ADAMTSL4- Related Eye Disorders

Excerpt

Clinical characteristics: 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. Typical eye findings are dislocation of the lens, congenital abnormalities of the iris, refractive errors that may lead to amblyopia, and early-onset cataract. Increased intraocular pressure and retinal detachment may occur on occasion. Eye findings can vary within a family and between the eyes in an individual. In general, no additional systemic manifestations are observed, although skeletal features have been reported in a few affected individuals.

Diagnosis/testing: The diagnosis is established in individuals with characteristic eye findings by the identification of biallelic pathogenic (or likely pathogenic) variants in ADAMTSL4 by molecular genetic testing.

Management: Treatment of manifestations: In children, the main objective is to prevent amblyopia by early correction of refractive errors and patching. Surgery should be considered in individuals with cataracts, those at risk for complications caused by the dislocated lens, those in whom patching does not result in improvement of visual acuity, those in whom the lens edge is in the middle of the pupil, and those with insufficient correction of refractive errors, in particular large degrees of astigmatism. While lensectomy with anterior vitrectomy and correction of the aphakia with contact lenses or secondary intraocular lens (IOL) replacement has been the usual procedure in the past, capsule-sparing lens surgery has recently been introduced. Sphincterotomy can benefit individuals with small and highly displaced pupils. Increased intraocular pressure can in most cases be controlled by topical anti-glaucoma medication. Retinal detachment is treated in the usual manner by vitrectomy and scleral buckling if necessary.

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

Agents/circumstances to avoid: Care during contact sports to avoid trauma to the head. Avoid boxing and martial arts.

Evaluation of relatives at risk: Sibs of a proband should undergo complete ophthalmologic evaluation (determination of visual acuity, measurement of intraocular pressure, slit lamp examination, and ophthalmoscopy) to allow for early diagnosis and treatment of findings, primarily to prevent amblyopia. If the pathogenic variants in a family are known, molecular genetic testing is likely to be more helpful in clarifying the genetic status of at-risk sibs given the wide variability even within the same family.

Genetic counseling: ADAMTSL4-related eye disorders are inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives, prenatal testing for pregnancies at increased risk, and preimplantation genetic testing are possible if the pathogenic variants in the family are known.