Iridogoniodysgenesis Syndrome

Group of disorders characterized by malformations of the iridocorneal angle of the anterior chamber of the eye, resulting in juvenile glaucoma.

Glaucoma Iridogoniodysgenesis; IGDA Syndrome.

Iridogoniodysgenesis Type I (Autosomal Dominant Iridogoniodysgenesis Anomaly): Characterized by iris hypoplasia, goniodysgenesis, and juvenile glaucoma as a result of aberrant migration or terminal induction of the neural crest cells involved in formation of the anterior segment of the eye.

Iridogoniodysgenesis Type II (Iridogoniodysgenesis Syndrome; Autosomal Dominant Iris Hypoplasia with Early-Onset Glaucoma): Characterized by an autosomal dominant iris hypoplasia associated with early-onset glaucoma caused by maldevelopment of the trabecular meshwork and the iris. Glaucoma usually is detected in the second decade of life but may begin at any age.

Most cases are transmitted as an autosomal dominant trait with variable expressivity and complete penetrance. Two chromosomal loci can be involved: 4q25 and 6p25, corresponding to PITX2 (or RIEG) and FKHL7, respectively. PITX2, the most studied gene, is an homeobox gene coding for a transcription factor. Different levels of expression of this gene supposedly are responsible for the phenotypic variability of the syndrome.

Abnormal differentiation of neural crest cells causes “goniodysgenesis” (abnormalities in differentiation of the iridocorneal angle tissue). The anterior iris stroma is hypoplastic and associated with increased intraocular pressure, resulting in glaucoma.

Affected individuals often have an unusual dark-gray or chocolate-brown eye color as a result of the iris epithelium showing through the hypoplastic iris stroma. All patients are at risk for developing juvenile glaucoma, which is often diagnosed in the second decade of life, although it can begin at any age. The glaucoma is often resistant to medical therapy and, in the absence of surgical intervention, blindness may occur. Nonocular features, such as maxillary hypoplasia, dental anomalies (microdontia, hypodontia), umbilical hernia, and hypospadias, may present as part of the syndrome.

Inquire about severity of glaucoma and associated nonocular features. Obtain a list of topical antiglaucoma medications: echothiophate (long-acting anticholinesterase, which prolongs the effects of drugs that are metabolized by plasma cholinesterase such as succinylcholine, mivacurium, procaine, chloroprocaine, and cocaine), epinephrine (hypertension and dysrhythmias), and timolol (nonselective beta-blocker with potential for bradycardia, hypotension, bronchospasm in asthmatic patients, and decompensation of congestive heart failure). Selective beta-blockers such as betaxolol are considered safer in asthmatics.

The main anesthetic challenge is avoidance of intraocular pressure increases during direct laryngoscopy and tracheal intubation, as well as coughing, straining, and vomiting. In the presence of maxillary hypoplasia, intubation per se should not be technically difficult because the mandible remains normal. Intravenous lidocaine, adequate anesthetic depth, and use of a nondepolarizing muscle relaxant are the key elements in providing minimal changes in intraocular pressure during tracheal intubation. Like intracranial pressure, intraocular pressure is increased by hypercarbia and hypoxia and is reduced by hyperventilation, slight elevation of the head, osmotic diuretics, and carbonic anhydrase inhibitors.

The majority of central nervous system depressants drugs—barbiturates, narcotics, and neuroleptics—as well as inhalational anesthetics, contribute to decreasing intraocular pressure. Both ketamine and succinylcholine increase intraocular pressure. If a rapid-sequence induction is indicated, a nondepolarizing muscle relaxant such as rocuronium can replace succinylcholine. If succinylcholine remains the only alternative, no reported method has been shown to consistently prevent the transient increases in intraocular pressure caused by the drug, although pretreatment with a nondepolarizing muscle relaxant followed by the administration of a barbiturate and then by succinylcholine may provide slightly lower changes in intraocular pressure.

Rieger Anomaly or Syndrome (Iridogoniodysgenesis with Somatic Anomalies; Rieger Syndrome Type I): Characterized by hypodontia (partial anodontia) with malformation of the anterior chamber of the eye. The ocular features are microcornea with opacity, hypoplasia of the iris, and anterior synechiae. Myotonic dystrophy and anal stenosis are considered consistent associated features, although some authors have failed to find the presence of myotonia. Until proven otherwise, the potential association of myopathy should be considered in anesthesia. Renal malformations have been suggested.

Cat Eye Syndrome: Characterized by facies consisting of broad nasal root with telecanthus and maxillary hypoplasia with protruding lower lip. Severe developmental anomalies of the iris associated with maldevelopment of the ear and maxilla, umbilical hernia, and anal stenosis are features of this syndrome. Glaucoma is often found in association with this anomaly.

Axenfeld Anomaly: Defects limited to the peripheral anterior segment of the eye associated with bridges of iris tissue crossing the angle to Schwalbe ring; considered a separate entity. It is one feature of Rieger syndrome. It is associated with a male-to-male transmission.

Anterior Segmental Ocular Dysgenesis (ASOD): Characterized by the presence of iridogoniodysgenesis, glaucoma, maxillary hypoplasia, short philtrum, protruding lower lip of mild prognathism, dental anomalies (microdontia, hypodontia, and cone-shaped teeth), and failure of involution of the umbilicus (often treated surgically in the neonatal period because of confusion with umbilical hernia). Resembles Rieger syndrome.

Posterior Embryotoxon: Characterized by an anterior displacement and prominence of the Schwalbe line. The thickened (hypertrophied) Schwalbe's ring is visible through a clear cornea as a sharply defined, concentric white line or opacity anterior to the limbus. In the presence of posterior embryotoxon it is very important to eliminate the possibility of the Jagged syndrome.

Jagged Syndrome Type I (Deafness, Congenital Heart Defects, and Posterior Embryotoxon Syndrome): Characterized by multiple systemic defects with significant major development of the distal cardiac outflow tract and pulmonary artery, major arteries, portal vein, optic vesicle, otocyst, branchial arches, metanephros, pancreas, mesocardium, around the major bronchial branches, and in the neural tube. The authors conclude that the JAG1 gene is expressed in the structures affected in Alagille syndrome.