Syndrome

L. Jay Katz


BASICS


DESCRIPTION


• A spectrum of developmental disorders resulting in bilateral iris and angle abnormalities frequently associated with secondary glaucoma and systemic anomalies including dental and facial bone abnormalities


• Nomenclature has changed through the years. Axenfeld anomaly, Rieger anomaly, and Axenfeld–Rieger syndrome have previously been classified separately but now are all considered to be a single entity representing a spectrum of related anterior segment developmental disorders collectively referred to as Axenfeld–Rieger syndrome.


EPIDEMIOLOGY


Incidence


Rare


Prevalence


Unknown


RISK FACTORS


Family history


Genetics


• Autosomal dominant with high penetrance


• Mutations at the following loci have been linked to Axenfeld–Rieger syndrome (1).


– Paired-like homeodomain transcription factor 2 (PITX2, 4p25): A transcription factor that regulates the expression of other genes in anterior segment structures, dental lamina, and the umbilical cord during embryonic development


– Forkhead box C1 (FOXC1) – formerly called Forkhead Drosophila homologue-like transcription factor gene – (FKHL7, 6p25): Another transcription factor


– Gap junction protein, alpha 1 (GJA1, 6q21q23.2): Encodes connexin 43 protein which forms gap junctions


– Paired box gene 6 (PAX6, 11p13)


– V-MAF avian musculoaponeurotic fibrosarcoma oncogene (MAF, 16q24)


– 13q14 (gene unknown)


GENERAL PREVENTION


No known modes of prevention, other than genetic counseling.


PATHOPHYSIOLOGY


• A neural crestopathy resulting from a genetically triggered arrest in anterior segment development during late gestation (2)


• Consequently, the aqueous outflow structures are incomplete and retained primordial endothelium covers the angle and iris (2)[C].


ETIOLOGY


• A genetic developmental disorder


• See “Pathophysiology


COMMONLY ASSOCIATED CONDITIONS


• The most common systemic anomalies associated with Axenfeld–Rieger syndrome are dental and facial bone abnormalities:


– Microdontia


– Hypodontia


– Oligodontia


– Anodontia


– Maxillary hypoplasia


– Hypertelorism


– Telecanthus


– Broad, flat nose


• Other less common systemic associations include:


– Pituitary anomalies including empty sella syndrome and growth hormone deficiency


– Redundant periumbilical skin


– Hypospadias


– Heart defects


– Middle ear deafness


– Mental retardation


• Ocular abnormalities that are not identified as part of the Axenfeld–Rieger spectrum but have been infrequently associated with Axenfeld–Rieger syndrome include:


– Strabismus


– Limbal dermoids


– Cataracts


– Iris transillumination defects


– Retinal detachment


– Macular degeneration


– Chorioretinal colobomas


– Choroidal hypoplasia


– Optic nerve hypoplasia


DIAGNOSIS


HISTORY


• Most cases are identified in infancy or childhood during a routine exam, often prompted by a positive family history.


• Often asymptomatic, but may present with the symptoms of infantile glaucoma such as blepharospasm, epiphora, and/or photophobia


• Glaucoma develops in 50%.


PHYSICAL EXAM


• Typically bilateral


• Ocular findings include a range of the following corneal, angle, and iris anomalies (3)[C]:


– A prominent, anteriorly displaced Schwalbe’s line (posterior embryotoxon) noted 360° or limited to the temporal quadrant with adherent peripheral iris strands.


– The cornea is usually otherwise normal, although megalocornea, microcornea, and central opacities have rarely been described.


– On gonioscopy, the iris inserts into the posterior meshwork, obscuring the scleral spur.


– The iris may be normal or stromal thinning, pseudopolycoria, corectopia, and/or ectropion uvea may be present.


– Peripheral iris changes usually do not progress after birth, but central iris anomalies have progressed during childhood in a small number of individuals.


– Elevated intraocular pressure may be present.


– Optic nerve cupping may develop. When the onset is in childhood, cupping is usually concentric with healthy surrounding disk tissue until late stages.


Pediatric Considerations


• In children, exams under anesthesia are often required. However, all children should also be examined without sedation to screen for amblyopia and monitor ocular motility.


• In children <3 years of age, monitor for the following signs as they may be indicative of the onset of glaucoma:


– Progressive corneal enlargement


– Increasing axial length


– Progressive myopia or rapid loss of hyperopia


DIAGNOSTIC TESTS & INTERPRETATION


Imaging


• Optic disc photos


• Consider optic nerve head imaging (optical coherence tomography, confocal scanning laser ophthalmoscopy, scanning laser polarimetry); hand-held optical coherence tomography (if available) may be used during exams under anesthesia.


Diagnostic Procedures/Other


Visual field (once the child is old enough to complete this test reliably, the age will vary depending on the child)


Pathological Findings


• Peripheral iris strands attached to (or sometimes anterior or posterior to) an anteriorly displaced, prominent Schwalbe’s line.


• A monolayer of spindle-shaped cells extends from the cornea to cover the angle and anterior surface of the iris.


• This layer of spindle-shaped cells is frequently seen covering the iris in areas toward which the pupil is displaced.


• The iris stroma may be thin or absent in areas away from the corectopia.


• Iris not adherent to the cornea typically inserts into the posterior aspect of the meshwork.


• The trabecular meshwork is composed of a reduced number of attenuated lamellae.


• Schlemm’s canal may be rudimentary or absent.


DIFFERENTIAL DIAGNOSIS


• Iridocorneal endothelial syndrome


• Posterior polymorphous dystrophy (PPMD)


• Posterior embryotoxon


• Peters anomaly


TREATMENT


MEDICATION


First Line


• Observation may be appropriate if no signs of ocular hypertension or glaucoma are present.


• Once elevated intraocular pressure develops, medical therapy should be initiated:


– Topical beta-blockers (in children, timolol 0.25%, levobunolol 0.25%, or betaxolol are reasonable options)


– Topical carbonic anhydrase inhibitors (e.g., dorzolamide, brinzolamide)


– Prostaglandin analogs (e.g., latanoprost, travoprost, bimatoprost)


– Topical alpha2-agonists (e.g., brimonidine)



ALERT


• Use of alpha2-agonists (e.g., iopidine, brimonidine) in children <1 year of age is not recommended due to potential central nervous system depression.

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Nov 9, 2016 | Posted by in OPHTHALMOLOGY | Comments Off on Syndrome

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