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.

Treatment of glaucoma in iridogoniodysgenesis is primarily surgical.

It is listed as a "rare disease" by the Office of Rare Diseases (ORD). This means that Iridogoniodysgenesis, dominant type, or a subtype of Iridogoniodysgenesis, dominant type, affects less than 200,000 people in the US population.

The diagnosis is based on the combination of unusual facial features and the dysplastic or absent femurs.

Diagnosis may be made antenatally.

Identification of 45,X/46,XY karyotype has significant clinical implications due to known effects on growth, hormonal balance, gonadal development and histology. 45,X/46,XY is diagnosed by examining the chromosomes in a blood sample.

The age of diagnosis varies depending on manifestations of disease prompting reason for cytogenetic testing. Many patients are diagnosed prenatally due to fetal factors (increased nuchal fold, or abnormal levels of serum), maternal age or abnormal ultrasounds, while others will be diagnosed postnatal due to external genital malformation. It is not uncommon for patients to be diagnosed later in life due to short stature or delayed puberty, or a combination of both.

45,X/46,XY mosaicism can be detected prenatally through amniocentesis however, it was determined that the proportion of 45,X cells in the amniotic fluid cannot predict any phenotypic outcomes, often making prenatal genetic counselling difficult.

Anterior segment mesenchymal dysgenesis is a failure of the normal development of the tissues of the anterior segment of the eye. It leads to anomalies in the structure of the mature anterior segment, associated with an increased risk of glaucoma and corneal opacity.

Peters' (frequently misspelled Peter's) anomaly is a specific type of mesenchymal anterior segment dysgenesis, in which there is central corneal leukoma, adhesions of the iris and cornea, and abnormalities of the posterior corneal stroma, Descemet's membrane, corneal endothelium, lens, and anterior chamber.

It is named after the German ophthalmologist Theodor Axenfeld who studied anterior segment disorders, especially those such as Rieger Syndrome and the Axenfeld Anomaly.

Axenfeld-Rieger syndrome is characterized by abnormalities of the eyes, teeth, and facial structure. Rieger Syndrome, by medical definition, is determined by the presence of malformed teeth, underdeveloped anterior segment of the eyes, and cardiac problems associated with the Axenfeld anomaly. The term "Rieger syndrome" is sometimes used to indicate an association with glaucoma. Glaucoma occurs in up to 50% of patients with Rieger Syndrome. Glaucoma develops during adolescence or late-childhood, but often occurs in infancy. In addition, a prominent Schwalbe's line, an opaque ring around the cornea known as posterior embryotoxon, may arise with hypoplasia of the iris. Below average height and stature, stunted development of the mid-facial features and mental deficiencies may also be observed in patients.

Iridogoniodysgenesis, dominant type (type 1, IRID1) refers to a spectrum of diseases characterized by malformations of the irido-corneal angle of the anterior chamber of the eye. Iridogoniodysgenesis is the result of abnormal migration or terminal induction of neural crest cells. These cells lead to formation of most of the anterior segment structures of the eye (corneal stroma & endothelium, iris stroma, trabeculum).

There is no known specific treatment for this condition. Management is supportive.

The prognosis for children with NMDs varies depending on the specific disorder and the degree of brain abnormality and subsequent neurological signs and symptoms.

The heterogeneity of the Klippel–Feil syndrome has made it difficult to outline the diagnosis as well as the prognosis classes for this disease. Because of this, it has complicated the exact explanation of the genetic cause of the syndrome.

The prognosis for most individuals with KFS is good if the disorder is treated early on and appropriately. Activities that can injure the neck should be avoided, as it may contribute to further damage. Other diseases associated with the syndrome can be fatal if not treated, or if found too late to be treatable.

The first noticeable signs of the syndrome usually do not appear until after the first twelve months of the child’s life. The child usually has severe balance issues as he or she learns to sit or walk, often leaning or tilting the head toward the good eye to correct the brain’s skewed perception of the world. Often the child will fall in the same direction while walking or run into objects that are placed on his or her blind side. Additionally, family members may notice a white reflex in the pupil of an affected child instead of the normal red reflex when taking photographs. The presence of this phenomenon is dependent on the degree of the coloboma, with larger colobomas more likely to manifest this particular phenomenon.

This anomaly must be confirmed through pupillary dilation and examination of the optic disc, as the symptoms alone do not constitute a diagnosis.

People with optic nerve colobomas live relatively normal lives. Although non-prescription glasses should be worn for eye protection, this syndrome does not usually prevent the individual from living a normal life, driving cars, playing sports, reading, etc. Certain activities, however, may be more difficult for patients with optic nerve colobomas due to a compromised view of the world. Like most other eye conditions, a diagnosis of optic nerve coloboma precludes a person from certain occupations.

