Alström syndrome

Alström syndrome
SpecialtyMedical genetics, ophthalmology, neurology 
Symptomscone-rod dystrophy, photophobia, nystagmus, hearing impairment, cardiomyopathy, childhood obesity, extreme insulin resistance, accelerated non-alcoholic fatty liver disease, renal dysfunction, respiratory disease, endocrine and urologic disorders
Usual onsetClinical symptoms often appear in infancy but have great variability in both age of onset and symptom severity.
CausesVariants in the ALMS1 gene on chromosome 2p13
Diagnostic methodBased on symptoms and genetic testing
TreatmentManagement of symptoms
PrognosisLife expectancy is typically between 40-50 years
Named afterCarl-Henry Alström

Alström syndrome (AS) is a very rare multi-system, autosomal recessive genetic disorder characterized by type 2 diabetes, cone-rod dystrophy resulting in blindness, sensorineural hearing loss and cardiomyopathy. Endocrine disorders typically also occur, such as hypergonadotrophic hypogonadism and hypothyroidism, as well as acanthosis nigricans resulting from hyperinsulinemia.

AS is caused by variants in the ALMS1 gene, which is located on the chromosome 2-13 and is involved in the formation of cellular cilia, making Alström syndrome a ciliopathy. At least 300 disease-causing variants in ALMS1 have been described as of 2023. Alström syndrome is sometimes confused with Bardet–Biedl syndrome, another ciliopathy which has similar symptoms, but Bardet–Biedl syndrome tends to be associated with multiple genes, rather than just one like in AS, and includes polydactyly.

There is no cure or specific therapy for Alström syndrome. However, various treatments target the individual symptoms and can include diet, specialized glasses, hearing aids, medications for diabetes and heart issues, and dialysis and/or transplantation in the case of kidney or liver failure. Prognosis varies depending on the specific combination of symptoms, but individuals with Alström syndrome rarely live beyond 50.

Incidence of AS is cited as 1 in 1,000,000 individuals in the general population, but this is expected to be an underestimation due to the phenotypic variation of the disease and the high rate of misdiagnosis. There is a higher frequency of variants within French Acadians and English populations.