Axenfeld syndrome (also known as Axenfeld-Rieger syndrome or Hagedoom syndrome) is a rare autosomal dominant disorder, which affects the development of the teeth, eyes, and abdominal region.

Dental features:

- small teeth in males

- pointed (screwdriver shaped or conical) incisors (sometimes called Hutchinson teeth)

- incisors with an irregulal incisal edge

- canines: enlarged and globular; may be dome or bud shaped with trilobed edge

- premolars and molars: small, round and globular; may have supernumary lobes (mulberry or lotus flower shape)

- widely separated teeth (diastemma)

- hypoplastic enamel

- dental agenesis

- presence of mesiodents (median incisor behind normal upper incisors)

- pulp chamber anomalies

Facial features:

- anteverted pinnae

- long face

- prominent nasal bridge and nose

- prognathism occasionally

Ophthalmic features:

- bilateral congenital nuclear opacities (100%)

- severe amblyopia

- nystagmus (93%)

- strabismus (43%)

- microcornea (96%)

- congenital glaucoma

- scleral staphylomas

- retinal cystoid degeneration

- microphthalmia

These lead to severe visual impairment in affected males.

Other:

- The fourth metacarpal may be shortened

30% of patients also have some degree of intellectual impairment: of these 80% are mildly to moderately affected: the other 20% may have developmental delays and behavior problems.

Carrier females display milder variable symptoms of disease. Ocular signs are present in 90% of heterozygous females. These are typically lens opacities often involving the posterior Y sutures. More rarely dental anomalies and the characteristic facial features may also occur.

Acorea or fibrous occlusion of the pupil, microphthalmia and cataracts are present in both eyes. Microcornea and iridocorneal dysgenesis also occur. The retina and optic disc are normal.

Nance–Horan syndrome is a rare X linked syndrome characterized by congenital cataract leading to profound vision loss, characteristic dysmorphic features and dental anomalies. Microcornea, microphthalmia and mild or moderate mental retardation may accompany these features. Heterozygous females often manifest similarly but with less severe features than affected males.

Acorea, microphthalmia and cataract syndrome is a rare genetically inherited condition.

Aniridia is the absence of the iris, usually involving both eyes. It can be congenital or caused by a penetrant injury. Isolated aniridia is a congenital disorder which is not limited to a defect in iris development, but is a panocular condition with macular and optic nerve hypoplasia, cataract, and corneal changes. Vision may be severely compromised and the disorder is frequently associated with a number of ocular complications: nystagmus, amblyopia, buphthalmos, and cataract. Aniridia in some individuals occurs as part of a syndrome, such as WAGR syndrome (kidney nephroblastoma (Wilms tumour), genitourinary anomalies and intellectual disability), or Gillespie syndrome (cerebellar ataxia).

The cataract-microcornea syndrome is the association of congenital cataract and microcornea.

SHORT is an acronym for short stature, hyperextensibility of joints and/or inguinal hernia, ocular depression, rieger anomaly and teething delay.

Other characteristics common in SHORT syndrome are a triangular face, small chin with a dimple, a loss of fat under the skin (lipodystrophy), abnormal position of the ears, hearing loss and delayed speech.

Zonular cataract and nystagmus, also referred as Nystagmus with congenital zonular cataract is a rare congenital disease associated with Nystagmus and zonular cataract of the eye.

It has been suggested that the disease follows a x-linked pattern of inheritance though studies done on this particular disease are few.

People with the combination of Duane anomaly and radial ray malformations may have a variety of other signs and symptoms. These features include:

- Unusually shaped ears

- Hearing loss

- Heart and kidney defects

- A distinctive facial appearance

- An inward- and downward-turning foot (a clubfoot)

- Fused vertebrae.

This is characterized by hand and arm abnormalities. The following are specific characteristics:

- Malformed or absent (aplasia) thumb

- A thumb that looks more like a finger

- Partial or complete absence of a radius

- Shortening and radial deviation of the forearms

- Triphalangeal thumb

- Duplication of the thumb (preaxial polydactyly)

Although most recognized for its correlation with the onset of glaucoma, the malformation is not limited to the eye, as Axenfeld syndrome when associated with the PITX2 genetic mutation usually presents congenital malformations of the face, teeth, and skeletal system.

