Diagnostic Criteria

The spectrum of ADAMTSL4-related eye disorders is a continuum that includes the phenotypes known as autosomal recessive isolated ectopia lentis and ectopia lentis et pupillae as well as more minor eye anomalies with no displacement of the pupil and very mild displacement of the lens. Variability in the eye findings is observed among affected individuals in a family and between the eyes of the same individual. No formal diagnostic criteria have been published.

Suggestive Findings

ADAMTSL4-related eye disorders should be suspected in individuals with the following characteristics:

Source: GeneReviews — "ADAMTSL4-Related Eye Disorders"

Differential Diagnosis

Table 2.

Disorders with Ectopia Lentis and/or Iris Anomalies to Consider in the Differential Diagnosis of ADAMTSL4-Related Eye Disorders

Disorder | Gene(s) | MOI | Distinguishing Clinical Features of Disorder

Ectopia lentis (OMIM 129600) | FBN11 | AD | May incl the systemic features of Marfan syndrome

Homocystinuria caused by cystathionine beta-synthase deficiency

| CBS | AR | • Tall, thin stature

• High-arched feet

• Chest anomalies

• Intellectual disability

• Seizures

• Arterial atheroma formation

Isolated sulfite oxidase deficiency

| SUOX | AR | • Seizures

• Ataxia

• Dystonia

• Choreoathetotic movements

Weill-Marchesani syndrome (WMS) | ADAMTS10

FBN1

LTPBP2

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease and the needs of an individual diagnosed with an ADAMTSL4-related eye disorder, routine ophthalmologic examination that includes the following is recommended if it has not already been completed:

• Determination of visual acuity and refractive error

• Measurement of intraocular pressure

Note: Affected individuals may have increased central corneal thickness that could explain, to some extent, why some individuals have moderately elevated intraocular pressure, but few have glaucomatous damage of the optic nerve head.

• Slit lamp examination

• Dilated fundus examination

The following may also provide important information:

• Orthoptic examination, particularly in children

• Measurement of axial length

• Anterior segment examination with optical coherence tomography and in selected individuals ultrasound biomicroscopy

• Corneal topography including measurement of corneal diameter and central corneal thickness

• Gonioscopy

Consultation with a clinical geneticist and/or genetic counselor is also recommended.

Treatment of Manifestations

Refractive errors. In children, the main objective is to prevent amblyopia by early correction of refractive errors. Patching is necessary when correction of the refractive error is insufficient in restoring vision. Lens abnormality. Surgery should be considered in individuals with cataracts, those at risk for complications caused by the dislocated lens (e.g.

Source: GeneReviews — "ADAMTSL4-Related Eye Disorders"

Surveillance Guidelines

Assess visual acuity, refractive error, and intraocular pressure one to three times per year: adults who are stable may be examined yearly, whereas children require more frequent examinations. Ultrasonography may be necessary to evaluate for retinal detachment if the view of the fundus is limited.

Source: GeneReviews — "ADAMTSL4-Related Eye Disorders"