Several gene mutations have been identified underlying these anomalies with the majority of ASD genes encoding transcriptional regulators. In this review, the role of the ASD genes, PITX2 and FOXC1, is considered in relation to the embryology of the anterior segment, the biochemical function of these proteins, and their role in development and disease aetiology. The emerging view is that these genes act in concert to specify a population of mesenchymal progenitor cells, mainly of neural crest origin, as they migrate anteriorly around the embryonic optic cup. These same genes then regulate mesenchymal cell differentiation to give rise to distinct anterior segment tissues. Development appears critically sensitive to gene dosage, and variation in the normal level of transcription factor activity causes a range of anterior segment anomalies. Interplay between PITX2 and FOXC1 in the development of different anterior segment tissues may partly explain the phenotypic variability and the genetic heterogeneity characteristic of ASD. In the most recent research, the PAX6 gene has been implicated in Peters' Anomaly

A 1994 review of 150 cases reported in the literature found that 38% had died with a mean age of death of 2 years. 32% were still alive at the time of the report with a mean age of 4.65. No data were available for the remainder. The author described living with DDS as "walking a multidimensional tight rope".

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

The consequences to the girl with XX gonadal dysgenesis:

1. Her gonads cannot make estrogen, so her breasts will not develop and her uterus will not grow and menstruate until she is given estrogen. This is often given through the skin now.

2. Her gonads cannot make progesterone, so her menstrual periods will not be predictable until she is given a progestin, still usually as a pill.

3. Her gonads cannot produce eggs so she will not be able to conceive children naturally. A woman with a uterus but no ovaries may be able to become pregnant by implantation of another woman's fertilized egg (embryo transfer).

Treatment is symptomatic, and may include anti-seizure medication and special or supplemental education consisting of physical, occupational, and speech therapies.

The cause of this condition is not presently known. It appears to be inherited in an autosomal dominant fashion.

The prevalence of Klippel–Feil syndrome is unknown due to the fact that there was no study done to determine the true prevalence.

Although the actual occurrence for the KFS syndrome is unknown, it is estimated to occur 1 in 40,000 to 42,000 newborns worldwide. In addition, females seem to be affected slightly more often than males.

Aphalangy, hemivertebrae and urogenital-intestinal dysgenesis is an extremely rare syndrome, described only in three siblings. It associates hypoplasia or aplasia of phalanges of hands and feet, hemivertebrae and various urogenital and/or intestinal abnormalities. Intrafamilial variability is important as one sister had lethal abnormalities (Potter sequence and pulmonary hypoplasia), while her affected brother was in good health with normal psychomotor development at 6 months of age. Prognosis seems to depend mainly on the severity of visceral malformations. Etiology and inheritance remain unknown.

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.

Although both optic nerve colobomas and morning glory disc anomaly (MGDA) involve mutations of the PAX6 gene, these two separate diseases represent two distinct causes. An optic nerve coloboma is easily differentiated from morning glory anomaly. Colobomas affect only the inferior aspect of the nerve as it represents an incomplete closure of the embryonic fissure, whereas MGDA encompasses all aspects of the nerve and represents more generally a dysgenesis of the mesoderm.

Researchers are also investigating the genetic similarities between Dubowitz Syndrome and Smith-Lemli-Opitz syndrome (SLOS). Patients with SLOS and Dubowitz syndromes experience many of the same abnormalities, and the two disorders are hypothesized to be linked. A characteristic of SLOS is a low cholesterol level and a high 7-dehydrocholesterol level. Cholesterol is essential for several key functions of the body, including cell membrane structure, embryogenesis, and steroid and sex hormone synthesis. Impaired cholesterol biosynthesis or transport possibly accounts for most of the symptoms of both SLOS and Dubowitz. Although only a few patients with Dubowitz Syndrome have been identified with altered cholesterol levels, researchers are exploring whether Dubowitz Syndrome, like SLOS, carries a link to a defect in the cholesterol biosynthetic pathway.

The exact biochemical pathology of the disease is still under research because of the low prevalence of the disease and the wide array of symptoms associated with it. Several studies have focused on different aspects of the disease to try to find its exact cause and expression. One study examined the specific oral features in one patient. Another found abnormalities in the brain, such as corpus callosum dysgenesis, an underdeveloped anterior pituitary and a brain stalk with an ectopic neurohypophysis.

Because of the inability of the streak gonads to produce sex hormones (both estrogens and androgens), most of the secondary sex characteristics do not develop. This is especially true of estrogenic changes such as breast development, widening of the pelvis and hips, and menstrual periods. Because the adrenal glands can make limited amounts of androgens and are not affected by this syndrome, most of these girls will develop pubic hair, though it often remains sparse.

Evaluation of delayed puberty usually reveals the presence of pubic hair, but elevation of gonadotropins, indicating that the pituitary is providing the signal for puberty but the gonads are failing to respond. The next steps of the evaluation usually include checking a karyotype and imaging of the pelvis. The karyotype reveals XX chromosomes and the imaging demonstrates the presence of a uterus but no ovaries (the streak gonads are not usually seen by most imaging). At this point it is usually possible for a physician to make a diagnosis of XX gonadal dysgenesis.

Bamforth–Lazarus syndrome is a genetic condition that results in thyroid dysgenesis. It is due to recessive mutations in forkhead/winged-helix domain transcription factor ("FKLH15" or "TTF2").

It is associated with "FOXE1".

The cause of DDS is most commonly (96% of patients) an abnormality in the WT1 gene (Wilms tumor suppressor gene). These abnormalities include changes in certain exons (9 and 8) and mutations in some alleles of the WT1 gene. Genetically, the syndrome is due to mutations in the Wilms tumor suppressor gene, WT1, which is on chromosome 11 (11p13). These mutations are usually found in exons 8 or 9, but at least one has been reported in exon 4.