The most characteristic feature affecting the eye is a distinct corneal posterior arcuate ring, known as an "embryotoxon". The iris is commonly adherent to the Schwalbe's line (posterior surface of the cornea).

Diagnosis

One of the three known genetic mutations which cause Rieger Syndrome can be identified through genetic samples analysis. About 40% of Axenfeld-Rieger sufferers have displayed mutations in genes PITX2, FOXC1, and PAX6. The difference between Type 1, 2, and 3 Axenfeld Syndrome is the genetic cause, all three types display the same symptoms and abnormalities.

The OMIM classification is as follows:

Detection of any of these mutations can give patients a clear diagnosis and prenatal procedures such as preimplantation genetic diagnosis, Chorionic villus sampling and Amniocentesis can be offered to patients and prospective parents.

The effects a coloboma has on the vision can be mild or more severe depending on the size and location of the gap. If, for example, only a small part of the iris is missing, vision may be normal, whereas if a large part of the retina or optic nerve is missing, vision may be poor and a large part of the visual field may be missing. This is more likely to cause problems with mobility if the lower visual field is absent. Other conditions can be associated with a coloboma. Sometimes, the eye may be reduced in size, a condition called microphthalmia. Glaucoma, nystagmus, scotoma, or strabismus may also occur.

Other ocular malformations that include coloboma or are related to it:

- CHARGE syndrome, a term that came into use as an acronym for the set of unusual congenital features seen in a number of newborn children. The letters stand for: coloboma of the eye, heart defects, atresia of the nasal choanae, retardation of growth and/or development, genital and/or urinary abnormalities, and ear abnormalities and deafness. Although these features are no longer used in making a diagnosis, the name has remained.

- Cat eye syndrome, caused by the short arm (p) and a small section of the long arm (q) of human chromosome 22 being present three (trisomic) or four times (tetrasomic) instead of the usual two times. The term "cat eye" was coined because of the particular appearance of the vertical colobomas in the eyes of some patients.

- Patau syndrome (trisomy 13), a chromosomal abnormality that can cause a number of deformities, some of which include structural eye defects, including microphthalmia, Peters anomaly, cataract, iris and/or fundus coloboma, retinal dysplasia or retinal detachment, sensory nystagmus, cortical visual loss, and optic nerve hypoplasia.

- Treacher Collins syndrome, autosomal dominant syndrome caused by mutation of "TCOF1". Coloboma is part of a set of characteristic facies that features craniofacial malformations, such as downslanting eyes, ear anomalies, or hypoplasia of zygomatic bone and jaw (micrognathia).

Aniridia may be broadly divided into hereditary and sporadic forms. Hereditary aniridia is usually transmitted in an autosomal dominant manner (each offspring has a 50% chance of being affected), although rare autosomal recessive forms (such as Gillespie syndrome) have also been reported. Sporadic aniridia mutations may affect the WT1 region adjacent to the AN2 aniridia region, causing a kidney cancer called nephroblastoma (Wilms tumor). These patients often also have genitourinary abnormalities and intellectual disability (WAGR syndrome).

Several different mutations may affect the PAX6 gene. Some mutations appear to inhibit gene function more than others, with subsequent variability in the severity of the disease. Thus, some aniridic individuals are only missing a relatively small amount of iris, do not have foveal hypoplasia, and retain relatively normal vision. Presumably, the genetic defect in these individuals causes less "heterozygous insufficiency," meaning they retain enough gene function to yield a milder phenotype.

