Leber congenital amaurosis is a rare autosomal recessive genetic disease of the retina characterized by an early onset of nystagmus, subnormal pupillary function, and blindness. A complete ophthalmologic exam, electroretinography, as well as genetic studies, are necessary steps in order to make the diagnosis.
Leber congenital amaurosis (LCA) is considered to be one of the most common (but also one of the most severe) hereditary disorders of impaired vision that develop during the first several years of life [1]. LCA is principally transferred through an autosomal recessive mode of inheritance, and first clinical signs appear after only 6 months in most patients [2] [3] [4] [5]. Phenotypic features are broad in this inherited retinal dystrophy, as numerous mutations cause variably progressive degeneration of the retina and loss of its function [2] [3] [6]. In virtually all cases, however, the clinical presentation is comprised of vision loss and diminished pupillary responses [2]. The inability of eye fixation is readily observed during the first few months of life, whereas refractive errors (hypermetropia, myopia), as well as photophobia, constant eye poking, pressing, or rubbing (known as Franceschetti signs) and consequent enophthalmos are commonly encountered [2] [7]. Other notable features include nystagmus, keratoconus, night blindness (in later life), and the development of juvenile cataracts [2] [7]. In many patients, unfortunately, visual acuity is severely reduced, and the perception of light is markedly impaired [2]. Thus, with a somewhat different clinical course, permanent and irreversible blindness ensues, but rare patients have known to improve overall visual function [2] [3] [6] [7].
Although several forms of inherited retinal disorders may be included in the differential diagnosis, initial recognition of LCA in early life can be made with a comprehensive clinical assessment. Firstly, a detailed patient history addressing the course and progression of symptoms should be obtained from the parents, after which a complete physical examination needs to be carried out. If the ocular exam is conducted properly, typical signs and symptoms of LCA can be observed and a presumptive diagnosis of a retinal dystrophy might be made [2]. In fact, the physical examination is considered to be the pivotal part of the diagnostic workup, as both physical and ophthalmoscopy findings (a myriad of fundus abnormalities is seen, such as the salt-and-pepper appearance of the retina) are highly indicative of LCA [2] [6]. A more concrete diagnosis is made through the use of an electroretinogram (ERG), which shows reduced or completely absent activity of the retina, pointing toward retinal dysfunction as the cause of symptoms [1] [2] [4] [6]. In addition, optical coherence tomography (OCT) is also recommended by some authors, as it allows measuring of the retinal thickness that is often reduced in LCA patients [1] [4] [6]. To exclude other retinal dystrophies and confirm LCA as the underlying disorder, genetic testing is mandatory. More than 20 different genes have been linked with the pathogenesis of LCA (most important being GUCY2D and RPE65), and a detailed evaluation of respective genes is helpful in determining the exact mutations that have led to LCA [1] [2] [3] [4] [6].