, CHILD syndrome, Becker's nevus syndrome, and phakomatosis pigmentokeratotica.

The classic Schimmelpenning syndrome diagnosis comprises a triad of sebaceous nevi, seizures, and mental retardation. The condition was first reported by Gustav Schimmelpenning in 1957 and independently reported by Feuerstein and Mims in 1962.

Sturge–Weber syndrome is usually manifested at birth by a port-wine stain on the forehead and upper eyelid of one side of the face, or the whole face. The birthmark can vary in color from light pink to deep purple and is caused by an overabundance of capillaries around the ophthalmic branch of the trigeminal nerve, just under the surface of the face. There is also malformation of blood vessels in the pia mater overlying the brain on the same side of the head as the birthmark. This causes calcification of tissue and loss of nerve cells in the cerebral cortex.

Neurological symptoms include seizures that begin in infancy and may worsen with age. Convulsions usually happen on the side of the body opposite the birthmark which vary in severity. There may also be muscle weakness on the side of the body opposite the birthmark.

Some children will have developmental delays and cognitive delays; about 50% will have glaucoma (optic neuropathy often associated with increased intraocular pressure), which can be present at birth or develop later. Glaucoma can be expressed as leukocoria, which should include also further evaluation for retinoblastoma. Increased pressure within the eye can cause the eyeball to enlarge and bulge out of its socket (buphthalmos).

Sturge–Weber syndrome rarely affects other body organs.

Typically not diagnosed until late childhood or later, Bonnet–Dechaume–Blanc syndrome usually presents itself with a combination of central nervous system features (midbrain), ophthalmic features (retina), and facial features. The degree of expression of the syndrome's components varies both clinically and structurally. Common symptoms that lead to diagnosis are headaches, retro-orbital pain and hemianopia.

The ophthalmic features of the Bonnet–Dechaume–Blanc syndrome occur as retinal arteriovenous malformation (AVMs). There are three categories of AVMs that are categorized depending on the severity of the malformation. The first category consists of the patient having small lesions that usually are asymptomatic. The second category, more severe than the first, is when the patient’s malformation is missing a connecting capillary. The missing capillary is meant to serve as a link between an artery and a vein; without it, edemas, hemorrhages, and visual impairments can result. Category three, the most severe, occurs when the patient’s malformations are so severe that the dilated vessels cause no distinction between artery and vein. When the symptoms are this severe, the patient has a significantly increased risk of developing vision loss. Since the retinal lesions categorized vary from large vascular malformations that affect a majority of the retina to malformations that are barely visible, the lesions cause a wide range of symptoms including decrease in visual sharpness, proptosis, pupillary defects, optic degeneration and visual field defects. The most common type of visual field impairment due to AVMs is homonymous hemianopia. Homonymous hemianopia typically presents unilaterally, but bilateral cases have been reported as well.

The extent of the central nervous system (CNS) features/symptoms of Bonnet–Dechaume–Blanc syndrome is highly dependent of the location of the cerebral AVMs and the extent of the malformation. The most common symptom affecting the CNS is an intracranial hemangioma in the midbrain. Along with hemangiomas, the malformations result in severe headaches, cerebral hemorrhages, vomiting, meningism, seizures, acute strokes or progressive neurological deficits due to acute or chronic ischaemia caused by arteriovenous shunting.

The distinguishable facial features that result from Bonnet–Dechaume–Blanc syndrome vary from case to case. A person showing signs of the syndrome may display faint skin discoloration, nevi and angiomas of the skin. Some patients with this disorder also present with high flow arteriovenous malformations of the maxillofacial or mandibular (jaw) regions. Another facial indicator of this disease is malformations affecting the frontal and/or maxillary sinuses.

The term "cat eye" syndrome was coined because of the particular appearance of the vertical colobomas in the eyes of some patients. However, over half of the CES patients in the literature do not present with this trait.

Phakomatosis pigmentokeratotica is a rare neurocutanous condition characterized by the combination of an organoid sebaceous nevus and speckled lentiginous nevus. It is an unusual variant of epidermal naevus syndrome. It was first described by Happle "et al". It is often associated with neurological or skeletal anomalies such as hemiatrophy, dysaesthesia and hyperhidrosis in a segmental pattern, mild mental retardation, seizures, deafness, ptosis and strabismus.