- AN

- Aniridia and absent patella

- Aniridia, microcornea, and spontaneously reabsorbed cataract

- Aniridia, cerebellar ataxia, and mental deficiency (Gillespie syndrome)

This syndrome consists a number of typical features. These include

- Agenesis of the corpus callosum (80-99% patients)

- Hypopigmentation of the eyes and hair (80-99% patients)

- Cardiomyopathy (80-99% patients)

- Combined immunodeficiency (80-99% patients)

- Muscular hypotonia (80-99% patients)

- Abnormality of retinal pigmentation (80-99% patients)

- Recurrent chest infections (80-99% patients)

- Abnormal EEG (80-99% patients)

- Intellectual disability (80-99% patients)

- Cataracts (75%)

- Seizures (65%)

- Renal abnormalities (15%)

Infections of the gastrointestinal and urinary tracts are common. Swallowing and feeding difficulties early on may result in a failure to thrive. Optic nerve hypoplasia, nystagmus and photophobia may occur. Facial dysmorphism (cleft lip/palate and micrognathia) and syndactyly may be present. Sensorineural hearing loss may also be present.

Death in infancy is not uncommon and is usually due to cardiac complications or severe infections.

Microspherophakia is a rare congenital autosomal recessive condition where the lens of the eye is smaller than normal and spherically shaped. This condition may be associated with a number of disorders including Peter's anomaly, Marfan syndrome, and Weill–Marchesani syndrome. The spherical shape is caused by an underdeveloped zonule of Zinn, which doesn't exert enough force on the lens to make it form the usual oval shape. It is a result of a homozygous mutation to the LTBP2 gene.

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.

While inclusion criteria for Rud syndrome have varied considerably, the major manifestations includes congenital ichthyosis, hypogonadism, small stature, mental retardation, and epilepsy. Ocular findings were inconsistently reported and included strabismus, blepharoptosis, blepharospasm, glaucoma, cataract, nystagmus, and retinitis pigmentosa. Other systemic includes metabolic, bony, neurologic, and muscular abnormalities.

Vision in the affected eye is impaired, the degree of which depends on the size of the defect, and typically affects the visual field more than visual acuity. Additionally, there is an increased risk of serous retinal detachment, manifesting in 1/3 of patients. If retinal detachment does occur, it is usually not correctable and all sight is lost in the affected area of the eye, which may or may not involve the macula.

Of those fetuses that do survive to gestation and subsequent birth, common abnormalities may include:

- Nervous system

- Intellectual disability and motor disorder

- Microcephaly

- Holoprosencephaly (failure of the forebrain to divide properly).

- Structural eye defects, including microphthalmia, Peters' anomaly, cataract, iris or fundus (coloboma), retinal dysplasia or retinal detachment, sensory nystagmus, cortical visual loss, and optic nerve hypoplasia

- Meningomyelocele (a spinal defect)

- Musculoskeletal and cutaneous

- Polydactyly (extra digits)

- Cyclopia

- Proboscis

- Congenital trigger digits

- Low-set ears

- Prominent heel

- Deformed feet known as rocker-bottom feet

- Omphalocele (abdominal defect)

- Abnormal palm pattern

- Overlapping of fingers over thumb

- Cutis aplasia (missing portion of the skin/hair)

- Cleft palate

- Urogenital

- Abnormal genitalia

- Kidney defects

- Other

- Heart defects (ventricular septal defect) (Patent Ductus Arteriosus)

- Dextrocardia

- Single umbilical artery

The key affected features of this condition are described in its name.

Scalp: There are raised nodules over the posterior aspect of the scalp, covered by scarred non-hair bearing skin.

Ears: The shape of the pinnae is abnormal, with the superior edge of the pinna being turned over more than usual. The size of the tragus, antitragus and lobule may be small.

Nipples: The nipples are absent or rudimentary. The breasts may be small or virtually absent.

Other features of the condition include:

Dental abnormalities: missing or widely spaced teeth

Syndactyly: toes or fingers may be partially joined proximally

Renal abnormalities: renal hypoplasia, pyeloureteral duplication

Eye abnormalities: Cataract, coloboma of the iris and asymmetric pupils.

Fleischer's syndrome is an extremely rare congenital anomaly characterized by displacement of the nipples, occasional polymastia, and hypoplasia of both kidneys.

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.