Ординатура / Офтальмология / Английские материалы / Shields Textbook of Glaucoma, 6th edition_Allingham, Damji, Freedman_2010

119, 120, 121 and 122). Glaucoma drainage-device surgery can successfully control glaucoma in children, although

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many patients need postoperative glaucoma medication therapy and repeated surgery. In one retrospective study, glaucoma drainage-device surgery had 5- and 10-year success rates of approximately 60% and 45%, respectively, in children with refractory PCG (123).

In contrast to trabeculectomy and glaucoma drainagedevice surgeries, cyclodestructive procedures reduce the rate of aqueous production by injuring the ciliary processes; success is only modest (about 50%), results are often unpredictable, and complications occur frequently. Cyclodestruction nonetheless constitutes a valid means of attempting control of especially refractory cases of PCG after medical and other surgical means have been exhausted or have proved inadequate to the task. This modality may be reasonable to decrease aqueous production in eyes with elevated IOP despite patent glaucoma drainagedevice surgery (Freedman SF, unpublished data). Cyclocryotherapy has been used to treat difficult childhood glaucomas for many years. Unfortunately, overall success (i.e., pressure control without severe visual loss or phthisis) has been poor (i.e., 30% success in a large series of children with advanced congenital glaucoma), and retreatment has been the rule (124). Transscleral cyclophotocoagulation with the contact Nd:YAG and diode lasers has reduced IOP in a fashion at least comparable to cyclocryotherapy in children with refractory glaucomas, and with a lower reported incidence of phthisis and hypotony (125, 126, 127 and 128). The endoscopic use of the diode laser for cycloablation has been applied to children (mostly with glaucoma in aphakia), with modestly encouraging results (129, 130).

Penetrating Keratoplasty

Corneal cloudiness due to permanent scarring may persist after normalization of the IOP in some severe cases, prompting consideration of penetrating keratoplasty. Penetrating keratoplasty in young children is difficult, especially when the case is complicated by glaucoma and buphthalmos (131, 132, 133 and 134). These patients often do not fare well, with only 25% of eyes achieving 20/40 or better vision in one series (131). The most common postoperative complications are IOP elevation and graft failure. Although significant visual improvement can be achieved with penetrating keratoplasty (135), it is suggested that it be reserved for patients with severe visual disability whose glaucoma is well controlled (131). Optical iridectomy may be a less risky surgical compromise in eyes with central corneal opacity. Postoperative Care, Prognosis, and Follow-up

The follow-up care of patients with PCG has several important facets. In the early postoperative period, close observation is required to maximize proper healing and odds of surgical success. In addition to IOP reduction, other clinical indicators of successful glaucoma control include clearing of corneal edema, reversal of optic nerve cupping, and even reduction in myopia in some cases (136). The IOP has also been related to postoperative visual capacity, with substantially better vision reported among those whose IOP remained no higher than 19 mm Hg in one series (105).

As with older patients, the target IOP for children with PCG should be guided by the severity of the optic nerve damage, with lower targets set for those eyes with lower central corneal thickness. In infants with healthy-appearing optic nerves (e.g., cupto-disc ratio <0.5), a target pressure of about 20 mm Hg is often adequate; the stability of the optic nerve, corneal diameter, and refraction help confirm the adequacy of the IOP. Conversely, target pressures in the mid-teens are usually set for infants and children with severe pre-existing optic nerve damage. In selected cases, eyes can remain stable despite IOPs in the lowto mid-20s when optic nerve cupping and ocular expansion have been minimal. Medications should be used to further reduce the IOP after surgery if the target IOP is not met. As with adults, auxiliary techniques such as visual fields and serial optic nerve examination should be used and the target IOP altered if progression occurs despite IOP control at the previously set target level.

Even when the IOP is well controlled, a substantial number of children never achieve good vision. In previous studies, approximately one half of the patients had visual acuities of less than 20/50 (105, 136, 137). This reduction may result from persistent corneal changes or from irreversible optic nerve damage.

A high percentage of patients, however, suffer amblyopia from the induced anisometropia, and it is critical that this condition be diagnosed early and managed appropriately.