Congenital cystic eye (also known as "CCE" or "cystic eyeball") is an extremely rare ocular malformation where the eye fails to develop correctly "in utero" and is replaced by benign, fluid-filled tissue. Its incidence is unknown, due to the very small number of cases reported. An audit by Duke-Elder of the medical literature from 1880 to 1963 discovered only 28 cases. The term was coined in 1937 by the renowned ophthalmologist Ida Mann.

Embryologically, the defect is thought to occur around day 35 of gestation, when the vesicle fails to invaginate. Dysgenesis of the vesicle later in development may result in coloboma, a separate and less severe malformation of the ocular structures.

CCE is almost always unilateral, but at least 2 cases of bilateral involvement have been described. Patients may also present with skin appendages attached to the skin surrounding the eyes. Association with intracranial anomalies has been reported.

Treatment of CCE is usually by enucleation, followed by insertion of an ocular implant and prosthesis.

Bonnet–Dechaume–Blanc syndrome, also known as Wyburn-Mason syndrome, is a rare congential arteriovenous malformation of the brain, retina or facial nevi. The syndrome has a number of possible symptoms and can affect the skin, bones, kidneys, muscles, and gastrointestinal tract. When the syndrome affects the brain, people can experience severe headaches, seizures, acute stroke, meningism and progressive neurological deficits due to acute or chronic ischaemia caused by arteriovenous shunting.

As for the retina, the syndrome causes retinocephalic vascular malformations that tend to be present with intracranial hemorrhage and lead to decreased visual acuity, proptosis, pupillary defects, optic atrophy, congestion of bulbar conjunctiva, and visual field defects. Retinal lesions can be unilateral and tortuous, and symptoms begin to appear in the second and third decades of life.

The syndrome can present cutaneous lesions, or skin with different texture, thickness, and color, usually on the face. The facial features caused by the syndrome vary from slight discoloration to extensive nevi and angiomas of the skin. In some cases, the frontal and maxillary sinus can present problems in the subject due to the syndrome.

There have only been 52 reported cases of patients with Bonnet–Dechaume–Blanc syndrome as of 2012. Symptoms are rarely noticed in children and the syndrome is often diagnosed in late childhood or early adulthood when visual impairment is noticed. Fluorescein angiography is commonly used to diagnose the syndrome.

There have been several methods in treating patients who display Bonnet–Dechaume–Blanc syndrome. However, which method seems to work the most is within argument. Patients with intracranial lesions have been treated with surgical intervention and in some cases, this procedure has been successful. Other treatments include embolization, radiation therapy, and continued observation.

With limited research on Bonnet–Dechaume–Blanc syndrome, researchers have focused on the clinical and radiological findings rather than how to manage this rare and non-heritable syndrome.

Sturge–Weber syndrome or Sturge–Weber–Krabbe disease, sometimes referred to as encephalotrigeminal angiomatosis, is a rare congenital neurological and skin disorder. It is one of the phakomatoses and is often associated with port-wine stains of the face, glaucoma, seizures, mental retardation, and ipsilateral leptomeningeal angioma (cerebral malformations and tumors). Sturge Weber Syndrome can be classified into three different types. Type 1 includes facial and leptomeningeal angiomas as well as the possibility of glaucoma or choroidal lesions. Normally, only one side of the brain is affected. This type is the most common. Type 2 involvement includes a facial angioma (port wine stain) with a possibility of glaucoma developing. There is not any evidence of brain involvement. Symptoms can show at any time beyond the initial diagnosis of the facial angioma. The symptoms can include glaucoma, cerebral blood flow abnormalities and headaches. More research is needed on this type of Sturge Weber Syndrome. Type 3 has leptomeningeal angioma involvement exclusively. The facial angioma is absent and glaucoma rarely occurs. This type is only diagnosed via brain scan.

Sturge-Weber is an embryonal developmental anomaly resulting from errors in mesodermal and ectodermal development. Unlike other neurocutaneous disorders (phakomatoses), Sturge-Weber occurs sporadically (i.e., does not have a hereditary cause). It is caused by a somatic activating mutation occurring in the GNAQ gene. Radiological findings will show tram track calcifications on CT, bilaterally.

