ALMS1 gene


Gene (OMIM no.)
Function of gene/protein
  • Protein: centrosome and basal body associated protein
  • Localized to centrosomes and base of primary cilia
  • Ubiquitously expressed
  • Exact function unknown but thought to be involved in cilium formation, intracellular trafficking and cytoskeletal organisation
Clinical phenotype
(OMIM phenotype no.)
  • Autosomal recessive
Ocular features
  • Ocular features are one of the earliest manifestations
  • Cone-rod dystrophy
  • Nystagmus (during infancy)
  • Photophobia
  • Vascular attenuation
  • RPE atrophy in the mid-periphery
  • Bull’s eye maculopathy/macular pigmentary changes
  • Optic disc pallor
  • Posterior sub-capsular cataract may be present
Visual function
  • Rapid progressive photoreceptor dysfunction eventually leading to blindness (usually in the 1st to 2nd decade of life)
  • Intra- and interfamilial variability in terms of age of onset, disease severity and rate of progression
Systemic features
  • Systemic features may be absent initially and manifest later in life
  • Bilateral progressive sensorineural hearing loss
  • Childhood truncal obesity
  • Metabolic disorders (insulin resistance, hyperinsulinaemia, type 2 diabetes mellitus, leptin resistance, hypertriglyceridaemia, hyperlipidaemia)
  • Hypogonadotrophic hypogonadism
  • Short stature due to growth hormone deficiency and hypothyroidism
  • Dilated cardiomyopathy
  • Acanthosis nigricans
  • Can also be associated with renal, pulmonary and hepatic fibrosis
  • Life expectancy rarely exceeds 40 years of age
Key investigations
  • Full field ERG: cone-rod dystrophy progressing to generalised retinal dysfunction over time
  • FAF: Areas of hypo-AF indicating RPE atrophy
  • OCT: progressive outer retinal thinning and attenuation (more severe changes outside the fovea)
  • Assessment with a paediatrician and other relevant specialists
Molecular diagnosisNext generation sequencing
  • Targeted gene panels (retinal)
  • Whole exome sequencing
  • Whole genome sequencing
Therapies under research
Further information

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Supporting Organisation

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Updated on November 30, 2020
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