Patients with PCG constitute a heterogeneous group, with overall IOP control achievable in more than 80% of cases. Although in rare cases primary infantile glaucoma has seemed to spontaneously remit (138, 139), most untreated cases result in buphthalmos and blindness (3). The prognosis for control of PCG varies with the patient's age at initial presentation and at surgery. Most favorable for IOP control with angle surgery are patients presenting after the first 2 months and within the first year of life (90%). Children presenting with glaucoma at birth or after the first year have a poorer prognosis for IOP control with angle surgery (50%) (7, 140). Even children whose glaucoma is well controlled after surgical therapy (with or without adjunctive medical therapy) deserve lifelong follow-up. Loss of IOP control (reported in as many as approximately one third of cases (7)) may occur months or even decades after initial success with surgery and may be asymptomatic in the older child or young adult.

Congenital glaucoma is usually managed surgically, initially with a goniotomy or trabeculotomy. Visual loss due to amblyopia is common and should be aggressively treated. Lifelong follow-up is needed to guard against late loss of IOP control and to detect associated ocular problems such as corneal decompensation, cataract, and progressive optic nerve injury from inadequate IOP.

PRIMARY GLAUCOMAS WITH ASSOCIATED ABNORMALITIES (DEVELOPMENTAL GLAUCOMAS)

General Terminology

There have been considerable discussion and confusion regarding the lumping, splitting, and classifying of this large number of disorders. As the molecular genetics of anterior

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segment dysgenesis is further elucidated, the genetic classification of many of these disorders may supersede our current phenotypic descriptions. Nonetheless, the historical basis of our current classification system is worthy of further description here because management of many of these cases still rests firmly on their phenotypic presentation.

For simplicity, we consider all of the primary glaucomas that have associated ocular abnormalities to be forms of anterior segment dysgenesis. Based on the observation that most of the ocular and facial structures involved in these developmental disorders are of neural crest origin (67, 141), the term neurocristopathies has been used as a unifying concept for diseases arising from neural crest maldevelopment (142, 143). Hoskins and colleagues (144) advocated a shift away from eponyms and syndrome names for individual disorders and toward an emphasis on descriptive terminology. Noting that the trabecular meshwork, iris, and cornea are the three major structures involved in these conditions, they suggested using the terms trabeculodysgenesis, iridodysgenesis, and corneodysgenesis, or combinations thereof, to classify the developmental defects. In a recent review, Idrees and colleagues (145) consider the anterior segment dysgenesis to include not only Axenfeld-Rieger syndrome, iridogoniodysgenesis-iris hypoplasia, and Peters anomaly, but also PCG, sclerocornea, megalocornea, congenital hereditary endothelial dystrophy, and aniridia. Although most of these anterior segment dysgeneses are attributed to defects in neural crest migration or differentiation, aniridia is considered to be of non-neural crest origin. Many of the anterior segment dysgeneses also may occur with associated systemic abnormalities, further blurring the distinction between primary glaucomas with associated ocular abnormalities and those with associated systemic abnormalities (Table 13.1).

Although there is value in categorizing disorders on the basis of anatomic descriptions and mechanisms, the overlapping of manifestations and limited understanding of disease mechanisms make it difficult to apply such a system in all cases of developmental glaucomas with associated anomalies. There is often great phenotypic variability between individuals with the identical genetic cause for a disease; variation may even occur among members of the same family, making tissue classification inaccurate. For these reasons, traditional eponyms and syndrome names are retained with some suggested modifications for the purpose of discussion in this chapter. (For additional genetic information related to these conditions, see Table 8.1.)