Phakomatosis pigmentovascularis is subdivided into five types:

- Type 1 PWS + epidermal nevus

- Type 2 (most common): PWS + dermal melanocytosis +/- nevus anemicus

- Type 3: PWS + nevus spilus +/- nevus anemicus

- Type 4: PWS + nevus spilus + dermal melanocytosis +/- nevus anemicus

- Type 5: CMTC (Cutis marmorata telangiectatica congenita) + dermal melanocytosis

They all can contain capillary malformation. Type 2 is the most common and can be associated with granular cell tumor. Some further subdivide each type into categories A & B; with A representing oculocutaneous involvement and subtype B representing extra oculocutaneous involvement. Others have proposed fewer subtypes but currently this rare entity is mostly taught as having five subtypes currently.

Familial exudative vitreoretinopathy (FEVR) ( ) is a genetic disorder affecting the growth and development of blood vessels in the retina of the eye. This disease can lead to visual impairment and sometimes complete blindness in one or both eyes. FEVR is characterized by exudative leakage and hemorrhage of the blood vessels in the retina, along with incomplete vascularization of the peripheral retina. The disease process can lead to retinal folds, tears, and detachments.

The skin lesions evolve through characteristic stages:

1. blistering (from birth to about four months of age),

2. a wart-like rash (for several months),

3. swirling macular hyperpigmentation (from about six months of age into adulthood), followed by

4. linear hypopigmentation.

Alopecia, hypodontia, abnormal tooth shape, and dystrophic nails are observed. Some patients have retinal vascular abnormalities predisposing to retinal detachment in early childhood. Cognitive delays/mental retardation are occasionally seen.

Discolored skin is caused by excessive deposits of melanin (normal skin pigment).

Most newborns with IP will develop discolored skin within the first two weeks.

The pigmentation involves the trunk and extremities, is slate-grey, blue or brown, and is distributed in irregular marbled or wavy lines.

The discoloration sometimes fades with age.

Neurological problems can include: cerebral atrophy, the formation of small cavities in the central white matter of the brain, and the loss of neurons in the cerebellar cortex.

About 20% of children with IP will have slow motor development, muscle weakness in one or both sides of the body, mental retardation, and seizures.

They are also likely to have visual problems, which can include: crossed eyes, cataracts, and severe visual loss.

Dental problems are common, and include missing or peg-shaped teeth - patients with IP often keep milk teeth into adult life.

Breast anomalies can occur in 1% of patients; anomalies can include hypoplasia and supernumerary nipples.

Skeletal and structural anomalies can occur in approximately 14% of patients, including:

- Somatic asymmetry,

- Hemivertebrae,

- Scoliosis,

- Spina bifida,

- Syndactyly,

- Acheiria (congenital absence of the hands - note: other limbs may be affected),

- Ear anomalies,

- Extra ribs,

- Skull deformities,

- Primary pulmonary hypertension,

- Cardiopulmonary failure

The additional chromosome 22 usually arises spontaneously. It may be hereditary and parents may be mosaic for the marker chromosome but show no phenotypic symptoms of the syndrome.

The chromosomal area included in the cat eye syndrome "critical region" is 22pter→q11.

Phakomatosis pigmentovascularis is a rare neurocutanous condition where there is coexistence of a capillary malformation (port-wine stain) with various melanocytic lesions, including dermal melanocytosis (Mongolian spots), nevus spilus, and nevus of Ota.

Symptoms, if any, can be mild even in the presence of significant swelling or masses.

Lacrimal gland involvement may cause swelling of the upper eyelid, or proptosis if there is severe swelling. Other orbital masses or inflammation can result in visual disturbance (blurred vision, double vision, visual field impairment), restricted eye movements, pain or discomfort, numbness in the distribution of the supraorbital and/or infraorbital nerves, or proptosis.

IgG4-related ophthalmic disease has been estimated to account for approximately 25% of all cases of proptosis, eyelid swelling and other features of orbital swelling.

Incontinentia pigmenti (IP) is a rare genetic disorder that affects the skin, hair, teeth, nails, and central nervous system. It is named from its appearance under a microscope. It is also known as Bloch–Siemens syndrome, Bloch–Sulzberger disease, Bloch–Sulzberger syndrome, melanoblastosis cutis, and nevus pigmentosus systematicus.

