Characterisation of the peripheral retinopathy in X-linked and autosomal recessive Alport syndrome. Nephrol Dial Transplant

Launceston General Hospital, Patersonia, Tasmania, Australia
Nephrology Dialysis Transplantation (Impact Factor: 3.58). 02/2007; 22(1):104-8. DOI: 10.1093/ndt/gfl607
Source: PubMed


Alport syndrome is an inherited disease resulting in kidney failure, hearing loss and ocular abnormalities. Alport syndrome is however often unrecognized, and the aim of this study was to characterize the associated but rarely described peripheral retinopathy and determine whether its demonstration was diagnostically helpful.
Index cases were diagnosed with Alport syndrome on renal biopsy in themselves or a family member. Inheritance and affected status were determined using microsatellite markers at the COL4A5 and COL4A3/COL4A4 loci, respectively. Participants' eyes were dilated, and examined with direct and indirect ophthalmoscopy, and slit lamp biomicroscopy by an expert ophthalmologist who was unaware of the patients' disease status.
Ten males and nine females with X-linked Alport syndrome and seven with autosomal recessive disease were studied. Of the 26 patients, 16 had central retinopathy (62%), and 19 patients had peripheral retinopathy (74%). The peripheral changes occurred in both males and females with X-linked and autosomal recessive Alport syndrome, and were more common when renal failure, hearing loss, lenticonus and the central changes were present, but were also noted in 3 X-linked carriers with normal renal function.
The peripheral retinopathy occurs in X-linked and autosomal recessive Alport syndrome even when the central retinopathy is absent. Careful retinal examination and photography that includes the periphery is a safe and inexpensive method that may help in the diagnosis of Alport syndrome especially in carriers of X-linked disease.

Download full-text


Available from: Robert G Fassett, Feb 04, 2014
  • [Show abstract] [Hide abstract]
    ABSTRACT: Remarkable progress has been made in the past decade in identifying genes involved with deafness in man and mouse. The identification of these genes and functional analysis of the proteins they encode are paving the way towards a better understanding of the physiology and pathophysiology of the auditory system. Given the complexity of auditory transduction and diversity of cochlear structures, it is not surprising that an estimate of at least 1 percent of human protein-coding genes are involved in perception of sound. Over 400 distinct syndromes of which hearing loss is a component have been reported ( Approximately 113 loci for monogenic disorders for which hearing loss is the only manifestation and therefore is nonsyndromic, have been mapped to the human genome ( As of August 2007, there are approximately 46 genes identified from these loci. Here, we review some of the major advances in our knowledge of auditory function within an evolving understanding of the structure and regulation of the machinery of hearing.
    Frontiers in Bioscience 02/2008; 13(13):4972-83. DOI:10.2741/3056 · 3.52 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction : Le syndrome d’Alport est une affection héréditaire caractérisée par l’existence d’une néphropathie hématurique progressive qui peut s’associer à une surdité de perception et des anomalies oculaires. Le but de notre étude est de déterminer l’incidence et les aspects cliniques de ces anomalies oculaires et d’identifier les modes de transmission au sein de notre population. Patients et méthodes : Trente-deux patients atteints de syndrome d’Alport appartenant à 10 familles différentes du Sud Tunisien ont été inclus dans l’étude. Tous les patients ont eu un examen ophtalmologique complet avec angiographie rétinienne selon les indications. L’étude génétique a été réalisée par l’étude des arbres généalogique et le génotypage. Résultats : Nous avons trouvé une meilleure acuité visuelle corrigée moyenne de 7,6/10e, une atteinte cornéenne à type de dystrophie postérieure polymorphe dans 3 %, une atteinte cristallinienne dans 47 %, un lenticône antérieur dans 28 %, des opacités cristalliniennes dans 3 %, une cataracte dans 19 % et des ponctuations rétiniennes dans 37 %. L’étude génétique a trouvé une transmission selon le mode dominant lié à l’X dans 5 familles, selon le mode autosomique récessif dans 4 familles et selon le mode autosomique dominant dans une famille. Discussion : L’atteinte oculaire associée à ce syndrome était rapportée dans 9 à 82 % selon les séries. Elle est rare chez les enfants et les jeunes patients et augmente en fréquence et en sévérité avec l’âge. Elle peut concerner le cristallin, la rétine et plus rarement la cornée. Les lésions caractéristiques sont le lenticône antérieur et les ponctuations rétiniennes maculaires. Le syndrome d’Aport se transmet selon le mode dominant lié à l’X dans 85 %. Dans 15 %, il se transmet selon le mode autosomique récessif et exceptionnellement selon le mode autosomique dominant. Conclusion : L’examen ophtalmologique peut présenter une aide précieuse au diagnostic du syndrome d’Alport. Il permet en plus de préjuger du pronostic de la néphropathie.
    Journal Français d Ophtalmologie 06/2008; 31(6):597-604. DOI:10.1016/S0181-5512(08)75461-5 · 0.39 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The diagnosis of X-linked Alport syndrome is often difficult, but the demonstration of lenticonus and retinopathy may facilitate the diagnosis in adult patients. The aim of this study was to determine the diagnostic usefulness of ocular examination in children. Fourteen families with at least one affected child were studied clinically, and COL4A5 mutations were determined. The families included 15 affected boys (median age 11 years, range 4-19 years). Two boys (13%) had renal failure, nine (60%) had a known hearing loss, one (7%) had lenticonus and five (33%) had a central (4/15, 27%) or peripheral (4/14, 29%) retinopathy. Lenticonus and retinopathy were first noted in 14 and 11 year olds, respectively. All boys with retinopathy had a hearing loss. The early onset retinopathy was associated with a severe mutation (Q1383X). Eight families (8/14, 57%) comprised only sons and mothers, and two mothers (2/12, 17%) had the retinopathy. Six boys (40%) would have been diagnosed with Alport syndrome on the basis of their own or their mother's ocular examinations. None of the six girls (median age 8 years, range 7-14 years) had ocular abnormalities. Hearing loss is usually highly sensitive for the diagnosis of Alport syndrome, but ocular examination of boys and their mothers at the initial consultation is a non-invasive test that is helpful in up to 40% cases.
    Pediatric Nephrology 09/2008; 23(8):1245-50. DOI:10.1007/s00467-008-0759-4 · 2.86 Impact Factor
Show more