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Introduction
Inherited ectopia lentis or ectopia lentis et pupillae can be either isolated or syndromic and have autosomal dominant or autosomal recessive modes of inheritance.1–4 The most common causes for ectopia lentis and ectopia lentis et pupillae are pathogenic variants in the FBN1 gene causing an autosomal dominant inheritance pattern (both syndromic and isolated) and the ADAMTSL4 gene causing autosomal recessive inheritance pattern (isolated).5,6 The ADAMTSL4 gene belongs to ADAMTS, a disintegrin and metalloproteinase with thrombospondin motifs gene family,7 and encodes proteins for cellular adhesion, angiogenesis, nervous system development, and anterior and posterior segment structures, especially the lens epithelium.8 In cell culture, ADAMTSL4 increases fibrillin-1 assembly into microfibrils.8 Abnormal ADAMTSL4 gene function disturbs this process, which results in abnormal stretching of zonular fibers.8,9
Additional genetic causes of inherited ectopia lentis with systemic features10 include: homocystinuria,11 Ehlers-Danlos syndrome,12 Weill-Marchesani syndrome,13 hyperlysinemia,14 and sulfite oxidase deficiency disorder.15 Ectopia lentis can also occur in other ophthalmologic conditions such as high myopia, buphthalmos, anterior uveal tumors, exfoliation syndrome, and hypermature cataracts.10
Case Report
We describe a 4-year-old girl referred to the genetics clinic by her ophthalmologist with the diagnosis of ectopia lentis et pupillae for evaluation of an underlying inherited syndrome. Her mother was a 22-year-old, otherwise healthy, gravida 1 para 1 woman with an uncomplicated pregnancy and normal spontaneous vaginal delivery. Our proband was healthy with no other significant medical history and no known cardiac abnormalities. Laboratory tests that were performed during an earlier evaluation included a normal urine homocysteine level and a normal gene panel for thoracic aortic aneurysm and dissection, Marfan syndrome, and related disorders.
A three-generation pedigree (Figure 1) was obtained and was negative for ectopia lentis, sudden deaths in the family, tall stature, or cardiac issues. The only significant history was in her paternal grandfather, who was born deaf and had vision loss due to retinitis pigmentosa in his teenage years. His history was suggestive of Usher syndrome and not associated with ectopia lentis.
Physical examination with special attention to height, arm span, wrist and thumb sign, and skeletal features of Marfan syndrome was negative. Ophthalmologic examination revealed corrected visual acuity of 20/200 in the right eye and 20/80 in the left eye. Extraocular movements were full and pupillary...