Ophthalmic features of cone-rod dystrophy caused by pathogenic variants in the ALMS1 gene.

Authors

Nasser F1, Weisschuh N2, Maffei P3, Milan G3, Heller C4, Zrenner E1,5, Kohl S2, Kuehlewein L1.
  1. Institute for Ophthalmic Research, Centre for Ophthalmology, Eberhard Karls University, Tuebingen, Germany.
  2. Molecular Genetics Laboratory, Institute for Ophthalmic Research, Centre for Ophthalmology, Eberhard Karls University, Tuebingen, Germany.
  3. Department of Medicine (DIMED), University of Padua, Padua, Italy.
  4. CeGaT GmbH and Praxis fuer Humangenetik Tuebingen, Tuebingen, Germany.
  5. Werner Reichardt Centre for Integrative Neuroscience (CIN), Tuebingen, Germany.

Abstract

PURPOSE:

We aim to describe ophthalmic characteristics and systemic findings in a cohort of seven patients with cone-rod retinal dystrophy (CORD) caused by pathogenic variants in the ALMS1 gene.

METHODS:

Seven patients with Alström syndrome (ALMS) were included in the study. A comprehensive ophthalmological examination was performed, including best-corrected visual acuity (BCVA), a semiautomated kinetic visual field exam, colour vision testing, full-field electroretinography testing according to International Society for Clinical Electrophysiology of Vision (ISCEV) standards, spectral domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF) imaging, and slit lamp and dilated fundus examination. DNA samples were analysed using Sanger sequencing or exome sequencing.

RESULTS:

In our cohort, the ocular phenotype presented with a wide variability in retinal function and disease severity. However, age of symptom onset (i.e. nystagmus and photophobia) was at 6-9 months in all patients. These symptoms mostly mislead to the diagnosis of congenital achromatopsia (ACHM), Leber congenital amaurosis (LCA), isolated CORD or Bardet-Biedl syndrome. The systemic manifestations in our cohort were highly variable.

CONCLUSION:

In summary, we can report that most of our ALMS patients primarily presented with nystagmus and severe photophobia since early childhood interestingly without night blindness in the absence of systemic symptoms. Only genetic testing analysing both nonsyndromic retinal disease (RD) genes and syndromic ciliopathy genes by comprehensive panel sequencing can result in the correct diagnosis, genetically and clinically, with important implication for the physical health of the individual.