Axenfeld-Rieger Syndrome Terminology

In 1920, Axenfeld (146) described a patient with a white line in the posterior aspect of the cornea, near the limbus, and tissue strands extending from peripheral iris to this prominent line. Beginning in the mid-1930s, Rieger (147, 148 and 149) reported cases with similar anterior segment anomalies, but with additional changes in the iris, including corectopia, atrophy, and hole formation. Some of these patients also had associated systemic developmental defects, especially of the teeth and facial bones (150, 151). Axenfeld referred to his case as posterior embryotoxon of the cornea (146), and Rieger used the term mesodermal dysgenesis of the cornea and iris (149). Traditionally, these conditions have been designated by three eponyms: (a) Axenfeld anomaly (i.e., limited to peripheral anterior segment defects), (b) Rieger anomaly (i.e., peripheral abnormalities with additional changes in the iris), and (c) Rieger syndrome (i.e., ocular anomalies plus systemic developmental defects).

The similarity of anterior chamber angle abnormalities in the Axenfeld anomaly and the Rieger anomaly and syndrome led most investigators to agree that these three arbitrary categories represent a spectrum of developmental disorders (79, 152, 153). The overlap of ocular and systemic anomalies is such that the traditional classification is difficult to apply in all cases. Various collective terms have been applied to this spectrum of disorders, such as anterior chamber cleavage syndrome and mesodermal dysgenesis of the cornea and iris (149, 152). As discussed earlier, the theories of normal development on which these names are based are no longer believed to be correct. The former collective term included the central ocular defects of Peters anomaly (discussed later in this chapter). Although some patients may have the combined defects of the Axenfeld anomaly or the Rieger anomaly and the Peters anomaly, the association is rare and the mechanisms of the two disorders differ in most cases.

The alternative term, Axenfeld-Rieger syndrome, was proposed for all clinical variations within this spectrum of developmental disorders and is now commonly used in the literature (79, 154). This name retains reference to the original eponyms and does not depend on any theory of normal development, the understanding of which is still incomplete, nor does it require arbitrary subclassification of the clinical variations.

General Features

All patients with the Axenfeld-Rieger syndrome, irrespective of ocular manifestations, share the same general features: a bilateral, developmental disorder of the eyes; a frequent family history of the disorder, with an autosomal dominant mode of inheritance; no sex predilection; frequent systemic developmental defects; and a high incidence of associated glaucoma. The age at which the AxenfeldRieger syndrome is diagnosed ranges from birth to adulthood, with most cases recognized in infancy or childhood. The diagnosis may result from the discovery of an abnormal iris or other ocular anomaly, signs of congenital glaucoma, reduced vision in older patients, or systemic anomalies. In other cases, the condition is diagnosed during a routine examination, which might have been prompted by a family history of the disorder.

Ocular Features

Ocular defects in the Axenfeld-Rieger syndrome are typically bilateral. The structures most commonly involved are the peripheral cornea, anterior chamber angle, and iris.

Cornea

The characteristic abnormality of the cornea is a prominent, anteriorly displaced Schwalbe line. This appears on slitlamp

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examination as a white line on the posterior cornea near the limbus. The prominent line may be incomplete, usually limited to the temporal quadrant; in other patients, it may be seen for 360 degrees (Fig. 14.9). In some cases, the line can only be seen by gonioscopy, although rare cases with other ocular and systemic features of the syndrome may have grossly normal Schwalbe lines (155).

Figure 14.9 Right eye of a 6-year-old girl with Axenfeld-Rieger syndrome and congenital glaucoma. Note the prominent anteriorly displaced Schwalbe line, visible for almost 360 degrees. Ectropion uveae is also prominent. The pupil peaks toward the 11-o'clock position as a result of a glaucoma drainage device placed at 2 months of age. The tube also caused a focal cataract and an endothelial scar (before tube-shortening procedure). IOP is controlled and vision corrected to 20/40.

It is not uncommon for an individual to have a prominent Schwalbe line with no other evidence of Axenfeld-Rieger syndrome. This isolated defect is often referred to as posterior embryotoxon, the term originally used by Axenfeld (146), and it reportedly occurs in 8% to 15% of the general population (156, 157). Although it may represent a forme fruste of the Axenfeld-Rieger syndrome in some cases, it is not usually included in this spectrum of anomalies. A prominent Schwalbe line may only rarely be associated with other disorders, including congenital glaucoma and the iridocorneal endothelial (ICE) syndrome (83, 158) (Chapter 16).