It is characterized by skin abnormalities that begin in childhood, usually a blistering rash which heals, followed by the development of harder skin growths. The skin may develop grey or brown patches which fade with time. Other symptoms can include hair loss, dental abnormalities, eye abnormalities that can lead to vision loss, and lined or pitted fingernails and toenails. Associated problems can include delayed development, intellectual disability, seizures, and other neurological problems. There is no specific treatment, individual conditions must be managed by specialists.

Symptoms of scleritis include:

- Redness of the sclera and conjunctiva, sometimes changing to a purple hue

- Severe ocular pain, which may radiate to the temple or jaw. The pain is often described as deep or boring.

- Photophobia and tearing

- Decrease in visual acuity, possibly leading to blindness

The pain of episcleritis is less severe than in scleritis. In hyperemia, there is a visible increase in the blood flow to the sclera (hyperaemia), which accounts for the redness of the eye. Unlike in conjunctivitis, this redness will not move with gentle pressure to the conjunctiva.

IgG4-related ophthalmic disease (IgG4-ROD) is the recommended term to describe orbital (eye socket) manifestations of the systemic condition IgG4-related disease, which is characterised by infiltration of lymphocytes and plasma cells and subsequent fibrosis in involved structures. It can involve one or more of the orbital structures.

Frequently involved structures include the lacrimal glands, extraocular muscles, infraorbital nerve, supraorbital nerve and eyelids. It has also been speculated that ligneous conjunctivitis may be a manifestation of IgG4-related disease (IgG4-RD).

As is the case with other manifestations of IgG4-related disease, a prompt response to steroid therapy is a characteristic feature of IgG4-ROD in most cases, unless significant fibrosis has already occurred.

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.

The eye involvement can cause the following inflammatory disorders:

- endophthalmitis

- uveitis

- chorioretinitis

KSS results in a pigmentation of the retina, primarily in the posterior fundus. The appearance is described as a "salt-and-pepper" appearance. There is diffuse depigmentation of the retinal pigment epithelium with the greatest effect occurring at the macula. This is in contrast to retinitis pigmentosa where the pigmentation is peripheral. The appearance of the retina in KSS is similar to that seen in myotonic dystrophy type 1 (abbreviated DM1). Modest night-blindness can be seen in patients with KSS. Visual acuity loss is usually mild and only occurs in 40–50% of patients.

The most prominent symptoms of Norrie disease are ocular. The first visible finding is leukocoria, a grayish-yellow pupillary reflex that originates from a mass of unorganized tissue behind the lens. This material, which possibly includes an already detached retina, may be confused with a tumor and thus is termed pseudoglioma. However, an affected baby may have a normally sized eye globe and inconspicuous iris, anterior chamber, cornea and intraocular pressure.

Over the first few months of life, complete or partial retinal detachment evolves. From infancy through childhood, the patient may undergo progressive changes in the disease. These progressions include the formation of cataracts, deterioration of the iris with adhesions forming between the iris and the lens or the cornea, and shallowing of the anterior chamber which may increase intraocular pressure, causing eye pain. As the situation worsens, there is corneal opacification, where the cornea becomes opaque, and band keratopathy. Intraocular pressure is lost and the globe shrinks. In the last stage of Norrie disease, the globes appear small and sunken in (phthisis bulbi) and the cornea appears to be milky .

Norrie disease can also have cognitive and behavioral symptoms. Developmental delay or learning difficulties are present in about 30 to 50% of males who have Norrie disease. Psychotic-like features and poorly characterized behavior abnormalities may also be present. Auditory symptoms are common with Norrie disease. Progressive hearing loss starts in early childhood for a majority of males with the condition. Early hearing loss is sensorineural, mild and asymmetric. By adolescence, high-frequency hearing loss begins to appear. Hearing loss is severe, symmetric, and broad-spectrum by the age of 35. However, studies show that while the hearing loss is deteriorating, the ability to speak well is highly preserved. The slowly progressing hearing loss is more problematic to adjust to than the congenital blindness for most people with Norrie disease.

Secondary keratitis or uveitis may occur with scleritis. The most severe complications are associated with necrotizing scleritis.