The cornea is otherwise normal in the typical patient with the Axenfeld-Rieger syndrome, with the exception of occasional variation in the overall size (i.e., megalocornea or, less often, microcornea) or shape of the cornea (156). Congenital opacities of the central cornea have also been observed in a few cases. The corneal endothelium is typically normal. By specular microscopy, the cells have distinct margins, although mild-tomoderate variations in the size and shape are commonly observed, especially in older patients and those with long-standing glaucoma or previous intraocular surgery (79).

Anterior Chamber Angle

Gonioscopic examination typically reveals a prominent Schwalbe line, although the extent of enlargement and anterior displacement of the Schwalbe line varies considerably among patients. Occasionally, the line is suspended from the cornea in some areas by a thin membrane (79, 159). Tissue strands bridge the anterior chamber angle from the peripheral iris to the prominent ridge. These iridocorneal adhesions are typically similar in color and texture to the adjacent iris. The strands range in size from threadlike structures to broad bands extending for a clock-hour or more of the circumference. In some eyes, only one to two tissue strands are seen, whereas others have several per quadrant. Beyond the tissue strands, the anterior chamber angle is open and the trabecular meshwork is visible, but the scleral spur is typically obscured by peripheral iris, which inserts into the posterior portion of the

Figure 14.10 Left eye of a 16-year-old patient with Axenfeld-Rieger syndrome and congenital glaucoma. Note the corectopia, with the pupil displaced toward prominent peripheral tissue strands superiorly.

Iris

Aside from the peripheral abnormalities, the iris may be normal in some patients with the AxenfeldRieger syndrome. In other cases, defects of the iris range from mild stromal thinning to marked atrophy with hole formation, corectopia, and ectropion uveae. When corectopia is present, the pupil is usually displaced toward a prominent peripheral tissue strand, which is often visible by slitlamp biomicroscopy (Fig. 14.10). The atrophy and hole formation typically occur in the quadrant away from the direction of the corectopia.

In a small number of patients with the Axenfeld-Rieger syndrome, abnormalities of the central iris have been observed to progress (79, 161). This is more often seen in the first years of life, but may also occur in older patients. The progressive changes usually consist of displacement or distortion of the pupil and occasional thinning or hole formation of the iris. In some cases, these progressive iris changes may be confused with those of ICE syndrome. Abnormalities of the peripheral iris or anterior chamber angle do not appear to progress after birth, except for occasional thickening of iridocorneal tissue strands (79). Additional Ocular Abnormalities

Many additional ocular abnormalities have been reported in one or more cases or pedigrees. Although none occurs with sufficient frequency to be included as a typical feature of the Axenfeld-Rieger syndrome and they may represent separate

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entities, these patients can have a wide range of ocular anomalies—including strabismus, limbal dermoids, corneal pannus, cataracts, congenital ectropion uveae, congenital pupillary-iris-lens membrane, peripheral spokelike transillumination defects of the iris, retinal detachment, macular degeneration, chorioretinal colobomas, choroidal hypoplasia, and hypoplasia of the optic nerve heads (79, 156, 162, 163, 164, 165 and 166).

Glaucoma

Slightly more than one half of the patients with the Axenfeld-Rieger syndrome develop glaucoma. The glaucoma may manifest in infancy, although it more commonly appears in childhood or young adulthood. The extent of the iris defects and iridocorneal strands does not correlate precisely with the presence or severity of the glaucoma. However, the high insertion of peripheral iris into the trabecular meshwork, which is present to some degree in all cases, appears to be more pronounced in those eyes with glaucoma (79). The proposed mechanism of glaucoma in these cases relates to abnormalities of the trabecular meshwork and Schlemm canal (discussed in the Histopathologic Features and Theories of Mechanism section).

Systemic Features

The systemic anomalies most commonly associated with the Axenfeld-Rieger syndrome are developmental defects of the teeth and facial bones. The dental abnormalities include a reduced crown size (i.e., microdontia), a decreased but evenly spaced number of teeth (i.e., hypodontia), and a focal absence of teeth (i.e., oligodontia or anodontia) (150, 151, 167). The teeth most commonly missing are anterior maxillary primary and permanent central incisors. Facial anomalies include maxillary hypoplasia with flattening of the midface and a receding upper lip and prominent lower lip, especially in association with dental hypoplasia. Hypertelorism, telecanthus, a broad flat nose, micrognathia, and mandibular prognathism have also been described (156, 162).

Anomalies in the region of the pituitary gland are a less common but more serious finding associated with the Axenfeld-Rieger syndrome. A primary empty sella syndrome has been documented in several patients (154, 168), and in one case of congenital parasellar, an arachnoid cyst was reported (154). Growth hormone deficiency and short stature have also been described in association with the entity (169, 170). Other associated abnormalities include redundant periumbilical skin and hypospadias, oculocutaneous albinism, heart defects, middle-ear deafness, mental deficiency, and various neurologic, dermatologic, and skeletal disorders (156, 171, 172 and 173).

Histopathologic Features and Theories of Mechanism

The central cornea is typically normal, but the peripheral cornea has the characteristic prominent, anteriorly displaced Schwalbe line. The latter structure is composed of dense collagen and ground substance covered by a monolayer of spindleshaped cells with a basement membrane (79, 157, 159) (Fig. 14.11). The peripheral iris is attached in some areas to the corneoscleral junction by tissue strands, which usually connect with the prominent Schwalbe line. Occasionally, however, the adhesions insert anterior or posterior to the Schwalbe line or on both sides of the ridge (79). The strands consist of iris stroma, a membrane composed of a monolayer of spindleshaped cells or a basement membrane-like layer, or both.

Figure 14.11 Light microscopic view of an eye with Axenfeld-Rieger syndrome shows a prominent Schwalbe line, composed of dense collagen and ground substance covered by a monolayer of spindleshaped cells with a basement membrane. A: Anterior insertion of the iris is present; this may be seen in

several forms of developmental glaucoma. (Courtesy of Ramesh C. Tripathi, MD, PhD.) B: An iridocorneal adhesion (arrow) extending from the peripheral iris to the prominent Schwalbe line.

A membrane, similar to that associated with the iridocorneal tissue strands, has been observed on the iris, usually on the portion toward which the pupil is distorted (79, 156, 174). In the quadrants away from the direction of pupillary displacement, the stroma of the iris is often thin or absent, exposing pigment epithelium, which may also contain holes.

The iris peripheral to the iridocorneal adhesions inserts into the posterior aspect of the trabecular meshwork. The meshwork may be composed of a scant number of attenuated lamellae, which extend from beneath peripheral iris to the prominent Schwalbe line and are often compressed, especially in the outer layers. Transmission electron microscopic study suggests that the apparent compression may be caused by incomplete development of the trabecular meshwork (79). The Schlemm canal is rudimentary or absent.

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Figure 14.12 Theory of the mechanism for ocular abnormalities of Axenfeld-Rieger syndrome; insets show cross-sectional views of anterior chamber angle corresponding to area within the rectangle. A: Partial retention of the primordial endothelium (e) on the iris (i) and anterior chamber angle (aca); incomplete posterior recession of peripheral uvea from trabecular meshwork (tm); and abnormal differentiation between corneal and chamber angle endothelium with a prominent, anteriorly displaced Schwalbe line (SL). B: Development of tissue strands from retained endothelium crossing the anterior chamber angle. C: Contraction of retained endothelium with iris changes of corectopia (c), ectropion uvea (eu), and iris atrophy (ia), which may continue after birth; a tissue strand (ts) can also be seen. D: Incomplete development of trabecular meshwork and Schlemm canal (SC); continued traction on the iris with possible secondary ischemia leads to hole formation (h). (From Shields MB. Axenfeld-Rieger syndrome: a theory of mechanism and distinctions from the iridocorneal endothelial syndrome. Trans Am Ophthalmol Soc. 1983;81:736-784. Republished with permission of the American Ophthalmological Society.)

On the basis of clinical and histopathologic observations and the current concepts of normal anterior segment development, a developmental arrest, occurring late in gestation, of certain anterior segment structures derived from neural crest cells has been postulated as the mechanism of the Axenfeld-Rieger syndrome (79). This leads to the abnormal retention of the primordial endothelial layer on portions of the iris and anterior chamber angle and alterations in the aqueous outflow structures (Fig. 14.12). The retained endothelium with associated basement membrane is believed to create the iridocorneal strands,

whereas contraction of this tissue layer on the iris leads to the iris changes, which sometimes continue to progress after birth. The developmental arrest also accounts for the high insertion of anterior uvea into the posterior trabecular meshwork, similar to the alterations seen in congenital glaucoma. This results in the incomplete maturation of the trabecular meshwork and Schlemm canal, and these defects are thought to be responsible for the associated glaucoma.

The neural crest cells also give rise to most of the mesenchyme related to the forebrain and pituitary gland, bones and cartilages of the upper face, and dental papillae (142, 143). This may explain the developmental anomalies involving the pituitary gland, the facial bones, and the teeth. Neural crest cells also contribute to many other structures, including the walls of the aortic arches, genitalia, spinal ganglia, long bones, and melanocytes (172, 173), which appears to explain the wide range of systemic anomalies that may be seen in some patients with the Axenfeld-Rieger syndrome.

Genetic Linkage

The Axenfeld-Rieger syndrome is thought to have a genetic basis, with an autosomal dominant pattern of inheritance. Tremendous advances have been made in the understanding of the molecular genetics of Axenfeld-Rieger malformations (175, 176, 177, 178, 179, 180, 181, 182, 183, 184 and 185) (Table 8.2). Three chromosomal loci have been demonstrated to link to the Axenfeld-Rieger syndrome and related phenotypes. These loci are on chromosomes 4q25, 6p25, and 13q14. The genes at chromosomes 4q25 and 6p25 have been identified as PITX2 and FOXC1, respectively (182). Mutations in these genes can cause a wide variety of phenotypes that share features with the Axenfeld-Rieger syndrome, Axenfeld anomaly, Rieger anomaly, Rieger syndrome, iridogoniodysgenesis anomaly, iridogoniodysgenesis syndrome, iris hypoplasia, and familial glaucoma iridogoniodysplasia; these conditions all have sufficient genotypic and phenotypic overlap to be considered one disorder (16, 182). Genetically, the P.232

Axenfeld-Rieger syndromes can be considered in three types. Axenfeld-Rieger syndrome type 1 is caused by mutation in a homeobox transcription factor gene, PITX2 (OMIM 601542) (16). Linkage studies indicate that a second type of Axenfeld-Rieger syndrome maps to chromosome 13q14 (RIEG2; OMIM 601499). A third form of Axenfeld-Rieger syndrome (RIEG3; OMIM 602482) is caused by mutation in the FOXC1 gene (OMIM 601090) on chromosome 6p25 (16).

In a clinical series of patients with Axenfeld-Rieger syndrome and mutations in the PITX2 or FOXC1 genes (186), 75% of the patients had glaucoma that developed in adolescence or early adulthood, and patients with PITX2 defects or FOXC1 duplications had a more severe prognosis for glaucoma development than patients with FOXC1 mutations did (186). This complex genetic disorder has overlap with other anterior segment dysgeneses, and future studies may someday help predict how phenotypegenotype classification may assist in genetic counseling, as well as prognosis for glaucoma treatment and vision preservation in affected individuals.

Differential Diagnosis

Molecular genetic studies may ultimately make the differentiation among the following phenotypic entities less relevant. The following items are nonetheless useful for phenotypic classification of these disorders.

Iridocorneal Endothelial (ICE) Syndrome

The iris and anterior chamber angle abnormalities in this spectrum of disease (Chapter 16) resemble those of Axenfeld-Rieger syndrome clinically and histopathologically. This has led some investigators to suggest that the two syndromes are parts of a common spectrum of disorders (174, 187). However, clinical features that distinguish the ICE syndrome from the Axenfeld-Rieger syndrome include corneal endothelial abnormalities, unilaterality, absence of family history, and onset in young adulthood. Both conditions are characterized histopathologically by a membrane over the angle and iris, which is associated with many of the alterations in each disorder. Although the membrane in the Axenfeld-Rieger syndrome represents a primordial remnant, that of the ICE syndrome results from proliferation of the abnormal corneal endothelium.

Posterior Polymorphous Corneal Dystrophy

One variation of this developmental disorder of the corneal endothelium (Chapter 16) has changes of the iris and anterior chamber angle similar to those of the Axenfeld-Rieger syndrome. However, differentiation can be made on the basis of the typical corneal endothelial abnormality.

Peters Anomaly

The spectrum of disorders that constitutes Peters anomaly involves the central portion of the cornea, the iris, and the lens. Similar changes have been reported in association with the peripheral defects of the Axenfeld-Rieger syndrome, and the two conditions were once included in a single category of developmental disorders (153). However, this association is rare, and the mechanisms for the two groups of disorders are distinctly different. Nonetheless, families with known mutation in the FOXC1 gene have been reported with Axenfeld-Rieger syndrome in most members but Peters anomaly in others (177, 188).

Aniridia

The rudimentary iris and anterior chamber abnormalities with associated glaucoma in this developmental disorder (discussed later) may lead to confusion with the Axenfeld-Rieger syndrome in some cases. Mutations in the PITX2 gene may manifest with a wide variation in anterior segment anomalies, including those phenotypically similar to aniridia (185).

Iridogoniodysgenesis: Congenital Hypoplasia of the Iris

Patients may have congenital hypoplasia of the iris without the anterior chamber angle defects of the Axenfeld-Rieger syndrome. Autosomal dominant iridogoniodysgenesis anomaly type I (gene map locus 6p26) is caused by mutations in the FOXC1 gene and is characterized by iris hypoplasia, goniodysgenesis, and juvenile glaucoma. A distinct form of this condition also includes nonocular features and is referred to as iridogoniodysgenesis syndrome or iridogoniodysgenesis type 2. It maps to 4q25, is caused by mutations in the gene PITX2 (OMIM 601631, 137600), and may be allelic with Axenfeld-Rieger syndrome (16).

Oculodentodigital Dysplasia

The dental anomalies in oculodentodigital dysplasia are similar to those seen in the Axenfeld-Rieger syndrome. These patients occasionally have mild stromal hypoplasia of the iris, anterior chamber angle defects, microphthalmia, and glaucoma (189). This condition is caused by mutation in the connexin-43 gene (GJA1, gene map locus 6q21-q23.2, OMIM 164200) (16).

Ectopia Lentis et Pupillae

Ectopia lentis et pupillae is an autosomal recessive condition characterized by bilateral displacement of the lens and pupil (190), with the two typically displaced in opposite directions. The corectopia in this disorder may resemble that of the Axenfeld-Rieger syndrome, but the absence of anterior chamber angle defects is a differential feature (see Chapter 18).

Congenital Ectropion Uveae

Congenital ectropion uveae is a rare, nonprogressive anomaly characterized by the presence of pigment epithelium on the stroma of the iris (191, 192). It may be an isolated finding or appear in association with systemic anomalies, including neurofibromatosis, facial hemiatrophy, and the Prader-Willi syndrome (191). Glaucoma is present in a high percentage of cases, and the ectropion uvea may be confused with that found in some patients with the Axenfeld-Rieger syndrome.

Congenital Microcoria and Myopia

The condition of congenital microcoria and myopia, characterized by bilateral small pupils and myopia, results from an underdevelopment of the dilator pupillae muscle of the iris. Transmitted as an autosomal dominant trait, this disorder has been associated with goniodysgenesis and glaucoma

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(193, 194 and 195). Congenital microcoria has been linked to gene map locus 13q31-q32 (EntrezGene symbol MCOR, OMIM 156600) (16).

Patients with the Axenfeld-Rieger syndrome may have a wide variety of associated ocular and systemic developmental abnormalities, and it has not yet been established in many of these cases whether the patient has a variation of the Axenfeld-Rieger syndrome or whether the findings should be considered a